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The book highlights important aspects of Molecular Psychiatry, including molecular mechanisms, animal models, biomarkers, advanced methods, drugs and antidepressant response, as well as genetics and epigenetics. Molecular mechanisms are a vital part of the search for the biological basis of psychiatric disorders, providing molecular hints that can later be tested as biomarkers or targets for drug development. Animal models represent a commonly used approach to aid in this bench-to-bed translation; the examples here are social defeat stress and the Roman High-Avoidance (RHA) and the Roman Low-Avoidance (RLA) rats. For biomarkers, psychiatric disorders pose a particular challenge due to the tissue specificity of many currently investigated biomarkers; i.e., not all blood-based measures directly represent changes in the brain. The Ebook includes five articles focused on the challenges of identifying clinically and biologically relevant biomarkers for psychiatric disorders. Scientific progress typically is fostered by the development of new methods. The application of machine learning methods for the proper analysis of Big Data and induced pluripotent stem cells are examples outlined in this Ebook. Furthermore, three articles are devoted to the understanding of the mechanisms of actions of existing drugs with the ultimate goal of identifying ways to predict treatment response in patients. Finally, three articles deepen the insight into the genetics and epigenetics of psychiatric disorders.

Medicine --- Mental health services --- cardiovascular disease --- cell adhesion molecules --- immunology --- inflammation --- nervous system --- schizophrenia --- bipolar disorder --- major depressive disorder --- DNA methylation --- response variability --- antipsychotics --- drug design --- multi-target drugs --- polypharmacology --- multi-task learning --- machine learning --- biomarker discovery --- psychiatry --- serotonin --- 5-HT 4 receptor --- 5-HT4R --- depression --- mood disorder --- expression --- Alzheimer's disease --- cognition --- Parkinson's disease --- forced swimming --- Roman rat lines --- stress --- hippocampus --- BDNF --- trkB --- PSA-NCAM --- western blot --- immunohistochemistry --- general cognitive function --- intelligence --- GWAS --- genetic correlation --- childhood-onset schizophrenia (COS) --- induced pluripotent stem cell (iPSC) --- copy number variation (CNV) --- early neurodevelopment --- neuronal differentiation --- synapse --- dendritic arborization --- miRNAs --- stress physiology --- cytoskeleton --- actin dynamics --- DRR1 --- TU3A --- FAM107A --- acid sphingomyelinase --- alcohol dependence --- liver enzymes --- sphingolipid metabolism --- withdrawal --- Hsp90 --- GR --- stress response --- steroid hormones --- molecular chaperones --- psychiatric disease --- circadian rhythms --- FKBP51 --- FKBP52 --- CyP40 --- PP5 --- DISC1 --- neurodevelopment --- CRMP-2 --- proteomics --- antidepressant treatment --- HPA axis --- gene expression --- FKBP5 --- sleep --- sleep EEG --- biomarkers --- antidepressants --- cordance --- gender --- sex difference --- antidepressant --- rapid-acting --- Ketamine --- endocrinology --- (2R,6R)-Hydroxynorketamine --- electroconvulsive therapy --- basic-helix-loop-helix --- brain --- coactivator --- glucocorticoids --- mineralocorticoid receptor knockout --- transcription biology --- dopaminergic gene polymorphisms --- affective temperament --- obesity --- alpha-synuclein --- SNCA --- major depression --- Hamilton Scale of Depression --- chemokines --- neuroinflammation --- social defeat --- Immune response --- T cells --- susceptibility --- resilience --- Treg cells --- Th17 cells --- behavior --- PPARγ --- cardiovascular disease --- cell adhesion molecules --- immunology --- inflammation --- nervous system --- schizophrenia --- bipolar disorder --- major depressive disorder --- DNA methylation --- response variability --- antipsychotics --- drug design --- multi-target drugs --- polypharmacology --- multi-task learning --- machine learning --- biomarker discovery --- psychiatry --- serotonin --- 5-HT 4 receptor --- 5-HT4R --- depression --- mood disorder --- expression --- Alzheimer's disease --- cognition --- Parkinson's disease --- forced swimming --- Roman rat lines --- stress --- hippocampus --- BDNF --- trkB --- PSA-NCAM --- western blot --- immunohistochemistry --- general cognitive function --- intelligence --- GWAS --- genetic correlation --- childhood-onset schizophrenia (COS) --- induced pluripotent stem cell (iPSC) --- copy number variation (CNV) --- early neurodevelopment --- neuronal differentiation --- synapse --- dendritic arborization --- miRNAs --- stress physiology --- cytoskeleton --- actin dynamics --- DRR1 --- TU3A --- FAM107A --- acid sphingomyelinase --- alcohol dependence --- liver enzymes --- sphingolipid metabolism --- withdrawal --- Hsp90 --- GR --- stress response --- steroid hormones --- molecular chaperones --- psychiatric disease --- circadian rhythms --- FKBP51 --- FKBP52 --- CyP40 --- PP5 --- DISC1 --- neurodevelopment --- CRMP-2 --- proteomics --- antidepressant treatment --- HPA axis --- gene expression --- FKBP5 --- sleep --- sleep EEG --- biomarkers --- antidepressants --- cordance --- gender --- sex difference --- antidepressant --- rapid-acting --- Ketamine --- endocrinology --- (2R,6R)-Hydroxynorketamine --- electroconvulsive therapy --- basic-helix-loop-helix --- brain --- coactivator --- glucocorticoids --- mineralocorticoid receptor knockout --- transcription biology --- dopaminergic gene polymorphisms --- affective temperament --- obesity --- alpha-synuclein --- SNCA --- major depression --- Hamilton Scale of Depression --- chemokines --- neuroinflammation --- social defeat --- Immune response --- T cells --- susceptibility --- resilience --- Treg cells --- Th17 cells --- behavior --- PPARγ

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The pestiviruses encompass some of the most economically important viral infections in the cattle, swine, and sheep industries worldwide. Discovered more than 70 years ago, bovine viral diarrhea virus (BVDV) and classical swine fever virus (CSFV) were long the main concern, but many new pestiviruses have emerged in recent years, which may also present additional threats to biosecurity and food safety. This issue brings together contributions from multiple disciplines – virology, immunology, veterinary clinical medicine, epidemiology, and pathology – on the subject of BVDV and related pestiviruses, and cover host–virus interactions, virus–cell interactions, cross-species transmission as well as the role of wildlife species as reservoirs of some of the pestiviruses.

Linda virus --- serological profile --- virus neutralization assay --- virus pathogenicity --- humoral immune response --- pestivirus --- pig --- APPV --- phylogenetic analysis --- Italy --- bvdv --- epidemiology --- reindeer --- border disease virus --- Norway --- Pestivirus --- BVDV --- CD46 --- life cell imaging --- attachment --- surface transport --- experimental infection --- natural infection --- pigs --- bovine viral diarrhoea virus --- persistent testicular infection --- prolonged testicular infection --- bovine --- testes --- semen --- wild boar --- ML tree --- Clade --- Bungowannah virus --- pestivirus F --- ruminant infection --- foetus --- porcine --- real-time PCR --- serology --- virology --- bovine viral diarrhea virus --- cytopathic BVDV --- immunosuppression --- lymphocyte apoptosis --- monocyte-derived macrophages --- non-cytopathic BVDV --- Australia --- deer --- prevalence --- ruminants --- serosurveillance --- wildlife disease --- diarrhea --- bovine respiratory disease --- milk production --- somatic cells count (SCC) --- reproductive performance --- BVDV persistent infection --- fetus --- thymus --- immune response --- flavivirus --- reverse genetics --- single round infectious particle --- bovine viral diarrhea virus (BVDV) --- escape mutant --- ERNS --- adaptation --- CRISPR --- knockout --- MDBK --- cell entry --- pestiviruses --- congenital tremor type A-II --- persistent infection --- rangeland beef herds --- northern Australia --- atypical porcine pestivirus (APPV) --- viral persistence --- congenital tremor --- swine --- asymptomatic --- genomic sequence --- purifying selection --- bovine pestiviruses --- bovine viral diarrhoea --- vaccination --- control --- diagnosis --- antigenic cross-reactivity --- n/a

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Every minute, 34 new patients are diagnosed with cancer globally. Although over the past 50 years treatments have improved and survival rates have increased dramatically for several types of cancers, many remain incurable. Several aggressive types of blood and solid cancers form when mutations occur in a critical cellular signaling pathway, the JAK-STAT pathway; (Janus Kinase-Signal Transducer and Activator of Transcription). Currently, there are no clinically available drugs that target the oncogenic STAT3/5 proteins in particular or their Gain of Function hyperactive mutant products. Here, we summarize targeting approaches on STAT3/5, as the field moves towards clinical applications as well as we illuminate on upstream or downstream JAK-STAT pathway interference with kinase inhibitors, heat shock protein blockers or changing nuclear import/export processes. We cover the design paradigms and medicinal chemistry approaches to illuminate progress and challenges in understanding the pleiotropic role of STAT3 and STAT5 in oncogenesis, the microenvironment, the immune system in particular, all culminating in a complex interplay towards cancer progression.

Research & information: general --- Biology, life sciences --- multiple myeloma --- STAT3 --- S3I-1757 --- nanoparticle --- CD38 --- siRNA/RNAi --- polyethylenimine --- PEI --- lipopolyplex --- siRNA delivery --- glioma --- glioblastoma --- STAT5 --- AKT --- ERK1/2 --- prolactin --- androgens --- prostate cancer --- knockout --- escape mechanisms --- stem/progenitor cells --- cell hierarchy --- cancer --- CD4+ T cells --- CD8+ T cells --- myeloid cells --- immune check point --- hepatitis C virus (HCV) --- cirrhosis --- hepatocellular carcinoma (HCC) --- endoplasmic reticulum (ER) stress --- oxidative stress (OS) --- unfolded protein response (UPR) --- microRNA-122 (miR-122) --- nuclear factor erythroid 2-related factor 2 (NRF2) --- signal transducer and activator of transcription 3 (STAT3) --- hepatocyte nuclear factor 4 alpha (HNF4A) --- solid cancers --- cell cycle --- apoptosis --- inflammation --- mitochondria --- stemness --- tumor suppression --- melanoma --- autoimmune disease --- immunotherapy --- tumor-immune cell interactions --- breast cancer --- PD-L1 --- M2 macrophages --- NK cells --- STAT3 inhibitor XIII --- hedging --- transaction costs --- dynamic programming --- risk management --- post-decision state variable --- cancer progression --- cancer-stem cell --- cytokine --- therapy resistance --- metastasis --- immunosuppression --- tumor microenvironment --- proliferation --- tyrosine kinase 2 --- JAK family of protein tyrosine kinases --- signal transducer and activator of transcription --- cytokine receptor signaling --- gain-of-function mutation --- tumorigenesis --- ADAM17 --- interleukin-6 --- trans-signaling --- epidermal growth factor receptor (EGF-R) --- shedding --- metalloprotease --- tumor necrosis factor alpha (TNFα) --- inflammation associated cancer --- colon cancer --- lung cancer --- SH2 domain --- mutations --- autosomal-dominant hyper IgE syndrome --- inflammatory hepatocellular adenomas --- T-cell large granular lymphocytic leukemia --- T-cell prolymphocytic leukemia --- growth hormone insensitivity syndrome --- nuclear pore complex --- nuclear transport receptors --- nucleocytoplasmic shuttling --- targeting --- tumor-associated macrophages --- adoptive T cell therapy --- immune suppression --- STAT transcription factors --- JAK --- STAT --- T-PLL --- T-cell leukemia --- meta-analysis --- STAT5B signaling --- small-molecule inhibitors --- cancer models --- companion animals --- comparative oncology --- pharmacological inhibitor --- STAT5 signaling --- chemotherapy resistance --- myeloid leukemia --- heat shock proteins --- chaperones --- stabilization --- targeted therapy --- ovarian cancer --- hematopoietic cancers --- therapeutic targeting --- pharmacological inhibitors --- mTOR --- Bone Marrow Failure Syndromes --- lymphocytes --- lymphoma --- T-cells --- RHOA --- NGS --- MPN --- JAK2 V617F --- neoplastic stem cells --- multiple myeloma --- STAT3 --- S3I-1757 --- nanoparticle --- CD38 --- siRNA/RNAi --- polyethylenimine --- PEI --- lipopolyplex --- siRNA delivery --- glioma --- glioblastoma --- STAT5 --- AKT --- ERK1/2 --- prolactin --- androgens --- prostate cancer --- knockout --- escape mechanisms --- stem/progenitor cells --- cell hierarchy --- cancer --- CD4+ T cells --- CD8+ T cells --- myeloid cells --- immune check point --- hepatitis C virus (HCV) --- cirrhosis --- hepatocellular carcinoma (HCC) --- endoplasmic reticulum (ER) stress --- oxidative stress (OS) --- unfolded protein response (UPR) --- microRNA-122 (miR-122) --- nuclear factor erythroid 2-related factor 2 (NRF2) --- signal transducer and activator of transcription 3 (STAT3) --- hepatocyte nuclear factor 4 alpha (HNF4A) --- solid cancers --- cell cycle --- apoptosis --- inflammation --- mitochondria --- stemness --- tumor suppression --- melanoma --- autoimmune disease --- immunotherapy --- tumor-immune cell interactions --- breast cancer --- PD-L1 --- M2 macrophages --- NK cells --- STAT3 inhibitor XIII --- hedging --- transaction costs --- dynamic programming --- risk management --- post-decision state variable --- cancer progression --- cancer-stem cell --- cytokine --- therapy resistance --- metastasis --- immunosuppression --- tumor microenvironment --- proliferation --- tyrosine kinase 2 --- JAK family of protein tyrosine kinases --- signal transducer and activator of transcription --- cytokine receptor signaling --- gain-of-function mutation --- tumorigenesis --- ADAM17 --- interleukin-6 --- trans-signaling --- epidermal growth factor receptor (EGF-R) --- shedding --- metalloprotease --- tumor necrosis factor alpha (TNFα) --- inflammation associated cancer --- colon cancer --- lung cancer --- SH2 domain --- mutations --- autosomal-dominant hyper IgE syndrome --- inflammatory hepatocellular adenomas --- T-cell large granular lymphocytic leukemia --- T-cell prolymphocytic leukemia --- growth hormone insensitivity syndrome --- nuclear pore complex --- nuclear transport receptors --- nucleocytoplasmic shuttling --- targeting --- tumor-associated macrophages --- adoptive T cell therapy --- immune suppression --- STAT transcription factors --- JAK --- STAT --- T-PLL --- T-cell leukemia --- meta-analysis --- STAT5B signaling --- small-molecule inhibitors --- cancer models --- companion animals --- comparative oncology --- pharmacological inhibitor --- STAT5 signaling --- chemotherapy resistance --- myeloid leukemia --- heat shock proteins --- chaperones --- stabilization --- targeted therapy --- ovarian cancer --- hematopoietic cancers --- therapeutic targeting --- pharmacological inhibitors --- mTOR --- Bone Marrow Failure Syndromes --- lymphocytes --- lymphoma --- T-cells --- RHOA --- NGS --- MPN --- JAK2 V617F --- neoplastic stem cells