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https://www.readbyqxmd.com/read/28700581/corrigendum-crystal-structure-of-the-glp-1-receptor-bound-to-a-peptide-agonist
#1
Ali Jazayeri, Mathieu Rappas, Alastair J H Brown, James Kean, James C Errey, Nathan J Robertson, Cédric Fiez-Vandal, Stephen P Andrews, Miles Congreve, Andrea Bortolato, Jonathan S Mason, Asma H Baig, Iryna Teobald, Andrew S Doré, Malcolm Weir, Robert M Cooke, Fiona H Marshall
This corrects the article DOI: 10.1038/nature22800.
July 12, 2017: Nature
https://www.readbyqxmd.com/read/28611376/allopregnanolone-mediates-the-exacerbation-of-tourette-like-responses-by-acute-stress-in-mouse-models
#2
Laura J Mosher, Sean C Godar, Marianela Nelson, Stephen C Fowler, Graziano Pinna, Marco Bortolato
Tourette syndrome (TS) is a neuropsychiatric disorder characterized by multiple tics and sensorimotor abnormalities, the severity of which is typically increased by stress. The neurobiological underpinnings of this exacerbation, however, remain elusive. We recently reported that spatial confinement (SC), a moderate environmental stressor, increases tic-like responses and elicits TS-like sensorimotor gating deficits in the D1CT-7 mouse, one of the best-validated models of TS. Here, we hypothesized that these adverse effects may be mediated by neurosteroids, given their well-documented role in stress-response orchestration...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28591303/translation-and-cross-cultural-adaptation-of-the-clinical-competence-questionnaire-for-use-in-brazil
#3
Danielle Ritter Kwiatkoski, Maria de Fátima Mantovani, Evani Marques Pereira, Carina Bortolato-Major, Ângela Taís Mattei, Aida Maris Peres
Objective: translating and transculturally adapting the Clinical Competence Questionnaire to Brazilian senior undergraduate Nursing students, as well as measuring psychometric properties of the questionnaire. Method: a methodological study carried out in six steps: translation of the Clinical Competence Questionnaire instrument, consensus of the translations, back-translation, analysis by an expert committee, pre-testing and then presentation of the cross-cultural adaptation process to the developers...
June 5, 2017: Revista Latino-americana de Enfermagem
https://www.readbyqxmd.com/read/28562585/crystal-structure-of-the-glp-1-receptor-bound-to-a-peptide-agonist
#4
Ali Jazayeri, Mathieu Rappas, Alastair J H Brown, James Kean, James C Errey, Nathan J Robertson, Cédric Fiez-Vandal, Stephen P Andrews, Miles Congreve, Andrea Bortolato, Jonathan S Mason, Asma H Baig, Iryna Teobald, Andrew S Doré, Malcolm Weir, Robert M Cooke, Fiona H Marshall
Glucagon-like peptide 1 (GLP-1) regulates glucose homeostasis through the control of insulin release from the pancreas. GLP-1 peptide agonists are efficacious drugs for the treatment of diabetes. To gain insight into the molecular mechanism of action of GLP-1 peptides, here we report the crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist. The peptide agonist retains an α-helical conformation as it sits deep within the receptor-binding pocket. The arrangement of the transmembrane helices reveals hallmarks of an active conformation similar to that observed in class A receptors...
June 8, 2017: Nature
https://www.readbyqxmd.com/read/28498599/prevalence-incidence-and-mortality-from-cardiovascular-disease-in-patients-with-pooled-and-specific-severe-mental-illness-a-large-scale-meta-analysis-of-3-211-768-patients-and-113-383-368-controls
#5
Christoph U Correll, Marco Solmi, Nicola Veronese, Beatrice Bortolato, Stella Rosson, Paolo Santonastaso, Nita Thapa-Chhetri, Michele Fornaro, Davide Gallicchio, Enrico Collantoni, Giorgio Pigato, Angela Favaro, Francesco Monaco, Cristiano Kohler, Davy Vancampfort, Philip B Ward, Fiona Gaughran, André F Carvalho, Brendon Stubbs
People with severe mental illness (SMI) - schizophrenia, bipolar disorder and major depressive disorder - appear at risk for cardiovascular disease (CVD), but a comprehensive meta-analysis is lacking. We conducted a large-scale meta-analysis assessing the prevalence and incidence of CVD; coronary heart disease; stroke, transient ischemic attack or cerebrovascular disease; congestive heart failure; peripheral vascular disease; and CVD-related death in SMI patients (N=3,211,768) versus controls (N=113,383,368) (92 studies)...
June 2017: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
https://www.readbyqxmd.com/read/28470927/systematic-assessment-of-environmental-risk-factors-for-bipolar-disorder-an-umbrella-review-of-systematic-reviews-and-meta-analyses
#6
REVIEW
Beatrice Bortolato, Cristiano A Köhler, Evangelos Evangelou, Jordi León-Caballero, Marco Solmi, Brendon Stubbs, Lazaros Belbasis, Isabella Pacchiarotti, Lars V Kessing, Michael Berk, Eduard Vieta, André F Carvalho
OBJECTIVES: The pathophysiology of bipolar disorder is likely to involve both genetic and environmental risk factors. In our study, we aimed to perform a systematic search of environmental risk factors for BD. In addition, we assessed possible hints of bias in this literature, and identified risk factors supported by high epidemiological credibility. METHODS: We searched the Pubmed/MEDLINE, EMBASE and PsycInfo databases up to 7 October 2016 to identify systematic reviews and meta-analyses of observational studies that assessed associations between putative environmental risk factors and BD...
March 2017: Bipolar Disorders
https://www.readbyqxmd.com/read/28414491/associations-between-emotional-abuse-and-neglect-and-dimensions-of-alexithymia-the-moderating-role-of-sex
#7
Shaquanna Brown, Paula J Fite, Katie Stone, Allora Richey, Marco Bortolato
OBJECTIVE: Child maltreatment, specifically emotional maltreatment (i.e., an act, such as belittling, blaming, or rejection, that is potentially harmful to a child's emotional development), has emerged as an important correlate of alexithymia. However, the evidence is mixed with regard to how emotional abuse and neglect might relate to dimensions of alexithymia (i.e., externally oriented thinking, difficulty describing feelings, and difficulty identifying feelings). Furthermore, research is needed to identify individual factors that might influence these associations...
April 17, 2017: Psychological Trauma: Theory, Research, Practice and Policy
https://www.readbyqxmd.com/read/28292646/follow-up-of-elderly-patients-with-urogenital-cancers-evaluation-of-geriatric-care-needs-and-related-actions
#8
Silvio Monfardini, Sara Morlino, Riccardo Valdagni, Mario Catanzaro, Ardit Tafa, Barbara Bortolato, Giovanni Petralia, Elisa Bonetto, Elisa Villa, Stefano Picozzi, Maria Cristina Locatelli, Giuseppe Galetti, Andrea Millul, Yasmin Albanese, Elisa Bianchi, Claudia Panzarino, Francesca Gerardi, Ettore Beghi
OBJECTIVES: To investigate a comprehensive geriatric assessment (CGA) with subsequent investigation of healthcare patterns in older patients with urological cancers undergoing initial surgery or radiotherapy, to verify the usefulness of the incorporation of geriatric principles in future care plans. MATERIAL AND METHODS: This is a prospective cohort study. From November 2011 to March 2015, CGA was offered to all patients aged 70+ years treated with radiotherapy or surgery at seven tertiary centers...
July 2017: Journal of Geriatric Oncology
https://www.readbyqxmd.com/read/28262605/impulsivity-as-a-moderator-of-the-associations-between-child-maltreatment-types-and-body-mass-index
#9
Shaquanna Brown, Tarrah B Mitchell, Paula J Fite, Marco Bortolato
Child maltreatment has emerged as an important risk factor for adult obesity (Danese & Tan, 2014; Hemmingsson et al., 2014). However, there is a need for research delineating the factors that play a role in this association. Impulsivity has been shown to be associated with both child maltreatment (Brodsky et al., 2001) and body mass index (BMI; Cortese et al., 2008; Thamotharan et al., 2013). Further, given previous research showing that adverse events interact with impulsivity to predict hazardous drinking behaviors (Fox et al...
May 2017: Child Abuse & Neglect
https://www.readbyqxmd.com/read/28237575/modeling-tics-in-rodents-conceptual-challenges-and-paths-forward
#10
Marco Bortolato, Christopher Pittenger
BACKGROUND: Recent advances in our understanding of the neurobiology of tics have led to the development of novel rodent models capturing different pathophysiological and phenotypic aspects of Tourette syndrome. The proliferation of these models, however, raises vexing questions on what standards should be adopted to assess their theoretical validity and empirical utility. Assessing the homology of a rodent motoric burst with a tic remains problematic, due to our incomplete knowledge of the underpinnings of tics, their high phenotypic complexity and variability, limitations in our ability test key aspects of tic phenomenology (such as premonitory sensory phenomena) in animals, and between-species differences in neuroanatomy and behavioral repertoire...
February 22, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28183242/decoding-corticotropin-releasing-factor-receptor-type-1-crystal-structures
#11
Andrew S Doré, Andrea Bortolato, Kaspar Hollenstein, Robert K Y Cheng, Randy J Read, Fiona H Marshall
The structural analysis of class B G protein-coupled receptors (GPCR), cell surface proteins responding to peptide hormones, has until recently been restricted to the extracellular domain (ECD). Corticotropin-releasing factor receptor type 1 (CRF1R) is a class B receptor mediating stress response and also considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of human CRF1R in complex with the small-molecule antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry...
January 10, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28131725/the-5-alpha-reductase-inhibitor-finasteride-reduces-dyskinesia-in-a-rat-model-of-parkinson-s-disease
#12
Roberto Frau, Paola Savoia, Silvia Fanni, Chiara Fiorentini, Camino Fidalgo, Elisabetta Tronci, Roberto Stancampiano, Mario Meloni, Antonino Cannas, Francesco Marrosu, Marco Bortolato, Paola Devoto, Cristina Missale, Manolo Carta
Levodopa-induced dyskinesia (LID) is a disabling motor complication occurring in Parkinson's disease patients (PD) after long-term l-DOPA treatment. Although its etiology remains unclear, there is accumulating evidence that LID relies on an excessive dopamine receptor transmission, particularly at the downstream signaling of D1 receptors. We previously reported that the pharmacological blockade of 5-alpha reductase (5AR), the rate limiting enzyme in neurosteroids synthesis, rescued a number of behavioral aberrations induced by D1 receptor-selective and non-selective agonists, without inducing extrapyramidal symptoms...
May 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28102229/the-neurosteroidogenic-enzyme-5%C3%AE-reductase-mediates-psychotic-like-complications-of-sleep-deprivation
#13
Roberto Frau, Valentina Bini, Alessio Soggiu, Simona Scheggi, Alessandra Pardu, Silvia Fanni, Paola Roncada, Monica Puligheddu, Francesco Marrosu, Donatella Caruso, Paola Devoto, Marco Bortolato
Acute sleep deprivation (SD) can trigger or exacerbate psychosis- and mania-related symptoms; the neurobiological basis of these complications, however, remains elusive. Given the extensive involvement of neuroactive steroids in psychopathology, we hypothesized that the behavioral complications of SD may be contributed by 5α-reductase (5αR), the rate-limiting enzyme in the conversion of progesterone into the neurosteroid allopregnanolone. We first tested whether rats exposed to SD may exhibit brain-regional alterations in 5αR isoenzymes and neuroactive steroid levels; then, we assessed whether the behavioral and neuroendocrine alterations induced by SD may be differentially modulated by the administration of the 5αR inhibitor finasteride, as well as progesterone and allopregnanolone...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28099872/assessment-of-gait-and-sensorimotor-deficits-in-the-d1ct-7-mouse-model-of-tourette-syndrome
#14
Stephen C Fowler, Laura J Mosher, Sean C Godar, Marco Bortolato
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and phonic tics. While TS patients have been also shown to exhibit subtle abnormalities of sensorimotor integration and gait, animal models of this disorder are seldom tested for these functions. To fill this gap, we assessed gait and sensorimotor integration in the D1CT-7 mouse, one of the best-validated animal models of TS. D1CT-7 mice exhibit spontaneous tic-like manifestations, which, in line with the clinical phenomenology of TS, are markedly exacerbated by environmental stress...
January 15, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/27939782/what-makes-you-tic-translational-approaches-to-study-the-role-of-stress-and-contextual-triggers-in-tourette-syndrome
#15
REVIEW
Sean C Godar, Marco Bortolato
Tourette syndrome (TS) is a neurodevelopmental condition characterized by multiple, recurring motor and phonic tics. Rich empirical evidence shows that the severity of tics and associated manifestations is increased by several stressors and contextual triggers; however, the neurobiological mechanisms responsible for symptom exacerbation in TS remain poorly understood. This conceptual gap partially reflects the high phenotypic variability in tics, as well as the existing difficulties in operationalizing and standardizing stress and its effects in a clinical setting...
May 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27936453/biological-mechanisms-of-depression-following-treatment-with-interferon-for-chronic-hepatitis-c-a-critical-systematic-review
#16
REVIEW
Myrela O Machado, Giovanni Oriolo, Beatrice Bortolato, Cristiano A Köhler, Michael Maes, Marco Solmi, Iria Grande, Rocío Martín-Santos, Eduard Vieta, André F Carvalho
BACKGROUND: A significant subset of patients infected by the hepatitis C virus (HCV) develops a major depressive episode (MDE) during Interferon-alpha (IFN-α) based immunotherapy. We performed a systematic review of studies which examined biological mechanisms contributing to the onset of a MDE during IFN-α-based immunotherapy for HCV. METHODS: Major electronic databases were searched from inception up until 15th February 2016 for peer-reviewed prospective studies that had enrolled HCV infected patients who received IFN-α treatment...
February 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/27894012/depression-in-cancer-the-many-biobehavioral-pathways-driving-tumor-progression
#17
REVIEW
Beatrice Bortolato, Thomas N Hyphantis, Sara Valpione, Giulia Perini, Michael Maes, Gerwyn Morris, Marta Kubera, Cristiano A Köhler, Brisa S Fernandes, Brendon Stubbs, Nicholas Pavlidis, André F Carvalho
Major Depressive Disorder (MDD) is common among cancer patients, with prevalence rates up to four-times higher than the general population. Depression confers worse outcomes, including non-adherence to treatment and increased mortality in the oncology setting. Advances in the understanding of neurobiological underpinnings of depression have revealed shared biobehavioral mechanisms may contribute to cancer progression. Moreover, psychosocial stressors in cancer promote: (1) inflammation and oxidative/nitrosative stress; (2) a decreased immunosurveillance; and (3) a dysfunctional activation of the autonomic nervous system and of the hypothalamic-pituitaryadrenal axis...
January 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27889491/pramipexole-enhances-disadvantageous-decision-making-lack-of-relation-to-changes-in-phasic-dopamine-release
#18
Romina Pes, Sean C Godar, Andrew T Fox, Lauren M Burgeno, Hunter J Strathman, David P Jarmolowicz, Paola Devoto, Beth Levant, Paul E Phillips, Stephen C Fowler, Marco Bortolato
Pramipexole (PPX) is a high-affinity D2-like dopamine receptor agonist, used in the treatment of Parkinson's disease (PD) and restless leg syndrome. Recent evidence indicates that PPX increases the risk of problem gambling and impulse-control disorders in vulnerable patients. Although the molecular bases of these complications remain unclear, several authors have theorized that PPX may increase risk propensity by activating presynaptic dopamine receptors in the mesolimbic system, resulting in the reduction of dopamine release in the nucleus accumbens (NAcc)...
March 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27750143/exploring-the-neural-mechanisms-of-finasteride-a-proteomic-analysis-in-the-nucleus-accumbens
#19
Alessio Soggiu, Cristian Piras, Viviana Greco, Paola Devoto, Andrea Urbani, Luigino Calzetta, Marco Bortolato, Paola Roncada
The enzyme 5α-reductase (5αR) catalyzes the conversion of progesterone and testosterone into neuroactive steroids implicated in a wide array of behavioral functions. The prototypical 5αR inhibitor, finasteride (FIN), is clinically approved for the treatment of androgenic alopecia and benign prostatic hyperplasia. Recent evidence has shown that FIN, albeit generally well tolerated, can induce untoward psychological effects in a subset of patients; furthermore, this drug may have therapeutic efficacy for a number of different neuropsychiatric conditions, ranging from Tourette syndrome to schizophrenia...
December 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27643714/identification-of-ligand-binding-hot-spots-of-the-histamine-h1-receptor-following-structure-based-fragment-optimization
#20
Sebastiaan Kuhne, Albert J Kooistra, Reggie Bosma, Andrea Bortolato, Maikel Wijtmans, Henry F Vischer, Jonathan S Mason, Chris de Graaf, Iwan J P de Esch, Rob Leurs
Developments in G protein-coupled receptor (GPCR) structural biology provide insights into GPCR-ligand binding. Compound 1 (4-(2-benzylphenoxy)piperidine) with high ligand efficiency for the histamine H1 receptor (H1R) was used to design derivatives to investigate the roles of (i) the amine-binding region, (ii) the upper and lower aromatic region, and (iii) binding site solvation. SAR analysis showed that the amine-binding region serves as the primary binding hot spot, preferably binding small tertiary amines...
October 13, 2016: Journal of Medicinal Chemistry
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