Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder thought to be caused by predisposing high-risk genes that may be altered during the early development by environmental factors. The impact of maternal challenges during pregnancy on the prevalence of ASD has been widely studied in clinical and animal studies. Here, we review some clinical and pre-clinical evidence that links environmental

A substantive volume of research on autism spectrum disorder (ASD) has emerged in recent years adding to our understanding of the etiopathological process. Preclinical models in mice and rats have been highly instrumental in modeling and dissecting the contributions of a multitude of known genetic and environmental risk factors. However, the translation of preclinical data into suitable drug targets

Autism spectrum disorder is a neurodevelopmental disorder characterized by impaired development and by abnormal function in regards to social interaction, communication and restricted, repetitive behavior. It affects approximately 1% of the worldwide population. Like other psychiatric disorders the diagnosis is based on observation of, and interview with the patient and next of kin, and diagnostic

Autism spectrum disorder (ASD) is a set of pervasive neurodevelopmental disorders. The causation is multigenic in most cases, which makes it difficult to model the condition in vitro. Advances in pluripotent stem cell technology has made it possible to generate in vitro models of human brain development. Induced pluripotent stem cells (iPSCs) can be generated from somatic cells and have the ability

Correlation and association analyses are one of the most widely used statistical methods in research fields, including microbiome and integrative multiomics studies. Correlation and association have two implications: dependence and co-occurrence. Microbiome data are structured as phylogenetic tree and have several unique characteristics, including high dimensionality, compositionality, sparsity with

Highly complex endophenotypes and underlying molecular mechanisms have prevented effective diagnosis and treatment of autism spectrum disorder. Despite extensive studies to identify relevant biosignatures, no biomarker and therapeutic targets are available in the current clinical practice. While our current knowledge is still largely incomplete, -omics technology and machine learning-based big data

Altered sensory processing and perception has been one of the characteristics of autism spectrum disorder (ASD). In this chapter, we review the neural underpinnings of sensory abnormalities of ASD by examining the literature on clinical, behavioral and neurobiological evidence that underlies the main patterns of sensory integration function and dysfunction. Furthermore, neural differences in anatomy

The development of new approaches for the clinical management of autism spectrum disorder (ASD) can only be realized through a better understanding of the neurobiological changes associated with ASD. One strategy for gaining deeper insight into the neurobiological mechanisms associated with ASD is to identify converging pathogenic processes associated with human idiopathic clinicopathology that are

Neurodevelopmental impairment remains a significant morbidity in former very low birth weight premature infants. There is increasing evidence the microbiome affects neurodevelopment but mechanistic causes are largely unknown. There are many factors which affect the developing microbiome in infants including mode of delivery, feeding, medications, and environmental exposures. The overall impact of these

Since the initial psychological report by Leo Kanner in 1943, relatively little formal biochemical/neurological research on the cause of autism, other than peripheral searches for genomic mutations, had been carried until the end of the 20th century. As a result of studies on twin sets and the conclusion that autism was largely a hereditary defect, numerous investigations have sought various genetic

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social communication and the presence of restricted interests and repetitive behaviors. Although behavioral interventions are numerous, there are no Federal Drug Administration approved pharmacological treatments for the core symptoms of ASD. The neuropeptide oxytocin has been studied in animals for decades

A reliable diagnosis of autism spectrum disorder (ASD) is difficult to make until after toddlerhood. Detection in an earlier age enables early intervention, which is typically more effective. Recent studies of the development of brain and behavior in infants and toddlers have provided important insights in the diagnosis of autism. This extensive review focuses on published studies of predicting the

Various genetic and environmental factors have been suggested to cause autism spectrum disorders (ASDs). A variety of animal models of ASDs have been developed and used to investigate the mechanisms underlying the pathogenesis of ASDs. These animal models have contributed to clarifying that abnormalities in neuronal morphology and neurotransmission are responsible for the onset of ASDs. In recent years

Neuroglia are a large class of neural cells of ectodermal (astroglia, oligodendroglia, and peripheral glial cells) and mesodermal (microglia) origin. Neuroglial cells provide homeostatic support, protection, and defense to the nervous tissue. Pathological potential of neuroglia has been acknowledged since their discovery. Research of the recent decade has shown the key role of all classes of glial

The posterior cingulate cortex (PCC) plays pivotal roles in cognitive, social and emotional processing, as well as early neural development that supports complex interactions among different neural networks. Alterations in its local and long-range connectivity during resting state are often implicated in neuropathology of neurodevelopmental disorders such as autism spectrum disorder (ASD). ASD is characterized

In the past decades, the fields of microbiology and immunology have largely advanced by using germ-free animals and next-generation sequencing. Many studies revealed the relationship among gut microbiota, activation of immune system, and various diseases. Especially, some gut commensals can generate their antigen-specific T cells. It is becoming clear that commensal bacteria have important roles in

Cancer treatment has been evolving in recent decades from surgery, conventional chemotherapy and radiation therapy to targeted therapies and more recently immunotherapies. Despite significant improvement in the efficacy of treatment with the discovery of novel therapies targeting particular cancer-related gene and proteins and more recently the immune system-modulating biologics, still only patients

Type 1 diabetes (T1D) is an autoimmune disease caused by complex interactions between host genetics and environmental factors, culminating in the T-cell mediated destruction of the insulin producing cells in the pancreas. The rapid increase in disease frequency over the past 50 years or more has been too rapid to attribute to genetics. Dysbiosis of the gut microbiota is currently being widely investigated

Although there is associative evidence linking fecal microbiome profile to health and disease, many studies have not considered the confounding effects of dietary intake. Consuming food provides fermentable substrate which sustains the microbial ecosystem that resides with most abundance in the colon. Western, Mediterranean and vegetarian dietary patterns have a role in modulating the gut microbiota

Many components of the gastric non-Helicobacter pylori microbiota have been identified recently thanks to advances in DNA sequencing techniques. Several lines of evidence support the hypothesis that the gastric microbiome is essential for gastric disorders such as gastric cancer. Microbial interactions impact the pathophysiology of various gastric disorders. This chapter provides an overview of recent

The influence of the microbiota on viral infection susceptibility and disease outcome is undisputable although varies among viruses. The purpose of understanding the interactions between microbiota, virus, and host is to identify practical, effective, and safe approaches that target microbiota for the prevention and treatment of viral diseases in humans and animals, as currently there are few effective

Gut bacteria are predominant microorganisms in the gut microbiota and have been recognized to mediate a variety of biotransformations of xenobiotic compounds in the gut. This review is focused on one of the gut bacterial xenobiotic metabolisms, reduction. Xenobiotics undergo different types of reductive metabolisms depending on chemically distinct groups: azo (-NN-), nitro (-NO2), alkene (-CC-), ketone

The gut microbiota (GM) composition varies among individuals and is influenced by intrinsic (genetics, age) and extrinsic (environment, diet, lifestyle) factors. An imbalance or dysbiosis is directly associated with the development of several illnesses, due to the potential increase in intestinal permeability leading to a systemic inflammation triggered by higher levels of circulating lipopolysaccharides

Growing evidence suggests that imbalances in resident microbes (dysbiosis) can promote chronic inflammation, immune-subversion, and production of carcinogenic metabolites, thus leading to neoplasia. Yet, evidence to support a direct link of individual bacteria species to human sporadic cancer is still limited. This chapter focuses on several emerging bacterial toxins that have recently been characterized

The interactions between proteins and membranes play critical roles in signal transduction, cell motility, and transport, and they are involved in many types of diseases. Molecular dynamics (MD) simulations have greatly contributed to our understanding of protein-membrane interactions, promoted by a dramatic development of MD-related software, increasingly accurate force fields, and available computer

In this chapter the scale-consistent approach to the derivation of coarse-grained force fields developed in our laboratory is presented, in which the effective energy function originates from the potential of mean force of the system under consideration and embeds atomistically detailed interactions in the resulting energy terms through use of Kubo's cluster-cumulant expansion, appropriate selection

Molecular dynamics simulation is a powerful computational technique to study biomolecular systems, which complements experiments by providing insights into the structural dynamics relevant to biological functions at atomic scale. It can also be used to calculate the free energy landscapes of the conformational transitions to better understand the functions of the biomolecules. However, the sampling

Molecular dynamics (MD) studies of biomolecules require the ability to simulate complex biochemical systems with an increasingly larger number of particles and for longer time scales, a problem that cannot be overcome by computational hardware advances alone. A main problem springs from the intrinsically high-dimensional and complex nature of the underlying free energy landscape of most systems, and

Proteins, in general, fold to a well-organized three-dimensional structure in order to function. The stability of this functional shape can be perturbed by external environmental conditions, such as temperature. Understanding the molecular factors underlying the resistance of proteins to the thermal stress has important consequences. First of all, it can aid the design of thermostable enzymes able

Molecular simulations and biophysical experiments can be used to provide independent and complementary insights into the molecular origin of biological processes. A particularly useful strategy is to use molecular simulations as a modeling tool to interpret experimental measurements, and to use experimental data to refine our biophysical models. Thus, explicit integration and synergy between molecular

Protein aggregation into oligomeric species has been linked to a number of neurodegenerative diseases. The ability to assemble into ordered fibril-like forms under certain conditions is now regarded as a very common property of polypeptide chains. A different form of assembly is known for some proteins in which protein molecules sequester into liquid-like droplets. Understanding the biophysical mechanisms

Protein force fields have been undergoing continual development since the first complete parameter sets were introduced nearly four decades ago. The functional forms that underlie these models have many common elements for the treatment of bonded and nonbonded forces, which are reviewed here. The most widely used force fields to date use a fixed-charge convention in which electronic polarization effects

Amyloid formation by proteins and peptides is the hallmark of many diseases. Growing evidence suggests that oligomeric species arising during aggregation are toxic, but the molecular mechanism of aggregation and oligomer generation remains unclear. Recent discoveries that amyloid fibrils can convert soluble proteins into oligomeric nuclei to facilitate aggregation highlight the role played by fibrils

Protein misfolding and aggregation of amyloid proteins is the fundamental cause of more than 20 diseases. Molecular mechanisms of the self-assembly and the formation of the toxic aggregates are still elusive. Computer simulations have been intensively used to study the aggregation of amyloid peptides of various amino acid lengths related to neurodegenerative diseases. We review atomistic and coarse-grained

GPCR oligomerization has emerged as a hot topic in the GPCR field in the last years. Receptors that are part of these oligomers can influence each other's function, although it is not yet entirely understood how these interactions work. The existence of such a highly complex network of interactions between GPCRs generates the possibility of alternative targets for new therapeutic approaches. However

This chapter will focus on the therapeutic potential of oligomeric GPCR structures. We will discuss the history of these complexes and their connection with treatment. We will highlight several examples from the literature of complexes of therapeutic or theranostic opportunity. As part of this we will discuss different mechanisms that oligomers use to modulate their partner that could be taken advantage

Protein-protein interactions (PPIs) are of fundamental importance in several cellular processes. While "classical" biochemical methods are commonly used to monitor protein multimerization in biological samples, fluorescence microscopy offers the possibility to investigate PPIs directly in living cells, even distinguishing among different cellular compartments. In this chapter, we shortly describe the

Human dopamine D2 receptor (D2R) gene has polymorphic variants, three of them alter its amino acid sequence: Val96Ala, Pro310Ser and Ser311Cys. Their functional role never became the object of extensive studies, even though there are some evidence that they correlate with schizophrenia. The present work reviews data indicating that these mutations play a role in dimer formation with dopamine D1 receptor

The spontaneous formation of virus capsids from multiple copies of capsid proteins is a fascinating example of supramolecular self-assembling processes. Most known viruses protect their genome with icosahedral capsids, but other morphologies exist as well, including elongated, conical, tubular, head-tail structures. The mechanisms of assembly can be diverse and are still not perfectly understood. In

Non-native intermolecular contacts often lead to aberrant protein oligomerization and aggregation. This phenomenon is behind the onset of several human disorders and is a bottleneck for the production of proteins of biotechnological interest. Intrinsically disordered proteins have evolved to avoid aberrant oligomerization, but mutations or aging-promoted degeneration of the protein quality machinery

Experimental data accumulated during the last 10 years strongly support the existence and functional significance of oligomerization of G protein-coupled receptors (GPCRs). In this essay, we discuss the unique biochemical properties of GPCR oligomers in the frame of "allosterism" and how these properties can be used to identify GPCR oligomers in artificial systems and in native tissues. We also address

As the largest family of cell surface receptors, G protein-coupled receptors (GPCRs) represent an important strategic class of therapeutic targets. Attaining a clearer perspective of how such signaling complexes set molecular events in motion could have significant impact on our understanding and treatment of human diseases. As such, many experimental approaches have set out to better understand signaling

Porphobilinogen synthase (PBGS) is an essential enzyme that catalyzes an early step in heme biosynthesis. An unexpected human PBGS quaternary structure dynamic drove the definition of morpheeins, which are protein multimers that dissociate, change shape, and re-assemble differently with functional consequences. Each PBGS monomer has two domains that can reposition through a hinge motion. Human PBGS

Formation of G protein-coupled receptors (GPCRs) dimers and higher order oligomers represents a key mechanism in pleiotropic signaling, yet how individual protomers function within oligomers remains poorly understood. For the Class A/rhodopsin subfamily of glycoprotein hormone receptors (GpHRs), di/oligomerization has been demonstrated to play a significant role in regulating its signaling activity

The discovery of receptor-receptor interactions in the early 1980s, together with a more accurate focusing of allosteric mechanisms in proteins, expanded the knowledge on the G protein-coupled receptor (GPCR)-mediated signaling processes. GPCRs were seen to operate not only as monomers, but also as quaternary structures shaped by allosteric interactions. These integrative mechanisms can change the

The failure to date of all disease modifying therapies for Alzheimer's disease and related dementias requires a serious rethinking of the field's approach to therapeutic interventions. This begins with the acknowledgement that the great majority of sporadic neurodegenerative dementias are the result of more than one toxic protein/species. While there are challenges to the initiation of clinical trials

The perceived role of the immune system in neurodegenerative diseases has undergone drastic changes over time. Initially considered as a passive bystander, then condemned as a mediator of neurodegeneration and now established as an important player in the pathogenetic cascade, neuroimmune interactions have come a long way to arrive center stage in Alzheimer's disease research. Despite major breakthroughs

Alzheimer's disease (AD) is the most common neurodegenerative disease, leading to dementia in the aging human brain. Although a huge amount of research has been done to date, the pathogenesis of AD remains largely unknown. Given the dominance of mRNA splicing in the nervous system, it would be invaluable to precisely identify mis-splicing in the AD brain to understand more deeply how the gene network

Alzheimer's disease (AD) was first described by Alois Alzheimer in 1906 but the protein composition of neurofibrillary tangles and amyloid plaques was not decoded till about seven to eight decades later, respectively. The bulk of studies during the last four decades were focused on Aβ amyloid and led to many human clinical trials, none of which showed any beneficial therapeutic effects. Though the

Cannabis sativa (cannabis) is one of the oldest plants cultivated by men. Cannabidiol (CBD) is the major non-psychomimetic compound derived from cannabis. It has been proposed to have a therapeutic potential over a wide range of neuropsychiatric disorders. In this narrative review, we have summarized a selected number of pre-clinical and clinical studies, examining the effects of CBD in neuropsychiatric

There are growing genetic, transcriptomic and proteomic data pointing to the complexity of Alzheimer's disease (AD) pathogenesis. Unbiased "omics" approaches are essential for the future development of effective AD research, which will need to be combined and personalized, given that multiple distinct pathways can drive AD pathology. It is essential to gain a better understanding of the AD pathogenesis

Pathologic aggregates of tau protein are observed in several neurodegenerative diseases and are used to diagnose and stage disease postmortem. Recent advances in positron emission tomography radioligands allow for the detection of aggregated tau proteins in living persons. This chapter describes the development and characterization of several positron emission tomography radioligands used to detect

Parkinson's disease (PD) devastates 6.3 million people, ranking it as one of the most prevalent neurodegenerative motor disorders worldwide. PD patients may manifest symptoms of postural instability, bradykinesia, and resting tremors as a result of increasing α-synuclein aggregation and neuron death with disease progression. Therapy options are limited, and those available to patients may worsen their

Converging lines of evidence point to a significant role of neuroinflammation in a host of psychiatric conditions, including alcohol use disorder, TBI, and PTSD. A complex interaction of both peripheral and central signaling underlies processes involved in neuroinflammation. Calcineurin is a molecule that sits at the nexus of these processes and has been clearly linked to a number of psychiatric disorders

The cerebral microvasculature is exceptionally vulnerable to changes due to aging. Both the radiological and clinical manifestations of cerebral small vessel disease (cSVD) in older age are highly heterogeneous, ranging from no symptomatology to devastating neurocognitive complications, including stroke, dementia, and depression. To date, the exact pathogenesis of cSVD is unknown; neither prevention

The immune system plays a key role in the interactions between host and tumor. Immune selection pressure is a driving force behind the sculpting and evolution of malignant cancer cells to escape this immune attack. Several common tumor cell-based mechanisms of resistance to immune attack have been identified and can be broadly categorized into three main classes: loss of antigenicity, loss of immunogenicity