Miracle-dz/UniFAR-FTUs huggingface dataset:
fhuA of Actinobacillus pleuropneumoniae Encodes a Ferrichrome Receptor but Is Not Regulated by Iron

ABSTRACT The swine pathogen Actinobacillus pleuropneumoniae possesses a 75-kDa outer membrane protein (OMP), FhuA, the receptor for ferrichrome, a hydroxamate-type siderophore. Polyclonal serum to FhuA reacted with OMP preparations from 12 serotypes of A. pleuropneumoniae under conditions of iron repletion and restriction. Reverse transcription-PCR confirmed that A. pleuropneumoniae fhuA expression is not upregulated in response to low iron levels. An A. pleuropneumoniae fhuA deletion mutant was generated and showed abolishment of ferrichrome uptake.
Polyacetylenes from Notopterygium incisum–New Selective Partial Agonists of Peroxisome Proliferator-Activated Receptor-Gamma

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of glucose and lipid metabolism and therefore an important pharmacological target to combat metabolic diseases. Since the currently used full PPARγ agonists display serious side effects, identification of novel ligands, particularly partial agonists, is highly relevant. Searching for new active compounds, we investigated extracts of the underground parts of Notopterygium incisum, a medicinal plant used in traditional Chinese medicine, and observed significant PPARγ activation using a PPARγ-driven luciferase reporter model. Activity-guided fractionation of the dichloromethane extract led to the isolation of six polyacetylenes, which displayed properties of selective partial PPARγ agonists in the luciferase reporter model. Since PPARγ activation by this class of compounds has so far not been reported, we have chosen the prototypical polyacetylene falcarindiol for further investigation. The effect of falcarindiol (10 µM) in the luciferase reporter model was blocked upon co-treatment with the PPARγ antagonist T0070907 (1 µM). Falcarindiol bound to the purified human PPARγ receptor with a Ki of 3.07 µM. In silico docking studies suggested a binding mode within the ligand binding site, where hydrogen bonds to Cys285 and Glu295 are predicted to be formed in addition to extensive hydrophobic interactions. Furthermore, falcarindiol further induced 3T3-L1 preadipocyte differentiation and enhanced the insulin-induced glucose uptake in differentiated 3T3-L1 adipocytes confirming effectiveness in cell models with endogenous PPARγ expression. In conclusion, we identified falcarindiol-type polyacetylenes as a novel class of natural partial PPARγ agonists, having potential to be further explored as pharmaceutical leads or dietary supplements.
Strange and Unconventional Isotope Effects in Ozone Formation

The puzzling mass-independent isotopic enrichment in ozone formation contrasts markedly with the more recently observed large unconventional mass-dependent ratios of the individual ozone formation rate constants in certain systems. An RRKM (Rice, Ramsperger, Kassel, Marcus)-based theory is used to treat both effects. Restrictions of symmetry on how energy is shared among the rotational/vibrational states of the ozone isotopomer, together with an analysis of the competition between the transition states of its two exit channels, permit the calculation of isotope effects consistent with a wide array of experimental results.
Purification of bacteriocin LS1 produced by human oral isolate Lactobacillus salivarius BGHO1.

INTRODUCTION Lactobacillus salivarius BGHO1, a human oral isolate with antagonistic activity against growth of Streptococcus mutans, Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis, Micrococcus flavus, and Salmonella enteritidis, probably produces more than one proteinaceous antimicrobial substance. The objective of this study was the purification of a bacteriocin, named LS1, produced by L. salivarius BGHO1. METHODS A simple and fast procedure for bacteriocin purification was developed, consisting of reverse-phase chromatography of the ammonium sulfate precipitate of cell-free culture supernatant by fast protein liquid chromatography and high-performance liquid chromatography, followed by tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), with the subsequent extraction of bacteriocin from the gel. RESULTS The supernatant of L. salivarius BGHO1 culture retained its antimicrobial activity after boiling in a water bath for 15 min. Its antimicrobial activity was also maintained even after treatment for 20 min at 121 degrees C in an autoclave. Bacteriocin LS1 was purified to homogeneity. The molecular mass of bacteriocin LS1 was estimated to be approximately 10 kDa, based on tricine SDS-PAGE. During purification, another compound with antimicrobial activity, produced by L. salivarius BGHO1, was detected. The molecular mass of this compound was estimated to be approximately 5 kDa, based on tricine SDS-PAGE. CONCLUSION Our results imply that LS1 is most probably a new bacteriocin, different from previously described bacteriocins produced by L. salivarius strains. The purification of bacteriocin LS1 enabled the further characterization of LS1 on both the molecular and genetic levels.
The Influence of Contrast Agent's Osmolarity on Iodine Delivery Protocol in Coronary Computed Tomography Angiography: Comparison Between Iso-Osmolar Iodixanol-320 and Low-Osmolar Iomeprol-370

Objectives This study aims to assess whether iodine-contained contrast agents with different osmolarity affect iodine delivery protocol during coronary computed tomography angiography (CCTA). Methods Patients who underwent CCTA were randomized to receive contrast media either iodixanol-320 (iso-osmolar group) or iopromide-370 (low-osmolar group). Contrast protocols were recorded. Tube voltage of 100 kV was chosen for patients with body mass index of less than or equal to 25 (n = 224) and tube voltage of 120 kV for patients with body mass index of greater than 25 (n = 165). Both groups applied automatic current modulation technique. Mean contrast enhancement of the ascending aorta, left main coronary artery, and descending aorta was calculated. Simulated contrast flow rate and iodine delivery rate (IDR) to reach a mean contrast enhancement level of 350 HU were calculated. Results A total of the 389 patients were enrolled in the study. To achieve the same contrast enhancement of 350 HU, iso-osmolar group required higher simulated contrast flow rate (3.90 vs 3.62 mL/s, P = 0.017) but lower simulated IDR (1.34 vs 1.25 g/s, P = 0.024) compared with low-osmolar group. Conclusions To maintain a similar level of contrast enhancement during CCTA, iodixanol-320 needs larger contrast flow rate with lower IDR compared with low-osmolar iopromide-370.
Dietary fiber intake and subsequent risk of colorectal cancer: The Japan Public Health Center‐Based Prospective Study

Results on the association of dietary fiber intake with colorectal cancer risk were inconsistent among previous large prospective studies, but studies in non‐Western populations are lacking. Consequently, the authors investigated the association between dietary fiber intake and the subsequent risk of colorectal cancer in a prospective cohort study of a Japanese population. Dietary fiber intake was estimated from food‐frequency questionnaires comprising 44 or 52 items at the baseline survey and 138 food items at a 5‐year follow‐up survey. The authors identified 907 cases of colorectal adenocarcinoma diagnosed pathologically in 86,412 subjects during a 10‐year follow‐up from the baseline survey. After the 5‐year follow‐up survey, 522 cases were identified in 78,326 subjects during a 5.8‐year follow‐up. The authors estimated the multivariate‐adjusted hazard ratios of colorectal cancer for dietary fiber intake using Cox's proportional hazards model. The authors found no statistically significant association between dietary fiber intake and colorectal cancer in analyses using data either from the baseline survey or from the 5‐year follow‐up survey. However, the risk of only the lowest quintile was high, compared with the second to the fifth quintiles. Furthermore, the lowest subtertile in the lowest quintile was associated with an increased risk in women (hazard ratioSub1 vs. Q5, 2.3; 95% confidence interval, 1.0–5.2). In conclusion, although a minor effect cannot be ruled out, the results did not support a hypothesis of a dose‐dependent protective effect of dietary fiber intake against colorectal cancer. © 2006 Wiley‐Liss, Inc.
Generating ground truth for music mood classification using mechanical turk

Mood is an important access point in music digital libraries and online music repositories, but generating ground truth for evaluating various music mood classification algorithms is a challenging problem. This is because collecting enough human judgments is time-consuming and costly due to the subjectivity of music mood. In this study, we explore the viability of crowdsourcing music mood classification judgments using Amazon Mechanical Turk (MTurk). Specifically, we compare the mood classification judgments collected for the annual Music Information Retrieval Evaluation eXchange (MIREX) with judgments collected using MTurk. Our data show that the overall distribution of mood clusters and agreement rates from MIREX and MTurk were comparable. However, Turkers tended to agree less with the pre-labeled mood clusters than MIREX evaluators. The system evaluation results generated using both sets of data were mostly the same except for detecting one statistically significant pair using Friedman's test. We conclude that MTurk can potentially serve as a viable alternative for ground truth collection, with some reservation with regards to particular mood clusters.
Efficient Optimal Learning for Contextual Bandits

We address the problem of learning in an online setting where the learner repeatedly observes features, selects among a set of actions, and receives reward for the action taken. We provide the first efficient algorithm with an optimal regret. Our algorithm uses a cost sensitive classification learner as an oracle and has a running time polylog(N), where N is the number of classification rules among which the oracle might choose. This is exponentially faster than all previous algorithms that achieve optimal regret in this setting. Our formulation also enables us to create an algorithm with regret that is additive rather than multiplicative in feedback delay as in all previous work.
Community Structure and Environmental Conditions in Florida Shallow Lakes Dominated by Submerged Aquatic Vegetation

Abstract Florida inland waters are dominated by shallow lakes, many of which support the growth of submerged aquatic vegetation (SAV). We examined the species composition and selected environmental variables of SAV-dominated lakes using data from the Florida LAKEWATCH program. Our analysis revealed eight genera with approximately 15 species of SAV among these shallow lakes, which range in size from <2–2,300 ha. The SAV community within each lake primarily consisted of a single or a few species. Utricularia and Hydrilla were the most common SAV genera found in these lakes. Many SAV species grew well in a wide range of water quality conditions, although biodiversity and biomass tended to increase with increasing alkalinity and calcium concentration. More SAV species were also found in lakes with higher pH and Secchi depth. On average, Ceratophyllum, Najas and Vallisneria dominated lakes with high total phosphorus (TP) concentrations (0.034–0.053 mg/L) while Chara, Utricularia, Potamogeton and Myriophyllum corresponded with relatively low TP concentrations (0.008–0.013 mg/L). However, there was a large overlap in nutrient concentrations in lakes dominated by different species.
Potential consequences of healthcare recommendations: A focus on the U.S. Preventive Services Task Force

Healthcare guidelines and recommendations have broad‐reaching impact. They serve as the evidence to enforce medical testing by establishing a bar for standard of care through their intrinsic credibility but also by affecting reimbursement. In this article, we discuss the various organizations in the United States that develop healthcare policy and guidelines. We focus on the recent recommendations for hepatitis C virus (HCV) screening put forward by these agencies and the potential effect of these documents. Additional discussion is provided on the recent draft HCV screening recommendations provided by the United States Preventive Services Task Force (USPSTF), comparison of these to the Centers for Disease Control and Prevention (CDC) guidelines, and professional societies' response to these. Conclusion: As written, the USPSTF recommendations may reduce physician adoption of HCV screening in the 1945‐1965 birth cohort as advocated by the CDC. Conflicting guidelines may further confuse providers and the public. This will ultimately hinder recognition of chronic HCV in an otherwise easily identifiable, high prevalence group, allowing progression of disease at a time when therapeutic advances make cure a realistic opportunity for many. (HEPATOLOGY 2013 )
Enhanced Levels of Interleukin-8 Are Associated with Hepatitis B Virus Infection and Resistance to Interferon-Alpha Therapy

The objective of this study was to analyze the expression levels of IL-8 in serum and liver tissues from patients with chronic hepatitis B (CHB) infection and to investigate whether IL-8 may antagonize interferon-alpha (IFN-α) antiviral activity against HBV. IL-8 expression in serum was determined by enzyme linked immunosorbent assay (ELISA), and fluorescence-based quantitative real-time PCR (RT-qPCR) was used to measure IL-8 mRNA in peripheral blood mononuclear cells (PBMCs) in patients with CHB. IL-8 protein expression was detected in liver biopsy tissues by immunohistochemistry. In addition, the differences in serum IL-8 and PBMCs mRNA levels were also observed in patients with different anti-viral responses to IFN-α. Compared to normal controls, serum IL-8 protein and mRNA levels were increased in CHB patients, IL-8 levels were positively correlated with the severity of liver inflammation/fibrosis. Moreover, serum IL-8 protein and mRNA levels were positively correlated with serum alanine aminotransferase (ALT) level and negatively correlated with serum prealbumin (PA) level. IL-8 expression was mainly located in portal area of liver tissues and was increased with the severity of liver inflammation and fibrosis stage. The expression serum and mRNA levels of IL-8 in the CHB patients with a complete response to IFN-α are significantly lower than that of the patients with non-response to IFN-α treatment. It is suggested that IL-8 might play important roles in the pathogenesis of CHB. Moreover, interferon resistance may be related to the up-regulation of IL-8 expression in the patients did not respond to IFN-α treatment.
Analysis of a Growth-Phase-Regulated Two-Component Regulatory System in the Periodontal Pathogen Treponema denticola

ABSTRACT Nothing is currently known regarding the global regulatory networks of Treponema denticola and other oral spirochetes. In this report, we assess the properties and potential phosphotransfer capability of a putative two-component regulatory system (TCS) of T. denticola that is formed by the products of open reading frames tde0032 (a sensor kinase) and tde0033 (a response regulator), henceforth designated AtcS and AtcR, respectively. Using PCR and DNA sequence analyses, atcS and atcR were demonstrated to be widely distributed and conserved among T. denticola isolates. Reverse transcription-PCR (RT-PCR) analyses revealed that these genes are cotranscribed and may also be expressed as part of a larger operon that includes several flanking genes. Analyses using 5′ rapid amplification of cDNA ends identified the transcriptional start sites for these operons and provided evidence that some of these genes may be independently transcribed from internal promoters. Real-time RT-PCR and Western blot analysis revealed significant upregulation of atcRS during late-stage growth, indicating growth-phase-dependent expression. Lastly, the phosphorelay capability of the AtcRS system was assessed and demonstrated using recombinant proteins. AtcS was found to undergo autophosphorylation and to transfer phosphate to AtcR. These analyses represent the first description of a functional TCS in an oral spirochetes and provide insight into the transcriptional regulatory mechanisms of these important bacteria.
A neurobiological enquiry into the origins of our experience of the sublime and beautiful

Philosophies of aesthetics have posited that experience of the sublime—commonly but not exclusively derived from scenes of natural grandeur—is distinct from that of beauty and is a counterpoint to it. We wanted to chart the pattern of brain activity which correlates with the declared intensity of experience of the sublime, and to learn whether it differs from the pattern that correlates with the experience of beauty, reported in our previous studies (e.g., Ishizu and Zeki, 2011). 21 subjects participated in a functional magnetic resonance imaging experiment. Prior to the experiment, they viewed pictures of landscapes, which they rated on a scale of 1–5, with 5 being the most sublime and 1 being the least. This allowed us to select, for each subject, five sets of stimuli—from ones experienced as very sublime to those experienced as not at all sublime—which subjects viewed and re-rated in the scanner while their brain activity was imaged. The results revealed a distinctly different pattern of brain activity from that obtained with the experience of beauty, with none of the areas active with the latter experience also active during experience of the sublime. Sublime and beautiful experiences thus appear to engage separate and distinct brain systems.
Mechanisms of Caffeine-Induced Inhibition of UVB Carcinogenesis

Sunlight-induced non-melanoma skin cancer is the most prevalent cancer in the United States with more than two million cases per year. Several studies have shown an inhibitory effect of caffeine administration on UVB-induced skin cancer in mice, and these studies are paralleled by epidemiology studies that indicate an inhibitory effect of coffee drinking on non-melanoma skin cancer in humans. Strikingly, decaffeinated coffee consumption had no such inhibitory effect. Mechanism studies indicate that caffeine has a sunscreen effect that inhibits UVB-induced formation of thymine dimers and sunburn lesions in the epidermis of mice. In addition, caffeine administration has a biological effect that enhances UVB-induced apoptosis thereby enhancing the elimination of damaged precancerous cells, and caffeine administration also enhances apoptosis in tumors. Caffeine administration enhances UVB-induced apoptosis by p53-dependent and p53-independent mechanisms. Exploration of the p53-independent effect indicated that caffeine administration enhanced UVB-induced apoptosis by inhibiting the UVB-induced increase in ATR-mediated formation of phospho-Chk1 (Ser345) and abolishing the UVB-induced decrease in cyclin B1 which resulted in caffeine-induced premature and lethal mitosis in mouse skin. In studies with cultured primary human keratinocytes, inhibition of ATR with siRNA against ATR inhibited Chk1 phosphorylation and enhanced UVB-induced apoptosis. Transgenic mice with decreased epidermal ATR function that were irradiated chronically with UVB had 69% fewer tumors at the end of the study compared with irradiated littermate controls with normal ATR function. These results, which indicate that genetic inhibition of ATR (like pharmacologic inhibition of ATR via caffeine) inhibits UVB-induced carcinogenesis support the concept that ATR-mediated phosphorylation of Chk1 is an important target for caffeine’s inhibitory effect on UVB-induced carcinogenesis.
IRG and GBP Host Resistance Factors Target Aberrant, “Non-self” Vacuoles Characterized by the Missing of “Self” IRGM Proteins

Interferon-inducible GTPases of the Immunity Related GTPase (IRG) and Guanylate Binding Protein (GBP) families provide resistance to intracellular pathogenic microbes. IRGs and GBPs stably associate with pathogen-containing vacuoles (PVs) and elicit immune pathways directed at the targeted vacuoles. Targeting of Interferon-inducible GTPases to PVs requires the formation of higher-order protein oligomers, a process negatively regulated by a subclass of IRG proteins called IRGMs. We found that the paralogous IRGM proteins Irgm1 and Irgm3 fail to robustly associate with “non-self” PVs containing either the bacterial pathogen Chlamydia trachomatis or the protozoan pathogen Toxoplasma gondii. Instead, Irgm1 and Irgm3 reside on “self” organelles including lipid droplets (LDs). Whereas IRGM-positive LDs are guarded against the stable association with other IRGs and GBPs, we demonstrate that IRGM-stripped LDs become high affinity binding substrates for IRG and GBP proteins. These data reveal that intracellular immune recognition of organelle-like structures by IRG and GBP proteins is partly dictated by the missing of “self” IRGM proteins from these structures.
Enhancement of Signal-to-Noise Ratio and Phase Locking for Small Inputs by a Low-Threshold Outward Current in Auditory Neurons

Neurons possess multiple voltage-dependent conductances specific for their function. To investigate how low-threshold outward currents improve the detection of small signals in a noisy background, we recorded from gerbil medial superior olivary (MSO) neurons in vitro. MSO neurons responded phasically, with a single spike to a step current injection. When bathed in dendrotoxin (DTX), most cells switched to tonic firing, suggesting that low-threshold potassium currents (IKLT) participated in shaping these phasic responses. Neurons were stimulated with a computer-generated steady barrage of random inputs, mimicking weak synaptic conductance transients (the “noise”), together with a larger but still subthreshold postsynaptic conductance, EPSG (the “signal”). DTX reduced the signal-to-noise ratio (SNR), defined as the ratio of probability to fire in response to the EPSG and the probability to fire spontaneously in response to noise. The reduction was mainly attributable to the increase of spontaneous firing in DTX. The spike-triggered reverse correlation indicated that, for spike generation, the neuron with IKLTrequired faster inward current transients. This narrow temporal integration window contributed to superior phase locking of firing to periodic stimuli before application of DTX. A computer model including Hodgkin-Huxley type conductances for spike generation and forIKLT (Rathouz and Trussell, 1998) showed similar response statistics. The dynamic low-threshold outward current increased SNR and the temporal precision of integration of weak subthreshold signals in auditory neurons by suppressing false positives.