Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes ...inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19.
Pymetrozine represents a class of compounds for the control of sucking insects. However, chewing insects have also shown sensitivity to this compound. Therefore, although pymetrozine has been ...demonstrated to have a direct action on sucking insects, it could also affect species like the boll worm Anthonomus grandis by promoting histological changes in the intestine and alterations in biochemical parameters such as glycogen, lipids, and glucose. The pymetrozine promoted histological changes are characterized by protrusions and detachments of columnar cells toward the intestinal lumen, presence of vacuolated regenerative cells, and removal of the epithelial lamina in some areas of the muscle layer. The ultrastructure of the midgut in the control group exhibited the basal labyrinth near the mid region of the cell, rough endoplasmic reticulum, Golgi complex, glycogen granules, mitochondria, electron-lucent vesicles, nucleus with well-defined nucleoli, and elongated microvillus. Pymetrozine promoted disarrangement in the basal labyrinth and generated numerous vacuoles and large protrusions between the epithelial lamina and muscular layer. No significant difference was observed in glucose content at 48 h after treatment; however, a significant increase was observed at 144 h after treatment. The glycogen content was reduced in the first 48 h of exposure to pmetrozine and reached the average content of the control insects at 144 h. Significant effects were observed in lipid contents, both in the first 48 h and at 144 h after treatment. Thus, we conclude that pymetrozine compromises the digestive physiology in these insects, affects reproduction, and consequently, it can be a potential alternative to reduce this pest species.
•Inactivated recombinant E. coli expressing rETX (recombinant bacterin).•Non-purified vaccine induced protective immunity in rabbits, sheep and cattle.•Recombinant vaccines are produced using a safe, ...simpler and faster production process.•Production process requires no steps of lysis, purification and refolding.
We present spectroscopic determinations of the effective temperatures, surface gravities, and metallicities for 21 M dwarfs observed at high resolution (R ∼ 22,500) in the H band as part of the Sloan ...Digital Sky Survey (SDSS)-IV Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey. The atmospheric parameters and metallicities are derived from spectral syntheses with 1D LTE plane-parallel MARCS models and the APOGEE atomic/molecular line list, together with up-to-date H2O and FeH molecular line lists. Our sample range in Teff from ∼3200 to 3800 K, where 11 stars are in binary systems with a warmer (FGK) primary, while the other 10 M dwarfs have interferometric radii in the literature. We define an M K S -radius calibration based on our M-dwarf radii derived from the detailed analysis of APOGEE spectra and Gaia DR2 distances, as well as a mass-radius relation using the spectroscopically derived surface gravities. A comparison of the derived radii with interferometric values from the literature finds that the spectroscopic radii are slightly offset toward smaller values, with Δ = −0.01 0.02 R /R . In addition, the derived M-dwarf masses based upon the radii and surface gravities tend to be slightly smaller (by ∼5%-10%) than masses derived for M-dwarf members of eclipsing binary systems for a given stellar radius. The metallicities derived for the 11 M dwarfs in binary systems, compared to metallicities obtained for their hotter FGK main-sequence primary stars from the literature, show excellent agreement, with a mean difference of Fe/H(M dwarf - FGK primary) = +0.04 0.18 dex, confirming the APOGEE metallicity scale derived here for M dwarfs.
Abstract
Background
Focal cortical dysplasia (FCD) is a malformation of cortical development that causes medical refractory seizures, and one of the main treatments may be surgical resection of the ...affected area of the brain. People affected by FCD may present with seizures of variable severity since childhood. Despite many medical treatments available, only surgery can offer cure. The pathophysiology of the disease is not yet understood; however, it is known that several gene alterations may play a role. The WNT/β-catenin pathway is closely related to the control and balance of cell proliferation and differentiation in the central nervous system. The aim of this study was to explore genes related to the WNT/β-catenin pathway in lesional and perilesional brain tissue in patients with FCD type II.
Methods
Dysplastic and perilesional tissue from the primary dysplastic lesion of patients with FCD type IIa were obtained from two patients who underwent surgical treatment. The analysis of the relative expression of genes was performed by a qRT-PCR array (super array) containing 84 genes related to the WNT pathway.
Results
Our results suggest the existence of molecular alteration in some genes of the WNT pathway in tissue with dysplastic lesions and of perilesional tissue. We call this tissue of normal-appearing adjacent cortex (NAAC). Of all genes analyzed, a large number of genes show similar behavior between injured, perilesional and control tissues. However, some genes have similar characteristics between the perilesional and lesional tissue and are different from the control brain tissue, presenting the perilesional tissue as a molecularly altered material.
Conclusion
Our results suggest that the perilesional area after surgical resection of tissue with cortical dysplasia presents molecular changes that may play a role in the recurrence of seizures in these patients. The perilesional tissue should receive expanded attention beyond the somatic mutations described and associated with FCD, such as mTOR, for example, to new signaling pathways that may play a crucial role in seizure recurrence.
Abstract
We present a spectroscopic analysis of a sample of 48 M-dwarf stars (0.2
M
⊙
<
M
< 0.6
M
⊙
) from the Hyades open cluster using high-resolution
H
-band spectra from the Sloan Digital Sky ...Survey/Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey. Our methodology adopts spectrum synthesis with LTE MARCS model atmospheres, along with the APOGEE Data Release 17 line list, to determine effective temperatures, surface gravities, metallicities, and projected rotational velocities. The median metallicity obtained for the Hyades M dwarfs is M/H = 0.09 ± 0.03 dex, indicating a small internal uncertainty and good agreement with optical results for Hyades red giants. Overall, the median radii are larger than predicted by stellar models by 1.6% ± 2.3% and 2.4% ± 2.3%, relative to a MIST and DARTMOUTH isochrone, respectively. We emphasize, however, that these isochrones are different, and the fractional radius inflation for the fully and partially convective regimes have distinct behaviors depending on the isochrone. Using a MIST isochrone there is no evidence of radius inflation for the fully convective stars, while for the partially convective M dwarfs the radii are inflated by 2.7% ± 2.1%, which is in agreement with predictions from models that include magnetic fields. For the partially convective stars, rapid rotators present on average higher inflation levels than slow rotators. The comparison with SPOTS isochrone models indicates that the derived M-dwarf radii can be explained by accounting for stellar spots in the photosphere of the stars, with 76% of the studied M dwarfs having up to 20% spot coverage, and the most inflated stars with ∼20%–40% spot coverage.
Over the last few years, considerable effort has been spent by Embrapa in the construction of a plant disease database representative enough for the development of effective methods for automatic ...plant disease detection and recognition. In October of 2016, this database, called PDDB, had 2326 images of 171 diseases and other disorders affecting 21 plant species. PDDB size, although considerable, is not enough to allow the use of powerful techniques such as deep learning. In order to increase its size, each image was subdivided according to certain criteria, increasing the number of images to 46,513. Both the original (PDDB) and subdivided (XDB) databases are now being made freely available for academic research purposes, thus supporting new studies and contributing to speed up the advances in the area. Both collections are expected to grow continuously in order to expand their reach. PDDB and XDB can be accessed in the link https://www.digipathos-rep.cnptia.embrapa.br/.
We evaluated the fungal diversity associated with carbonate veins and two types of salt encrustation in rocks in a polar desert region of continental Antarctica using DNA a metabarcoding approach. We ...detected 262,268 reads grouped into 517 amplicon sequence variants (ASVs) assigned to the phyla
Ascomycota
,
Basidiomycota
,
Mortierellomycota
and
Mucoromycota
. Fourteen ASVs belonging to the genera
Trichosporon
,
Mortierella
,
Penicillium
,
Aspergillus
,
Cladosporium
,
Coprinellus
,
Pleurotus
and
Pseudogymnoascus
were assessed to be dominant taxa. The fungal communities of the three habitats sampled displayed high diversity indices when compared with other habitats of Antarctica, although differing in detail, with the highest diversity indices in the gypsum crust type 2. Only 48 of the 517 ASVs (9.28%) were detected in all three habitats, including dominant, intermediate and minor components. In contrast with previous studies of fungal communities living in the ultra-extreme conditions of continental Antarctica, application of metabarcoding revealed the DNA of a rich and complex resident fungal community. The ASVs detected included fungi with different ecological roles, with xerophilic, human- and animal-associated, phytopathogenic, saprotrophic, mutualistic, psychrotolerant and cosmopolitan taxa. This sequence diversity may be the result of deposition of fungal propagules over time driven by air currents, precipitation or human activities in the region.
Impaired glucose metabolism reflects neuronal/synaptic dysfunction and cognitive function decline in patients with obstructive sleep apnea (OSA). The study investigated the extent to which exercise ...training (ET) improves cerebral metabolic glucose rate (CMRgl) and cognitive function in patients with OSA. Patients with moderate to severe OSA were randomly assigned to ET (3 times/week, n = 23) or no intervention (control, n = 24). Echocardiography and apolipoprotein ε4 (APOEε4) genotyping were obtained at baseline. Both groups underwent cardiopulmonary exercise testing, polysomnography, cognitive tests, brain magnetic resonance imaging, and
F-fluoro-2-deoxy-D-Glucose positron emission tomography (
FDG-PET) at baseline and study end. Compared with control, exercise-trained group had improved exercise capacity, decreased apnea-hypopnea index (AHI), oxygen desaturation and arousal index; increased attention/executive functioning, increased CMRgl in the right frontal lobe (P < 0.05). After ET an inverse relationships occurred between CMRgl and obstructive AHI (r = - 0.43, P < 0.05) and apnea arousal index (r = - 0.53, P < 0.05), and between the changes in CMRgl and changes in mean O
saturation during sleep and non-rapid eye movement sleep (r = - 0.43, P < 0.05), desaturation during arousal (r = - 0.44, P < 0.05), and time to attention function testing (r = - 0.46, P < 0.05). ET improves OSA severity and CMRg in the frontal lobe, which helps explain the improvement in attention/executive functioning. Our study provides promising data that reinforce the growing idea that ET may be a valuable tool to prevent hypoxia associated with decreased brain metabolism and cognitive functioning in patients with moderate to severe OSA.Trial registration: NCT02289625 (13/11/2014).
Parkinson’s disease (PD) is characterized by motor and non-motor signs, which are accompanied by progressive degeneration of dopaminergic neurons in the substantia nigra. Although the exact causes ...are unknown, evidence links this neuronal loss with neuroinflammation and oxidative stress. Repeated treatment with a low dose of reserpine—inhibitor of VMAT2—has been proposed as a progressive pharmacological model of PD. The aim of this study was to investigate whether this model replicates the neuroinflammation characteristic of this disease. Six-month-old Wistar rats received repeated subcutaneous injections of reserpine (0.1 mg/kg) or vehicle on alternate days. Animals were euthanized after 5, 10, or 15 injections, or 20 days after the 15th injection. Catalepsy tests (motor assessment) were conducted across treatment. Brains were collected at the end of each treatment period for immunohistochemical and RT-PCR analyzes. Reserpine induced a significant progressive increase in catalepsy duration. We also found decreased immunostaining for tyrosine hydroxylase (TH) in the substantia nigra
pars compacta
(SNpc) and increased GFAP + cells in the SNpc and dorsal striatum after 10 and 15 reserpine injections. Phenotyping microglial M1 and M2 markers showed increased number of CD11b + cells and percentage of CD11b + /iNOS + cells in reserpine-treated animals after 15 injections, which is compatible with tissue damage and production of cytotoxic factors. In addition, increased CD11b + /ArgI + cells were found 20 days after the last reserpine injection, together with an increment in IL-10 gene expression in the dorsal striatum, which is indicative of tissue repair or regeneration. Reserpine also induced increases in striatal interleukin TNF-alpha mRNA levels in early stages. In view of these results, we conclude that reserpine-induced progressive parkinsonism model leads to neuroinflammation in regions involved in the pathophysiology of PD, which is reversed 20 days after the last injection. These findings reveal that withdrawal period, together with the shift of microglial phenotypes from the pro-inflammatory to the anti-inflammatory stage, may be important for the study of the mechanisms involved in reversing this condition, with potential clinical applicability.
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