Modulation of the glutamatergic transmission by Dopamine: a focus on Parkinson, Huntington and Addiction diseases.

Dopamine (DA) plays a major role in motor and cognitive functions as well as in reward processing by regulating glutamatergic inputs. In particular in the striatum the release of DA rapidly influences synaptic transmission modulating both AMPA and NMDA receptors. Several neurodegenerative and neuropsychiatric disorders, including Parkinson, Huntington and addiction-related diseases, manifest a dysregulation of glutamate and DA signaling. Here, we will focus our attention on the mechanisms underlying the modulation of the glutamatergic transmission by DA in striatal circuits

Mechanisms of synaptic depression triggered by metabotropic glutamate receptors

Abstract.: Glutamate, by activation of metabotropic receptors (mGluRs), can lead to a reduction of synaptic efficacy at many synapses. These forms of synaptic plasticity are referred to as long-term depression (mGluR-LTD). We will distinguish between mGluR-LTD induced by pre- or postsynaptic receptors and mGluR-LTD induced by the locus of the expression mechanism of the synaptic depression. We will also review recent evidence that mGluR-mediated responses themselves are subject to depression, which may constitute a form of metaplasticit

Il trattamento delle osservazioni di Il Decamoron di Giovanni Boccaccio nel 700° della sua nascita.

Il Decameron di Giovanni Boccaccio è una opera capolavoro della letteratura italiana e, nel suo piccolo, questo lavoro, scritto nel 700° dalla nascita del Boccaccio, intende celebrare lo evento con i mezzi del Trattamento delle Osservazioni e della Geomatica, propri degli autori, applicati per ibridare culture diverse

3D STRUCTURE ANALYSIS: ARCHITECTURE AS AN EXPRESSION OF THE TIES BETWEEN GEOMETRY AND PHILOSOPHY

Abstract. In recent decades many Geomatics-based methods have been created to reconstruct and visualize objects, and these include digital photogrammetry, Lidar, remote sensing and hybrid techniques. The methods used to process such data are the result of research straddling the fields of Geomatics and Computer Vision, and employ techniques arising from approaches of analytical, geometric and statistical nature. One of the most fascinating fields of application concerns Architecture, which, moreover, has always depended on Mathematics generally and, more specifically, on Geometry. Throughout history the link between Geometry and Architecture has been strong and while architects have used mathematics to construct their buildings, geometry has always been the essential tool allowing them to choose spatial shapes which are aesthetically appropriate. Historically, mathematics and philosophy have been interrelated; many philosophers of the past were also mathematicians. The link between Philosophy and Architecture is twofold: on the one hand, philosophers have discussed what architecture is, on the other, philosophy has contributed to the development of architecture. We will deal with the ties between Architecture, Geometry and Philosophy over the centuries. Although there are artistic suggestions that go beyond time and space, and there are genial precursors, we can identify, in principle, some epochs: the ancient era, the modern era, and finally the contemporary epoch, from the crisis of positivistic sciences to globalisation.</p

ON OUTLIER DETECTION IN A PHOTOGRAMMETRIC MOBILE MAPPING DATASET

Various types of technology are used for Terrestrial Mobile Mapping (TMM) such as IMU, cameras, odometers, laser scanner etc., which are integrated in order to determine the attitude and the position of the vehicle in use, especially in the absence of GNSS signal i.e. in an urban canyon. The aim of this study is to use only photogrammetric measurements obtained with a low cost camera (with a reduced focal length and small frames) located on the vehicle, in order to improve the quality of TMM solution in the absence of a GNSS signal. It is essential to have good quality frames in order to solve this problem. In fact it is generally quite easy to extract a large number of common points between the frames (the so-called 'tie points'), but this does not necessarily imply the goodness of the matching quality, which might be uncorrected due to the presence of obstacles that may occlude the camera sight. The Authors used two different methods for solving the problem of the presence of outliers: RANSAC and the Forward Search. In this article the Authors show the results obtainable with good quality frames (frames without occlusions) and under difficult conditions that simulate better reality

SHANK3 controls maturation of social reward circuits in the VTA.

Haploinsufficiency of SHANK3, encoding the synapse scaffolding protein SHANK3, leads to a highly penetrant form of autism spectrum disorder. How SHANK3 insufficiency affects specific neural circuits and how this is related to specific symptoms remains elusive. Here we used shRNA to model Shank3 insufficiency in the ventral tegmental area of mice. We identified dopamine (DA) and GABA cell-type-specific changes in excitatory synapse transmission that converge to reduce DA neuron activity and generate behavioral deficits, including impaired social preference. Administration of a positive allosteric modulator of the type 1 metabotropic glutamate receptors mGluR1 during the first postnatal week restored DA neuron excitatory synapse transmission and partially rescued the social preference defects, while optogenetic DA neuron stimulation was sufficient to enhance social preference. Collectively, these data reveal the contribution of impaired ventral tegmental area function to social behaviors and identify mGluR1 modulation during postnatal development as a potential treatment strategy

Alexithymia and psychological distress affect perceived quality of life in patients with type 2 diabetes mellitus

Backgrounds: Psychological factors may affect patients' ability to cope with chronic illness, which occur with a high incidence as they represent age related disorder. Anxiety, depression and alexithymia could specifically interfere with compliance and adherence leading to predictable consequences and predicting morbidity and mortality independently of several confounders. The present work aims at investigating the relationship between alexithymia and affective dimension such as anxiety and depression levels, and health related quality of life in T2DM patients. Particularly, alexithymia was analyzed in its three main facets and time since diagnosis was considered with also metabolic control. Methods: Forty seven patients with T2DM were consecutively enrolled and assessed with a gold standard interview and with a psycho-diagnostic evaluation. Clinical psychological exploration consisted of HAM-A, BECK-II, SF-36 and TAS-20 administration. Statistical analysis was performed using IBM SPSS statistical version 25. Data were analyzed anonymously. Results: 47 participants showed moderate depressive symptoms as confirmed by the mean BDI-II and HAMA-A score (15.14 ± 8.95 and 24.31 ± 6.95, respectively), suggesting a high prevalence of anxiety in the enrolled subjects. It was observed a lower perceived QoL as resulted by the MCS and PCS mean values (37.68 ± 9.41 and 39.31 ± 12.29, respectively) and TAS-20 highlighted considerable mean values of 60.53 ± 7.93 in the recruited participants with a prevalence in EOT values (27.51± 4.27), in comparison with mean DID and DDF values (17.26 ± 5.52 and 15.48 ± 3.84, respectively). Conclusions: Our study may suggest a predictive role of alexithymia in patients with T2DM. Moreover, lower PCS and MCS, revealing worst perceived QoL were associated to both higher anxiety and disease duration

The Mycobacterium tuberculosis protein tyrosine phosphatase MptpA features a pH dependent activity overlapping the bacterium sensitivity to acidic conditions

The Mycobacterium tuberculosis low-molecular weight protein tyrosine phosphatase (MptpA) is responsible for the inhibition of phagosome-lysosome fusion and is essential for the bacterium patho-genicity. This inhibition implies that M. tuberculosis is not exposed to a strongly acidic environment in vivo, enabling successful propagation in host cells. Remarkably, MptpA has been previously structurally and functionally investigated, with special emphasis devoted to the enzyme properties at pH 8.0. Considering that the virulence of M. tuberculosis is strictly dependent on the avoidance of acidic con-ditions in vivo, we analysed the pH-dependence of the structural and catalytic properties of MptpA. Here we show that this enzyme undergoes pronounced conformational rearrangements when exposed to acidic pH conditions, inducing a severe decrease of the enzymatic catalytic efficiency at the expense of phosphotyrosine (pTyr). In particular, a mild decrease of pH from 6.5 to 6.0 triggers a significant increase of K0.5 of MptpA for phosphotyrosine, the phosphate group of which we determined to feature a pKa2 equal to 5.7. Surface plasmon resonance experiments confirmed that MptpA binds poorly to pTyr at pH values &lt; 6.5. Notably, the effectiveness of the MptpA competitive inhibitor L335-M34 at pH 6 does largely outperform the inhibition exerted at neutral or alkaline pH values. Overall, our observations indicate a pronounced sensitivity of MptpA to acidic pH conditions, and suggest the search for competitive in-hibitors bearing a negatively charged group featuring pKa values lower than that of the substrate phosphate group. (c) 2023 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved

Clustering and Alignment of Polymorphic Sequences for HLA-DRB1 Genotyping

Located on Chromosome 6p21, classical human leukocyte antigen genes are highly polymorphic. HLA alleles associate with a variety of phenotypes, such as narcolepsy, autoimmunity, as well as immunologic response to infectious disease. Moreover, high resolution genotyping of these loci is critical to achieving long-term survival of allogeneic transplants. Development of methods to obtain high resolution analysis of HLA genotypes will lead to improved understanding of how select alleles contribute to human health and disease risk. Genomic DNAs were obtained from a cohort of n = 383 subjects recruited as part of an Ulcerative Colitis study and analyzed for HLA-DRB1. HLA genotypes were determined using sequence specific oligonucleotide probes and by next-generation sequencing using the Roche/454 GSFLX instrument. The Clustering and Alignment of Polymorphic Sequences (CAPSeq) software application was developed to analyze next-generation sequencing data. The application generates HLA sequence specific 6-digit genotype information from next-generation sequencing data using MUMmer to align sequences and the R package diffusionMap to classify sequences into their respective allelic groups. The incorporation of Bootstrap Aggregating, Bagging to aid in sorting of sequences into allele classes resulted in improved genotyping accuracy. Using Bagging iterations equal to 60, the genotyping results obtained using CAPSeq when compared with sequence specific oligonucleotide probe characterized 4-digit genotypes exhibited high rates of concordance, matching at 759 out of 766 (99.1%) alleles. © 2013 Ringquist et al

High-end normal adrenocorticotropic hormone and cortisol levels are associated with specific cardiovascular risk factors in pediatric obesity: a cross-sectional study.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents. METHODS: This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined. RESULTS: ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides 6590th percentile (P 5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population. CONCLUSIONS: In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia, while high cortisol is associated with hypertension and high LDL-cholesterol. These specific relationships suggest complex mechanisms through which the HPA axis may contribute to metabolic impairments in obesity, and merit further investigations