Reactive oxygen species

Coronaviruses (CoVs) have formerly been regarded as relatively harmless respiratory pathogens to humans. However, two outbreaks of severe respiratory tract infection, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), as a result of zoonotic CoVs crossing the species barrier, caused high pathogenicity and mortality rates in human populations. This brought CoVs global attention and highlighted the importance of controlling infectious pathogens at international borders. In this review, we focus on our current understanding of the epidemiology, pathogenesis, prevention, and treatment of SARS-CoV and MERS-CoV, as well as provides details on the pivotal structure and function of the spike proteins (S proteins) on the surface of each of these viruses. For building up more suitable animal models, we compare the current animal models recapitulating pathogenesis and summarize the potential role of host receptors contributing to diverse host affinity in various species. We outline the research still needed to fully elucidate the pathogenic mechanism of these viruses, to construct reproducible animal models, and ultimately develop countermeasures to conquer not only SARS-CoV and MERS-CoV, but also these emerging coronaviral diseases.

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From SARS to MERS, Thrusting Coronaviruses into the Spotlight

For more information on the USGS—the Federal source for science about the Earth, its natural and living resources, natural hazards, and the environment, visit http://www.usgs.gov or call 1–888–ASK–USGS. For an overview of USGS information products, including maps, imagery, and publications, Any use of trade, product, or firm names is for descriptive purposes only and does not imply endorsement by the U.S. Government. Although this report is in the public domain, permission must be secured from the individual copyright owners to reproduce any copyrighted materials contained within this report. 10. Diagram showing the GMTED2010 layer extents (minimum and maximum latitude and longitude) are a result of the coordinate system inherited from the 1-arc-second SRTM

Global Multi-resolution Terrain Elevation Data 2010 (GMTED2010)

Opposing Effects of Retinoic Acid on Cell Growth Result from Alternate Activation of Two Different Nuclear Receptors

COVID-19 Vaccine: A comprehensive status report.

Analytical modeling of TCP flow in wireless LANs

Merosin deficient congenital muscular dystrophy (MDC1A) is a severe neuromuscular disorder with onset in infancy that is associated with severe morbidities (particularly wheelchair dependence) and early mortality. It is caused by recessive mutations in the LAMA2 gene that encodes a subunit of the extracellular matrix protein laminin 211. At present, there are no treatments for this disabling disease. The zebrafish has emerged as a powerful model system for the identification of novel therapies. However, drug discovery in the zebrafish is largely dependent on the identification of phenotypes suitable for chemical screening. Our goal in this study was to elucidate novel, early onset abnormalities in the candyfloss (caf) zebrafish, a model of MDC1A. We uncovered and characterize abnormalities in spontaneous coiling, the earliest motor movement in the zebrafish, as a fully penetrant change specific to caf mutants that is ideal for future drug testing.

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A novel early onset phenotype in a zebrafish model of merosin deficient congenital muscular dystrophy.

Nemaline myopathy (NM) is the most common form of congenital myopathy that results in hypotonia and muscle weakness. This disease is clinically and genetically heterogeneous, but three recently discovered genes in NM encode for members of the Kelch family of proteins. Kelch proteins act as substrate-specific-adapters for CUL3 E3 ubiquitin ligase to regulate protein turn-over through the ubiquitin-proteasome machinery. Defects in thin filament formation and/or stability are key molecular processes that underlie the disease pathology in NM, however, the role of Kelch proteins in these processes in normal and diseases conditions remains elusive in vivo . Here, we describe a role of NM causing Kelch protein, KLHL41, in premyofibil-myofibil transition during skeletal muscle development through a regulation of the thin filament chaperone, NRAP. KLHL41 binds to the thin filament chaperone NRAP and promotes ubiquitination and subsequent degradation of NRAP, a process that is critical for the formation of mature myofibrils. KLHL41 deficiency results in abnormal accumulation of NRAP in muscle cells. NRAP overexpression in transgenic zebrafish resulted in a severe myopathic phenotype and absence of mature myofibrils demonstrating a role in disease pathology. Reducing Nrap levels in KLHL41 deficient zebrafish rescues the structural and function defects associated with disease pathology. We conclude that defects in KLHL41-mediated ubiquitination of sarcomeric protein contribute to structural and functional deficits in skeletal muscle. These findings further our understanding of how the sarcomere assembly is regulated by disease causing factors in vivo , which will be imperative for developing mechanism-based specific therapeutic interventions.

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Dysregulation of NRAP degradation by KLHL41 contributes to pathophysiology in Nemaline Myopathy

Introduction RNA-binding proteins (RBPs) play an important role in skeletal muscle development and disease by regulating RNA splicing. In myotonic dystrophy type 1 (DM1), the RBP MBNL1 (muscleblind-like) is sequestered by toxic CUG repeats, leading to missplicing of MBNL1 targets. Mounting evidence from the literature has implicated other factors in the pathogenesis of DM1. Herein we sought to evaluate the functional role of the splicing factor hnRNP L in normal and DM1 muscle cells. Methods Co-immunoprecipitation assays using hnRNPL and MBNL1 expression constructs and splicing profiling in normal and DM1 muscle cell lines were performed. Zebrafish morpholinos targeting hnrpl and hnrnpl2 were injected into one-cell zebrafish for developmental and muscle analysis. In human myoblasts downregulation of hnRNP L was achieved with shRNAi. Ascochlorin administration to DM1 myoblasts was performed and expression of the CUG repeats, DM1 splicing biomarkers, and hnRNP L expression levels were evaluated. Results Using DM1 patient myoblast cell lines we observed the formation of abnormal hnRNP L nuclear foci within and outside the expanded CUG repeats, suggesting a role for this factor in DM1 pathology. We showed that the antiviral and antitumorigenic isoprenoid compound ascochlorin increased MBNL1 and hnRNP L expression levels. Drug treatment of DM1 muscle cells with ascochlorin partially rescued missplicing of established early biomarkers of DM1 and improved the defective myotube formation displayed by DM1 muscle cells. Discussion Together, these studies revealed that hnRNP L can modulate DM1 pathologies and is a potential therapeutic target.

hnRNP L is essential for myogenic differentiation and modulates myotonic dystrophy pathologies.

Ectomycorrhizal (EM) fungi can be grown in surface, submerged as well as solid state cultivations. While growing, EM fungi excrete several enzymes, phytohormones, siderophores, antimicrobial substances as well as organic acids like oxalic acid. These are slow growing fungi with a doubling time of around 50 hours. The EM fungi exhibit physiological as well as ecological diversity within and among species. Variations are seen in biochemical function measured by enzyme production and regulation, production of phytohormones and substances which may be crucial to the symbiotic balance. Many EM fungi are bifactorial with multiple A and B alleles. The attempts to understand EM fungus-plant root interactions have suggested the involvement of symbiosis specific proteins, called ectomycorrhizins. The possibilities of induction of mutations, generation of protoplasts and their regeneration with at least Hebeloma and Laccaria, and transformation of EM fungi have been reported. These features of EM fungi make them suitable for use as experimental organisms.

Vandana Gupta

Papers

Analytical modeling of TCP flow in wireless LANs

A novel early onset phenotype in a zebrafish model of merosin deficient congenital muscular dystrophy.

Dysregulation of NRAP degradation by KLHL41 contributes to pathophysiology in Nemaline Myopathy

hnRNP L is essential for myogenic differentiation and modulates myotonic dystrophy pathologies.

Ectomycorrhizal fungi as experimental organisms