By the long rains of 2018, 23% of farmers were affected, with a loss among affected farmers of 36%; overall annual loss was estimated at 8.5% or 0.37 million metric tons, valued at US$109 million, concentrated in western Kenya (79%). Of the recommended control measures, only the removal of diseased plants was commonly used (by 62% of affected communities), but not the use of agronomic practices (11%) or resistant varieties (9.5%). The reasons for the reduction in MLN are not well understood; external factors such as spraying insecticide against fall armyworm and unfavorable weather likely played a role, as did using disease-free seed, but not the use of resistant varieties or appropriate management practices. Still, as the pathogen remains in the fields, it is important to keep disseminating these control methods, particularly resistant varieties.A meta-analysis of anaerobic soil disinfestation (ASD) efficacy against Fusarium oxysporum (Fo) and Fo f. sp. lycopersici (Fol) was conducted emphasizing effects of environment and organic amendment characteristics, and pot and field studies conducted on ASD amendment CN ratio and soil temperature effects on Fol inoculum survival. In a pot study, two organic amendments, dry molasses-based or wheat bran-based applied at 4 mg C/g soil, with 401, 301, 201, and 101 CN ratios, were evaluated against Fol at 15-25°C. This was followed by a pot study at temperature regimes of 15-25°C and 25-35°C, and two CN ratios (201 and 401), and a field study at 401, 301, 201, and 101 CN ratios, 301 CN ratio at lower C rate (2 mg C/g soil), and an anaerobic control. Soil temperature above 25°C, and more labile amendments, increased ASD suppression of Fo/Fol in the meta-analysis. In pot studies, Fol survival was reduced for molasses-based mixtures at 201 and 301 CN ratios, compared to wheat bran-based, but not compared to the anaerobic control. At 25-35°C, all ASD treatments suppressed Fol relative to controls. In the field, all ASD treatments reduced Fol survival compared to the anaerobic control, and 4 mg C/g soil amendment rates induced increased anaerobic conditions and higher Fol mortality compared to the 2 mg C/g soil rate. While amendment CN ratios from 10 to 401 were similarly suppressive of Fo, lower temperatures reduced ASD effectiveness against Fo/Fol and further work is warranted to enhance suppression at soil temperatures below 25°C.Tetrandrine (TET) is a potent calcium channel blocker used for the treatment of hypertension and inflammation. Currently, TET is predominantly used to treat a variety of human diseases, and there is little information regarding the use of TET against plant pathogens. In this study, we explored the antifungal activity of TET on a plant pathogen, Botrytis cinerea. We show that administration of low concentrations of TET effectively inhibited hyphal growth of fungus grown on potato dextrose agarose, and decreased the virulence of B. cinerea in tomato plants. Real-time PCR revealed that the expression of drug efflux pump related genes (alcohol dehydrogenase 1, multi-drug/pheromone exporter, pleiotropic drug resistance protein 1, and synaptic vesicle transporter) were down-regulated in the presence of TET. Finally, we show that TET acts synergistically with iprodione, resulting in increased inhibition of B. cinerea both in vitro and in vivo. These results indicate that TET might act as an effective antifungal agent in reducing grey mold disease.Cercospora leaf blight (CLB), primarily caused by Cercospora cf. flagellaris, is one of the most important diseases of soybean (Glycine max L. Merr.) in Louisiana. The pathogen produces cercosporin, a non-specific toxin and an important virulence factor. https://www.selleckchem.com/products/escin.html So far, there are no commercial cultivars with CLB resistance, and the pathogen has developed substantial resistance to the frequently used fungicides. Consequently, alternative methods are needed to manage CLB. One possibility is the RNA interference-based topical application of dsRNA. The present study addressed the two most critical steps for this novel approach to be practical inexpensively producing large quantities of dsRNA and identifying the right target genes for silencing. A screening method was developed to compare the effectiveness of Escherichia coli-produced dsRNAs targeting five fungal genes involved in cercosporin production for silencing in liquid culture. As **** as 151.6 mg of dsRNA-containing total nucleic acids (TNAs) was produced from 1 L of E. coli LB culture using the L4440 vector. All tested dsRNAs reduced cercosporin production. However, significant target gene suppression was only detected in the cultures treated with dsRNAs from Avr4 and CTB8. The most potent dsRNA was from Avr4 which reduced 50% of cercosporin production at an estimated TNA concentration of 10.4 µg/mL (EC50) and the least potent dsRNA was from HN-2 with an estimated EC50 of 46.7 µg/mL TNA. The present study paves the road for managing CLB under field conditions using dsRNA. Additionally, this approach could be adapted to identify the best dsRNAs to manage other fungal diseases.Epithelioid sarcoma (ES) is an aggressive ultra-rare soft-tissue sarcoma marked by SMARCB1/INI1 deficiency. SMARCB1/INI1 deficiency leads to elevated expression of EZH2, a component of polycomb repressive complex 2, which mediates gene silencing by catalyzing H3K27me3. Tazemetostat is an oral, SAM-competitive inhibitor of EZH2, whose blockade prevents the methylation of histone H3K27, thus decreasing the growth of EZH2 mutated or over-expressing cancer cells. Tazemetostat has been approved for the treatment of patients aged 16 years and older with metastatic or advanced ES not eligible for complete resection, based on the positive results of a single-arm Phase II basket study. Tazemetostat though represents a new treatment option for ES patients, although clinical/molecular predictors of response are still to be identified. The combination of tazemetostat with other drugs like doxorubicin and immunotherapeutic agents is currently under investigation in ES patients.
Ultrashort echo time (UTE) magnetic resonance imaging (MRI) sequences have improved imaging of short T2 musculoskeletal (MSK) tissues. UTE-MRI combined with magnetization transfer modeling (UTE-MT) has demonstrated robust assessment of MSK tissues. This study aimed to investigate the variation of UTE-MT measures under mechanical loading in tibiofemoral cartilage and meniscus of cadaveric knee joints.
Fourteen knee joints from young (
= 8, 42 ± 12 years old) and elderly (
= 6, 89 ± 4 years old) donors were scanned on a 3-T scanner under 3 loading conditions load = 300 N (Load1), load = 500 N (Load2), and load = 0 N (Unload). UTE-MT sequences were performed at each loading condition. Macromolecular proton fraction (MMF) was calculated from UTE-MT modeling. Wilcoxon rank sum test was used to examine the MRI data differences between loading conditions.
For young donors, MMF increased in all grouped regions of interest (meniscus [M], femoral articular cartilage [FAC], tibial articular cartilage [TAC], articular cartilage regions covered by meniscus [AC-**], and articular cartilage regions uncovered by meniscus [AC-UC]) when the load increased from 300 to 500 N.
By the long rains of 2018, 23% of farmers were affected, with a loss among affected farmers of 36%; overall annual loss was estimated at 8.5% or 0.37 million metric tons, valued at US$109 million, concentrated in western Kenya (79%). Of the recommended control measures, only the removal of diseased plants was commonly used (by 62% of affected communities), but not the use of agronomic practices (11%) or resistant varieties (9.5%). The reasons for the reduction in MLN are not well understood; external factors such as spraying insecticide against fall armyworm and unfavorable weather likely played a role, as did using disease-free seed, but not the use of resistant varieties or appropriate management practices. Still, as the pathogen remains in the fields, it is important to keep disseminating these control methods, particularly resistant varieties.A meta-analysis of anaerobic soil disinfestation (ASD) efficacy against Fusarium oxysporum (Fo) and Fo f. sp. lycopersici (Fol) was conducted emphasizing effects of environment and organic amendment characteristics, and pot and field studies conducted on ASD amendment CN ratio and soil temperature effects on Fol inoculum survival. In a pot study, two organic amendments, dry molasses-based or wheat bran-based applied at 4 mg C/g soil, with 401, 301, 201, and 101 CN ratios, were evaluated against Fol at 15-25°C. This was followed by a pot study at temperature regimes of 15-25°C and 25-35°C, and two CN ratios (201 and 401), and a field study at 401, 301, 201, and 101 CN ratios, 301 CN ratio at lower C rate (2 mg C/g soil), and an anaerobic control. Soil temperature above 25°C, and more labile amendments, increased ASD suppression of Fo/Fol in the meta-analysis. In pot studies, Fol survival was reduced for molasses-based mixtures at 201 and 301 CN ratios, compared to wheat bran-based, but not compared to the anaerobic control. At 25-35°C, all ASD treatments suppressed Fol relative to controls. In the field, all ASD treatments reduced Fol survival compared to the anaerobic control, and 4 mg C/g soil amendment rates induced increased anaerobic conditions and higher Fol mortality compared to the 2 mg C/g soil rate. While amendment CN ratios from 10 to 401 were similarly suppressive of Fo, lower temperatures reduced ASD effectiveness against Fo/Fol and further work is warranted to enhance suppression at soil temperatures below 25°C.Tetrandrine (TET) is a potent calcium channel blocker used for the treatment of hypertension and inflammation. Currently, TET is predominantly used to treat a variety of human diseases, and there is little information regarding the use of TET against plant pathogens. In this study, we explored the antifungal activity of TET on a plant pathogen, Botrytis cinerea. We show that administration of low concentrations of TET effectively inhibited hyphal growth of fungus grown on potato dextrose agarose, and decreased the virulence of B. cinerea in tomato plants. Real-time PCR revealed that the expression of drug efflux pump related genes (alcohol dehydrogenase 1, multi-drug/pheromone exporter, pleiotropic drug resistance protein 1, and synaptic vesicle transporter) were down-regulated in the presence of TET. Finally, we show that TET acts synergistically with iprodione, resulting in increased inhibition of B. cinerea both in vitro and in vivo. These results indicate that TET might act as an effective antifungal agent in reducing grey mold disease.Cercospora leaf blight (CLB), primarily caused by Cercospora cf. flagellaris, is one of the most important diseases of soybean (Glycine max L. Merr.) in Louisiana. The pathogen produces cercosporin, a non-specific toxin and an important virulence factor. https://www.selleckchem.com/products/escin.html So far, there are no commercial cultivars with CLB resistance, and the pathogen has developed substantial resistance to the frequently used fungicides. Consequently, alternative methods are needed to manage CLB. One possibility is the RNA interference-based topical application of dsRNA. The present study addressed the two most critical steps for this novel approach to be practical inexpensively producing large quantities of dsRNA and identifying the right target genes for silencing. A screening method was developed to compare the effectiveness of Escherichia coli-produced dsRNAs targeting five fungal genes involved in cercosporin production for silencing in liquid culture. As much as 151.6 mg of dsRNA-containing total nucleic acids (TNAs) was produced from 1 L of E. coli LB culture using the L4440 vector. All tested dsRNAs reduced cercosporin production. However, significant target gene suppression was only detected in the cultures treated with dsRNAs from Avr4 and CTB8. The most potent dsRNA was from Avr4 which reduced 50% of cercosporin production at an estimated TNA concentration of 10.4 µg/mL (EC50) and the least potent dsRNA was from HN-2 with an estimated EC50 of 46.7 µg/mL TNA. The present study paves the road for managing CLB under field conditions using dsRNA. Additionally, this approach could be adapted to identify the best dsRNAs to manage other fungal diseases.Epithelioid sarcoma (ES) is an aggressive ultra-rare soft-tissue sarcoma marked by SMARCB1/INI1 deficiency. SMARCB1/INI1 deficiency leads to elevated expression of EZH2, a component of polycomb repressive complex 2, which mediates gene silencing by catalyzing H3K27me3. Tazemetostat is an oral, SAM-competitive inhibitor of EZH2, whose blockade prevents the methylation of histone H3K27, thus decreasing the growth of EZH2 mutated or over-expressing cancer cells. Tazemetostat has been approved for the treatment of patients aged 16 years and older with metastatic or advanced ES not eligible for complete resection, based on the positive results of a single-arm Phase II basket study. Tazemetostat though represents a new treatment option for ES patients, although clinical/molecular predictors of response are still to be identified. The combination of tazemetostat with other drugs like doxorubicin and immunotherapeutic agents is currently under investigation in ES patients.
Ultrashort echo time (UTE) magnetic resonance imaging (MRI) sequences have improved imaging of short T2 musculoskeletal (MSK) tissues. UTE-MRI combined with magnetization transfer modeling (UTE-MT) has demonstrated robust assessment of MSK tissues. This study aimed to investigate the variation of UTE-MT measures under mechanical loading in tibiofemoral cartilage and meniscus of cadaveric knee joints.
Fourteen knee joints from young (
= 8, 42 ± 12 years old) and elderly (
= 6, 89 ± 4 years old) donors were scanned on a 3-T scanner under 3 loading conditions load = 300 N (Load1), load = 500 N (Load2), and load = 0 N (Unload). UTE-MT sequences were performed at each loading condition. Macromolecular proton fraction (MMF) was calculated from UTE-MT modeling. Wilcoxon rank sum test was used to examine the MRI data differences between loading conditions.
For young donors, MMF increased in all grouped regions of interest (meniscus [M], femoral articular cartilage [FAC], tibial articular cartilage [TAC], articular cartilage regions covered by meniscus [AC-MC], and articular cartilage regions uncovered by meniscus [AC-UC]) when the load increased from 300 to 500 N.
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