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Developmental Dynamics : An Official... Nov 2017Genetic mapping studies reveal that mutations in cohesion pathways are responsible for multispectrum developmental abnormalities termed cohesinopathies. These include... (Review)
Review
Genetic mapping studies reveal that mutations in cohesion pathways are responsible for multispectrum developmental abnormalities termed cohesinopathies. These include Roberts syndrome (RBS), Cornelia de Lange Syndrome (CdLS), and Warsaw Breakage Syndrome (WABS). The cohesinopathies are characterized by overlapping phenotypes ranging from craniofacial deformities, limb defects, and mental retardation. Though these syndromes share a similar suite of phenotypes and arise due to mutations in a common cohesion pathway, the underlying mechanisms are currently believed to be distinct. Defects in mitotic failure and apoptosis i.e. trans DNA tethering events are believed to be the underlying cause of RBS, whereas the underlying cause of CdLS is largely modeled as occurring through defects in transcriptional processes i.e. cis DNA tethering events. Here, we review recent findings described primarily in zebrafish, paired with additional studies in other model systems, including human patient cells, which challenge the notion that cohesinopathies represent separate syndromes. We highlight numerous studies that illustrate the utility of zebrafish to provide novel insights into the phenotypes, genes affected and the possible mechanisms underlying cohesinopathies. We propose that transcriptional deregulation is the predominant mechanism through which cohesinopathies arise. Developmental Dynamics 246:881-888, 2017. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; Craniofacial Abnormalities; De Lange Syndrome; Ectromelia; Genetic Association Studies; Humans; Hypertelorism; Nervous System Diseases; Transcription, Genetic; Zebrafish; Cohesins
PubMed: 28422453
DOI: 10.1002/dvdy.24510 -
Trends in Pharmacological Sciences Sep 2022Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) with a well-documented role in the innate and adaptive immune responses. Interestingly, TLR... (Review)
Review
Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) with a well-documented role in the innate and adaptive immune responses. Interestingly, TLR activation has also been linked to several brain functions including neurogenesis and synaptogenesis. Increasing evidence supports TLR involvement in peripheral and central inflammation underlying normal aging and the pathogenesis of clinical conditions characterized by cognitive decline. These include not only major neurodegenerative diseases but also traumatic brain injuries, surgeries, and alcohol consumption- and chemotherapy-induced cognitive impairment. We first summarize the physiological roles of TLRs in the nervous system, and then illustrate the emerging involvement of TLRs in cognitive functions, pointing to these receptors as novel enticing pharmacological targets to develop more efficient drugs for the treatment of cognitive impairment.
Topics: Cognitive Dysfunction; Humans; Immunity, Innate; Inflammation; Neurodegenerative Diseases; Neuroinflammatory Diseases; Toll-Like Receptors
PubMed: 35753845
DOI: 10.1016/j.tips.2022.05.004 -
Advances in Experimental Medicine and... 2020Wnt molecules are a class of cysteine-rich secreted glycoproteins that participate in various developmental events during embryogenesis and adult tissue homeostasis.... (Review)
Review
Wnt molecules are a class of cysteine-rich secreted glycoproteins that participate in various developmental events during embryogenesis and adult tissue homeostasis. Since its discovery in 1982, the roles of Wnt signaling have been established in various key regulatory systems in biology. Wnt signals exert pleiotropic effects, including mitogenic stimulation, cell fate specification, and differentiation. The Wnt signaling pathway in humans has been shown to be involved in a wide variety of disorders including colon cancer, sarcoma, coronary artery disease, tetra-amelia, Mullerian duct regression, eye vascular defects, and abnormal bone mass. The canonical Wnt pathway functions by regulating the function of the transcriptional coactivator β-catenin, whereas noncanonical pathways function independent of β-catenin. Although the role of Wnt signaling is well established in epithelial malignancies, its role in mesenchymal tumors is more controversial. Some studies have suggested that Wnt signaling plays a pro-oncogenic role in various sarcomas by driving cell proliferation and motility; however, others have reported that Wnt signaling acts as a tumor suppressor by committing tumor cells to differentiate into a mature lineage. Wnt signaling pathway also plays an important role in regulating cancer stem cell function. In this review, we will discuss Wnt signaling pathway and its role in osteosarcoma.
Topics: Bone Neoplasms; Cell Differentiation; Humans; Osteosarcoma; Wnt Proteins; Wnt Signaling Pathway; beta Catenin
PubMed: 32767238
DOI: 10.1007/978-3-030-43085-6_8 -
APSP Journal of Case Reports 2016
PubMed: 27672584
DOI: 10.21699/ajcr.v7i4.459 -
Wiley Interdisciplinary Reviews.... 2015Cohesin is a chromosome-associated protein complex that plays many important roles in chromosome function. Genetic screens in yeast originally identified cohesin as a... (Review)
Review
Cohesin is a chromosome-associated protein complex that plays many important roles in chromosome function. Genetic screens in yeast originally identified cohesin as a key regulator of chromosome segregation. Subsequently, work by various groups has identified cohesin as critical for additional processes such as DNA damage repair, insulator function, gene regulation, and chromosome condensation. Mutations in the genes encoding cohesin and its accessory factors result in a group of developmental and intellectual impairment diseases termed 'cohesinopathies.' How mutations in cohesin genes cause disease is not well understood as precocious chromosome segregation is not a common feature in cells derived from patients with these syndromes. In this review, the latest findings concerning cohesin's function in the organization of chromosome structure and gene regulation are discussed. We propose that the cohesinopathies are caused by changes in gene expression that can negatively impact translation. The similarities and differences between cohesinopathies and ribosomopathies, diseases caused by defects in ribosome biogenesis, are discussed. The contribution of cohesin and its accessory proteins to gene expression programs that support translation suggests that cohesin provides a means of coupling chromosome structure with the translational output of cells.
Topics: Animals; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; Craniofacial Abnormalities; De Lange Syndrome; Ectromelia; Humans; Hypertelorism; Protein Biosynthesis; Cohesins
PubMed: 25847322
DOI: 10.1002/wdev.190 -
Advances in Immunology 2016Ectromelia virus is a mouse-specific orthopoxvirus that, following footpad infection or natural transmission, causes mousepox in most strains of mice, while a few... (Review)
Review
Ectromelia virus is a mouse-specific orthopoxvirus that, following footpad infection or natural transmission, causes mousepox in most strains of mice, while a few strains, such as C57BL/6, are resistant to the disease but not to the infection. Mousepox is an acute, systemic, highly lethal disease of remarkable semblance to smallpox, caused by the human-specific variola virus. Starting in 1929 with its discovery by Marchal, work with ECTV has provided essential information for our current understanding on how viruses spread lympho-hematogenously, the genetic control of antiviral resistance, the role of different components of the innate and adaptive immune system in the control of primary and secondary infections with acute viruses, and how the mechanisms of immune evasion deployed by the virus affect virulence in vivo. Here, I review the literature on the pathogenesis and immunobiology of ECTV infection in vivo.
Topics: Adaptive Immunity; Animals; Disease Models, Animal; Disease Resistance; Ectromelia virus; Ectromelia, Infectious; Humans; Mice; Mice, Inbred C57BL; Smallpox; Vaccination; Vaccinia virus; Viral Proteins; Virulence
PubMed: 26791861
DOI: 10.1016/bs.ai.2015.10.001 -
The Veterinary Clinics of North... Jul 2020
PubMed: 32451039
DOI: 10.1016/j.cvfa.2020.04.001 -
Pathogens (Basel, Switzerland) Aug 2021The ubiquitin system has emerged as a master regulator of many, if not all, cellular functions. With its large repertoire of conjugating and ligating enzymes, the... (Review)
Review
The ubiquitin system has emerged as a master regulator of many, if not all, cellular functions. With its large repertoire of conjugating and ligating enzymes, the ubiquitin system holds a unique mechanism to provide selectivity and specificity in manipulating protein function. As intracellular parasites viruses have evolved to modulate the cellular environment to facilitate replication and subvert antiviral responses. Poxviruses are a large family of dsDNA viruses with large coding capacity that is used to synthetise proteins and enzymes needed for replication and morphogenesis as well as suppression of host responses. This review summarises our current knowledge on how poxvirus functions rely on the cellular ubiquitin system, and how poxviruses exploit this system to their own advantage, either facilitating uncoating and genome release and replication or rewiring ubiquitin ligases to downregulate critical antiviral factors. Whilst much remains to be known about the intricate interactions established between poxviruses and the host ubiquitin system, our knowledge has revealed crucial viral processes and important restriction factors that open novel avenues for antiviral treatment and provide fundamental insights on the biology of poxviruses and other virus families.
PubMed: 34451498
DOI: 10.3390/pathogens10081034 -
Pathogens (Basel, Switzerland) Aug 2021Tumour necrosis factor (TNF) is an inflammatory cytokine produced in response to viral infections that promotes the recruitment and activation of leukocytes to sites of... (Review)
Review
Tumour necrosis factor (TNF) is an inflammatory cytokine produced in response to viral infections that promotes the recruitment and activation of leukocytes to sites of infection. This TNF-based host response is essential to limit virus spreading, thus poxviruses have evolutionarily adopted diverse molecular mechanisms to counteract TNF antiviral action. These include the expression of poxvirus-encoded soluble receptors or proteins able to bind and neutralize TNF and other members of the TNF ligand superfamily, acting as decoy receptors. This article reviews in detail the various TNF decoy receptors identified to date in the genomes from different poxvirus species, with a special focus on their impact on poxvirus pathogenesis and their potential use as therapeutic molecules.
PubMed: 34451529
DOI: 10.3390/pathogens10081065