Background
Diarrhea‐predominant irritable bowel syndrome (IBS‐D) is a functional gastrointestinal (GI) disorder, which occurs more frequently in women than men. The aim of our study was to determine ...the role of activation of classical estrogen receptors (ER) and novel membrane receptor, G protein‐coupled estrogen receptor (GPER) in human and mouse tissue and to assess the possible cross talk between these receptors in the GI tract.
Methods
Immunohistochemistry was used to determine the expression of GPER in human and mouse intestines. The effect of G‐1, a GPER selective agonist, and estradiol, a non‐selective ER agonist, on muscle contractility was characterized in isolated preparations of the human and mouse colon. To characterize the effect of G‐1 and estradiol in vivo, colonic bead expulsion test was performed. G‐1 and estradiol activity on the visceral pain signaling was assessed in the mustard oil‐induced abdominal pain model.
Key Results
GPER is expressed in the human colon and in the mouse colon and ileum. G‐1 and estradiol inhibited muscle contractility in vitro in human and mouse colon. G‐1 or estradiol administered intravenously at the dose of 20 mg/kg significantly prolonged the time to bead expulsion in females. Moreover, G‐1 prolonged the time to bead expulsion and inhibited GI hypermotility in both genders. The injection of G‐1 or estradiol resulted in a significant reduction in the number of pain‐induced behaviors in mice.
Conclusions and Inferences
GPER and ER receptors are involved in the regulation of GI motility and visceral pain. Both may thus constitute an important pharmacological target in the IBS‐D therapy.
Estrogen receptors (ER) and G protein‐coupled estrogen receptors are involved in colonic motility and visceral pain. GPER is expressed in the human colon. G‐1, a selective GPER agonist, and estradiol, a non‐selective ER agonist, inhibited muscle contractility in vitro in human colon.
Graphical abstract VEGF and VEGF-derived peptide protect against hyperglycemia-and paclitaxel-induced neuronal stress (A, B). VEGF also has therapeutic potential in vivo , in models for ...hyperglycemia- and paclitaxel-induced peripheral neuropathies (C, D).
Silkmoths and their relatives constitute the ecologically and taxonomically diverse superfamily Bombycoidea, which includes some of the most charismatic species of Lepidoptera. Despite displaying ...spectacular forms and diverse ecological traits, relatively little attention has been given to understanding their evolution and drivers of their diversity. To begin to address this problem, we created a new Bombycoidea-specific Anchored Hybrid Enrichment (AHE) probe set and sampled up to 571 loci for 117 taxa across all major lineages of the Bombycoidea, with a newly developed DNA extraction protocol that allows Lepidoptera specimens to be readily sequenced from pinned natural history collections.
The well-supported tree was overall consistent with prior morphological and molecular studies, although some taxa were misplaced. The bombycid Arotros Schaus was formally transferred to Apatelodidae. We identified important evolutionary patterns (e.g., morphology, biogeography, and differences in speciation and extinction), and our analysis of diversification rates highlights the stark increases that exist within the Sphingidae (hawkmoths) and Saturniidae (wild silkmoths).
Our study establishes a backbone for future evolutionary, comparative, and taxonomic studies of Bombycoidea. We postulate that the rate shifts identified are due to the well-documented bat-moth "arms race". Our research highlights the flexibility of AHE to generate genomic data from a wide range of museum specimens, both age and preservation method, and will allow researchers to tap into the wealth of biological data residing in natural history collections around the globe.
Characterizing trophic networks is fundamental to many questions in ecology, but this typically requires painstaking efforts, especially to identify the diet of small generalist predators. Several ...attempts have been devoted to develop suitable molecular tools to determine predatory trophic interactions through gut content analysis, and the challenge has been to achieve simultaneously high taxonomic breadth and resolution. General and practical methods are still needed, preferably independent of PCR amplification of barcodes, to recover a broader range of interactions. Here we applied shotgun-sequencing of the DNA from arthropod predator gut contents, extracted from four common coccinellid and dermapteran predators co-occurring in an agroecosystem in Brazil. By matching unassembled reads against six DNA reference databases obtained from public databases and newly assembled mitogenomes, and filtering for high overlap length and identity, we identified prey and other foreign DNA in the predator guts. Good taxonomic breadth and resolution was achieved (93% of prey identified to species or genus), but with low recovery of matching reads. Two to nine trophic interactions were found for these predators, some of which were only inferred by the presence of parasitoids and components of the microbiome known to be associated with aphid prey. Intraguild predation was also found, including among closely related ladybird species. Uncertainty arises from the lack of comprehensive reference databases and reliance on low numbers of matching reads accentuating the risk of false positives. We discuss caveats and some future prospects that could improve the use of direct DNA shotgun-sequencing to characterize arthropod trophic networks.
Background
The endogenous cannabinoid system (ECS) plays a crucial role in multiple physiological processes in the central nervous system and in the periphery. The discovery that selective ...cannabinoid (CB) receptor agonists exert a potent inhibitory action on gastrointestinal (GI) motility and pain has placed the ECS in the center of attention as a possible target for the treatment of functional GI diseases. However, side effects of CB agonists prompted the search for novel therapeutic targets. Here, the effect of PF‐3845, a potent and selective fatty acid amide hydrolase (FAAH) inhibitor in the GI tract was investigated.
Methods
The effect of PF‐3845 on GI motility was characterized in vitro and in vivo, using mouse models that mimic physiological and pathophysiological conditions. The antinociceptive action of PF‐3845 was evaluated on the basis of behavioral pain models. Endocannabinoid degradation product levels after inhibition of FAAH were quantified using HPLC‐MS/MS.
Key Results
PF‐3845 significantly inhibited mouse colonic motility in vitro and in vivo. Selective inhibition of FAAH reversed hypermotility and reduced pain in mouse models mimicking functional GI disorders. The effects of PF‐3845 were mediated by endogenous CBs and non‐CB lipophilic compounds via classical (CB1) and atypical CB receptors.
Conclusions & Inferences
These data expand our understanding of the ECS function and provide a novel framework for the development of future potential treatments of functional GI disorders.
The endogenous cannabinoid system (ECS) is implicated in several physiological and pathophysiological functions in the gastrointestinal (GI) tract, including motility and pain signaling. Finding that natural and synthetic cannabinoid (CB) receptor ligands are able to penetrate into the central nervous system (CNS) causing adverse side effects, such as impaired cognition and motor control, prompted the search for novel safer therapeutics targeting the ECS. The main finding of the study is that selective inhibition of fatty acid amide hydrolase (FAAH) activity regulates intestinal motility and pain signaling in physiological and pathophysiological conditions indirectly, through the CB receptors and possibly also the non‐CB sites via changes in the levels of endogenous cannabinoids. Moreover, there were no CNS‐related side effects of selective inhibition of FAAH. Our observations give new opportunities for the design of novel treatments for functional GI ailments, including diarrhea‐predominant irritable bowel syndrome (IBS‐D).
•Mechanismsof passenger assignment and energy allocation aredeveloped in an energy regenerative metro system.•Aparallelogram-based method is developed to generate random ...irregulartimetables.•Abi-objective optimization model is formulated foroptimizingregenerative energy use and passenger travel time.•An NSGA-IIbasedalgorithmisadoptedtosolve the bi-objective optimization model.•Operators based on domain knowledge are developed toexplore and exploit the solution space.
Complex passenger demand and electricity transmission processes in metro systems cause difficulties in formulating optimal timetables and train speed profiles, often leading to inefficiency in energy consumption and passenger service. Based on energy-regenerative technologies and smart-card data, this study formulates an optimization model incorporating energy allocation and passenger assignment to balance energy use and passenger travel time. The Non-Dominated Sorting Genetic Algorithm II (NSGA-II) is applied and the core components are redesigned to obtain an efficient Pareto frontier of irregular timetables for maximizing the use of regenerative energy and minimizing total travel time. Particularly, a parallelogram-based method is developed to generate random feasible timetables; crossover and local-search-driven mutation operators are proposed relying on the graphic representations of the domain knowledge. The suggested approach is illustrated using real-world data of a bi-directional metro line in Beijing. The results show that the approach significantly improves regenerative energy use and reduces total travel time compared to the fixed regular timetable.
This paper develops an error component mixed logit model to analyze the multi-dimensional residential, work and transportation mode choice. It expanse previous studies based on life-trajectory theory ...which predominantly only considered two life domains. In contributing to this emerging field of research, we design an integrated pivoted stated choice experiment considering the multi-dimensional choice of job, residence and transportation mode for the journey to work. The results of the estimated error component mixed logit model with panel effects indicate that most selected attributes of the residential environment, job profile and transportation mode are significantly related to individual differences in multidimensional choices. Moreover, the estimation of various sources of unobserved heterogeneity signals significant unobserved heterogeneity in selected taste parameters, and choice dependent heteroscedasticity in error component variance.
Due to the wide applications of lithium-ion capacitors (LiCs) in various fields and due to the lack of comprehensive study regarding LiC modeling, there is a need for an accurate electrical model, ...which can predict the LiC's behavior at different load conditions. Characterization helps better understanding of investigated energy storage system and reveals its functioning range, linear and nonlinear variations and also its limits. As the electrochemical based energy storages are non-linear, the presented model should be linearized in the range of the specific application. Therefore the identification procedures should be performed under various conditions as needed. Results from hybrid pulse power characterization (HPPC) test have been used for the system identification of LiC in the time domain. Since system identification in the time domain cannot provide a complete map of variation of model parameters, a wide range frequency impedance spectroscopy (10 kHz–20 mHz) and at various conditions such as current, state of charge (SoC) levels and temperatures has been performed in order to identify the parameters of assumed model in the frequency domain, which is an unique analysis and never has been performed for lithium ion capacitors. The used model has been chosen based on probable chemical reactions, which occur within a specific frequency range. Frequency domain analysis can identify model variation, which is not possible in time domain identification. In this paper a new identification approach has been introduced based on combination of time and frequency domains. Based on proposed method, identification process in frequency domain helps to identify parameters which are not variable in function of current and SoC variations. Therefore the mentioned parameters can be withdrawn from the cost function in the time domain and it improves the performance of system identification procedure. The proposed method improves the model accuracy around 2% at time domain and around 5% at frequency domain.
•We investigate new high power-high energy lithium ion capacitor technology.•We modeled the LiC in both time and frequency domain under various conditions.•A new equivalent circuit for frequency model is proposed.•Proposed models (time and frequency) are validated in time and frequency domain.•A new estimation method by combining of time and frequency methods is proposed.
Myocardial infarction is the major cause of death in the world. Over the last two decades, coronary reperfusion therapy has become established for the management of acute myocardial infarction (AMI). ...However, restoration of blood flow to previously ischemic myocardium results in the so-called ischemia/reperfusion (IR)-injury. The different clinical manifestations of this injury include myocardial necrosis, arrhythmia, myocardial stunning and endothelial- and microvascular dysfunction including the no-reflow phenomenon. The pathogenesis of ischemia/reperfusion injury consists of many mechanisms. Recently, there's increasing evidence for an important role in IR-injury on hypercontracture induced by high levels of cytosolic calcium or by low concentrations of ATP.
In the last years, many studies on experimental models were investigated, but the clinical trials confirming these effects remain spare. Recently, the beneficial effect of Na
+/H
+-exchange inhibitor cariporide and of the oxygen-derived free radical (ODFR) scavenger vitamin E on coronary bypass surgery-induced IR-injury were demonstrated. Also recently, the beneficial effect of allopurinol on the recovery of left ventricular function after rescue balloon-dilatation was demonstrated. The beneficial effect of magnesium and trimetazidine on IR-injury remains controversial. The beneficial effect of adenosine remains to be further confirmed. There's also increasing interest in agentia combining the property of upregulating NO-synthase (e.g.
l-arginine) and restoring the balance between NO and free radicals (e.g. tetrahydrobiopterin). One of such agents could be folic acid.
In this review article the authors give an overview of the recent insights concerning pathogenesis and therapeutic possibilities to prevent IR-induced injury.
New developments in the field of microscopy enable to acquire increasing amounts of information from large sample areas and at an increased resolution. Depending on the nature of the technique, the ...information may reveal morphological, structural, chemical, and still other sample characteristics. In research fields, such as cell biology and materials science, there is an increasing demand to correlate these individual levels of information and in this way to obtain a better understanding of sample preparation and specific sample properties. To address this need, integrated systems were developed that combine nanometer resolution electron microscopes with optical microscopes, which produce chemically or label specific information through spectroscopy. The complementary information from electron microscopy and light microscopy presents an opportunity to investigate a broad range of sample properties in a correlated fashion. An important part of correlating the differences in information lies in bridging the different resolution and image contrast features. The trend to analyse samples using multiple correlated microscopes has resulted in a new research field. Current research is focused, for instance, on (a) the investigation of samples with nanometer scale distribution of inorganic and organic materials, (b) live cell analysis combined with electron microscopy, and (c) in situ spectroscopic and electron microscopy analysis of catalytic materials, but more areas will benefit from integrated correlative microscopy.
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