21 research outputs found
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Acute hepatitis and myositis associated with Erythema infectiosum by Parvovirus B19 in an adolescent
Background: Erythema infectiosum is the most common clinical manifestation of Parvovirus B19 infection although it has also been associated with rheumatologic diseases and various types of systemic vasculitides. Acute hepatitis and benign myositis however are rarely reported in association with Parvovirus B19 infection. Case presentation: Here we report a 14-year old male, who developed acute hepatitis and benign myositis associated with erythema infectiosum following Parvovirus B19 infection. Conclusion: Parvovirus B19 infection has rarely been associated with acute hepatitis and exceptionally rarely with benign myositis. Parvovirus B19 should be considered in the differential diagnosis of acute non-A to E hepatitis and in the case of acute benign myositis presenting with a rash especially in children
An RNA interference-based screen of transcription factor genes identifies pathways necessary for sensory regeneration in the avian inner ear
Sensory hair cells of the inner ear are the mechano-electric transducers of sound and head motion. In mammals, damage to sensory hair cells leads to hearing or balance deficits. Non-mammalian vertebrates such as birds can regenerate hair cells after injury. In a previous study, we characterized transcription factor gene expression during chicken hair cell regeneration. In those studies, a laser micro-beam or ototoxic antibiotics were used to damage the sensory epithelia (SE). The current study focused on 27 genes that were up-regulated in regenerating SE compared to untreated SE in the previous study. Those genes were knocked down by siRNA, to determine their requirement for supporting cell proliferation and to measure resulting changes in the larger network of gene expression. We identified 11 genes necessary for proliferation and also identified novel interactive relationships between many of them. Defined components of the WNT, PAX and AP1 pathways were shown to be required for supporting cell proliferation. These pathways intersect on WNT4, which is also necessary for proliferation. Among the required genes, the CCAAT enhancer binding protein, CEBPG, acts downstream of Jun Kinase and JUND in the AP1 pathway. The WNT co-receptor LRP5 acts downstream of CEBPG as does the transcription factor BTAF1. Both of these genes are also necessary for supporting cell proliferation. This is the first large scale screen of its type and suggests an important intersection between the AP1 pathway, the PAX pathway and WNT signaling in the regulation of supporting cell proliferation during inner ear hair cell regeneration
Large Scale Gene Expression Profiles of Regenerating Inner Ear Sensory Epithelia
Loss of inner ear sensory hair cells (HC) is a leading cause of human hearing loss and balance disorders. Unlike mammals, many lower vertebrates can regenerate these cells. We used cross-species microarrays to examine this process in the avian inner ear. Specifically, changes in expression of over 1700 transcription factor (TF) genes were investigated in hair cells of auditory and vestibular organs following treatment with two different damaging agents and regeneration in vitro. Multiple components of seven distinct known signaling pathways were clearly identifiable: TGFβ, PAX, NOTCH, WNT, NFKappaB, INSULIN/IGF1 and AP1. Numerous components of apoptotic and cell cycle control pathways were differentially expressed, including p27KIP and TFs that regulate its expression. A comparison of expression trends across tissues and treatments revealed identical patterns of expression that occurred at identical times during regenerative proliferation. Network analysis of the patterns of gene expression in this large dataset also revealed the additional presence of many components (and possible network interactions) of estrogen receptor signaling, circadian rhythm genes and parts of the polycomb complex (among others). Equal numbers of differentially expressed genes were identified that have not yet been placed into any known pathway. Specific time points and tissues also exhibited interesting differences: For example, 45 zinc finger genes were specifically up-regulated at later stages of cochlear regeneration. These results are the first of their kind and should provide the starting point for more detailed investigations of the role of these many pathways in HC recovery, and for a description of their possible interactions
Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020
We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2
Orally Administered Drugs and Their Complicated Relationship with Our Gastrointestinal Tract
Orally administered compounds represent the great majority of all pharmaceutical compounds produced for human use and are the most popular among patients since they are practical and easy to self-administer. Following ingestion, orally administered drugs begin a “perilous” journey down the gastrointestinal tract and their bioavailability is modulated by numerous factors. The gastrointestinal (GI) tract anatomy can modulate drug bioavailability and accounts for interpatient drug response heterogeneity. Furthermore, host genetics is a contributor to drug bioavailability modulation. Importantly, a component of the GI tract that has been gaining notoriety with regard to drug treatment interactions is the gut microbiota, which shares a two-way interaction with pharmaceutical compounds in that they can be influenced by and are able to influence administered drugs. Overall, orally administered drugs are a patient-friendly treatment option. However, during their journey down the GI tract, there are numerous host factors that can modulate drug bioavailability in a patient-specific manner
A plasma membrane H(+)ATPase gene is germination-induced in wheat embryos
The expression pattern of a germination specific plasma membrane H+-ATPase was analyzed by RTPCR and in situ RNA hybridization methods. RT-PCR results revealed that germination specific plasma membrane H+-ATPase accumulation was detectable in all organs and tissues of germinating wheat embryos. H+-ATPase expression was not observed in dry wheat embryos and in immature wheat embryos. In situ RNA hybridization indicated that germination specific plasma membrane H+-ATPase gene expression was associated with all organs of germinating wheat tissues. The accumulation of H+-ATPase mRNA was more heavily on the cells of vascular bundles and epidermal cells of coleoptiles. Since germination specific plasma membrane H+-ATPase gene was identified as a growth related gene, interest was focused on the activity of growth regulators (GA, IAA, ABA) and stress factors, NaCl and Mannitol, on H+-ATPase gene expression. The results indicated that there were not any dramatic changes in the accumulation of germination specific plasma membrane H+-ATPase gene in any case. More rigorous analysis is necessary to evaluate the effect of growth regulators on germination specific plasma membrane H+-ATPase
Use of Metatranscriptomics in Microbiome Research
The human intestinal microbiome is a microbial ecosystem that expresses as many as 100 times more genes than the human host, thereby constituting an important component of the human holobiome , which contributes to multiple health and disease processes. As most commensal species are difficult or impossible to culture, genomic characterization of microbiome composition and function, under various environmental conditions, comprises a central tool in understanding its roles in health and disease. The first decade of microbiome research was mainly characterized by usage of DNA sequencing-based 16S rDNA and shotgun metagenome sequencing, allowing for the elucidation of microbial composition and genome structure. Technological advances in RNA-seq have recently provided us with an ability to gain insight into the genes that are actively expressed in complex bacterial communities, enabling the elucidation of the functional changes that dictate the microbiome functions at given contexts, its interactions with the host, and functional alterations that accompany the conversion of a healthy microbiome toward a disease-driving configuration. Here, we highlight some of the key metatranscriptomics strategies that are implemented to determine microbiota gene expression and its regulation and discuss the advantages and potential challenges associated with these approaches
Non-alcoholic fatty liver and the gut microbiota
Background: Non-alcoholic fatty liver (NAFLD) is a common, multi-factorial, and poorly understood liver disease whose incidence is globally rising. NAFLD is generally asymptomatic and associated with other manifestations of the metabolic syndrome. Yet, up to 25% of NAFLD patients develop a progressive inflammatory liver disease termed non-alcoholic steatohepatitis (NASH) that may progress towards cirrhosis, hepatocellular carcinoma, and the need for liver transplantation.
In recent years, several lines of evidence suggest that the gut microbiome represents a significant environmental factor contributing to NAFLD development and its progression into NASH. Suggested microbiome-associated mechanisms contributing to NAFLD and NASH include dysbiosis-induced deregulation of the gut endothelial barrier function, which facilitates systemic bacterial translocation, and intestinal and hepatic inflammation. Furthermore, increased microbiome-modulated metabolites such as lipopolysaccharides, short chain fatty acids (SCFAs), bile acids, and ethanol, may affect liver pathology through multiple direct and indirect mechanisms.
Scope of review: Herein, we discuss the associations, mechanisms, and clinical implications of the microbiome's contribution to NAFLD and NASH. Understanding these contributions to the development of fatty liver pathogenesis and its clinical course may serve as a basis for development of therapeutic microbiome-targeting approaches for treatment and prevention of NAFLD and NASH.
Major conclusions: Intestinal host–microbiome interactions play diverse roles in the pathogenesis and progression of NAFLD and NASH. Elucidation of the mechanisms driving these microbial effects on the pathogenesis of NAFLD and NASH may enable to identify new diagnostic and therapeutic targets of these common metabolic liver diseases.
This article is part of a special issue on microbiota