Staphylococcal enterotoxin-B (SEB) is one of the most potent bacterial superantigens that exerts profound toxic effects by inducing a cytokine storm. Inhaled SEB can cause acute respiratory distress syndrome (ARDS), which is often fatal and with no effective treatments.
Efficacy of Δ
-tetrahydrocannabinol (THC) was tested in a mouse model of SEB-mediated ARDS, in which lung inflammation, alterations in gut/lung microbiota and production of short-chain fatty acids (SCFAs) was measured. Gene dysregulation of lung epithelial cells was studied by transcriptome arrays. Faecal microbiota transplantation (FMT) was performed to confirm the role of microbiota in suppressing ARDS.
While SEB triggered ARDS and 100% mortality in ****, THC protected the **** from fatality. Pyrosequencing analysis revealed that THC caused significant and similar alterations in microbiota in the lungs and gut of **** exposed to SEB. https://www.selleckchem.com/products/indisulam.html THC significantly increased the abundance of beneficial bacterial species, Ruminococcus gnavus, but decreased pathogenic microbiota, Akkermansia muciniphila. FMT confirmed that THC-mediated reversal of microbial dysbiosis played crucial role in attenuation of SEB-mediated ARDS. THC treatment caused an increase in SCFA, of which propionic acid was found to inhibit the inflammatory response. Transcriptome array showed that THC up-regulated several genes like lysozyme1 and lysozyme2, β-defensin-2, claudin, zonula-1, occludin-1, Mucin2 and Muc5b while down-regulating β-defensin-1.
The study demonstrates for the first time that THC attenuates SEB-mediated ARDS and toxicity by altering the microbiota in the lungs and the gut as well as promoting antimicrobial and anti-inflammatory pathways.
The study demonstrates for the first time that THC attenuates SEB-mediated ARDS and toxicity by altering the microbiota in the lungs and the gut as well as promoting antimicrobial and anti-inflammatory pathways.
The National School Lunch and Breakfast Programs help to reduce food insecurity and improve nutrition. The Community Eligibility Provision (CEP) enables high-poverty schools to offer breakfast and lunch at no cost to all students. This study examines associations between CEP and participation among students eligible for free or reduced-price meals ("FRPM"), possibly eligible ("near-cutoff"), or ineligible ("full-price").
Using data from the 2013-2015 Healthy Communities Study, we compared school breakfast and lunch participation between 842 students in K-8 at 80 CEP schools and 1463 students at 118 schools without CEP. Cross-sectional difference-in-difference (DID) models compared meal participation among near-cutoff and full-price groups to that in the FRPM group.
Overall, FRPM students had high participation in school lunch and breakfast at both types of schools. In adjusted DID models, lunch participation among near-cutoff students was 12 points higher in CEP versus comparison schools (p < .05). Among full-price students, breakfast participation was 20 points higher and lunch participation 19 points higher in CEP than comparison schools (p < .001).
Community Eligibility Provision improves access to school breakfast and lunch in high-poverty schools, particularly for students who are near or above the cutoff for FRPM eligibility.
Community Eligibility Provision improves access to school breakfast and lunch in high-poverty schools, particularly for students who are near or above the cutoff for FRPM eligibility.
The young seedling life stage is critical for reforestation after disturbance and for species migration under climate change, yet little is known regarding their basic hydraulic function or vulnerability to drought. Here, we sought to characterize responses to desiccation including hydraulic vulnerability, xylem anatomical traits, and impacts on other stem tissues that contribute to hydraulic functioning.
Larix occidentalis, Pseudotsuga menziesii, and Pinus ponderosa (all ≤6 weeks old) were imaged using x-ray computed microtomography during desiccation to assess seedling biomechanical responses with concurrently measured hydraulic conductivity (k
) and water potential (Ψ) to assess vulnerability to xylem embolism formation and other tissue damage.
In non-stressed samples for all species, pith and cortical cells appeared circular and well hydrated, but they started to empty and deform with decreasing Ψ which resulted in cell tearing and eventual collapse. Despite the severity of this structural damage, the vascular cambium remained well hydrated even under the most severe drought. There were significant differences among species in vulnerability to xylem embolism formation, with 78% xylem embolism in L. occidentalis by Ψ of -2.1 MPa, but only 47.7% and 62.1% in P. ponderosa and P. menziesii at -4.27 and -6.73 MPa, respectively.
Larix occidentalis seedlings appeared to be more susceptible to secondary xylem embolism compared to the other two species, but all three maintained hydration of the vascular cambium under severe stress, which could facilitate hydraulic recovery by regrowth of xylem when stress is relieved.
Larix occidentalis seedlings appeared to be more susceptible to secondary xylem embolism compared to the other two species, but all three maintained hydration of the vascular cambium under severe stress, which could facilitate hydraulic recovery by regrowth of xylem when stress is relieved.Mutation of profilin 1 (PFN1) can cause amyotrophic lateral sclerosis (ALS). To assess how PFN1 mutation causes the disease, we created transgenic rats with human genomic DNA that harbors both the coding and the regulatory sequences of the human PFN1 gene. Selected transgenic lines expressed human PFN1 with or without the pathogenic mutation C71G at a moderate and a comparable level and in the similar pattern of spatial and temporal expression to rat endogenous PFN1. The artificial effects of arbitrary transgene expression commonly observed in cDNA transgenic animals were minimized in PFN1 transgenic rats. Expression of the mutant, but not the wild type, human PFN1 in rats recapitulated the cardinal features of ALS including the progressive loss of motor neurons and the subsequent denervation atrophy of skeletal muscles. Detergent-insoluble PFN1 inclusions were detected as the first pathology in otherwise asymptomatic transgenic rats expressing mutant human PFN1. The findings suggest that protein aggregation is involved in the neurodegeneration of ALS associated with PFN1 mutation.
Staphylococcal enterotoxin-B (SEB) is one of the most potent bacterial superantigens that exerts profound toxic effects by inducing a cytokine storm. Inhaled SEB can cause acute respiratory distress syndrome (ARDS), which is often fatal and with no effective treatments.
Efficacy of Δ
-tetrahydrocannabinol (THC) was tested in a mouse model of SEB-mediated ARDS, in which lung inflammation, alterations in gut/lung microbiota and production of short-chain fatty acids (SCFAs) was measured. Gene dysregulation of lung epithelial cells was studied by transcriptome arrays. Faecal microbiota transplantation (FMT) was performed to confirm the role of microbiota in suppressing ARDS.
While SEB triggered ARDS and 100% mortality in mice, THC protected the mice from fatality. Pyrosequencing analysis revealed that THC caused significant and similar alterations in microbiota in the lungs and gut of mice exposed to SEB. https://www.selleckchem.com/products/indisulam.html THC significantly increased the abundance of beneficial bacterial species, Ruminococcus gnavus, but decreased pathogenic microbiota, Akkermansia muciniphila. FMT confirmed that THC-mediated reversal of microbial dysbiosis played crucial role in attenuation of SEB-mediated ARDS. THC treatment caused an increase in SCFA, of which propionic acid was found to inhibit the inflammatory response. Transcriptome array showed that THC up-regulated several genes like lysozyme1 and lysozyme2, β-defensin-2, claudin, zonula-1, occludin-1, Mucin2 and Muc5b while down-regulating β-defensin-1.
The study demonstrates for the first time that THC attenuates SEB-mediated ARDS and toxicity by altering the microbiota in the lungs and the gut as well as promoting antimicrobial and anti-inflammatory pathways.
The study demonstrates for the first time that THC attenuates SEB-mediated ARDS and toxicity by altering the microbiota in the lungs and the gut as well as promoting antimicrobial and anti-inflammatory pathways.
The National School Lunch and Breakfast Programs help to reduce food insecurity and improve nutrition. The Community Eligibility Provision (CEP) enables high-poverty schools to offer breakfast and lunch at no cost to all students. This study examines associations between CEP and participation among students eligible for free or reduced-price meals ("FRPM"), possibly eligible ("near-cutoff"), or ineligible ("full-price").
Using data from the 2013-2015 Healthy Communities Study, we compared school breakfast and lunch participation between 842 students in K-8 at 80 CEP schools and 1463 students at 118 schools without CEP. Cross-sectional difference-in-difference (DID) models compared meal participation among near-cutoff and full-price groups to that in the FRPM group.
Overall, FRPM students had high participation in school lunch and breakfast at both types of schools. In adjusted DID models, lunch participation among near-cutoff students was 12 points higher in CEP versus comparison schools (p < .05). Among full-price students, breakfast participation was 20 points higher and lunch participation 19 points higher in CEP than comparison schools (p < .001).
Community Eligibility Provision improves access to school breakfast and lunch in high-poverty schools, particularly for students who are near or above the cutoff for FRPM eligibility.
Community Eligibility Provision improves access to school breakfast and lunch in high-poverty schools, particularly for students who are near or above the cutoff for FRPM eligibility.
The young seedling life stage is critical for reforestation after disturbance and for species migration under climate change, yet little is known regarding their basic hydraulic function or vulnerability to drought. Here, we sought to characterize responses to desiccation including hydraulic vulnerability, xylem anatomical traits, and impacts on other stem tissues that contribute to hydraulic functioning.
Larix occidentalis, Pseudotsuga menziesii, and Pinus ponderosa (all ≤6 weeks old) were imaged using x-ray computed microtomography during desiccation to assess seedling biomechanical responses with concurrently measured hydraulic conductivity (k
) and water potential (Ψ) to assess vulnerability to xylem embolism formation and other tissue damage.
In non-stressed samples for all species, pith and cortical cells appeared circular and well hydrated, but they started to empty and deform with decreasing Ψ which resulted in cell tearing and eventual collapse. Despite the severity of this structural damage, the vascular cambium remained well hydrated even under the most severe drought. There were significant differences among species in vulnerability to xylem embolism formation, with 78% xylem embolism in L. occidentalis by Ψ of -2.1 MPa, but only 47.7% and 62.1% in P. ponderosa and P. menziesii at -4.27 and -6.73 MPa, respectively.
Larix occidentalis seedlings appeared to be more susceptible to secondary xylem embolism compared to the other two species, but all three maintained hydration of the vascular cambium under severe stress, which could facilitate hydraulic recovery by regrowth of xylem when stress is relieved.
Larix occidentalis seedlings appeared to be more susceptible to secondary xylem embolism compared to the other two species, but all three maintained hydration of the vascular cambium under severe stress, which could facilitate hydraulic recovery by regrowth of xylem when stress is relieved.Mutation of profilin 1 (PFN1) can cause amyotrophic lateral sclerosis (ALS). To assess how PFN1 mutation causes the disease, we created transgenic rats with human genomic DNA that harbors both the coding and the regulatory sequences of the human PFN1 gene. Selected transgenic lines expressed human PFN1 with or without the pathogenic mutation C71G at a moderate and a comparable level and in the similar pattern of spatial and temporal expression to rat endogenous PFN1. The artificial effects of arbitrary transgene expression commonly observed in cDNA transgenic animals were minimized in PFN1 transgenic rats. Expression of the mutant, but not the wild type, human PFN1 in rats recapitulated the cardinal features of ALS including the progressive loss of motor neurons and the subsequent denervation atrophy of skeletal muscles. Detergent-insoluble PFN1 inclusions were detected as the first pathology in otherwise asymptomatic transgenic rats expressing mutant human PFN1. The findings suggest that protein aggregation is involved in the neurodegeneration of ALS associated with PFN1 mutation.
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