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This Research Topic will review and summarize the pathogenesis of Autism Spectrum Disorder (ASD) that underpin the translation of genetic vulnerability to clinically significant symptoms. Available research data in ASD suggests that it is a “neural connectivity disorder” and that the deficits in social cognition and related neurocognitive functions result from reduced synchronization between key brain regions known as the “social brain”. These interconnected neural systems can be understood through the relationship between functionally relevant anatomic areas and neurochemical pathways, the programming of which are genetically modulated during neurodevelopment and mediated through a range of neuropeptides and interacting neurotransmitter systems. Elucidating the underlying molecular mechanisms can provide an invaluable window for understanding the neural wiring that regulates higher brain functions and consequent clinical phenotypes. ASD is a heterogeneous condition and clinical heterogeneity is linked to genetic heterogeneity. Phenotypic variability within ASD and the phenotypic overlap between ASD and other neurodevelopmental disorders such as Tourette Syndrome, ADHD, Schizophrenia, language disorder and intellectual disability could be associated with the fact that the genes converge on a common neurodevelopmental pathway involved in synapse development/maintenance and circuitry formation through effects on neurogenesis, axon guidance in dendritic projections or neuronal migration. Thus defects in synaptic development can result in abnormal development across disorders and broad domains but yet carry distinct neurocognitive and behavioral profiles. The penetrance of the different co-morbidities may in turn be related to the dose effects of gene abnormality or the timing of events when different neuronal regions and circuitry are being formed, as may be the influence of gender, intrauterine and perinatal events, epigenetics and other environmental modulators. In keeping with the multi modal and diverse origins of neurodevelopmental disorders, this review will explore the genetic underpinnings and environmental modulation in the aetiology; neural substrates, biomarkers and endophenotypes that underlie clinical characteristics of ASD; as well as neurochemical pathways and pathophysiological mechanisms that pave the way for therapeutic interventions. Furthermore, since genetically mediated deficits and consequent functional impairments involve activity-dependent synapse development that depends on postnatal learning and experience, early intervention can prevent or reduce the risk of these deficits cascading into a trajectory toward full expression of the disorder by exploiting the neuronal maturation and brain plasticity. In addition to reviewing the current state of evidence in the literature, there will be a significant focus on ongoing original work as well as hypotheses and directions for future research.

Autism spectrum disorders. --- Autism --- Neuropsychiatry. --- Neurosciences. --- Pathophysiology. --- Research. --- Neuroimaging --- phenotypes --- neurodevelopment --- Early Intervention --- immune response --- genotypes --- Autism Spectrum Disorder --- Genetic Heterogeneity --- brain plasticity --- subtypes

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This Research Topic will review and summarize the pathogenesis of Autism Spectrum Disorder (ASD) that underpin the translation of genetic vulnerability to clinically significant symptoms. Available research data in ASD suggests that it is a “neural connectivity disorder” and that the deficits in social cognition and related neurocognitive functions result from reduced synchronization between key brain regions known as the “social brain”. These interconnected neural systems can be understood through the relationship between functionally relevant anatomic areas and neurochemical pathways, the programming of which are genetically modulated during neurodevelopment and mediated through a range of neuropeptides and interacting neurotransmitter systems. Elucidating the underlying molecular mechanisms can provide an invaluable window for understanding the neural wiring that regulates higher brain functions and consequent clinical phenotypes. ASD is a heterogeneous condition and clinical heterogeneity is linked to genetic heterogeneity. Phenotypic variability within ASD and the phenotypic overlap between ASD and other neurodevelopmental disorders such as Tourette Syndrome, ADHD, Schizophrenia, language disorder and intellectual disability could be associated with the fact that the genes converge on a common neurodevelopmental pathway involved in synapse development/maintenance and circuitry formation through effects on neurogenesis, axon guidance in dendritic projections or neuronal migration. Thus defects in synaptic development can result in abnormal development across disorders and broad domains but yet carry distinct neurocognitive and behavioral profiles. The penetrance of the different co-morbidities may in turn be related to the dose effects of gene abnormality or the timing of events when different neuronal regions and circuitry are being formed, as may be the influence of gender, intrauterine and perinatal events, epigenetics and other environmental modulators. In keeping with the multi modal and diverse origins of neurodevelopmental disorders, this review will explore the genetic underpinnings and environmental modulation in the aetiology; neural substrates, biomarkers and endophenotypes that underlie clinical characteristics of ASD; as well as neurochemical pathways and pathophysiological mechanisms that pave the way for therapeutic interventions. Furthermore, since genetically mediated deficits and consequent functional impairments involve activity-dependent synapse development that depends on postnatal learning and experience, early intervention can prevent or reduce the risk of these deficits cascading into a trajectory toward full expression of the disorder by exploiting the neuronal maturation and brain plasticity. In addition to reviewing the current state of evidence in the literature, there will be a significant focus on ongoing original work as well as hypotheses and directions for future research.

Autism spectrum disorders. --- Autism --- Neuropsychiatry. --- Neurosciences. --- Neuroimaging --- phenotypes --- neurodevelopment --- Early Intervention --- immune response --- genotypes --- Autism Spectrum Disorder --- Genetic Heterogeneity --- brain plasticity --- subtypes --- Pathophysiology. --- Research.

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Pulmonary arterial hypertension is a severe and progressive disorder affecting the blood vessels in the lungs. Typically, symptoms first appear at around 30–40 years of age and, without treatment, can lead to fatal heart disease within a few years. Genetic studies over the past decade have identified numerous genes that contribute to disease progression but, for many sufferers, the underlying genetic cause remains elusive. The collection of reviews and original research articles contained within this book provide an overview of recent advancements in understanding the genetic risk factors for pulmonary arterial hypertension. We further examine the emerging interplay between genetic variants and clinical outcomes, providing a framework for new treatments and improved patient care.

Research & information: general --- Biology, life sciences --- Genetics (non-medical) --- pulmonary arterial hypertension --- massive parallel sequencing --- NGS --- digenic inheritance --- and genetics --- BMPR2 promoter --- pathogenic variant --- heritable pulmonary arterial hypertension --- genetic analysis --- NGS gene panel --- BMPR2 --- TBX4 --- GDF2 --- EIF2AK4 --- genomics --- pediatrics --- lung disease --- endothelial cells --- smooth muscle cells --- DNA damage --- DNA repair --- expression quantitative trait locus --- eQTL --- blood --- genetics --- exome sequencing --- molecular genetics --- paediatrics --- bone morphogenetic protein receptor type 2 --- heritable --- familial --- estrogen --- estradiol --- penetrance --- gender --- PAH --- forward phenotyping --- forward genetics --- reverse genetics --- reverse phenotyping --- intermediate phenotypes --- whole-genome sequencing --- epigenetic inheritance --- genetic heterogeneity --- phenotypic heterogeneity --- pulmonary hypertension --- bone morphogenetic protein receptor 2 --- signaling --- repurposed drugs --- pharmaceuticals --- miRNA --- clinical trials --- n/a

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The cancer stem cell (CSC) paradigm represents one of the most prominent breakthroughs of the last decades in tumor biology. CSCs are that subpopulation within a tumor that can survive conventional therapies and as a consequence are able to fuel tumor recurrence. Nevertheless, the biological characteristics of CSCs and even their existence, remain the main topic among tumor biologists debates. The difficulty in achieving a better definition of CSC biology may actually be explained by the plasticity of such a cell subpopulation. Indeed, the emerging view is that CSCs represent a dynamic “state” of tumor cells that can acquire stemness-related properties under specific circumstances, rather than referring to a well-defined group of cells. Regardless of their origin, it is clear that designing novel antitumor treatments based on the eradication of CSCs will only be possible upon unraveling the biological mechanisms that underlie their pathogenic role in tumor progression and therapy resistance. The Special Issue on “New aspects of cancer stem cell biology: implications for innovative therapies” aims at highlighting recent insights into CSC features that can make them an attractive target for novel therapeutic strategies.

Cadherin 11 --- WNT signaling --- β-catenin --- cancer stem cells --- TNBC --- early breast cancer --- bevacizumab --- neoadjuvant chemotherapy --- ALDH1 --- solid cancer --- chemo-resistance --- HDAC inhibitors --- head and neck squamous cell carcinoma --- SRC --- dasatinib --- saracatinib --- EC-8042 --- Ovarian cancer --- Wnt signaling --- tumor progression --- therapy resistance --- exosomes --- oral cancer risk --- oral epithelial dysplasia --- SOX2 --- immunohistochemistry --- oral squamous cell carcinoma --- genome-wide --- transcriptome --- lung cancer --- ATAC-seq --- RNA-seq --- CSCs --- NSCLC --- B4GALT1 --- LUAD --- breast cancer --- lipid --- metabolism --- therapeutic resistance --- bowel cancer --- organoid --- tumoroid --- colorectal --- colon --- stem cell --- chemotherapy resistance --- ovarian cancer --- cancer stem cell --- genetic heterogeneity --- SNP array --- L1CAM --- chemoresistance --- epithelial-mesenchymal transition --- cancer therapy --- cell adhesion molecule

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The cancer stem cell (CSC) paradigm represents one of the most prominent breakthroughs of the last decades in tumor biology. CSCs are that subpopulation within a tumor that can survive conventional therapies and as a consequence are able to fuel tumor recurrence. Nevertheless, the biological characteristics of CSCs and even their existence, remain the main topic among tumor biologists debates. The difficulty in achieving a better definition of CSC biology may actually be explained by the plasticity of such a cell subpopulation. Indeed, the emerging view is that CSCs represent a dynamic “state” of tumor cells that can acquire stemness-related properties under specific circumstances, rather than referring to a well-defined group of cells. Regardless of their origin, it is clear that designing novel antitumor treatments based on the eradication of CSCs will only be possible upon unraveling the biological mechanisms that underlie their pathogenic role in tumor progression and therapy resistance. The Special Issue on “New aspects of cancer stem cell biology: implications for innovative therapies” aims at highlighting recent insights into CSC features that can make them an attractive target for novel therapeutic strategies.

Research & information: general --- Biology, life sciences --- Cadherin 11 --- WNT signaling --- β-catenin --- cancer stem cells --- TNBC --- early breast cancer --- bevacizumab --- neoadjuvant chemotherapy --- ALDH1 --- solid cancer --- chemo-resistance --- HDAC inhibitors --- head and neck squamous cell carcinoma --- SRC --- dasatinib --- saracatinib --- EC-8042 --- Ovarian cancer --- Wnt signaling --- tumor progression --- therapy resistance --- exosomes --- oral cancer risk --- oral epithelial dysplasia --- SOX2 --- immunohistochemistry --- oral squamous cell carcinoma --- genome-wide --- transcriptome --- lung cancer --- ATAC-seq --- RNA-seq --- CSCs --- NSCLC --- B4GALT1 --- LUAD --- breast cancer --- lipid --- metabolism --- therapeutic resistance --- bowel cancer --- organoid --- tumoroid --- colorectal --- colon --- stem cell --- chemotherapy resistance --- ovarian cancer --- cancer stem cell --- genetic heterogeneity --- SNP array --- L1CAM --- chemoresistance --- epithelial-mesenchymal transition --- cancer therapy --- cell adhesion molecule