Miracle-dz/UniFAR-FTUs huggingface dataset:
Frameshift mutations induced by three classes of acridines in the lacZ reversion assay in Escherichia coli: Potency of responses and relationship to slipped mispairing models

The frameshift mutagenicity of 9‐aminoacridine (9AA) was compared with that of quinacrine, the acridine mustards ICR‐191 and quinacrine mustard (QM), and the nitroacridine Entozon in the lacZ reversion assay in Escherichia coli. As intercalating agents, 9AA and quinacrine cause mutations through noncovalent associations with DNA. Mustards and nitroacridines form covalent adducts in DNA and give rise to different spectra of mutations. Quinacrine and 9AA most effectively induced −1 frameshifts in a run of guanine residues, with 9AA being the more potent mutagen. They also induced +G frameshifts. The acridine mustard ICR‐191 was a stronger mutagen than 9AA, owing largely to its potent induction of +G frameshifts. QM induced +G frameshifts more strongly than did its nonreactive counterpart quinacrine. The nitroacridine Entozon differed from the other acridines in being a potent inducer of −2 frameshifts, but it was less effective in inducing ±1 frameshifts. Quinacrine, although a simple intercalator, induced all five kinds of frameshift mutations detected in the assay, as did the acridine mustards. Although +A and −A frameshifts were induced, adenine runs were less susceptible to acridine mutagenesis than guanine runs. The patterns of frameshift mutagenicity in the lacZ assay are similar to those in an assay based on the reversion of mutations in the tetracycline‐resistance gene of the plasmid pBR322. The similarity suggests that the responses reflect the inherent bacterial mutagenicity of the compounds in the local sequence context and are not highly dependent on the broader sequence context. The results are interpreted with respect to slipped mispairing models of frameshift mutagenesis. Environ. Mol. Mutagen. 42:111–121, 2003. © 2003 Wiley‐Liss, Inc.
Impact of food consumption habits on the pesticide dietary intake: Comparison between a French vegetarian and the general population

This study aims to compare the pesticide residue dietary intake of the French general population and the vegetarian population, separated into five specific diets: omnivorous (OMN), lacto-vegetarian (LV), ovo-lacto-vegetarian (OLV), pesco-lacto-vegetarian (PLV) and vegan (VG). Theoretical Maximum Daily Intakes (TMDIs) based on Maximum Residue Levels (MRLs) were calculated as a percentage of the Acceptable Daily Intake (ADI). Among the 421 pesticides studied, only 48 had TMDI above ADI for at least one population subgroup. An excessive exposure was noticed for 44, 43, 42, 41 and 30 pesticides in the OLV, VG, OMN, LV and PLV groups, respectively, versus 29 in the general population. Meat and egg products consumption was responsible for higher intakes of organochlorine pesticides in the general population than in the vegetarian population (TMDI = 348% versus 146–183% ADI for aldrin). However, as the limited consumption of animal-origin commodities was largely offset by a higher fruit, vegetable and cereal intake in the vegetarian diets, vegetarians appear to be preferentially exposed to pesticides, for which fruit, vegetables and cereals are the main contributors, such as tri-allate, chlorpyrifos-methyl and diazinon. This study illustrates that consumption habits have a real impact on pesticide exposure in terms of intake levels, number and type of pesticides, representing a potential risk of dietary exposure. Except for organochlorine compounds, the vegetarian population may be more exposed to pesticide residues than the general population due to specific dietary habits. Thus, this population should be considered for risk assessment of pesticide residues.
Alternatively Activated Macrophages Regulate Extracellular Levels of the Hormone Placental Lactogen via Receptor-Mediated Uptake and Transcytosis1

Alternatively activated (M2) macrophages regulate immune responses and tissue remodelling. In many tissues including placenta, M2 express stabilin-1, a multidomain protein that exerts a dual role as a scavenger receptor for acetylated low density lipoprotein (acLDL) and SPARC (secreted protein acidic and rich in cysteine) and as an intracellular cargo carrier for SI-CLP. Using yeast two-hybrid screening, we identified the developmental hormone placental lactogen (PL) as a novel ligand of stabilin-1. In Chinese hamster ovary-stabilin-1 cells and M2, FACS and confocal microscopy demonstrated that stabilin-1 mediates internalization and endosomal sorting of PL. In M2 macrophages, PL was partially degraded in lysosomes; part of PL escaped degradation and was delivered to novel PL+ storage vesicles lacking endosomal/lysosomal markers. During formation, PL+ vesicles underwent transient interaction with the trans-Golgi network (TGN). Upon placement of PL-loaded M2 into PL-free medium, PL was secreted into the supernatant. Leupeptin, an inhibitor of lysosomal hydrolases, reduced PL degradation, enhanced sorting of PL into the TGN/storage vesicle pathway and increased PL secretion. Thus, processing of PL in M2 macrophages occurs either by the classical lysosomal pathway or by a novel TGN-associated trans-secretory pathway. Macrophages isolated from human placental villi efficiently endocytosed PL-FITC and transported it to the storage vesicles. Our data show that extracellular PL levels are determined by uptake, degradation, storage, and release in M2. During pregnancy PL concentration reaches 10 μg/ml in maternal circulation and stays below 0.5 μg/ml in fetal circulation. We propose that stabilin-1-positive macrophages determine the difference in PL levels between maternal and fetal circulation.
Infants' attention is biased by emotional expressions and eye gaze direction

This study investigates infants' processing of emotional expressions in combination with referential eye gaze cues. In experiment 1, 7-month-old infants' neural responses to fearful and neutral faces, which were looking at a novel object, were assessed. Infants' attention, as indexed by the negative central component of the event-related potential, was enhanced when the adult gazed at the object with a fearful expression compared with a neutral expression. In experiment 2, no effect of emotion on amplitude of the negative central was found when the face directed eye gaze at the infant and away from the object. We conclude that by 7 months, infants use emotional expressions in triadic person-object-person contexts to detect threat in the environment.
Renal Disease Associated with Antiretroviral Therapy in the Treatment of HIV

The introduction of potent combination antiretroviral therapy (ART) in the treatment of HIV infection has permitted reliable control of disease progression and has markedly improved survival among people with HIV. As a result, health care providers and patients have shifted clinical priorities; whereas once delaying opportunistic illness was a primary focus, increasing emphasis is now placed on preventative health, management of comorbid chronic disease and avoiding long-term toxicities of ART. Although renal disease is common in people with HIV, renal disease specifically due to ART remains relatively rare. Still, as the use of ART continues to increase, health care providers are likely to encounter this potentially serious complication with increasing frequency. Distinguishing ART-related nephrotoxicity from the myriad of other potential causes of renal disease in people with HIV is important in order to avoid unnecessary discontinuation of an appropriate ART regimen. This review focuses on the early recognition of renal disease associated with ART and suggests strategies for management and prevention.
Mucoid Pseudomonas aeruginosa Resists Nonopsonic Phagocytosis by Human Neutrophils and Macrophages

ABSTRACT. Mucoid Pseudomonas aeruginosa is an important respiratory pathogen in patients with cystic fibrosis, and once acquired is virtually impossible to eradicate. Although mucoid P. aeruginosa is generally believed to be resistant to phagocytosis, the mechanism is not understood fully. We studied the nonopsonic phagocytosis by human neutrophils or macrophages of eight mucoid/nonmucoid P. aeruginosa pairs (three isogenic and five “wild-type”). Mucoid strains were relatively resistant to nonopsonic phagocytosis but the nonmucoid types were phagocytosis-susceptible as assessed by visual inspection and chemiluminescence assays. The mucoid and nonmucoid variants had equal numbers of pili but different surface characteristics as determined by biphasic partitioning in polyethylene glycol and dextran. The mucoid exopolysaccharide of mucoid strains appears to alter the surface characteristics of P. aeruginosa thereby rendering them resistant to nonopsonic phagocytosis. The resistance of mucoid variants of P. aeruginosa to nonopsonic phagocytosis may provide a survival advantage to these bacteria early in the course of pulmonary infection before opsonic antibody and complement are present in respiratory secretions.
Madden‐Julian Oscillation in a climate model with a well‐resolved stratosphere

[1] This work evaluates how well a coupled ocean-atmospheric climate model with a well-resolved stratosphere captures the observed Madden-Julian Oscillation (MJO) signal in the upper troposphere and lower stratosphere. The model is the Centro Euro-Mediterraneo per i Cambiamenti Climatici (CMCC) coupled modeling system (CMCC-CMS) with 95 atmospheric levels. CMCC-CMS produces MJO composites of precipitation that are very similar to those of the observations and the ERA-40 reanalysis product. Furthermore, model precipitation is found to propagate eastward near the observed speed. There is also strong agreement in the tropics and subtropics in the temperature and flows at 100 and 200 hPa upon comparing the composites based on the full 340 years of model output and those for the past 20 years of the model output with those of the ERA-40 reanalysis. At the 100 hPa level the temperature anomalies in the model output and reanalysis propagate eastward at about 7 m s–1 at the equator, 25°N and 65°N. Longitude and height cross sections at 25°N suggest vertically propagating Rossby waves up to near the 10 hPa level in both the model and observations. Latitude and height cross sections of temperature and zonal and meridional winds indicate strong vertical propagation in the tropics in both the model and reanalysis. Overall, the CMCC-CMS model shows MJO characteristics in the tropical and subtropical troposphere and lower stratosphere that are in very good agreement with observed analyses.
Lico A Enhances Nrf2-Mediated Defense Mechanisms against t-BHP-Induced Oxidative Stress and Cell Death via Akt and ERK Activation in RAW 264.7 Cells

Licochalcone A (Lico A) exhibits various biological properties, including anti-inflammatory and antioxidant activities. In this study, we investigated the antioxidative potential and mechanisms of Lico A against tert-butyl hydroperoxide- (t-BHP-) induced oxidative damage in RAW 264.7 cells. Our results indicated that Lico A significantly inhibited t-BHP-induced cytotoxicity, apoptosis, and reactive oxygen species (ROS) generation and reduced glutathione (GSH) depletion but increased the glutamate-cysteine ligase modifier (GCLM) subunit and the glutamate-cysteine ligase catalytic (GCLC) subunit genes expression. Additionally, Lico A dramatically upregulated the antioxidant enzyme heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2), which were associated with inducing Nrf2 nuclear translocation, decreasing Keap1 protein expression and increasing antioxidant response element (ARE) promoter activity. Lico A also obviously induced the activation of serine/threonine kinase (Akt) and extracellular signal-regulated kinase (ERK), but PI3K/Akt and ERK inhibitors treatment displayed clearly decreased levels of LicoA-induced Nrf2 nuclear translocation and HO-1 expression, respectively. Furthermore, Lico A treatment markedly attenuated t-BHP-induced oxidative damage, which was reduced by treatment with PI3K/Akt, ERK, and HO-1 inhibitors. Therefore, Lico A might have a protective role against t-BHP-induced cytotoxicity by modulating HO-1 and by scavenging ROS via the activation of the PI3K/Akt and ERK/Nrf2 signaling pathways.
Areas activated during naturalistic reading comprehension overlap topological visual, auditory, and somatotomotor maps

Cortical mapping techniques using fMRI have been instrumental in identifying the boundaries of topological (neighbor-preserving) maps in early sensory areas. The presence of topological maps beyond early sensory areas raises the possibility that they might play a significant role in other cognitive systems, and that topological mapping might help to delineate areas involved in higher cognitive processes. In this study, we combine surface based visual, auditory, and somatomotor mapping methods with a naturalistic reading comprehension task in the same group of subjects to provide a qualitative and quantitative assessment of the cortical overlap between sensory-motor maps in all major sensory modalities, and reading processing regions. Our results suggest that cortical activation during naturalistic reading comprehension overlaps more extensively with topological sensory-motor maps than has been heretofore appreciated. Reading activation in regions adjacent to occipital lobe and inferior parietal lobe completely overlaps visual maps, whereas most of frontal activation for reading in dorsolateral and ventral prefrontal cortex overlaps both visual and auditory maps. Even classical language regions in superior temporal cortex are partially overlapped by topological visual and auditory maps. By contrast, the main overlap with somatomotor maps is restricted to dorsolateral frontal cortex.
The role of adenosine in the regulation of coronary blood flow.

THE coronary vasculature is influenced by physical (arterial pressure, extravascular compression, hematocrit), neural, and chemical factors, and although there is considerable interplay among these various factors, the predominant one is chemical. Furthermore, the chemical factors of greatest importance are those that take origin from the cardiac parenchyma! tissue and serve as a link between myocardial oxygen needs and supply. One of the principal contenders that can serve as a mediator of coronary blood flow (CBF) regulation in response to cardiac metabolic activity is the nucleoside, adenosine (Berne, 1963).
Does Global Warming Increase Establishment Rates of Invasive Alien Species? A Centurial Time Series Analysis

Background The establishment rate of invasive alien insect species has been increasing worldwide during the past century. This trend has been widely attributed to increased rates of international trade and associated species introductions, but rarely linked to environmental change. To better understand and manage the bioinvasion process, it is crucial to understand the relationship between global warming and establishment rate of invasive alien species, especially for poikilothermic invaders such as insects. Methodology/Principal Findings We present data that demonstrate a significant positive relationship between the change in average annual surface air temperature and the establishment rate of invasive alien insects in mainland China during 1900–2005. This relationship was modeled by regression analysis, and indicated that a 1°C increase in average annual surface temperature in mainland China was associated with an increase in the establishment rate of invasive alien insects of about 0.5 species year−1. The relationship between rising surface air temperature and increasing establishment rate remained significant even after accounting for increases in international trade during the period 1950–2005. Moreover, similar relationships were detected using additional data from the United Kingdom and the contiguous United States. Conclusions/Significance These findings suggest that the perceived increase in establishments of invasive alien insects can be explained only in part by an increase in introduction rate or propagule pressure. Besides increasing propagule pressure, global warming is another driver that could favor worldwide bioinvasions. Our study highlights the need to consider global warming when designing strategies and policies to deal with bioinvasions.
Reduced Risk of Hyperkalemia During Treatment of Heart Failure With Mineralocorticoid Receptor Antagonists by Use of Sacubitril/Valsartan Compared With Enalapril: A Secondary Analysis of the PARADIGM-HF Trial

Importance Consensus guidelines recommend the use of mineralocorticoid receptor antagonists (MRAs) for selected patients with symptomatic heart failure and reduced ejection fraction (HFrEF) to reduce morbidity and mortality; however, the use of MRAs in combination with other inhibitors of the renin-angiotensin-aldosterone system increases the risk of hyperkalemia. Objective To determine whether the risk of hyperkalemia associated with use of MRAs for patients with HFrEF is reduced by sacubitril/valsartan in comparison with enalapril. Design, Setting, and Participants The PARADIGM-HF (Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial randomly assigned 8399 patients with chronic HF, New York Heart Association class II to IV symptoms, and a left ventricular EF of 40% or less to treatment with enalapril 10 mg twice daily or sacubitril/valsartan 97/103 mg twice daily (previously known as LCZ696 [200 mg twice daily]) in addition to guideline-directed medical therapy. Use of MRAs was encouraged but left to the discretion of study investigators. Serum potassium level was measured at every study visit. The incidence of hyperkalemia (potassium level >5.5 mEq/L) and severe hyperkalemia (potassium level >6.0 mEq/L) among patients treated or not treated with an MRA at baseline and the risk of subsequent hyperkalemia for those newly treated with an MRA during study follow-up were defined in time-updated Cox proportional hazards models. Analyses were conducted between August 1 and October 15, 2016. Main Outcomes and Measures Incident hyperkalemia and severe hyperkalemia. Results In comparison with the 3728 patients (44.4% of enrolled participants [21.6% female]) not taking an MRA at baseline, the 4671 patients (55.6% [22.0% female]) taking an MRA tended to be younger, with a lower EF, lower systolic blood pressure, and more advanced HF symptoms. Among those taking an MRA at baseline, the overall rates of hyperkalemia were similar between treatment groups, but severe hyperkalemia was more common in patients randomly assigned to enalapril than to sacubitril/valsartan (3.1 vs 2.2 per 100 patient-years; HR, 1.37 [95% CI, 1.06-1.76]; P = .02). In analyses including patients who newly started taking MRAs during the PARADIGM-HF trial, severe hyperkalemia remained more common in those randomly assigned to enalapril than to those randomly assigned to sacubitril/valsartan (3.3 vs 2.3 per 100 patient-years; HR, 1.43 [95% CI, 1.13-1.81]; P = .003). Conclusions and Relevance Among MRA-treated patients with symptomatic HFrEF, severe hyperkalemia is more likely during treatment with enalapril than with sacubitril/valsartan. These data suggest that neprilysin inhibition attenuates the risk of hyperkalemia when MRAs are combined with other inhibitors of the renin-angiotensin-aldosterone system in patients with HF. Trial Registration clinicaltrials.gov Identifier: NCT01035255
Benefits of Motion in Animated Storybooks for Children’s Visual Attention and Story Comprehension. An Eye-Tracking Study

The present study provides experimental evidence regarding 4–6-year-old children’s visual processing of animated versus static illustrations in storybooks. Thirty nine participants listened to an animated and a static book, both three times, while eye movements were registered with an eye-tracker. Outcomes corroborate the hypothesis that specifically motion is what attracts children’s attention while looking at illustrations. It is proposed that animated illustrations that are well matched to the text of the story guide children to those parts of the illustration that are important for understanding the story. This may explain why animated books resulted in better comprehension than static books.
Duality Between the Two-Locus Wright–Fisher Diffusion Model and the Ancestral Process with Recombination

Known results on the moments of the distribution generated by the two-locus Wright–Fisher diffusion model, and the duality between the diffusion process and the ancestral process with recombination are briefly summarized. A numerical method for computing moments using a Markov chain Monte Carlo simulation and a method to compute closed-form expressions of the moments are presented. By applying the duality argument, the properties of the ancestral recombination graph are studied in terms of the moments.
Risks and complications in 160 living kidney donors who underwent nephroureterectomy.

BACKGROUND The rate of living donor renal transplantations has increased. However, in view of the possible complications, the question as to whether the condition of the recipient justifies operation of the donor still remains unanswered. The present retrospective study evaluates the perioperative and post-operative risks and complications for the donor at a single major transplantation centre. METHODS From 1994 to 2001, 160 live donor nephroureterectomies were performed. The median age of living donors was 51 years (range 21-77 years); 19 patients were older than 61 years. After confirming blood group compatibility and negative cross-match, donors underwent an extensive medical and psychological examination. Comorbidities and anatomical features of the donor were evaluated and the impact they may have on the outcome was determined. The nephroureterectomies were performed transperitoneally, with the right kidney being preferred. Pre-operative, intraoperative and post-operative complications were documented. Serum creatinine levels as well as new-onset proteinuria or hypertension were used as criteria for assessing long-term renal function. RESULTS Complications were observed in 41 donors: 35 were minor and six were major (splenectomy; revisions due to liver bleeding, incarcerated umbilical hernia or infected pancreatic pseudocyst; pneumothorax; and acute renal failure). No patient died. Multiple arteries (14 patients), significant renal artery stenosis (two patients) and additional risk factors (e.g. increased age and previous operations) did not affect the complication rate. In the post-operative follow-up period of 0.5-62 months (mean: 38 months), renal function remained stable in all donors. CONCLUSIONS Living donor nephrectomy appears to be a safe intervention in specialized centres, where it entails a low morbidity for the donor. Even in high-risk donors, long-term complications were not observed.