5,445 research outputs found
Crotalus scutulatus scutulatus Crude Venom and Its Purified Cysteine-Rich Secretory Protein (Css-CRiSP)
Increased vascular permeability is a frequent outcome of viperid snakebite envenomation, leading to local and systemic complications. We reported that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability both in vitro and in vivo. They also induce acute activation of several adhesion and signaling molecules that may play a critical role in the pathophysiology of snakebites. Extracellular vesicles (EVs) have gained interest for their diverse functions in intercellular communication, regulating cellular processes, blood-endothelium interactions, vascular permeability, and immune modulation. They also hold potential as valuable biomarkers for diagnosing, predicting, and monitoring therapeutic responses in different diseases. This study aimed to identify proteins in peritoneal exudate and plasma EVs isolated from BALB/c mice following a 30 min post-injection of Crotalus scutulatus scutulatus venom and its purified CRiSP (Css-CRiSP). EVs were isolated from these biofluids using the EVtrap method. Proteomic analysis of exudate- and plasma-derived EVs was performed using LC-MS/MS. We observed significant upregulation or downregulation of proteins involved in cell adhesion, cytoskeleton rearrangement, signal transduction, immune responses, and vesicle-mediated transports. These findings suggest that svCRiSPs play a crucial role in the acute effects of venom and contribute to the local and systemic toxicity of snakebites
Proteomic Profiling of Extracellular Vesicles Isolated from Plasma and Peritoneal Exudate in Mice Induced by Crotalus scutulatus scutulatus Crude Venom and Its Purified Cysteine-Rich Secretory Protein (Css-CRiSP)
Increased vascular permeability is a frequent outcome of viperid snakebite envenomation, leading to local and systemic complications. We reported that snake venom cysteine-rich secretory proteins (svCRiSPs) from North American pit vipers increase vascular permeability both in vitro and in vivo. They also induce acute activation of several adhesion and signaling molecules that may play a critical role in the pathophysiology of snakebites. Extracellular vesicles (EVs) have gained interest for their diverse functions in intercellular communication, regulating cellular processes, blood-endothelium interactions, vascular permeability, and immune modulation. They also hold potential as valuable biomarkers for diagnosing, predicting, and monitoring therapeutic responses in different diseases. This study aimed to identify proteins in peritoneal exudate and plasma EVs isolated from BALB/c mice following a 30 min post-injection of Crotalus scutulatus scutulatus venom and its purified CRiSP (Css-CRiSP). EVs were isolated from these biofluids using the EVtrap method. Proteomic analysis of exudate- and plasma-derived EVs was performed using LC-MS/MS. We observed significant upregulation or downregulation of proteins involved in cell adhesion, cytoskeleton rearrangement, signal transduction, immune responses, and vesicle-mediated transports. These findings suggest that svCRiSPs play a crucial role in the acute effects of venom and contribute to the local and systemic toxicity of snakebites. Key Contribution: This study reveals the immediate effects of crotaline CRiSP and crude venom by exploring the proteomic profile of peritoneal exudate- and plasma-derived EVs in mice injected with Css-CRiSP and C. s. scutulatus crude venom. Using the proteomic profile of exudate- and plasma-derived EVs provides a more comprehensive understanding of the pathophysiology of snakebites and allows for more precise targeting of therapeutic interventions. In addition, such profiling could also help identify novel biomarkers useful in predicting symptoms and progression of snakebite complications and facilitating the development of new treatments
Constraining the Magnetic Effects on HI Rotation Curves and the Need for Dark Halos
The density profiles of dark halos are usually inferred from the rotation
curves of disk galaxies based on the assumption that the gas is a good tracer
of the gravitational potential of the galaxies. Some authors have suggested
that magnetic pinching forces could alter significantly the rotation curves of
spiral galaxies. In contrast to other studies which have concentrated in the
vertical structure of the disk, here we focus on the problem of magnetic
confinement in the radial direction to bound the magnetic effects on the HI
rotation curves. It is shown that azimuthal magnetic fields can hardly speed up
the HI disk of galaxies as a whole. In fact, based on virial constraints we
show that the contribution of galactic magnetic fields to the rotation curves
cannot be larger than ~10 km/s at the outermost point of HI detection, if the
galaxies did not contain dark matter at all, and up to 20 km/s in the
conventional dark halo scenario. The procedure to estimate the maximum effect
of magnetic fields is general and applicable to any particular galaxy disk. The
inclusion of the surface terms, namely the intergalactic (thermal, magnetic or
ram) pressure, does not change our conclusions. Other problems related with the
magnetic alternative to dark halos are highlighted. The relevance of magnetic
fields in the cuspy problem of dark halos is also discussed.Comment: 12 pages, 1 figure, accepted for publication in The Astrophysical
Journa
Cherenkov Telescope Array Data Management
Very High Energy gamma-ray astronomy with the Cherenkov Telescope Array (CTA)
is evolving towards the model of a public observatory. Handling, processing and
archiving the large amount of data generated by the CTA instruments and
delivering scientific products are some of the challenges in designing the CTA
Data Management. The participation of scientists from within CTA Consortium and
from the greater worldwide scientific community necessitates a sophisticated
scientific analysis system capable of providing unified and efficient user
access to data, software and computing resources. Data Management is designed
to respond to three main issues: (i) the treatment and flow of data from remote
telescopes; (ii) "big-data" archiving and processing; (iii) and open data
access. In this communication the overall technical design of the CTA Data
Management, current major developments and prototypes are presented.Comment: 8 pages, 2 figures, In Proceedings of the 34th International Cosmic
Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions
at arXiv:1508.0589
Effects of ingesting a pre-workout supplement with and without synephrine on cognitive function, perceptions of readiness to perform, and exercise performance
The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes
Many cases of non-standard genetic codes are known in mitochondrial genomes.
We carry out analysis of phylogeny and codon usage of organisms for which the
complete mitochondrial genome is available, and we determine the most likely
mechanism for codon reassignment in each case. Reassignment events can be
classified according to the gain-loss framework. The gain represents the
appearance of a new tRNA for the reassigned codon or the change of an existing
tRNA such that it gains the ability to pair with the codon. The loss represents
the deletion of a tRNA or the change in a tRNA so that it no longer translates
the codon. One possible mechanism is Codon Disappearance, where the codon
disappears from the genome prior to the gain and loss events. In the
alternative mechanisms the codon does not disappear. In the Unassigned Codon
mechanism, the loss occurs first, whereas in the Ambiguous Intermediate
mechanism, the gain occurs first. Codon usage analysis gives clear evidence of
cases where the codon disappeared at the point of the reassignment and also
cases where it did not disappear. Codon disappearance is the probable
explanation for stop to sense reassignments and a small number of reassignments
of sense codons. However, the majority of sense to sense reassignments cannot
be explained by codon disappearance. In the latter cases, by analysis of the
presence or absence of tRNAs in the genome and of the changes in tRNA
sequences, it is sometimes possible to distinguish between the Unassigned Codon
and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments
follow the same scenario and that it is necessary to consider the details of
each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary
information). To appear in J.Mol.Evo
Mesenchymal Stromal Cell-Based Therapies as Promising Treatments for Muscle Regeneration After Snakebite Envenoming
Snakebite envenoming is a global neglected disease with an incidence of up to 2.7 million new cases every year. Although antivenoms are so-far the most effective treatment to reverse the acute systemic effects induced by snakebite envenoming, they have a limited therapeutic potential, being unable to completely neutralize the local venom effects. Local damage, such as dermonecrosis and myonecrosis, can lead to permanent sequelae with physical, social, and psychological implications. The strong inflammatory process induced by snake venoms is associated with poor tissue regeneration, in particular the lack of or reduced skeletal muscle regeneration. Mesenchymal stromal cells (MSCs)-based therapies have shown both anti-inflammatory and pro-regenerative properties. We postulate that using allogeneic MSCs or their cell-free products can induce skeletal muscle regeneration in snakebite victims, improving all the three steps of the skeletal muscle regeneration process, mainly by anti-inflammatory activity, paracrine effects, neovascularization induction, and inhibition of tissue damage, instrumental for microenvironment remodeling and regeneration. Since snakebite envenoming occurs mainly in areas with poor healthcare, we enlist the principles and potential of MSCs-based therapies and discuss regulatory issues, good manufacturing practices, transportation, storage, and related-procedures that could allow the administration of these therapies, looking forward to a safe and cost-effective treatment for a so far unsolved and neglected health problem.The authors are supported by the University Pablo de Olavide (Sevilla), the University Miguel Hernández (Elche, Alicante), National University Toribio Rodriguez de Mendoza (Chachapoyas, Peru) Grants: Contrato N° 09-2019-FONDECYT-BM-INC.INV to JRT, JDRF 2-SRA-2019-837-S-B and AVI-GVA COVID-19-68 to BS, Fundación Andaluza de I+D and Al-Andalus Biopharma Project (FAID-2018-1). The authors CC-O, CG-D, and TCSA were supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq) (Process: 406163/2018-9), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil - CAPES (Program COFECUB Process: 88881.191812/2018-01) and by Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Brazil (FAPEMIG)
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