Ft. Collins sugar beet germplasm evaluated for rhizomania and storage rot resistance in Idaho, 2018

Rhizomania caused by Beet necrotic yellow vein virus (BNYVV) and storage losses are serious sugar beet production problems. To identify sugar beet germplasm lines with resistance to BNYVV and storage rots, 30 lines from the USDA-ARS Ft. Collins sugar beet program and four check cultivars were screened. The lines were grown in a sugar beet field infested with BNYVV during the 2018 growing season in a randomized complete block design with 6 replications. At harvest on 15 October 2018, roots were dug and evaluated for rhizomania symptoms and also placed in an indoor commercial sugar beet storage building. After 119 days in storage, samples were evaluated for the percentage of root surface area covered by fungal growth or rot. Rhizomania symptom development in the field was uniform and other disease problems were not evident in the plot area. The BNYVV susceptible check plots had 97% foliar symptoms and high root disease severity ratings. The three resistant checks had 0 to 6% foliar symptoms and low root ratings. Based on root ratings, three entries (4, 13, and 14) had resistance similar to the resistant checks. However, entry 13 (20121018HO-119) was the only entry that performed well for all variables. Entry 13 may serve as a starting point for identifying additional sources of resistance to BNYVV and storage rots

Beet curly top resistance in USDA-ARS Ft. Collins germplasm, 2018

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to identify novel sources of curly top resistance, 30 sugar beet lines produced by the USDA-ARS Ft. Collins sugar beet program were screened in a disease nursery in 2018. The lines were arranged in a randomized complete block design with six replications. A curly top epiphytotic was created by releasing six viruliferous beet leafhoppers per plant at the four- to six-leaf growth stage on 25 June. Foliar symptoms were evaluated on 10 July using a scale of 0-9 (0 = healthy and 9 = dead) in a continuous manner. Curly top symptom development was uniform and no other disease problems were evident in the plot area. The disease pressure in the test was moderately severe with good symptom development in the susceptible checks. Based on the visual rating, entry 26 performed the same as the resistant checks. This germplasm line will be reevaluated for potential release to the general public so it can be utilized to improve BCTV resistance in commercial sugar beet cultivars

Beet curly top resistance in USDA-ARS Ft. Collins germplasm, 2017

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to identify novel sources of curly top resistance, 49 sugar beet lines produced by the USDA-ARS Ft. Collins sugar beet program were screened in a disease nursery in 2017. The lines were arranged in a randomized complete block design with four replications. A curly top epiphytotic was created by releasing six viruliferous beet leafhoppers per plant at the four- to six-leaf growth stage on 14 June. Foliar symptoms were evaluated on 6 July using a scale of 0-9 (0 = healthy and 9 = dead) in a continuous manner. Curly top symptom development was uniform and no other disease problems were evident in the plot area. The disease pressure in the test was moderately severe with good symptom development in the susceptible checks. Based on the visual rating, five entries (10, 16, 21, 34, and 46) performed the same as the resistant checks. These germplasm lines will be reevaluated for potential release to the general public so they can be utilized to improve BCTV resistance in commercial sugar beet cultivars

Ft. Collins sugar beet germplasm evaluated for rhizomania and storage rot resistance in Idaho, 2017

Rhizomania caused by Beet necrotic yellow vein virus (BNYVV) and storage losses are serious sugar beet production problems. To identify sugar beet germplasm lines with resistance to BNYVV and storage rots, 42 lines from the USDA-ARS Ft. Collins sugar beet program and five check cultivars were screened. The lines were grown in a sugar beet field infested with BNYVV during the 2017 growing season in a randomized complete block design with 6 replications. At harvest on 11 October 2017, roots were dug and evaluated for rhizomania symptoms and also placed in an indoor commercial sugar beet storage building. After 132 days in storage, samples were evaluated for the percentage of root surface area covered by fungal growth or rot. Rhizomania symptom development in the field was uniform and other disease problems were not evident in the plot area. The BNYVV susceptible check plots had 97 to 100% foliar symptoms and high root disease severity ratings. The three resistant checks had 0 to 6% foliar symptoms and low root ratings. Based on root ratings, all entries except entry 20151043PF had some level of resistance since they were all better than the susceptible checks. However, 20141018 was the only entry that performed well for all variables. 20161023PF also had a good root rating, but had considerable foliar symptoms. 20151044PFHO and 20151046PFHO had no foliar symptoms and very little storage rot, so the poor root rating may be related to inherently poor root shape and not a lack of BNYVV resistance. Twenty-six of the entries had resistance to fungal rots in storage, because they were not different from 20161014HO and Check 3. Some entries may serve as a starting point for identifying additional sources of resistance to BNYVV and storage rots

Ft. Collins sugar beet germplasm evaluated for rhizomania and storage rot resistance in Idaho, 2019

Rhizomania caused by Beet necrotic yellow vein virus (BNYVV) and storage losses are serious sugar beet production problems. To identify sugar beet germplasm lines with resistance to BNYVV and storage rots, 30 lines from the USDA-ARS Ft. Collins sugar beet program and four check cultivars were screened. The lines were grown in a sugar beet field infested with BNYVV during the 2019 growing season in a randomized complete block design with 6 replications. At harvest on 15 October 2019, roots were dug and evaluated for rhizomania symptoms and then placed in an indoor commercial sugar beet storage building. After 129 days in storage, samples were evaluated for the percentage of root surface area covered by fungal growth or rot. Rhizomania symptom development was uniform and other disease problems were not evident in the plot area. We were unsuccessful in establishing plants for entry 24, so data for only 29 entries were collected. The BNYVV susceptible check plots (Check 1 and Red beet) had 100% foliar symptoms and high root disease ratings. Resistant check 3 had 0 % foliar symptoms and a low root rating which indicates that resistance based on two genes is holding up. Single gene resistance (Checks 2 and 4) had foliar ratings ranging from 14 to 24% indicating single gene resistance is not completely effective, but the root ratings were still good. Four entries (4, 8, 13, and 23) had a level of BNYVV resistance similar to resistant check 3 based on both foliar and root ratings. A number of the entries had resistance to fungal rots in storage, but only entries 4, 8, and 13 performed well for all three variables. Some entries may serve as a starting point for identifying additional sources of resistance to BNYVV and storage rots

Beet curly top resistance in USDA-ARS Ft. Collins germplasm, 2019

Curly top caused by Beet curly top virus (BCTV) is a widespread disease problem vectored by the beet leafhopper in semiarid sugar beet production areas. Host resistance is the primary defense against this problem, but resistance in commercial cultivars is only low to intermediate. In order to identify novel sources of curly top resistance, 30 sugar beet lines produced by the USDA-ARS Ft. Collins sugar beet program were screened in a disease nursery in 2019. The lines were arranged in a randomized complete block design with six replications. A curly top epiphytotic was created by releasing six viruliferous beet leafhoppers per plant at the four- to six-leaf growth stage on 3 Jul. Foliar symptoms were evaluated on 22 July using a scale of 0-9 (0 = healthy and 9 = dead) in a continuous manner. Curly top symptom development was uniform and no other disease problems were evident in the plot area. The disease pressure in the test was moderately severe with good symptom development in the susceptible checks. Based on the visual rating, entries 9 and 27 were not significantly different from the resistant checks. These germplasm lines will be reevaluated for potential release to the general public so it can be utilized to improve BCTV resistance in commercial sugar beet cultivars

Beet curly top resistance in USDA-ARS Ft. Collins germplasm, 2020

Thirty sugar beet (Beta vulgaris L.) germplasm lines produced by the USDA-ARS Ft. Collins sugar beet program and three commercial check cultivars [Early Wonder (susceptible), HM PM90 (resistant), and SV2012RR (susceptible)] were screened for resistance to Beet curly top virus (BCTV). The curly top evaluation was conducted at the USDA-ARS North Farm in Kimberly, ID which has Portneuf silt loam soil and had been in barley in 2019. The field was plowed and then fertilized (110 lb N and 120 lb P2O5/A) and roller harrowed on 27 Mar. The germplasm was planted (density of 51,840 seeds/A) on 18 May. The plots were two rows 10-ft long with 22-in. row spacing and treatments were arranged in a randomized complete block design with six replications. The field was sprinkler irrigated, cultivated, and hand weeded as necessary. Plant populations were thinned to about 23,760 plants/A on 17 Jun. Plants were inoculated at the four- to six-leaf growth stage on 23 Jun with approximately six viruliferous (containing the following BCTV strains: California/Logan and Severe) beet leafhoppers (Circulifer tenellus Baker) per plant. The beet leafhoppers were redistributed three times a day during the first two days and then twice a day for five more days by dragging a tarp through the field. The plants were sprayed with Lorsban 4E (1.5 pints/A) on 7 Jul to kill the beet leafhoppers. Plots were rated for foliar symptom development on 13 Jul using a scale of 0 to 9 (0 = healthy and 9 = dead), with the scale treated as a continuous variable (Plant Dis. 90:1539-1544). Data were rank transformed and analyzed in SAS using the general linear model procedure (Proc GLM), and Fisher’s protected least significant difference (LSD; a = 0.05) was used for mean comparisons. The non-transformed means are presented in the table. Curly top symptom development was uniform and no other disease problems were evident in the plot area. The resistant and susceptible checks performed as expected for the visual ratings. Statistically, 22 of the entries contain at least some minor resistance since their visual ratings were significantly lower than those for both susceptible checks. However, only four entries 1,7,14, and 20 were not significantly different from the resistant check. These four entries along with entries with similar levels of resistance will be retested and, if resistance is confirmed, these lines will be considered for incorporation into the USDA-ARS germplasm improvement program as a source of resistance to BCTV

Apparently synonymous substitutions in FGFR2 affect splicing and result in mild Crouzon syndrome

Background: Mutations of fibroblast growth factor receptor 2 (FGFR2) account for a higher proportion of genetic cases of craniosynostosis than any other gene, and are associated with a wide spectrum of severity of clinical problems. Many of these mutations are highly recurrent and their associated features well documented. Crouzon syndrome is typically caused by heterozygous missense mutations in the third immunoglobulin domain of FGFR2.Case presentation: Here we describe two families, each segregating a different, previously unreported FGFR2 mutation of the same nucleotide, c.1083A>G and c.1083A>T, both of which encode an apparently synonymous change at the Pro361 codon. We provide experimental evidence that these mutations affect normal FGFR2 splicing and document the clinical consequences, which include a mild Crouzon syndrome phenotype and reduced penetrance of craniosynostosis.Conclusions: These observations add to a growing list of FGFR2 mutations that affect splicing and provide important clinical information for genetic counselling of families affected by these specific mutations

[Accepted Manuscript] A call to strengthen the global strategy against schistosomiasis and soil-transmitted helminthiasis: the time is now.

In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy. In this Personal View, we highlight recent advances that, taken together, support a call to revise the global strategy and guidelines for preventive chemotherapy and complementary interventions against schistosomiasis and soil-transmitted helminthiasis. These advances include the development of guidance that is specific to goals of morbidity control and elimination of transmission. We quantify the result of forgoing this opportunity by computing the yearly disease burden, mortality, and lost economic productivity associated with maintaining the status quo. Without change, we estimate that the population of sub-Saharan Africa will probably lose 2·3 million disability-adjusted life-years and US$3·5 billion of economic productivity every year, which is comparable to recent acute epidemics, including the 2014 Ebola and 2015 Zika epidemics. We propose that the time is now to strengthen the global strategy to address the substantial disease burden of schistosomiasis and soil-transmitted helminthiasis

Characterisation of the NRF2 transcriptional network and its response to chemical insult in primary human hepatocytes: implications for prediction of drug-induced liver injury

The transcription factor NRF2, governed by its repressor KEAP1, protects cells against oxidative stress. There is interest in modelling the NRF2 response to improve the prediction of clinical toxicities such as drug-induced liver injury (DILI). However, very little is known about the makeup of the NRF2 transcriptional network and its response to chemical perturbation in primary human hepatocytes (PHH), which are often used as a translational model for investigating DILI. Here, microarray analysis identified 108 transcripts (including several putative novel NRF2-regulated genes) that were both downregulated by siRNA targeting NRF2 and upregulated by siRNA targeting KEAP1 in PHH. Applying weighted gene co-expression network analysis (WGCNA) to transcriptomic data from the Open TG-GATES toxicogenomics repository (representing PHH exposed to 158 compounds) revealed four co-expressed gene sets or 'modules' enriched for these and other NRF2-associated genes. By classifying the 158 TG-GATES compounds based on published evidence, and employing the four modules as network perturbation metrics, we found that the activation of NRF2 is a very good indicator of the intrinsic biochemical reactivity of a compound (i.e. its propensity to cause direct chemical stress), with relatively high sensitivity, specificity, accuracy and positive/negative predictive values. We also found that NRF2 activation has lower sensitivity for the prediction of clinical DILI risk, although relatively high specificity and positive predictive values indicate that false positive detection rates are likely to be low in this setting. Underpinned by our comprehensive analysis, activation of the NRF2 network is one of several mechanism-based components that can be incorporated into holistic systems toxicology models to improve mechanistic understanding and preclinical prediction of DILI in man.Medicinal Chemistr