A drug-resistant mutation in plant target of rapamycin validates the specificity of ATP-competitive TOR inhibitors in vivo.

Kinases are major components of cellular signaling pathways, regulating key cellular activities through phosphorylation. Kinase inhibitors are efficient tools for studying kinase targets and functions, however assessing their kinase specificity in vivo is essential. The identification of resistant kinase mutants has been proposed to be the most convincing approach to achieve this goal.

Involvement of A13 dopaminergic neurons in prehensile movements but not reward in the rat.

Tyrosine hydroxylase (TH)-containing neurons of the dopamine (DA) cell group A13 are well positioned to impact known DA-related functions as their descending projections innervate target regions that regulate vigilance, sensory integration, and motor execution. Despite this connectivity, little is known regarding the functionality of A13-DA circuits. Using TH-specific loss-of-function methodology and techniques to monitor population activity in transgenic rats in vivo, we investigated the contribution of A13-DA neurons in reward and movement-related actions.

The Impact of Beehive Proximity, Human Activity and Agricultural Intensity on Diptera Diversity in a Mediterranean Mosaic of Agroecosystems, with a Focus on Pest Species.

Diptera, with their participation in pollination, significantly contribute to the maintenance of plant diversity, and they also have great potential for assessing habitat health and preserving it. A decline in their abundance and diversity has been recorded worldwide as a consequence of biotic, abiotic, and anthropic alterations. In addition to pollinators, these orders include agricultural and forestry pests, which are a threat to both cultivated and wild plants that are very important to the economy.

Sex differences in the antidepressant-like response and molecular events induced by the imidazoline-2 receptor agonist CR4056 in rats.

In searching for novel targets to design antidepressants, among the characterized imidazoline receptors (IR), I2 receptors are an innovative therapeutical approach since they are dysregulated in major depressive disorder and by classical antidepressant treatments. In fact, several I2 agonists have been characterized for their antidepressant-like potential, but the results in terms of efficacy were mixed and exclusively reported in male rodents. Since there are well-known sex differences in antidepressant-like efficacy, this study characterized the potential effects induced by two I2 drugs, CR4056 (i.

Neuropeptide S Encodes Stimulus Salience in the Paraventricular Thalamus.

Evaluation of stimulus salience is critical for any higher organism, as it allows for prioritizing of vital information, preparation of responses, and formation of valuable memory. The paraventricular nucleus of the thalamus (PVT) has recently been identified as an integrator of stimulus salience but the neurochemical basis and afferent input regarding salience signaling have remained elusive. Here we report that neuropeptide S (NPS) signaling in the PVT is necessary for stimulus salience encoding, including aversive, neutral and reinforcing sensory input.

Ingested non-essential amino acids recruit brain orexin cells to suppress eating in mice.

Ingested nutrients are proposed to control mammalian behavior by modulating the activity of hypothalamic orexin/hypocretin neurons (HONs). Previous in vitro studies showed that nutrients ubiquitous in mammalian diets, such as non-essential amino acids (AAs) and glucose, modulate HONs in distinct ways. Glucose inhibits HONs, whereas non-essential (but not essential) AAs activate HONs.

Predictive and motivational factors influencing anticipatory contrast: A comparison of contextual and gustatory predictors in food restricted and free-fed rats.

In anticipation of palatable food, rats can learn to restrict consumption of a less rewarding food type resulting in an increased consumption of the preferred food when it is made available. This construct is known as anticipatory negative contrast (ANC) and can help elucidate the processes that underlie binge-like behavior as well as self-control in rodent motivation models. In the current investigation we aimed to shed light on the ability of distinct predictors of a preferred food choice to generate contrast effects and the motivational processes that underlie this behavior.

Quality of Colonoscopy Is Associated With Adenoma Detection and Postcolonoscopy Colorectal Cancer Prevention in Lynch Syndrome.

Background & Aims: Colonoscopy reduces colorectal cancer (CRC) incidence and mortality in Lynch syndrome (LS) carriers. However, a high incidence of postcolonoscopy CRC (PCCRC) has been reported. Colonoscopy is highly dependent on endoscopist skill and is subject to quality variability.

Intracellular amorphous Ca-carbonate and magnetite biomineralization by a magnetotactic bacterium affiliated to the Alphaproteobacteria.

Bacteria synthesize a wide range of intracellular submicrometer-sized inorganic precipitates of diverse chemical compositions and structures, called biominerals. Their occurrences, functions and ultrastructures are not yet fully described despite great advances in our knowledge of microbial diversity. Here, we report bacteria inhabiting the sediments and water column of the permanently stratified ferruginous Lake Pavin, that have the peculiarity to biomineralize both intracellular magnetic particles and calcium carbonate granules.

Orexin neurons and inhibitory Agrp→orexin circuits guide spatial exploration in mice.

Key Points: Photoinhibition of endogenous activity of lateral hypothalamic orexin neurons causes place preference and reduces innate avoidance Endogenous activity of orexin neurons correlates with place preference Mediobasal hypothalamic Agrp neurons inhibit orexin neurons via GABA, and chemogenetic suppression of Agrp neurons increases avoidance in an orexin receptor-dependent manner.

Abstract: Hypothalamic orexin/hypocretin neurons integrate multiple sensory cues and project brain-wide to orchestrate diverse innate behaviours. Their loss impairs many context-appropriate actions, but the motivational characteristics of orexin cell activity remain unclear.

Ultrasound-assisted extraction of ergosterol and antioxidant components from mushroom by-products and the attainment of a β-glucan rich residue.

Revalorization of mushroom by-product (stalks of A. bisporus) by extracting its components is proposed. The extraction kinetics at 25 °C of ergosterol, phenolic compounds and antioxidant activity by mechanical agitation (at 130 rpm) and ultrasound assistance (at 182 and 321 W/L) in 70 and 96% v/v ethanol/water solutions during 30 min were evaluated and satisfactorily modelled, using the Weibull model (mean relative error ≤ 7.

Clinical and Pathological Characterization of Lynch-Like Syndrome.

Background & Aims: Lynch syndrome is characterized by DNA mismatch repair (MMR) deficiency. Some patients with suspected Lynch syndrome have DNA MMR deficiencies but no detectable mutations in genes that encode MMR proteins-this is called Lynch-like syndrome (LLS). There is no consensus on management of patients with LLS.

Basic training in digestive endoscopy for resident physicians in gastroenterology. Recommendations by the Sociedad Española de Endoscopia Digestiva (SEED).

Digestive endoscopy is the most effective tool available for the diagnosis of multiple gastrointestinal (GI) tract conditions, and it represents a key aspect in the training of gastroenterology residents according to the Spanish MIR (médico interno residente) program. The Sociedad Española de Endoscopia Digestiva (SEED), aware of all the technical advances that have emerged during the past few years, deems it necessary to define a program of the skills specialists-in-training in gastroenterology should acquire during their residency. This paper describes the goals of endoscopy training, the techniques that should be mastered, and the diagnostic and therapeutic skills this specialty requires.

Author Correction: Accumbal D2 cells orchestrate innate risk-avoidance according to orexin signals.

In the version of this article initially published, a sentence in the third paragraph read, "Suppression of natural orexin signaling by orexin receptor antagonism (Fig. 3b-e) led to increased risk-avoidance behaviors." "Increased" has been changed to "decreased" in this sentence.

Accumbal D2 cells orchestrate innate risk-avoidance according to orexin signals.

Excitation of accumbal D2 cells governs vital actions, including avoidance of learned risks, but the origins of this excitation and roles of D2 cells in innate risk-avoidance are unclear. Hypothalamic neurons producing orexins (also called hypocretins) enhance innate risk-avoidance via poorly understood neurocircuits. We describe a direct orexin→D2 excitatory circuit and show that D2 cell activity is necessary for orexin-dependent innate risk-avoidance in mice, thus revealing an unsuspected hypothalamus-accumbens interplay in action selection.

Melanin concentrating hormone modulates oxytocin-mediated marble burying.

Repetitive and perseverative behaviors are common features of a number of neuropsychiatric diseases such as Angelman's syndrome, Tourette's syndrome, obsessive-compulsive disorder, and autism spectrum disorders. The oxytocin system has been linked to the regulation of repetitive behavior in both animal models and humans, but many of its downstream targets have still to be found. We report that the melanin-concentrating hormone (MCH) system is a target of the oxytocin system in regulating one repetitive behavior, marble burying.

Neuropeptide S precursor knockout mice display memory and arousal deficits.

Activation of neuropeptide S (NPS) signaling has been found to produce arousal, wakefulness, anxiolytic-like behaviors, and enhanced memory formation. In order to further study physiological functions of the NPS system, we generated NPS precursor knockout mice by homologous recombination in embryonic stem cells. NPS mice were viable, fertile, and anatomically normal, when compared to their wild-type and heterozygous littermates.

Exploring the needs of certified hand therapists regarding electronic applications.

Study Design: Survey.

Introduction: App technology may provide a beneficial clinical resource for CHTs.

Purpose Of Study: This descriptive study examined beneficial components for inclusion in a potential app for certified hand therapists to use as a clinical resource based on a nationwide survey.

Identification of neuropeptide S antagonists: structure-activity relationship studies, X-ray crystallography, and in vivo evaluation.

Modulation of the neuropeptide S (NPS) system has been linked to a variety of CNS disorders such as panic disorder, anxiety, sleeping disorders, asthma, obesity, PTSD, and substance abuse. In this study, a series of diphenyltetrahydro-1H-oxazolo[3,4-α]pyrazin-3(5H)-ones were synthesized and evaluated for antagonist activity at the neuropeptide S receptor. The absolute configuration was determined by chiral resolution of the key synthetic intermediate, followed by analysis of one of the individual enantiomers by X-ray crystallography.

Retrograde intrarenal surgery (RIRS) in the treatment of calyceal diverticulum with lithiasis.

Objectives: To evaluate the result of retrograde intrarenal surgery (RIRS) assisted by flexible ureterorenoscopy (FURS) and Holmium laser in the treatment of lithiasis within calyceal diverticula as a minimally invasive therapeutic option.

Methods: We retrospectively evaluated 11 cases of symptomatic lithiasis within calyceal diverticula treated between January 2010 and December 2011. We defined treatment success as absence of residual stones and absence/disappearance of symptomatology over the course of follow-up.

Intake of melatonin increases tryptophan hydroxylase type 1 activity in aged rats: Preliminary study.

Pineal melatonin is important not only for synchronization of biological rhythms, but also in the ageing process as a potential drug to relieve oxidative damage. During ageing, the nocturnal melatonin production decreases resulting in an increased incidence of disorders. Present in vivo experiments were performed to study the effects of exogenous melatonin chronically administered to old rats on the pineal biosynthesis of melatonin and the precursor serotonin (5-HT) mediated by tryptophan hydroxylase type 1 (TPH-1).

Results of retrograde intrarenal surgery in the treatment of renal stones greater than 2 cm.

Objective: To analyze the results of retrograde intrarenal surgery (RIRS) in patients with ≥2 cm stones treated in our center.

Material And Methods: A retrospective review of 106 patients with renal calculi underwent RIRS ≥2 cm (period January 2009-December 2011). The procedures were performed under general anesthesia as a source of fragmentation using the holmium laser (30 W Litho Quantasystem) and flexible ureteroscopes (X2 Flex Storz, Olympus P5) through ureteral access sheaths.

Cognitive improvement by acute growth hormone is mediated by NMDA and AMPA receptors and MEK pathway.

It has been reported that Growth hormone (GH) has an immediate effect enhancing excitatory postsynaptic potentials mediated by AMPA and NMDA receptors in hippocampal area CA1. As GH plays a role in adult memory processing, this work aims to study the acute effects of GH on working memory tasks in rodents and the possible involvement of NMDA and AMPA receptors and also the MEK/ERK signalling pathway. To evaluate memory processes, two different tests were used, the spatial working memory 8-arm radial maze, and the novel object recognition as a form of non-spatial working memory test.