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.

/pdf/from-sars-to-mers-thrusting-coronaviruses-into-the-spotlight-4yt0tzjx7o.pdf

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.

Objective: Hereditary neuropathies form a group of genetic disorders with a broad range of phenotypes, mode of inheritance and causative genes The objective of this study is to identify the genetic cause of disease in a congenital form of distal hereditary motor neuropathy (dHMN) Methods: A 2-year-old boy was diagnosed with arthrogryposis multiplex congenital, severe skeletal abnormalities, torticollis, vocal cord paralysis and diminished lower limb movement Whole exome sequencing was performed on the proband and family members Structure modeling and functional studies were performed to validate pathogenicity of the identified variant Results: Whole exome sequencing revealed a biallelic homozygous mutation in the TRPV4 gene (c281C>T; pS94L) The identification of a novel recessive mutation in TRPV4 extends the spectrum of mutations in recessive forms of the TRPV4-associated disease Structural modeling and functional studies were performed on pS94L and other previously identified TRPV4 variants in different protein domains Structural modeling suggests that the pS94L mutation is in the disordered N-terminal region proximal to important regulatory binding sites for phosphoinositides and for PACSIN3, which could lead to alternations in trafficking and/or channel sensitivity Functional studies show that pS94L reduces TRPV4 protein stability and therefore involves a loss-of-function mechanism Conclusion: This study identifies a novel biallelic mutation in TRPV4 as a cause of the recessive form of congenital form of distal hereditary motor neuropathy (dHMN)

/pdf/homozygous-trpv4-loss-of-function-mutation-causes-a-severe-3bkv38k09t.pdf

Homozygous TRPV4 loss-of-function mutation causes a severe form of distal Hereditary Motor Neuropathy (dHMN)

Picobirnaviruses (PBVs) are small non enveloped viruses with bi-segmented ds RNA. They have been observed in a wide variety of vertebrates, including mammals and birds with or without diarrhoea, as well as in sewage samples since its discovery (1988). The source of the viruses is uncertain. True hosts of PBVs and their role as primary pathogens or secondary opportunistic agents or innocuous viruses in the gut remains alien. The mechanisms by which they play a role in pathogenicity are still unclear based on the fact that they can be found in both symptomatic and asymptomatic cases. There is a need to determine their tropism since they have not only been associated with viral gastroenteritis but also been reported in the respiratory tracts of pigs. As zoonotic agents with diverse hosts, the importance of epidemiological and surveillance studies cannot be overstated. The segmented genome of PBV might pose a serious public health issue because of the possibility of continuous genetic reassortment. Aware of the growing attention being given to emerging RNA viruses, we reviewed the current knowledge on PBVs and described the current status of PBVs in animals. 

https://link.springer.com/content/pdf/10.1007/s11033-022-08133-2.pdf

Picobirnaviruses in animals: a review

Objective The objective of this study is to identify the genetic cause of disease in a congenital form of congenital spinal muscular atrophy and arthrogryposis (CSMAA). Methods A 2-year-old boy was diagnosed with arthrogryposis multiplex congenita, severe skeletal abnormalities, torticollis, vocal cord paralysis and diminished lower limb movement. Whole exome sequencing was performed on the proband and family members. In silico modeling of protein structure and heterologous protein expression and cytotoxicity assays were performed to validate pathogenicity of the identified variant. Results Whole exome sequencing revealed a homozygous mutation in the TRPV4 gene (c.281C>T; p.S94L). The identification of a recessive mutation in TRPV4 extends the spectrum of mutations in recessive forms of the TRPV4-associated disease. p.S94L and other previously identified TRPV4 variants in different protein domains were compared in structural modeling and functional studies. In silico structural modeling suggests that the p.S94L mutation is in the disordered N-terminal region proximal to important regulatory binding sites for phosphoinositides and for PACSIN3, which could lead to alterations in trafficking and/or channel sensitivity. Functional studies by western blot and immunohistochemical analysis show that p.S94L reduces TRPV4 protein stability because of increased cytotoxicity and therefore involves a gain-of-function mechanism. Conclusion This study identifies a novel homozygous mutation in TRPV4 as a cause of the recessive form of congenital spinal muscular atrophy and arthrogryposis.

/pdf/homozygous-trpv4-mutation-causes-congenital-distal-spinal-506dxjy8rd.pdf

Homozygous TRPV4 mutation causes congenital distal spinal muscular atrophy and arthrogryposis

Compounds have been identified and tested in a zebrafish model of dystroglycanopathy and found to be efficacious based on an increase in the survival rate of dystroglycan deficient fish. Several of the compounds affect the GABA and acetylcholine pathways. Accordingly, methods and compositions for the treatment of dystroglycanopathies are provided.

Methods and compounds for the treatment of dystroglycanopathies

Periodic or continuous exposure to very low temperatures in psychrotolerant enhances production of few specific molecules that prevent them from freezing, called Ice binding proteins. Psychrophiles is capable of synthesizing some important proteins & peptides that can regulate growth of ice crystals and these are named Ice Binding Proteins (IBPs). Ice binding proteins are specialized proteins that are less popular but extremely crucial. Antifreeze proteins (AFP) are among them only that enhance the formation of large grains of ice inside cells that damage cellular organs or cause cell death. The unique ice recrystallization inhibition properties (IRI) and thermal hysteresis (TH) have become one of the promising tools in industrial applications such as cryobiology, food storage and others. This article summarizes the functions and applications of the large group of IBPs.

Vandana Gupta

Papers

Homozygous TRPV4 loss-of-function mutation causes a severe form of distal Hereditary Motor Neuropathy (dHMN)

Picobirnaviruses in animals: a review

Homozygous TRPV4 mutation causes congenital distal spinal muscular atrophy and arthrogryposis

Methods and compounds for the treatment of dystroglycanopathies

Surviving attribute of psychrotolerant life forms: ice binding proteins