Miracle-dz/UniFAR-FTUs huggingface dataset:
Cutinolytic esterase activity of bacteria isolated from mixed-plant compost and characterization of a cutinase gene from Pseudomonas pseudoalcaligenes.

The objective of the current study was to examine cutinolytic esterase (i.e., cutinase) activity by pseudomonads and bacteria isolated from mixed-plant compost. Approximately 400 isolates representing 52 taxa recovered from mixed-plant compost using cuticle baits, along with 117 pseudomonad isolates obtained from a culture collection (i.e., non-compost habitats), were evaluated. The ability of isolates to degrade the synthetic cutin polycaprolactone (PCL) was initially measured. Isolates from 23 taxa recovered from the compost degraded PCL. As well, isolates from 13 taxa of pseudomonads cleared PCL. Secondary screening measured esterase activity induced by the presence of apple cuticle using the chromogenic substrate p-nitrophenyl butyrate. Eighteen isolates representing four taxa (Alcaligenes faecalis , Bacillus licheniformis , Bacillus pumilus , and Pseudomonas pseudoalcaligenes) recovered from compost exhibited substantial esterase activity when grown with cuticle. In contrast, none of the pseudomonad isolates from the culture collection produced appreciable esterase activity. Although degradation of PCL was not correlated with esterase activity, isolates that were unable to degrade PCL failed to produce measureable esterase activities. Zymogram analysis indicated that the esterases produced by bacteria from compost ranged in size from 29 to 47 kDa. A gene from P. pseudoalcaligenes (cutA) was found to code for a cutin-induced esterase consisting of 302 amino acids and a theoretical protein size of 32 kDa. The enzyme was unique and was most closely related to other bacterial lipases (≤48% similarity).
Cardiac responses to β‐adrenoceptor stimulation is partly dependent on mitochondrial calcium uniporter activity

Despite the importance of mitochondrial Ca2+ to metabolic regulation and cell physiology, little is known about the mechanisms that regulate Ca2+ entry into the mitochondria. Accordingly, we established a system to determine the role of the mitochondrial Ca2+ uniporter in an isolated heart model, at baseline and during increased workload following β‐adrenoceptor stimulation.
Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties

Agomelatine behaves both as a potent agonist at melatonin MT1 and MT2 receptors and as a neutral antagonist at 5‐HT2C receptors. Accumulating evidence in a broad range of experimental procedures supports the notion that the psychotropic effects of agomelatine are due to the synergy between its melatonergic and 5‐hydroxytryptaminergic effects. The recent demonstration of the existence of heteromeric complexes of MT1 and MT2 with 5‐HT2C receptors at the cellular level may explain how these two properties of agomelatine translate into a synergistic action that, for example, leads to increases in hippocampal proliferation, maturation and survival through modulation of multiple cellular pathways (increase in trophic factors, synaptic remodelling, glutamate signalling) and key targets (early genes, kinases). The present review focuses on the pharmacological properties of this novel antidepressant. Its mechanism of action, strikingly different from that of conventional classes of antidepressants, opens perspectives towards a better understanding of the physiopathological bases underlying depression.
TRP channels and STIM/ORAI proteins: sensors and effectors of cancer and stroma cell migration

Cancer cells are strongly influenced by host cells within the tumour stroma and vice versa. This leads to the development of a tumour microenvironment with distinct physical and chemical properties that are permissive for tumour progression. The ability to migrate plays a central role in this mutual interaction. Migration of cancer cells is considered as a prerequisite for tumour metastasis and the migration of host stromal cells is required for reaching the tumour site. Increasing evidence suggests that transient receptor potential (TRP) channels and STIM/ORAI proteins affect key calcium‐dependent mechanisms implicated in both cancer and stroma cell migration. These include, among others, cytoskeletal remodelling, growth factor/cytokine signalling and production, and adaptation to tumour microenvironmental properties such as hypoxia and oxidative stress. In this review, we will summarize the current knowledge regarding TRP channels and STIM/ORAI proteins in cancer and stroma cell migration. We focus on how TRP channel or STIM/ORAI‐mediated Ca2+ signalling directly or indirectly influences cancer and stroma cell migration by affecting the above listed mechanisms.
Themed Section: Opioids: New Pathways to Functional Selectivity

EXPERIMENTAL APPROACH δ-opioid receptor-eGFP mice were trained to perform two instrumental actions that delivered different food outcomes. Choice between the two actions was then tested in the presence of stimuli paired with either the delivery or the non-delivery of each of the two outcomes. Bilateral infusions of the δ-opioid receptor antagonist naltrindole into the NAc-S were used to determine the role of these receptors at the time of choice and δ-opioid receptor expression in the NAc-S used to assess functional activity.
Signalling pathways and mechanisms of protection in pre‐ and postconditioning: historical perspective and lessons for the future

Ischaemic pre‐ and postconditioning are potent cardioprotective interventions that spare ischaemic myocardium and decrease infarct size after periods of myocardial ischaemia/reperfusion. They are dependent on complex signalling pathways involving ligands released from ischaemic myocardium, G‐protein‐linked receptors, membrane growth factor receptors, phospholipids, signalling kinases, NO, PKC and PKG, mitochondrial ATP‐sensitive potassium channels, reactive oxygen species, TNF‐α and sphingosine‐1‐phosphate. The final effector is probably the mitochondrial permeability transition pore and the signalling produces protection by preventing pore formation. Many investigators have worked to produce a roadmap of this signalling with the hope that it would reveal where one could intervene to therapeutically protect patients with acute myocardial infarction whose hearts are being reperfused. However, attempts to date to show efficacy of such an intervention in large clinical trials have been unsuccessful. Reasons for this inability to translate successes in the experimental laboratory to the clinical arena are evaluated in this review. It is suggested that all patients with acute coronary syndromes currently presenting to the hospital and being treated with platelet P2Y12 receptor antagonists, the current standard of care, are indeed already benefiting from protection from the conditioning pathways outlined earlier. If that proves to be the case, then future attempts to further decrease infarction will have to rely on interventions which protect by a different mechanism.
Identification of muscarinic receptor subtypes involved in catecholamine secretion in adrenal medullary chromaffin cells by genetic deletion

Activation of muscarinic receptors results in catecholamine secretion in adrenal chromaffin cells in many mammals, and muscarinic receptors partly mediate synaptic transmission from the splanchnic nerve, at least in guinea pigs. To elucidate the physiological functions of muscarinic receptors in chromaffin cells, it is necessary to identify the muscarinic receptor subtypes involved in excitation.
Stage‐dependent benefits and risks of pimobendan in mice with genetic dilated cardiomyopathy and progressive heart failure

The Ca2+ sensitizer pimobendan is a unique inotropic agent that improves cardiac contractility with less of an increase in oxygen consumption and potentially fewer adverse effects on myocardial remodelling and arrhythmia, compared with traditional inotropes. However, clinical trials report contradictory effects of pimobendan in patients with heart failure (HF). We provide mechanistic experimental evidence of the efficacy of pimobendan using a novel mouse model of progressive HF.
COPD and squamous cell lung cancer: aberrant inflammation and immunity is the common link

Cigarette smoking has reached epidemic proportions within many regions of the world and remains the highest risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Squamous cell lung cancer is commonly detected in heavy smokers, where the risk of developing lung cancer is not solely defined by tobacco consumption. Although therapies that target common driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking‐related squamous cell lung cancer. Since COPD is characterized by an excessive inflammatory and oxidative stress response, this review details how aberrant innate, adaptive and systemic inflammatory processes can contribute to lung cancer susceptibility in COPD. Activated leukocytes release increasing levels of proteases and free radicals as COPD progresses and tertiary lymphoid aggregates accumulate with increasing severity. Reactive oxygen species promote formation of reactive carbonyls that are not only tumourigenic through initiating DNA damage, but can directly alter the function of regulatory proteins involved in host immunity and tumour suppressor functions. Systemic inflammation is also markedly increased during infective exacerbations in COPD and the interplay between tumour‐promoting serum amyloid A (SAA) and IL‐17A is discussed. SAA is also an endogenous allosteric modifier of FPR2 expressed on immune and epithelial cells, and the therapeutic potential of targeting this receptor is proposed as a novel strategy for COPD–lung cancer overlap.
Hypersensitivity to intravenous iron: classification, terminology, mechanisms and management

Intravenous (IV) iron therapy is widely used in iron deficiency anaemias when oral iron is not tolerated or ineffective. Administration of IV‐iron is considered a safe procedure, but severe hypersensitivity reactions (HSRs) can occur at a very low frequency. Recently, new guidelines have been published by the European Medicines Agency with the intention of making IV‐iron therapy safer; however, the current protocols are still non‐specific, non‐evidence‐based empirical measures which neglect the fact that the majority of IV‐iron reactions are not IgE‐mediated anaphylactic reactions. The field would benefit from new specific and effective methods for the prevention and treatment of these HSRs, and the main goal of this review was to highlight a possible new approach based on the assumption that IV‐iron reactions represent complement activation‐related pseudo‐allergy (CARPA), at least in part. The review compares the features of IV‐iron reactions to those of immune and non‐immune HSRs caused by a variety of other infused drugs and thus make indirect inferences on IV‐iron reactions. The process of comparison highlights many unresolved issues in allergy research, such as the unsettled terminology, multiple redundant classifications and a lack of validated animal models and lege artis clinical studies. Facts and arguments are listed in support of the involvement of CARPA in IV‐iron reactions, and the review addresses the mechanism of low reactogenic administration protocols (LRPs) based on slow infusion. It is suggested that consideration of CARPA and the use of LRPs might lead to useful new additions to the management of high‐risk IV‐iron patients.
Budd-Chiari Syndrome Mimicking Chronic Biliary Disease

Venous outflow obstruction in the liver is histologically characterized by sinusoidal dilatation, congestion, and red blood cell extravasation into the space of Disse. Necrosis can occur in acute or subacute cases, while fibrosis develops with chronicity. These changes can occur due to impairment of venous outflow at the level of large hepatic veins or the inferior vena cava (Budd-Chiari syndrome), sinusoids or small hepatic veins (sinusoidal obstruction syndrome) or right-sided heart disease. In addition, similar histologic changes can be seen in other vascular conditions like portal vein thrombosis, systemic inflammatory disorders like rheumatoid arthritis and Castleman disease and neoplasms like renal cell carcinoma and Hodgkin disease. Although centrizonal changes are well known in venous outflow obstruction, the portal changes are not well recognized. Bile ductular reaction with or without bile duct damage and periportal fibrosis can occur in venous outflow obstruction. These changes can be mistaken for biliary disease. Imaging studies can demonstrate the normal biliary tree, and these changes are likely to be due to low grade ischemic changes rather than primary biliary disease. Large regenerative nodules can occur in Budd-Chiari syndrome and can mimic cirrhosis or hepatic neoplasms on imaging. These can histologically resemble focal nodular hyperplasia or hepatic adenoma.
A Solution-Focused Approach to Mental Health Intervention in School Settings

This article describes the use of solution-focused brief therapy (SFBT) for working with children who present with mental health problems in the    Issue Section: Articles © 2001, National Association of Social Workers, Inc. You do not currently have access to this article. Download all figures school setting. SFBT eschews a pathology-based model of mental health, focusing instead on the client's strengths and desire to change. The article describes the techniques and application of SFBT and discusses the prevalence of child mental health problems. Emphasis throughout is placed on empirical support for the effectiveness of SFBT. Sign in Don't already have an Oxford Academic account? Register National Association of Social Workers members Sig n in via society site Sign in via your Institution Forg ot password? Don't have an account? Oxford Academic account Email address / Username
Effects of P2Y12 receptor antagonists beyond platelet inhibition – comparison of ticagrelor with thienopyridines

The effect and clinical benefit of P2Y12 receptor antagonists may not be limited to platelet inhibition and the prevention of arterial thrombus formation. Potential additional effects include reduction of the pro‐inflammatory role of activated platelets and effects related to P2Y12 receptor inhibition on other cells apart from platelets. P2Y12 receptor antagonists, thienopyridines and ticagrelor, differ in their mode of action being prodrugs instead of direct acting and irreversibly instead of reversibly binding to P2Y12. These key differences may provide different potential when it comes to additional effects. In addition to P2Y12 receptor blockade, ticagrelor is unique in having the only well‐documented additional target of inhibition, the equilibrative nucleoside transporter 1. The current review will address the effects of P2Y12 receptor antagonists beyond platelets and the protection against arterial thrombosis. The discussion will include the potential for thienopyridines and ticagrelor to mediate anti‐inflammatory effects, to conserve vascular function, to affect atherosclerosis, to provide cardioprotection and to induce dyspnea.
Inequidades en el diagnóstico de anomalías congénitas mayores en recién nacidos en Cali, Colombia

SUMMARY Background: Major Congenital Anomalies (MCA) are present in 2-3% of live births. Most of these are diagnosable by prenatal ultrasound (PNUS). Developing countries have inequities in access to this screening test. Objectives: To determine existing inequities access to PNUS in mothers of newborns (NB) with MCA hospitalized in two neonatal intensive care units (NICU) and to identify inequities in the diagnosis of MCA among mothers to whom it was made at least one PNUS. Methods: Cross-sectional study in NB with MCA diagnosable by PNUS hospitalized in two NICUs of Cali, Colombia, between 2005 and 2009. The index of agreement (kappa) between prenatal diagnosis and definitive MCA was calculated. It was
Emerging options to prevent stroke in atrial fibrillation patients

Correspondence: Brian Silver Department of Neurology, Rhode Island Hospital, 110 Lockwood Street, #324 Providence, RI 02903, USA Tel +1 401 444 8806 Fax +1 401 444 8781 Email bsilver@lifespan.org Abstract: Atrial fibrillation is a common condition in the population and increases in prevalence with age. A new method for evaluating stroke risk with atrial fibrillation, called CHA 2 DS 2 Vasc, has been developed, as has a novel method for estimating the risk of bleeding, called HAS-BLED. Further, the last decade has seen a dramatic increase in the number of treatment options tested for this condition. These include novel oral anticoagulants such as apixaban, dabigatran, and rivaroxaban, and devices that occlude the left atrial appendage, such as WATCHMAN. This review will compare these new agents with the historical gold standard of warfarin.
Synthetic non‐peptide low molecular weight agonists of the relaxin receptor 1

Relaxin is a small heterodimeric peptide hormone of the insulin/relaxin superfamily produced mainly in female and male reproductive organs. It has potent antifibrotic, vasodilatory and angiogenic effects and regulates the normal function of various physiological systems. Preclinical studies and recent clinical trials have shown the promise of recombinant relaxin as a therapeutic agent in the treatment of cardiovascular and fibrotic diseases. However, there are the universal drawbacks of peptide‐based pharmacology that apply to relaxin: a short half‐life in vivo requires its continuous delivery, and there are high costs of production, storage and treatment, as well as the possibility of immune responses. All these issues can be resolved by the development of low non‐peptide MW agonists of the relaxin receptors which are stable, bioavailable, easily synthesized and specific. In this review, we describe the discovery and characterization of the first series of such compounds. The lead compound, ML290, binds to an allosteric site of the relaxin GPCR, RXFP1. ML290 shows high activity and efficacy, measured by cAMP response, in cells expressing endogenous or transfected RXFP1. Relaxin‐like effects of ML290 were shown in various functional cellular assays in vitro. ML290 has excellent absorption, distribution, metabolism and excretion properties and in vivo stability. The identified series of low MW agonists does not activate rodent RXFP1 receptors and thus, the production of a RXFP1 humanized mouse model is needed for preclinical studies. The future analysis and clinical perspectives of relaxin receptor agonists are discussed.
Cholesterol metabolism: a potential therapeutic target in Mycobacteria

Tuberculosis (TB), although a curable disease, is still one of the most difficult infections to treat. Mycobacterium tuberculosis infects 10 million people worldwide and kills 1.5 million people each year. Reactivation of a latent infection is the major cause of TB. Cholesterol is a critical carbon source during latent infection. Catabolism of cholesterol contributes to the pool of propionyl‐CoA, a precursor that is incorporated into lipid virulence factors. The M. tuberculosis genome contains a large regulon of cholesterol catabolic genes suggesting that the microorganism can utilize host sterol for infection and persistence. The protein products of these genes present ideal targets for rational drug discovery programmes. This review summarizes the development of enzyme inhibitors targeting the cholesterol pathway in M. tuberculosis. This knowledge is essential for the discovery of novel agents to treat M. tuberculosis infection.
Comparative Aspects of the Healing of Excisional Wounds on the Leg and Body of Horses

Standardized 20 mm diameter excisional skin wounds were made on the body and distal limbs of 6 ponies at 18,12, 4, and 2 weeks prior to biopsy. The results of comparative area analysis of leg and body wounds show that leg wounds take significantly longer to heal than body wounds. There is a longer preparatory phase and a greater amount of wound retraction in the leg wounds. At 12 weeks postwounding, the area of the epithelium covering the wound site is significantly larger in the leg wounds compared to the flank wounds. Histological examination of the wounds showed that there is less epithelialization of leg wounds at 2 and 4 week postwounding, and that the granulation tissue of these wounds extends slightly above the level of the adjacent skin. Within the granulation tissue of leg wounds, there are clefts filled with fibrin and inflammatory cells. Once epithelialization is completed, the leg wounds are covered by acanthotic epidermis with numerous large epidermal projections. In contrast, the flank wounds are covered by thin epidermis devoid of epidermal projections. One wound at 18 weeks postwounding had histological features typical of a keloid.
Effect of parental fatness levels on the fatness of biological and adoptive children

As shown in pairings involving 2,845 biological children and 147 adopted children, fatness of the children increases in stepwise fashion according to parental fatness combinations (Lean X Lean through Obese X Obese) for both biological and for social (i.e., adopted) children as well, thus indicating that fatness (while strongly familial) is not necessarily genetic.
EPILEPSY COMORBIDITIES

Psychiatric and cognitive disorders in persons with epilepsy (PWE) are often overlooked or undertreated. Studies have shown that they occur in all types of epilepsy, but they are especially prominent when epilepsy is severe and multiple antiepileptic drugs are used. In particular, the clinician should be vigilant about the coexistence of depression with epilepsy. The depression must be properly treated to improve quality of life and also to prevent the mood disorder from interfering with epilepsy treatment. Mortality in PWE is overall twice that in the general population, but most of the increased mortality is due to major conditions with which the epilepsy is associated. The clinician should be aware that some PWE have increased risk for suicide. The phenomenon of sudden unexplained death in epilepsy occurs at the highest rate in persons with uncontrolled seizures, especially generalized convulsive seizures. For now, optimizing seizure control appears to be the best way to reduce the risk for this still mysterious and catastrophic event. Note: Text referenced in the Quintessentials Preferred Responses, which appear later in this issue, is indicated in yellow shading throughout this chapter.
Social Marketing and Motivational Interviewing as Community Interventions for Safe Water Behaviors: Follow-up Surveys in Zambia

To address the need for innovative approaches to diarrhea prevention in developing countries, we conducted two studies in Zambia to compare the effect of social marketing alone (SM) with social marketing plus motivational interviewing (SM+MI) on the adoption and continued use of a household-based water chlorination and storage intervention called the safe water system (SWS). In Study 1, we conducted a baseline survey, implemented SM+MI in intervention households, SM in comparison households, implemented the SWS, then compared chlorine residuals in stored water in SM and SM+MI households. In Study 2, we compared chlorine residuals in SM and SM+MI households 16 months after a similar implementation project in a different population. The proportion of SM+MI households with adequate chlorine residuals was 16-fold higher in Study 1 and 2-fold higher in Study 2 than SM households. MI is a promising method for motivating the adoption and sustained use of safe water behaviors.