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Biology subjects

Bradley, C. A.

Publications and source records attributed to Bradley, C. A..

7 recordsLinked to original sources

Orthoflaviviruses use diverse binding modes to engage LDLR family receptors

Orthoflaviviruses are major human pathogens that cause substantial morbidity and mortality worldwide. The viral envelope (E) mediates entry of orthoflaviviruses into host cells by interacting with cellular receptors, including members of the low-density lipoprotein receptor (LDLR) family. Here, we determined cryo-electron microscopy (cryo-EM) structures of yellow fever virus (YFV) E bound to low-density lipoprotein receptor-related protein 4 (LRP4) and LRP8, and of tick-borne encephalitis virus (TBEV) E bound to LRP8. Structural and functional studies reveal that YFV engages two low-density lipoprotein receptor class A (LA) repeats of LRP4 and LRP8 primarily through domain III (DIII) and the DI-DIII linker of its E protein, with each LA repeat making distinct contacts. In contrast, TBEV relies on a distinct surface on domain II (DII) of its E protein to interact with LRP8. Despite these differences, both viruses require engagement of two sequential receptor LA repeats for binding. Our findings identify key determinants of receptor specificity for these two orthoflaviviruses, with implications for vaccine development and therapeutic antibody targeting.

microbiology↗

Development and validation of methods to assess red crown rot (Calonectria ilicicola) severity in soybean: standard area diagram set for roots and diagrammatic scale for canopy

Red crown rot of soybean (RCR), caused by Calonectria ilicicola, is an emerging soilborne disease whose quantification is challenging due to its complex symptom development across root and foliage levels. This study developed and evaluated a multi-scale framework to improve the assessment of RCR severity from controlled environments to field conditions using root imaging and standardized visual scales. Under controlled conditions, a standard area diagram (SAD) for root necrosis was developed and validated, and SAD-assisted evaluations significantly improved accuracy, precision, and inter-rater agreement compared with unaided assessments. In field conditions, a diagrammatic symptom scale (DSS) was developed using consensus-rated images from experts and showed high reliability, repeatability, and reproducibility across 18 raters, with strong intra- and inter-rater agreement. This study developed and evaluated complementary methods to improve the assessment of RCR severity from controlled environments to field conditions using root imaging and standardized visual scales.

plant biology↗

Tau deletion results in sex-dependent modulation of synaptic weakening in rat hippocampus

Tangles, a defining characteristic of Alzheimers disease (AD), are composed principally of hyperphosphorylated and misfolded tau species. However, dysregulation of tau precedes tangle formation by many years and is associated with cognitive decline, the best functional correlate of which is synaptic weakening and eventual synaptic loss. Although tau is present at synapses, its normal synaptic function is poorly understood - information vital to the rational development of tau-modifying therapies. Since rats have a greater cognitive repertoire than mice and display more robust signs of tau pathology in AD models, we developed a tau knockout (Mapt-/-) rat to investigate the impact of tau elimination on synaptic function. We observed that long-term depression (LTD), a form of synaptic weakening, is enhanced in the hippocampus of male, but not female, rats. This enhanced LTD was dependent on the synaptic activation of group I metabotropic glutamate receptors and involved altered synaptic actin polymerization. These studies therefore provide mechanistic insights into how tau modulates synaptic function via regulation of the actin cytoskeleton. Our findings are relevant to the understanding of the physiological roles of synaptic tau, the functional consequences of tau-lowering therapies, and the influence of sex in AD susceptibility.

neuroscience↗

PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus

Long-term potentiation (LTP) at hippocampal CA1 synapses can be expressed by an increase either in the number (N) of AMPA (-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors or in their single channel conductance ({gamma}). Here we have established how these distinct synaptic processes contribute to the expression of LTP in hippocampal slices obtained from young adult rodents. LTP induced by compressed theta burst stimulation (TBS), with a 10 s inter-episode interval, involved purely an increase in N (LTPN). In contrast, either a spaced TBS, with a 10 min inter-episode interval, or a single TBS, delivered when PKA was activated, resulted in LTP that was associated with a transient increase in {gamma} (LTP{gamma}). This {gamma} increase was due to the insertion of calcium-permeable (CP)-AMPA receptors. Activation of CaMKII was necessary and sufficient for LTPN whilst PKA was additionally required for LTP{gamma}. Thus, two mechanistically distinct forms of LTP co-exist at these synapses.

neuroscience↗

Modeling the relationship between estimated foliar fungicide use and soybean yield losses due to foliar fungal diseases in the United States

Fungicide use in the United States to manage soybean diseases has increased in recent years. The ability of fungicides to reduce disease-associated yield losses varies greatly depending on multiple factors. Nonetheless, historical data are useful to understand the broad sense and long-term trends related to fungicide use practices. In the current study, the relationship between estimated soybean yield losses due to selected foliar diseases and foliar fungicide use was investigated using annual data from 28 soybean growing states over the period of 2005 to 2015. At a national scale, a significant quadratic relationship was observed between total estimated yield losses and total fungicide use (R2 = 0.123, P < 0.0001) where yield losses initially increased, reached a plateau, and subsequently decreased with increasing fungicide use. The positive phase of the quadratic curve could be associated with insufficient amount of fungicides being used to manage targeted diseases, application of more-than-recommended prophylactic fungicides under no/low disease pressure, application of curative fungicides after economic injury level, and reduced fungicide efficacy due to a variety of factors such as unfavorable environmental conditions and resistance of targeted pathogen populations to the specific active ingredient applied. Interestingly, a significant quadratic relationship was also observed between total soybean production and total foliar fungicide use (R2= 0.36, P < 0.0001). The positive phase of the quadratic curve may suggest that factors like plant physiological changes, including increased chlorophyll content, photosynthetic rates, water use efficiency, and delayed senescence that have been widely reported to occur after application of certain foliar fungicides could have potentially contributed to enhanced yield. Therefore, the current study provides evidence of the potential usefulness of foliar fungicide applications to mitigate soybean yield losses associated with foliar diseases and their potential to positively impact soybean production/yield at national and regional scales although discrepancies to the general trends observed at national and regional scales do prevail at the local (state) level.

pathology↗

Dissecting the economic impact of soybean diseases in the United States over two decades

Soybean (Glycine max L. Merrill) is a key commodity for United States agriculture. Here we analyze the economic impacts of 23 common soybean diseases in 28 soybean-producing states in the U.S., from 1996 to 2016. From 1996 to 2016, the total estimated economic loss due to soybean diseases in the U.S. was $81.39 billion, with $68.98 billion and $12.41 billion accounting for the northern and southern U.S. losses, respectively. Across states and years, soybean cyst nematode, charcoal rot, and seedling diseases were the most economically damaging pathogens/diseases while soybean rust, bacterial blight, and southern blight were the least economically damaging. Significantly positive linear correlation of mean soybean yield loss with the mean state-wide soybean production (MT) and mean soybean yield (kg ha-1) indicated that high production zones are more vulnerable to soybean diseases-associated yield losses. Our findings provide useful insights into how research, policy, and educational efforts should be prioritized in soybean disease management.

epidemiology↗

Soil microbial communities in diverse agroecosystems exposed to glyphosate

In spite of glyphosates wide use in agriculture, questions remain about effects of the herbicide on soil microbial communities. Conflicting scientific literature reports divergent results; from no observable effect of glyphosate to the enrichment of common agricultural pathogens such as Fusarium. We conducted a comprehensive field-based study to compare treatments that did and did not receive foliar application of glyphosate spray. The study included two field sites, Maryland and Mississippi; two crops, soybean and corn; four site years, 2013 and 2014; and a variety of organic and conventional farming systems. Using amplicon sequencing, the prokaryotic (16S rRNA) and fungal (ITS) communities were described along with chemical and physical properties of the soil. Sections of corn and soy roots were plated to screen for the presence of plant pathogens. Geography, farming system, and seasonal progression were significant factors determining composition of fungal and bacterial communities. Plots treated with or without glyphosate did not differ in overall microbial community composition after controlling for these factors. No differential effect of glyphosate treatment was found in the relative abundance of organisms such as Fusarium spp. or putative growth-promoting bacteria Pseudomonas spp.

ecology↗