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Journal of Medicine and Life Apr 2022Fibular hemimelia is defined as a partial or complete absence of the fibula. Alongside fibular deformities, there is a wide spectrum of anomalies, foot deformities, and... (Review)
Review
Fibular hemimelia is defined as a partial or complete absence of the fibula. Alongside fibular deformities, there is a wide spectrum of anomalies, foot deformities, and absent rays. A literature review showed only a handful of cases of prenatal diagnosis of fibular hemimelia. It is a rare disorder that might be isolated or associated with visceral anomalies.
Topics: Ectromelia; Female; Fibula; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 35646168
DOI: 10.25122/jml-2021-0397 -
The Pan African Medical Journal 2021
Topics: Abnormalities, Multiple; Child, Preschool; Ectromelia; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Male; Nose
PubMed: 34887989
DOI: 10.11604/pamj.2021.40.115.28167 -
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 -
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 -
Journal of Medical Genetics Mar 1973
Review
Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Anemia, Aplastic; Anorexia Nervosa; Arm; Cleft Lip; Cleft Palate; Ectromelia; Female; Genes; Heart Defects, Congenital; Hot Temperature; Humans; Phenotype; Pregnancy; Radius; Spine; Syndactyly; Thalidomide; Thrombocytopenia; Thumb; Tibia
PubMed: 4354695
DOI: 10.1136/jmg.10.1.34 -
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 -
Microbiological Reviews Mar 1991Poxviruses are a highly successful family of pathogens, with variola virus, the causative agent of smallpox, being the most notable member. Poxviruses are unique among... (Review)
Review
Poxviruses are a highly successful family of pathogens, with variola virus, the causative agent of smallpox, being the most notable member. Poxviruses are unique among animal viruses in several respects. First, owing to the cytoplasmic site of virus replication, the virus encodes many enzymes required either for macromolecular precursor pool regulation or for biosynthetic processes. Second, these viruses have a very complex morphogenesis, which involves the de novo synthesis of virus-specific membranes and inclusion bodies. Third, and perhaps most surprising of all, the genomes of these viruses encode many proteins which interact with host processes at both the cellular and systemic levels. For example, a viral homolog of epidermal growth factor is active in vaccinia virus infections of cultured cells, rabbits, and mice. At least five virus proteins with homology to the serine protease inhibitor family have been identified and one, a 38-kDa protein encoded by cowpox virus, is thought to block a host pathway for generating a chemotactic substance. Finally, a protein which has homology with complement components interferes with the activation of the classical complement pathway. Poxviruses infect their hosts by all possible routes: through the skin by mechanical means (e.g., molluscum contagiosum infections of humans), via the respiratory tract (e.g., variola virus infections of humans), or by the oral route (e.g., ectromelia virus infection of the mouse). Poxvirus infections, in general, are acute, with no strong evidence for latent, persistent, or chronic infections. They can be localized or systemic. Ectromelia virus infection of the laboratory mouse can be systemic but inapparent with no mortality and little morbidity, or highly lethal with death in 10 days. On the other hand, molluscum contagiosum virus replicates only in the stratum spinosum of the human epidermis, with little or no involvement of the dermis, and does not spread systemically from the site of infection. The host response to infection is progressive and multifactorial. Early in the infection process, interferons, the alternative pathway of complement activation, inflammatory cells, and natural killer cells may contribute to slowing the spread of the infection. The cell-mediated response involving learned cytotoxic T lymphocytes and delayed-type hypersensitivity components appears to be the most important in recovery from infection. A significant role for specific antiviral antibody and antibody-dependent cell-mediated cytotoxicity has yet to be demonstrated in recovery from a primary infection, but these responses are thought to be important in preventing reinfection.
Topics: Amino Acid Sequence; Animals; Growth Substances; Humans; Intercellular Signaling Peptides and Proteins; Molecular Sequence Data; Peptides; Poxviridae; Poxviridae Infections; Serpins; Virus Replication
PubMed: 1851533
DOI: 10.1128/mr.55.1.80-122.1991 -
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 -
Cell Reports Nov 2022Inflammatory monocytes (iMOs) and B cells are the main targets of the poxvirus ectromelia virus (ECTV) in the lymph nodes of mice and play distinct roles in surviving...
Inflammatory monocytes (iMOs) and B cells are the main targets of the poxvirus ectromelia virus (ECTV) in the lymph nodes of mice and play distinct roles in surviving the infection. Infected and bystander iMOs control ECTV's systemic spread, preventing early death, while B cells make antibodies that eliminate ECTV. Our work demonstrates that within an infected animal that survives ECTV infection, intrinsic and bystander infection of iMOs and B cells differentially control the transcription of genes important for immune cell function and, perhaps, cell identity. Bystander cells upregulate metabolism, antigen presentation, and interferon-stimulated genes. Infected cells downregulate many cell-type-specific genes and upregulate transcripts typical of non-immune cells. Bystander (Bys) and infected (Inf) iMOs non-redundantly contribute to the cytokine milieu and the interferon response. Furthermore, we uncover how type I interferon (IFN-I) or IFN-γ signaling differentially regulates immune pathways in Inf and Bys iMOs and that, at steady state, IFN-I primes iMOs for rapid IFN-I production and antigen presentation.
Topics: Animals; Mice; Monocytes; Poxviridae; Ectromelia, Infectious; Ectromelia virus; Antiviral Agents; Interferon Type I
PubMed: 36417857
DOI: 10.1016/j.celrep.2022.111676 -
Proceedings of the National Academy of... Feb 2022Viral causes of pneumonia pose constant threats to global public health, but there are no specific treatments currently available for the condition. Antivirals are...
Viral causes of pneumonia pose constant threats to global public health, but there are no specific treatments currently available for the condition. Antivirals are ineffective when administered late after the onset of symptoms. Pneumonia is caused by an exaggerated inflammatory cytokine response to infection, but tissue necrosis and damage caused by virus also contribute to lung pathology. We hypothesized that viral pneumonia can be treated effectively if both virus and inflammation are simultaneously targeted. Combined treatment with the antiviral drug cidofovir and etanercept, which targets tumor necrosis factor (TNF), down-regulated nuclear factor kappa B-signaling and effectively reduced morbidity and mortality during respiratory ectromelia virus (ECTV) infection in mice even when treatment was initiated after onset of clinical signs. Treatment with cidofovir alone reduced viral load, but animals died from severe lung pathology. Treatment with etanercept had no effect on viral load but diminished levels of inflammatory cytokines and chemokines including TNF, IL-6, IL-1β, IL-12p40, TGF-β, and CCL5 and dampened activation of the STAT3 cytokine-signaling pathway, which transduces signals from multiple cytokines implicated in lung pathology. Consequently, combined treatment with a STAT3 inhibitor and cidofovir was effective in improving clinical disease and lung pathology in ECTV-infected mice. Thus, the simultaneous targeting of virus and a specific inflammatory cytokine or cytokine-signaling pathway is effective in the treatment of pneumonia. This approach might be applicable to pneumonia caused by emerging and re-emerging viruses, like seasonal and pandemic influenza A virus strains and severe acute respiratory syndrome coronavirus 2.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antiviral Agents; Cell Line; Chlorocebus aethiops; Cidofovir; Cytokines; Drug Evaluation, Preclinical; Drug Therapy, Combination; Ectromelia virus; Etanercept; Female; Lung; Mice, Inbred C57BL; NF-kappa B; Pneumonia, Viral; STAT3 Transcription Factor; Signal Transduction; Tumor Necrosis Factor-alpha; Viral Load; Mice
PubMed: 35177474
DOI: 10.1073/pnas.2112725119