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Advances in Anatomy, Embryology, and Cell Biology

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https://www.readbyqxmd.com/read/28551757/genetic-and-pharmacological-reversibility-of-phenotypes-in-mouse-models-of-autism-spectrum-disorder
#1
Jan C Schroeder, Elena Deliu, Gaia Novarino, Michael J Schmeisser
As autism spectrum disorder (ASD) is largely regarded as a neurodevelopmental condition, long-time consensus was that its hallmark features are irreversible. However, several studies from recent years using defined mouse models of ASD have provided clear evidence that in mice neurobiological and behavioural alterations can be ameliorated or even reversed by genetic restoration or pharmacological treatment either before or after symptom onset. Here, we review findings on genetic and pharmacological reversibility of phenotypes in mouse models of ASD...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551756/extracerebral-dysfunction-in-animal-models-of-autism-spectrum-disorder
#2
Elisa L Hill-Yardin, Sonja J McKeown, Gaia Novarino, Andreas M Grabrucker
Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutations might interact with other risk factors is not fully understood though. Additionally, how systems outside of the brain are altered in the context of ASD is an emerging area of research...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551755/the-role-of-the-oxytocin-arginine-vasopressin-system-in-animal-models-of-autism-spectrum-disorder
#3
Rong Zhang, Xin-Jie Xu, Hong-Feng Zhang, Song-Ping Han, Ji-Sheng Han
The nonapeptides oxytocin (OXT) and arginine vasopressin (AVP) are two key mediators in regulating various aspects of mammalian social behaviours. There are several lines of evidence that genetic variants of the OXT/AVP system exist in autism spectrum disorder (ASD) and that this system is dysfunctional at least in some ASD entities. These findings have stimulated the interest to perform studies testing the potential therapeutic application of OXT/AVP in ASD. In this respect animal models are critical for investigating the pathophysiology and for compound screening leading to new therapeutic approaches...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551754/neurotrophic-factors-in-mouse-models-of-autism-spectrum-disorder-focus-on-bdnf-and-igf-1
#4
Dominik Reim, Michael J Schmeisser
Neurotrophic factors are secreted proteins promoting the development and maintaining the function of neural circuits. Studies in human individuals with autism spectrum disorder (ASD) and corresponding animal models have implicated that alterations of neurotrophic factor levels and the associated signalling pathways might contribute to the underlying pathophysiology. As most of this work has investigated the role of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) in ASD formation, we focus on these two molecules in this review...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551753/cerebellar-and-striatal-pathologies-in-mouse-models-of-autism-spectrum-disorder
#5
Saša Peter, Chris I De Zeeuw, Tobias M Boeckers, Michael J Schmeisser
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic component. To date, several hundred different genetic mutations have been identified to play a role in its aetiology. The heterogeneity of genetic abnormalities combined with the different brain regions where aberrations are found makes the search for causative mechanisms a daunting task. Even within a limited number of brain regions, a myriad of different neural circuit dysfunctions may lead to ASD. Here, we review mouse models that incorporate mutations of ASD risk genes causing pathologies in the cerebellum and striatum and highlight the vulnerability of related circuit dysfunctions within these brain regions in ASD pathophysiology...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551752/behavioural-phenotypes-and-neural-circuit-dysfunctions-in-mouse-models-of-autism-spectrum-disorder
#6
Allain-Thibeault Ferhat, Sonja Halbedl, Michael J Schmeisser, Martien J Kas, Thomas Bourgeron, Elodie Ey
Autism spectrum disorder (ASD) is a neurodevelopmental condition primarily characterised by alterations in social interaction and communication combined with the presence of restricted interests and stereotyped behaviours. Mutations in several genes have been associated with ASD resulting in the generation of corresponding mouse models. Here, we focus on the behavioural (social and stereotyped behaviours), functional and structural traits of mice with mutations in genes encoding defined synaptic proteins including adhesion proteins, scaffolding proteins and subunits of channels and receptors...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551751/modelling-autistic-features-in-mice-using-quantitative-genetic-approaches
#7
Remco T Molenhuis, Hilgo Bruining, Martien J Kas
Animal studies provide a unique opportunity to study the consequences of genetic variants at the behavioural level. Human studies have identified hundreds of risk genes for autism spectrum disorder (ASD) that can lead to understanding on how genetic variation contributes to individual differences in social interaction and stereotyped behaviour in people with ASD. To develop rational therapeutic interventions, systematic animal model studies are needed to understand the relationships between genetic variation, pathogenic processes and the expression of autistic behaviours...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551750/modelling-autistic-neurons-with-induced-pluripotent-stem-cells
#8
Annie Kathuria, Carlo Sala, Chiara Verpelli, Jack Price
Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects more than 1% of children per current estimates. It has been characterised by the following two core behavioural phenotypes: (1) deficits in social interaction and communication and (2) repetitive behaviours, restricted interests and activities. Due to the complex nature of ASD, there are currently no effective treatments. The reason behind this is the clinical and genetic heterogeneity between affected individuals on the one hand and the lack of understanding of the underpinning pathophysiological mechanisms on the other hand...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551749/neuroanatomy-and-neuropathology-of-autism-spectrum-disorder-in-humans
#9
Christine Ecker, Michael J Schmeisser, Eva Loth, Declan G Murphy
Autism spectrum disorder (ASD) is a lifelong heterogeneous neurodevelopmental condition that is associated with differences in brain anatomy and connectivity. Yet, the molecular and cellular mechanisms that underpin the atypical developmental of the brain in ASD remain poorly understood. Here, we review the findings of in vivo neuroimaging studies examining the time course of atypical brain development in ASD and relate the different neurodevelopmental stages that are atypical in ASD to the known neurobiological mechanisms that drive the maturation of the typically developing brain...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28551748/anatomy-and-cell-biology-of-autism-spectrum-disorder-lessons-from-human-genetics
#10
Kristel T E Kleijer, Guillaume Huguet, Julie Tastet, Thomas Bourgeron, J P H Burbach
Until recently autism spectrum disorder (ASD) was regarded as a neurodevelopmental condition with unknown causes and pathogenesis. In the footsteps of the revolution of genome technologies and genetics, and with its high degree of heritability, ASD became the first neuropsychiatric disorder for which clues towards molecular and cellular pathogenesis were uncovered by genetic identification of susceptibility genes. Currently several hundreds of risk genes have been assigned, with a recurrence below 1% in the ASD population...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528445/interindividual-spread-of-herpesviruses
#11
Keith W Jarosinski
Interindividual spread of herpesviruses is essential for the virus life cycle and maintenance in host populations. For most herpesviruses, the virus-host relationship is close, having coevolved over millions of years resulting in comparatively high species specificity. The mechanisms governing interindividual spread or horizontal transmission are very complex, involving conserved herpesviral and cellular proteins during the attachment, entry, replication, and egress processes of infection. Also likely, specific herpesviruses have evolved unique viral and cellular interactions during cospeciation that are dependent on their relationship...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528444/assembly-and-egress-of-an-alphaherpesvirus-clockwork
#12
Gregory A Smith
All viruses produce infectious particles that possess some degree of stability in the extracellular environment yet disassemble upon cell contact and entry. For the alphaherpesviruses, which include many neuroinvasive viruses of mammals, these metastable virions consist of an icosahedral capsid surrounded by a protein matrix (referred to as the tegument) and a lipid envelope studded with glycoproteins. Whereas the capsid of these viruses is a rigid structure encasing the DNA genome, the tegument and envelope are dynamic assemblies that orchestrate a sequential series of events that ends with the delivery of the genome into the nucleus...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528443/herpesvirus-nuclear-egress
#13
Richard J Roller, Joel D Baines
Herpesviruses assemble and package their genomes into capsids in the nucleus, but complete final assembly of the mature virion in the cell cytoplasm. This requires passage of the genome-containing capsid across the double-membrane nuclear envelope. Herpesviruses have evolved a mechanism that relies on a pair of conserved viral gene products to shuttle the capsids from the nucleus to the cytoplasm by way of envelopment and de-envelopment at the inner and outer nuclear membranes, respectively. This complex process requires orchestration of the activities of viral and cellular factors to alter the architecture of the nuclear membrane, select capsids at the appropriate stage for egress, and accomplish efficient membrane budding and fusion events...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528442/herpesvirus-capsid-assembly-and-dna-packaging
#14
Jason D Heming, James F Conway, Fred L Homa
Herpes simplex virus type I (HSV-1) is the causative agent of several pathologies ranging in severity from the common cold sore to life-threatening encephalitic infection. During productive lytic infection, over 80 viral proteins are expressed in a highly regulated manner, resulting in the replication of viral genomes and assembly of progeny virions. The virion of all herpesviruses consists of an external membrane envelope, a proteinaceous layer called the tegument, and an icosahedral capsid containing the double-stranded linear DNA genome...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528441/herpesvirus-latency-on-the-importance-of-positioning-oneself
#15
Patrick Lomonte
The nucleus is composed of multiple compartments and domains, which directly or indirectly influence many cellular processes including gene expression, RNA splicing and maturation, protein post-translational modifications, and chromosome segregation. Nuclear-replicating viruses, especially herpesviruses, have co-evolved with the cell, adopting strategies to counteract and eventually hijack this hostile environment for their own benefit. This allows them to persist in the host for the entire life of an individual and to ensure their maintenance in the target species...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528440/the-human-cmv-ie1-protein-an-offender-of-pml-nuclear-bodies
#16
Myriam Scherer, Eva-Maria Schilling, Thomas Stamminger
PML nuclear bodies (PML-NBs) are SUMOylation-dependent, highly complex protein assemblies that accumulate in the interchromosomal territories of the cell nucleus. Research of the last two decades revealed that many viruses have evolved effector proteins that modify PML-NBs. This correlates with antagonization of individual PML-NB components which act as host cell restriction factors. The multifunctional immediate-early protein IE1 of human cytomegalovirus directly interacts with the PML protein resulting in a disruption of the dot-like structure of PML-NBs...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528439/innate-immune-mechanisms-and-herpes-simplex-virus-infection-and-disease
#17
Evelyn A Kurt-Jones, Megan H Orzalli, David M Knipe
Innate immune responses play a major role in the control of herpes simplex virus (HSV) infections, and a multiplicity of mechanisms have emerged as a result of human evolution to sense and respond to HSV infections. HSV in turn has evolved a number of ways to evade immune detection and to blunt human innate immune responses. In this review, we summarize the major host innate immune mechanisms and the HSV evasion mechanisms that have evolved. We further discuss how disease can result if this equilibrium between virus and host response is disrupted...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528438/herpes-simplex-virus-membrane-fusion
#18
Darin J Weed, Anthony V Nicola
Herpes simplex virus mediates multiple distinct fusion events during infection. HSV entry is initiated by fusion of the viral envelope with either the limiting membrane of a host cell endocytic compartment or the plasma membrane. In the infected cell during viral assembly, immature, enveloped HSV particles in the perinuclear space fuse with the outer nuclear membrane in a process termed de-envelopment. A cell infected with some strains of HSV with defined mutations spread to neighboring cells by a fusion event called syncytium formation...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28528437/initial-contact-the-first-steps-in-herpesvirus-entry
#19
Walid Azab, Klaus Osterrieder
The entry process of herpesviruses into host cells is complex and highly variable. It involves a sequence of well-orchestrated events that begin with virus attachment to glycan-containing proteinaceous structures on the cell surface. This initial contact tethers virus particles to the cell surface and results in a cascade of molecular interactions, including the tight interaction of viral envelope glycoproteins to specific cell receptors. These interactions trigger intracellular signaling and finally virus penetration after fusion of the viral envelope with cellular membranes...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28389754/roles-of-grp78-in-female-mammalian-reproduction
#20
Cheng Zhang
The glucose-regulated protein (GRP78) also referred to as immunoglobulin heavy chain binding protein (Bip) is one of the best characterized endoplasmic reticulum (ER) chaperone proteins, which belongs to the heat-shock protein (HSP) family. GRP78 as a central regulator of ER stress (ERS) plays many important roles in cell survival and apoptosis through controlling the activation of transmembrane ERS sensors: PKR-like ER-associated kinase (PERK), inositol requiring kinase 1 (IRE1), and activating transcription factor 6 (ATF6)...
2017: Advances in Anatomy, Embryology, and Cell Biology
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