Miracle-dz/UniFAR-FTUs huggingface dataset:
The Macromolecular Machines that Duplicate the Escherichia coli Chromosome as Targets for Drug Discovery

DNA replication is an essential process. Although the fundamental strategies to duplicate chromosomes are similar in all free-living organisms, the enzymes of the three domains of life that perform similar functions in DNA replication differ in amino acid sequence and their three-dimensional structures. Moreover, the respective proteins generally utilize different enzymatic mechanisms. Hence, the replication proteins that are highly conserved among bacterial species are attractive targets to develop novel antibiotics as the compounds are unlikely to demonstrate off-target effects. For those proteins that differ among bacteria, compounds that are species-specific may be found. Escherichia coli has been developed as a model system to study DNA replication, serving as a benchmark for comparison. This review summarizes the functions of individual E. coli proteins, and the compounds that inhibit them.
Potassium channels mediate dilatation of cerebral arterioles in response to arachidonate.

We tested the hypothesis that cerebral vasodilatation in response to arachidonate is dependent on activation of cyclooxygenase and cytochrome P-450 pathways and formation of endogenous reactive oxygen species and is mediated by activation of potassium channels. The diameter of cerebral arterioles was measured using cranial windows in anesthetized rats. Under control conditions [baseline diameter = 45 ± 1 μm (mean ± SE)], arachidonate (1-100 μM) and papaverine (10-50 μM) produced concentration-dependent vasodilatation. Cerebral vasodilator responses to arachidonate, but not papaverine, were abolished during topical application of indomethacin (10 μM, an inhibitor of cyclooxygenase) or catalase (100 U/ml, which inactivates hydrogen peroxide). In contrast, clotrimazole (10 μM) and 17-ODYA (20 μM), inhibitors of cytochrome P-450 activity, had no effect on dilator responses of cerebral arterioles to arachidonate. Superoxide dismutase (SOD, 100 U/ml) had no effect on vasodilator responses to papaverine or lower concentrations of arachidonate, whereas dilator responses to 100 μM arachidonate were inhibited modestly (by 22%) by SOD. Similarly, deferoxamine (1 mM) partly inhibited dilator responses to 10 and 100 μM arachidonate (by ∼30% at each concentration). Tetraethylammonium ion (1 mM) or iberiotoxin (50 nM), inhibitors of calcium-activated potassium channels, markedly inhibited vasodilatation in response to arachidonate (by 70-90%) but not papaverine. These findings suggest that dilatation of cerebral arterioles in response to arachidonate is mediated largely by endogenously formed reactive oxygen species, which are generated from cyclooxygenase activity, and activation of calcium-activated potassium channels. Thus activation of potassium channels appears to be a major mechanism of cerebral vasodilatation in response to reactive oxygen species produced endogenously.
Helicobacter pylori infection modulates the expression of miRNAs associated with DNA mismatch repair pathway

Genetic and epigenetic inactivation of DNA mismatch repair (MMR) genes might lead to modifications in cancer‐related gene expression and cancer development. Recently, it has been shown that the infection by Helicobacter pylori, the major causative agent of gastric cancer, induces DNA damage and inhibits MMR DNA repair. Also, it has been reported that microRNAs (miRs) have an important role in regulating genomic stability and MMR DNA repair. Thus, the aim of this study was to identify miRs regulating MMR pathway in H. pylori‐associated gastric carcinogenesis. To address this question, a gastric epithelial cell line and AGS cancer gastric cells were infected with several H. pylori strains. MMR gene expression and miRs correlating with H. pylori strain infection were evaluated. The results showed that H. pylori infection significantly down‐regulated the expression of all selected MMR genes. Also, H. pylori infection modulated the expression of several miRs (including miR‐150‐5p, miR‐155‐5p, and miR‐3163), after 4, 8, and 12 h of infection. Computational prediction of candidate miRs and their predicted MMR targeting sites were obtained from TargetScan, mirDB, and MetaCore. The generated data indicated that the selected miRs (miR‐150‐5p, miR‐155‐5p, and miR‐3163) could possibly target and modulate MMR genes (POLD3, MSH2, and MSH3, respectively). The target validation was performed using mimics and luciferase gene reporter assays. Briefly, this study shows that H. pylori impairs MMR DNA repair pathway and identifies miRs that regulate MMR gene expression in gastric cancer. © 2016 Wiley Periodicals, Inc.
Novel Aspects of Polynucleotide Phosphorylase Function in Streptomyces

Polynucleotide phosphorylase (PNPase) is a 3′–5′-exoribnuclease that is found in most bacteria and in some eukaryotic organelles. The enzyme plays a key role in RNA decay in these systems. PNPase structure and function have been studied extensively in Escherichia coli, but there are several important aspects of PNPase function in Streptomyces that differ from what is observed in E. coli and other bacterial genera. This review highlights several of those differences: (1) the organization and expression of the PNPase gene in Streptomyces; (2) the possible function of PNPase as an RNA 3′-polyribonucleotide polymerase in Streptomyces; (3) the function of PNPase as both an exoribonuclease and as an RNA 3′-polyribonucleotide polymerase in Streptomyces; (4) the function of (p)ppGpp as a PNPase effector in Streptomyces. The review concludes with a consideration of a number of unanswered questions regarding the function of Streptomyces PNPase, which can be examined experimentally.
n-3 Fatty acids and health: DaVinci's code.

DaVinci admonishes the young to feed on the wisdom of the old. In this issue of the Journal, 3 studies regarding the role of n 3 fatty acids (FAs)—eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA)—in geriatric populations are published. They nourish us well. Two are prospective cohort studies based on n 3 FA biomarkers (as opposed to dietary intake estimates), and the third is a randomized controlled, dose-response study. Attesting to the pleiotrophic effects of the n 3 FAs, the endpoints in these studies ran the gamut from all-cause mortality and cognitive decline in the former 2 studies to mood and mental health in the latter study. In short, the story they tell is this: low in vivo concentrations of EPA and/or DHA predict an increased risk of death in frail, hospitalized octogenarians from Norway and an accelerated cognitive decline in free-living septuagenarians from France. Hence, the ability of markers of n 3 FA biostatus continue to provide potentially relevant prognostic information for clinically important endpoints. On the other hand, intervention with EPA DHA in the healthy elderly had no effect on mental well-being. Together, these findings suggest that dietary habits that include higher versus lower intakes of longchain n 3 FAs may bring certain health benefits that short-term supplementation cannot provide. Supplementation can, of course, affect other factors (eg, serum triglyceride concentrations, susceptibility to arrhythmic events, and platelet aggregation (1), all with potential clinical relevance.
Calcium solubility, intestinal sojourn time and paracellular permeability codetermine passive calcium absorption in rats.

To investigate the nonsaturable, paracellular pathway of intestinal Ca absorption, the luminal contents of 12-cm segments of the intestine of 8-wk-old male Sprague-Dawley rats were analyzed for pH, sojourn time and soluble and insoluble Ca over a 24-h period. The rats had been fed one of two high Ca diets for 2 wk: 1.5% Ca (diet group 3a) and 3.1% (diet group 5a). The pH of the small intestine increased from < 6.6 to > 8.0 from duodenum to ileum; transit time increased from 2.5 min in the duodenum to 58 min in the distal ileum, with the entire ileum accounting on the average for 74% of the transit time of 3 h. The amount of Ca solubilized throughout the intestine was 32 +/- 3.3 mumol in diet group 3a and 53 +/- 5.3 mumol in diet group 5a, i.e., 2.7% and 2.0% of the total luminal Ca. Because absorption by diet group 3a was 1.45 +/- 0.23 mmol/d and that by diet group 5a was 2.50 +/- 0.18 mmol/d, the amounts absorbed were 45.3 and 47.1 times greater than present in the lumen in soluble form at any one time. Thus, over a 24-h period, an average of 3.2% (46.2/1440) of the soluble Ca present in the lumen at any time was absorbed per min. Calculations involving the gradient between luminal and plasma Ca show that the rate of Ca diffusion from lumen to blood is < 2% of what it would be if the paracellular path were unrestricted. Thus, intestinal sojourn time, Ca solubility and mucosal permeability to Ca are factors that determine the rate of passive Ca absorption.
Chemical signaling from colonic smooth muscle cells to DRG neurons in culture.

Transduction mechanisms between target cells within the intestinal wall and peripheral terminals of extrinsic primary afferent neurons are poorly understood. The purpose of this study was to characterize the interactions between smooth muscle cells from the rat distal colon and lumbar dorsal root ganglion (DRG) neurons in coculture. DRG neurons visually appeared to make contact with several myocytes. We show that brief mechanical stimulation of these myocytes resulted in intracellular Ca2+ concentration ([Ca2+]i) transients that propagated into 57% of the contacting neurites. Direct mechanical stimulation of DRG neurites cultured without smooth muscle had no effect. We also show that colonic smooth muscle cells express multiple connexin mRNAs and that these connexins formed functional gap junctions, as evidenced by the intercellular transfer of Lucifer yellow. Furthermore, thapsigargin pretreatment and neuronal heparin injection abolished the increase in neurite [Ca2+]i, indicating that the neuronal Ca2+signal was triggered by inositol 1,4,5-trisphosphate-mediated Ca2+ release from intracellular stores. Our results provide evidence for intercellular chemical communication between DRG neurites and intestinal smooth muscle cells that mediates the exchange of second messenger molecules between different cell types.
Intra-Cardiac Release of Extracellular Vesicles Shapes Inflammation Following Myocardial Infarction

Rationale: A rapid and massive influx of inflammatory cells occurs into ischemic area after myocardial infarction (MI), resulting in local release of cytokines and growth factors. Yet, the mechanisms regulating their production are not fully explored. The release of extracellular vesicles (EVs) in the interstitial space curbs important biological functions, including inflammation, and influences the development of cardiovascular diseases. To date, there is no evidence for in situ release of cardiac EVs after MI. Objective: The present study tested the hypothesis that local EV generation in the infarcted heart coordinates cardiac inflammation after MI. Methods and Results: Coronary artery ligation in mice transiently increases EV levels in the left ventricle when compared with sham animals. EVs from infarcted hearts were characterized as large vesicles (252±18 nm) expressing cardiomyocyte and endothelial markers and small EVs (118±4 nm) harboring exosomal markers, such as CD (cluster of differentiation) 63 and CD9. Cardiac large EVs generated after MI, but not small EVs or sham EVs, increased the release of IL (interleukin)-6, CCL (chemokine ligand) 2, and CCL7 from fluorescence-activated cell–sorted Ly6C+ cardiac monocytes. EVs of similar diameter were also isolated from fragments of interventricular septum obtained from patients undergoing aortic valve replacement, thus supporting the clinical relevance of our findings in mice. Conclusions: The present study demonstrates that acute MI transiently increases the generation of cardiac EVs characterized as both exosomes and microvesicles, originating mainly from cardiomyocytes and endothelial cells. EVs accumulating in the ischemic myocardium are rapidly taken up by infiltrating monocytes and regulate local inflammatory responses.
Eating behavior among women with anorexia nervosa.

BACKGROUND Disturbed eating and severe caloric restriction are characteristic features of patients with anorexia nervosa (AN). Despite the importance of eating behavior in the presentation of AN, there have been relatively few objective laboratory studies of eating behavior among persons with eating disorders. OBJECTIVE The purpose of the study was to obtain objective measures of eating behavior among patients with AN before and immediately after weight restoration and to compare those measures with measures among control subjects. DESIGN Twelve patients hospitalized for AN and 12 control subjects participated in the study. Eleven of the 12 patients were retested at 90% of ideal body weight. RESULTS The average meal consumption was 103.97 +/- 102.08 g for patients at low weight and 178.03 +/- 202.97 g after weight restoration (NS). Control subjects consumed significantly more than did AN patients at both time points, and the average meal size was 489.58 +/- 187.64 g. Patients showed significant decreases in psychological and eating-disordered symptoms after weight restoration. CONCLUSION These data suggest that patients with AN show a persistent disturbance in eating behavior, despite the restoration of body weight and significant improvements in eating-disordered and psychological symptoms.
Evaluation of the ECG based Selvester scoring method to estimate myocardial scar burden and predict clinical outcome in patients with left bundle branch block, with comparison to late gadolinium enhancement CMR imaging

Myocardial scar burden quantification is an emerging clinical parameter for risk stratification of sudden cardiac death and prediction of ventricular arrhythmias in patients with left ventricular dysfunction. We investigated the relationships among semiautomated Selvester score burden and late gadolinium enhancement‐cardiovascular magnetic resonance (LGE‐CMR) assessed scar burden and clinical outcome in patients with underlying heart failure, left bundle branch block (LBBB) and implantable cardioverter‐defibrillator (ICD) treatment.
Human Nutrition and Metabolism Supplementation with Isoflavonoid Phytoestrogens Does Not Alter Serum Lipid Concentrations: A Randomized Controlled Trial in Humans

Isoflavonoids are a class of flavonoids that are derived in the human diet mainly from soybeanbased foods. The major dietary isoflavonoids, genistein and daidzein, have estrogen-like activity and are classed as phytoestrogens. Because estrogens can lower serum LDL cholesterol and raise HDL cholesterol, the objective of this study was to determine if isoflavonoids could improve serum lipids in healthy subjects. Forty-six men and 13 postmenopausal women not receiving hormone replacement therapy completed a randomized, double-blind, placebo-controlled trial of two-way parallel design and 8 wk duration. One tablet containing 55 mg of isoflavonoids (predominantly in the form of genistein) or one placebo tablet was taken daily with the evening meal. Subjects maintained their usual diet and physical activity, which were unchanged throughout the intervention. Measurement of isoflavonoids and their metabolites in 24-h urine samples provided an assessment of compliance and of isoflavonoid metabolism. Serum total, LDL, HDL and HDL subclass cholesterol, triglycerides and lipoprotein (a) were assessed at baseline and during the last week of intervention. After adjustment for baseline values, no significant differences in postintervention serum lipid and lipoprotein (a) concentrations between groups were identified. Further adjustment for age, gender and weight change did not alter the results. In addition, changes in urinary isoflavonoids were not significantly correlated with changes in serum lipids and lipoprotein (a). Therefore, this study does not support the hypothesis that isoflavonoid phytoestrogens can improve the serum lipids, at least in subjects with average serum cholesterol concentrations. J. Nutr. 128: 728–732, 1998.
Acute defense mechanisms against hemorrhage from mechanical gill injury in rainbow trout.

By cutting gill filaments in anesthetized rainbow trout ( Oncorhynchus mykiss), observing the bleeding through a stereomicroscope, and using blockers of various known endogenous filament artery vasoconstrictors, we have here attempted to characterize hemostatic mechanisms in gills. The immediate hemostatic response to a cut in a gill filament artery was a local vasoconstriction, stopping the hemorrhage within ∼20 s. In heparinized fish, the hemorrhage recommenced after ∼8 min, suggesting that the vasoconstriction soon subsides and blood clotting becomes responsible for the hemostasis. Antagonists of acetylcholine, adenosine, and serotonin receptors were unable to block the hemostatic vasoconstriction. Also, tetrodotoxin was without effect, indicating a nonnervous origin. By contrast, indomethacin significantly affected the measured bleeding times, suggesting that eicosanoids play a significant role in this process (possibly by stimulating vasoconstriction and/or by inducing local thrombocyte aggregation). By possessing several hundred virtually identical filaments with readily observable vasculature, the fish gill appears to be a good experimental model for studying hemostatic mechanisms.
Effect of fat-reduced diets on 24-h energy expenditure: comparisons between animal protein, vegetable protein, and carbohydrate.

BACKGROUND Single-meal tests have shown that protein has greater thermogenic and satiating effects than does carbohydrate, which may be relevant for the prevention and treatment of obesity if these effects can be maintained over 24 h. OBJECTIVE The effects of pork-meat protein, soy protein, and carbohydrate on 24-h energy expenditure were compared. DESIGN Twelve young, healthy, overweight and mildly obese [body mass index (in kg/m(2)): 26-32] nonsmoking men participated in a randomized, single-blind, 3-way crossover study lasting 4 d. The intervention had a 1-10-wk washout period. The 3 isoenergetic intervention diets were as follows: pork diet (29% of energy as fat and 29% as protein, mainly from pork meat), soy diet (29% of energy as fat and 28% as protein, mainly from soy), and carbohydrate diet (28% of energy as fat and 11% as protein). Twenty-four-hour energy expenditure was measured in a respiratory chamber at baseline and on day 4 of each intervention period. RESULTS Twenty-four-hour energy expenditure was higher with the pork than with the soy (248 kJ/d, 1.9%; P: = 0.05) or carbohydrate (492 kJ/d, 3.9%; P: < 0.0001) diet and higher with the soy than with the carbohydrate (244 kJ/d, 1.9%; P: < 0.05) diet. However, because of a higher satiating effect, energy intake was 10-15% lower during the chamber stay than at baseline (P: > 0.05) with all 3 diets. The differences in energy expenditure remained unchanged after adjustment for differences in 24-h energy balance. CONCLUSIONS Substitution of carbohydrate with 17-18% of energy as either pork-meat or soy protein produced a 3% higher 24-h energy expenditure. The animal protein in pork meat produced a 2% higher 24-h energy expenditure than did the vegetable protein in soy.
Internet Engineering Task Force (ietf) Objective Function Zero for the Routing Protocol for Low-power and Lossy Networks (rpl)

The Routing Protocol for Low-Power and Lossy Networks (RPL) specification defines a generic Distance Vector protocol that is adapted to a variety of network types by the application of specific Objective Functions (OFs). An OF states the outcome of the process used by a RPL node to select and optimize routes within a RPL Instance based on the Information Objects available; an OF is not an algorithm. This document specifies a basic Objective Function that relies only on the objects that are defined in the RPL and does not use any protocol extensions. Information about the current status of this document, any errata, and how to provide feedback on it may be obtained at include Simplified BSD License text as described in Section 4.e of the Trust Legal Provisions and are provided without warranty as described in the Simplified BSD License.
Is it possible to change of the duration of consolidation period in the distraction osteogenesis with the repetition of extracorporeal shock waves?

Background In this study we examined the effects of two different repeated Extracorporeal Shock Waves (ESW) on the consolidation period of the distraction osteogenesis (DO) of the rabbit mandible using stereological, radiological and immunohistochemical methods. Material and Methods DO was performed unilaterally in the mandible of 18 New Zealand rabbits (six months old, weighing between 2.5-3 kg). In the consolidation period, rabbits were divided into three groups randomly after the distraction period. The distraction zone of the mandible was received no treatment as controls (E0*2). Group 2 (E 500*2) received ESWT (twice 500 impulses at 14 kV and 0.19 mJ/mm2 energy) in the first and fourth days of the consolidation. Group 3 (E1000*2) treated with ESWT (twice 1000 impulses at 14 kV and 0.19 mJ/mm2 energy) in the first and fourth days of the consolidation period. After the sacrification, radiologically bone mineral density, new bone formation, new fibrous tissue and new vessel formation were analyzed by stereological. Results It was found a statistically significant difference between the study groups and control group in the bone mineral density measurements and the highest value was in the E1000*2 group. In the stereological analysis, new bone formation was highest in the E1000*2 group and there was a significant difference compared to the other groups (E0*2 and E500*2) (p=0.000). The lowest connective tissue volume was found in the E500*2 and there was a significant difference compared to the other groups (E0*2 and E1000*2) (p=0.000). The volume of the new vessel was highest in the E500*2 and lowest in the E0*2 group. It was found statistically significant difference between the values of the study and control groups. Conclusions Interestingly, we found that repetition of the 1000 impulses ESWT accelerated the consolidation, 500 impulses ESWT extended consolidation period of the DO. Key words:Distraction osteogenesis, extracorporeal shock waves, stereology, rabbit.
Follow-Up Data Improve the Estimation of the Prevalence of Heavy Alcohol Consumption

Aims We aim to adjust for potential non-participation bias in the prevalence of heavy alcohol consumption. Methods Population survey data from Finnish health examination surveys conducted in 1987-2007 were linked to the administrative registers for mortality and morbidity follow-up until end of 2014. Utilising these data, available for both participants and non-participants, we model the association between heavy alcohol consumption and alcohol-related disease diagnoses. Results Our results show that the estimated prevalence of heavy alcohol consumption is on average of 1.5 times higher for men and 1.8 times higher for women than what was obtained from participants only (complete case analysis). The magnitude of the difference in the mean estimates by year varies from 0 to 9 percentage points for men and from 0 to 2 percentage points for women. Conclusion The proposed approach improves the prevalence estimation but requires follow-up data on non-participants and Bayesian modelling.