scholarly journals Caudate transcriptome implicates decreased presynaptic autoregulation as the dopamine risk factor for schizophrenia

2020 ◽  
Author(s):  
Kynon JM Benjamin ◽  
Arthur S Feltrin ◽  
André Rocha Barbosa ◽  
Andrew E Jaffe ◽  
Leonardo Collado-Torres ◽  
...  
Keyword(s):  
Caudate Nucleus ◽  
Deep Neural Networks ◽  
Psychotic Symptoms ◽  
Common Variants ◽  
D2 Dopamine Receptor ◽  
Risk Genes ◽  
New Approach ◽  
New Genes ◽  
Da Release

AbstractIncreased dopamine (DA) signaling in the striatum has been a cornerstone hypothesis about psychosis for over 50 years. Increased dopamine release results in psychotic symptoms, while D2 dopamine receptor (DRD2) antagonists are antipsychotic. Recent schizophrenia GWAS identified risk-associated common variants near the DRD2 gene, but the risk mechanism has been unclear. We performed RNA-sequencing in postmortem caudate nucleus from 444 individuals and identified many new genes associated with risk for schizophrenia through genetic modulation of expression. Genetic risk for schizophrenia is associated specifically with decreased expression of the short isoform of DRD2, which encodes the presynaptic autoreceptor, and not with expression of the long isoform postsynaptic receptor. These data implicate decreased control of presynaptic DA release as a genetic mechanism of schizophrenia risk. Using a new approach based on deep neural networks, we construct caudate gene expression networks that highlight interactions involving schizophrenia risk genes and uncover potential novel therapeutic targets.One Sentence SummaryA comprehensive analysis of schizophrenia risk and of the role of DRD2 signaling within the caudate nucleus.

Role of trace amine associated receptor 1 (TAAR1) in D2 dopamine receptor-related behavior and signaling

2012 ◽  
Author(s):  
S. Espinoza ◽  
F. Manago ◽  
M. Messa ◽  
T. D. Sotnikova ◽  
M. Caron ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
D2 Dopamine Receptor ◽  
Trace Amine

Role of Trace Amine Associated Receptor 1 (TAAR1) in D2 Dopamine receptor-related behavior and signaling

2012 ◽  
Author(s):  
S. Espinoza ◽  
F. Manago ◽  
M. Messa ◽  
T. D. Sotnikova ◽  
M. Caron ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
D2 Dopamine Receptor ◽  
Trace Amine

METAMORPHOSES OF THE POSTMODERN DISCOURSEAND CURRENT CHALLENGES NEOMODERNISM

2019 ◽  
Author(s):  
Yu.V. IRKHIN
Keyword(s):  
World Politics ◽  
New Approach ◽  
Postmodern Theory ◽  
The World ◽  
Conservative Values

The article analyzes the problems, achievements and contradictions in the genesis of the contemporary postmodern discourse. The author has carried out complex research, systematized and showed the main features and differences of postmodernism and metamodernism, as well as the role of neoliberal values in their development. The author has considered a new approach to the study of society and politics: neomodernist discourse with the dominant conservative values, opposing postmodern theory, methodology and practice he has identified the features of neomodernism: historicism, patriotism and healthy nationalism, populism, transactionalismn and realism in the world politics.

Monitoring the marine environment for small round structured viruses (SRSVS): a new approach to combating the transmission of these viruses by molluscan shellfish

1998 ◽  
Vol 38 (12) ◽  
pp. 51-56 ◽  
Author(s):  
K. Henshilwood ◽  
J. Green ◽  
D. N. Lees
Keyword(s):  
Enteric Virus ◽  
Winter Period ◽  
Rt Pcr ◽  
Cloning And Sequencing ◽  
New Approach ◽  
Human Enteric Virus ◽  
Different Strains ◽  
The Uk ◽  
Public Health Protection

This study investigates human enteric virus contamination of a shellfish harvesting area. Samples were analysed over a 14-month period for Small Round Structured Viruses (SRSVs) using a previously developed nested RT-PCR. A clear seasonal difference was observed with the largest numbers of positive samples obtained during the winter period (October to March). This data concurs with the known winter association of gastroenteric illness due to oyster consumption in the UK and also with the majority of the outbreaks associated with shellfish harvested from this area during the study period. RT-PCR positive amplicons were further characterised by cloning and sequencing. Sequence analysis of the positive samples identified eleven SRSV strains, of both Genogroup I and Genogroup II, occurring throughout the study period. Many shellfish samples contained a mixture of strains with a few samples containing up to three different strains with both Genogroups represented. The observed common occurrence of strain mixtures may have implications for the role of shellfish as a vector for dissemination of SRSV strains. These results show that nested RT-PCR can identify SRSV contamination in shellfish harvesting areas. Virus monitoring of shellfish harvesting areas by specialist laboratories using RT-PCR is a possible approach to combating the transmission of SRSVs by molluscan shellfish and could potentially offer significantly enhanced levels of public health protection.

Role of General Adversarial Networks in Mammogram Analysis: A Review

2020 ◽  
Vol 16 (7) ◽  
pp. 863-877
Author(s):  
Annapoorani Gopal ◽  
Lathaselvi Gandhimaruthian ◽  
Javid Ali
Keyword(s):  
Breast Tumor ◽  
Deep Neural Networks ◽  
Training Data ◽  
Learning Technology ◽  
Breast Cancers ◽  
Generative Adversarial Network ◽  
Adversarial Network ◽  
Adversarial Networks ◽  
Tumor Extraction

The Deep Neural Networks have gained prominence in the biomedical domain, becoming the most commonly used networks after machine learning technology. Mammograms can be used to detect breast cancers with high precision with the help of Convolutional Neural Network (CNN) which is deep learning technology. An exhaustive labeled data is required to train the CNN from scratch. This can be overcome by deploying Generative Adversarial Network (GAN) which comparatively needs lesser training data during a mammogram screening. In the proposed study, the application of GANs in estimating breast density, high-resolution mammogram synthesis for clustered microcalcification analysis, effective segmentation of breast tumor, analysis of the shape of breast tumor, extraction of features and augmentation of the image during mammogram classification have been extensively reviewed.

Lattice Thermal Conductivity Modelling of a Diatomic Nanoscale Material

2020 ◽  
Vol 10 (5) ◽  
pp. 602-609
Author(s):  
Adil H. Awad
Keyword(s):  
Thermal Conductivity ◽  
Lattice Thermal Conductivity ◽  
Phonon Scattering ◽  
Correction Term ◽  
Nanoscale Material ◽  
New Approach ◽  
Two Samples ◽  
Conductivity Modelling ◽  
Callaway Model

Introduction: A new approach for expressing the lattice thermal conductivity of diatomic nanoscale materials is developed. Methods: The lattice thermal conductivity of two samples of GaAs nanobeam at 4-100K is calculated on the basis of monatomic dispersion relation. Phonons are scattered by nanobeam boundaries, point defects and other phonons via normal and Umklapp processes. Methods: A comparative study of the results of the present analysis and those obtained using Callaway formula is performed. We clearly demonstrate the importance of the utilised scattering mechanisms in lattice thermal conductivity by addressing the separate role of the phonon scattering relaxation rate. The formulas derived from the correction term are also presented, and their difference from Callaway model is evident. Furthermore their percentage contribution is sufficiently small to be neglected in calculating lattice thermal conductivity. Conclusion: Our model is successfully used to correlate the predicted lattice thermal conductivity with that of the experimental observation.

scholarly journals Neuroimmune Response Mediated by Cytokines in Natural Scrapie after Chronic Dexamethasone Treatment

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 204
Author(s):  
Isabel M. Guijarro ◽  
Moisés Garcés ◽  
Pol Andrés-Benito ◽  
Belén Marín ◽  
Alicia Otero ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Global Approach ◽  
Profile Data ◽  
Dexamethasone Treatment ◽  
New Approach ◽  
Complex Interactions ◽  
Natural Scrapie ◽  
Anti Inflammatory

The actual role of prion protein-induced glial activation and subsequent cytokine secretion during prion diseases is still incompletely understood. The overall aim of this study is to assess the effect of an anti-inflammatory treatment with dexamethasone on different cytokines released by neuroglial cells that are potentially related to neuroinflammation in natural scrapie. This study emphasizes the complex interactions existent among several pleiotropic neuromodulator peptides and provides a global approach to clarify neuroinflammatory processes in prion diseases. Additionally, an impairment of communication between microglial and astroglial populations mediated by cytokines, mainly IL-1, is suggested. The main novelty of this study is that it is the first one assessing in situ neuroinflammatory activity in relation to chronic anti-inflammatory therapy, gaining relevance because it is based on a natural model. The cytokine profile data would suggest the activation of some neurotoxicity-associated route. Consequently, targeting such a pathway might be a new approach to modify the damaging effects of neuroinflammation.

scholarly journals The Power of Yeast in Modelling Human Nuclear Mutations Associated with Mitochondrial Diseases

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 300
Author(s):  
Camilla Ceccatelli Berti ◽  
Giulia di Punzio ◽  
Cristina Dallabona ◽  
Enrico Baruffini ◽  
Paola Goffrini ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mitochondrial Diseases ◽  
Yeast Saccharomyces Cerevisiae ◽  
Genome Data ◽  
New Genes ◽  
Eukaryotic Organism ◽  
Novel Variants ◽  
Therapeutic Molecules ◽  
Nuclear Mutations

The increasing application of next generation sequencing approaches to the analysis of human exome and whole genome data has enabled the identification of novel variants and new genes involved in mitochondrial diseases. The ability of surviving in the absence of oxidative phosphorylation (OXPHOS) and mitochondrial genome makes the yeast Saccharomyces cerevisiae an excellent model system for investigating the role of these new variants in mitochondrial-related conditions and dissecting the molecular mechanisms associated with these diseases. The aim of this review was to highlight the main advantages offered by this model for the study of mitochondrial diseases, from the validation and characterisation of novel mutations to the dissection of the role played by genes in mitochondrial functionality and the discovery of potential therapeutic molecules. The review also provides a summary of the main contributions to the understanding of mitochondrial diseases emerged from the study of this simple eukaryotic organism.

scholarly journals Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Na Zhu ◽  
◽  
Emilia M. Swietlik ◽  
Carrie L. Welch ◽  
Michael W. Pauciulo ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Candidate Genes ◽  
Rare Variant ◽  
De Novo ◽  
Risk Genes ◽  
International Consortium ◽  
Rare Variant Analysis ◽  
New Genes ◽  
Pulmonary Arterial ◽  
Variant Analysis

Abstract Background Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by pathogenic remodeling of pulmonary arterioles leading to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. PAH can be associated with other diseases (APAH: connective tissue diseases, congenital heart disease, and others) but often the etiology is idiopathic (IPAH). Mutations in bone morphogenetic protein receptor 2 (BMPR2) are the cause of most heritable cases but the vast majority of other cases are genetically undefined. Methods To identify new risk genes, we utilized an international consortium of 4241 PAH cases with exome or genome sequencing data from the National Biological Sample and Data Repository for PAH, Columbia University Irving Medical Center, and the UK NIHR BioResource – Rare Diseases Study. The strength of this combined cohort is a doubling of the number of IPAH cases compared to either national cohort alone. We identified protein-coding variants and performed rare variant association analyses in unrelated participants of European ancestry, including 1647 IPAH cases and 18,819 controls. We also analyzed de novo variants in 124 pediatric trios enriched for IPAH and APAH-CHD. Results Seven genes with rare deleterious variants were associated with IPAH with false discovery rate smaller than 0.1: three known genes (BMPR2, GDF2, and TBX4), two recently identified candidate genes (SOX17, KDR), and two new candidate genes (fibulin 2, FBLN2; platelet-derived growth factor D, PDGFD). The new genes were identified based solely on rare deleterious missense variants, a variant type that could not be adequately assessed in either cohort alone. The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. For pediatric PAH, predicted deleterious de novo variants exhibited a significant burden compared to the background mutation rate (2.45×, p = 2.5e−5). At least eight novel pediatric candidate genes carrying de novo variants have plausible roles in lung/heart development. Conclusions Rare variant analysis of a large international consortium identified two new candidate genes—FBLN2 and PDGFD. The new genes have known functions in vasculogenesis and remodeling. Trio analysis predicted that ~ 15% of pediatric IPAH may be explained by de novo variants.

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