Novel inductively coupled ear-bars (ICEs) to enhance restored fMRI signal from susceptibility compensation in rats.

Functional magnetic resonance imaging faces inherent challenges when applied to deep-brain areas in rodents, e.g. entorhinal cortex, due to the signal loss near the ear cavities induced by susceptibility artifacts and reduced sensitivity induced by the long distance from the surface array coil. Given the pivotal roles of deep brain regions in various diseases, optimized imaging techniques are needed. To mitigate susceptibility-induced signal losses, we introduced baby cream into the middle ear. To enhance the detection sensitivity of deep brain regions, we implemented inductively coupled ear-bars, resulting in approximately a 2-fold increase in sensitivity in entorhinal cortex. Notably, the inductively coupled ear-bar can be seamlessly integrated as an add-on device, without necessitating modifications to the scanner interface. To underscore the versatility of inductively coupled ear-bars, we conducted echo-planner imaging-based task functional magnetic resonance imaging in rats modeling Alzheimer's disease. As a proof of concept, we also demonstrated resting-state-functional magnetic resonance imaging connectivity maps originating from the left entorhinal cortex-a central hub for memory and navigation networks-to amygdala hippocampal area, Insular Cortex, Prelimbic Systems, Cingulate Cortex, Secondary Visual Cortex, and Motor Cortex. This work demonstrates an optimized procedure for acquiring large-scale networks emanating from a previously challenging seed region by conventional magnetic resonance imaging detectors, thereby facilitating improved observation of functional magnetic resonance imaging outcomes.

Comparative Transcriptomics of Soybean Genotypes with Partial Resistance Toward Phytophthora sojae, Conrad, and M92-220 to Moderately Susceptible Fast Neutron Mutant Soybeans and Sloan.

The breeding of disease-resistant soybeans cultivars to manage Phytophthora root and stem rot caused by the pathogen Phytophthora sojae involves combining quantitative disease resistance (QDR) and Rps gene-mediated resistance. To identify and confirm potential mechanisms of QDR toward P. sojae, we conducted a time course study comparing changes in gene expression among Conrad and M92-220 with high QDR to susceptible genotypes, Sloan, and three mutants derived from fast neutron irradiation of M92-220. Differentially expressed genes from Conrad and M92-220 indicated several shared defense-related pathways at the transcriptomic level but also defense pathways unique to each cultivar, such as stilbenoid, diarylheptanoid, and gingerol biosynthesis and monobactam biosynthesis. Gene Ontology pathway analysis showed that the susceptible fast neutron mutants lacked enrichment of three terpenoid-related pathways and two cell wall-related pathways at either one or both time points, in contrast to M92-220. The susceptible mutants also lacked enrichment of potentially important Kyoto Encyclopedia of Genes and Genomes pathways at either one or both time points, including sesquiterpenoid and triterpenoid biosynthesis; thiamine metabolism; arachidonic acid; stilbenoid, diarylheptanoid, and gingerol biosynthesis; and monobactam biosynthesis. Additionally, 31 genes that were differentially expressed in M92-220 following P. sojae infection were not expressed in the mutants. These 31 genes have annotations related to unknown proteins; valine, leucine, and isoleucine biosynthesis; and protein and lipid metabolic processes. The results of this study confirm previously proposed mechanisms of QDR, provide evidence for potential novel QDR pathways in M92-220, and further our understanding of the complex network associated with QDR mechanisms in soybean toward P. sojae.

Open Access and Reproducibility in Plant Pathology Research: Guidelines and Best Practices.

The landscape of scientific publishing is experiencing a transformative shift toward open access, a paradigm that mandates the availability of research outputs such as data, code, materials, and publications. Open access provides increased reproducibility and allows for reuse of these resources. This article provides guidance for best publishing practices of scientific research, data, and associated resources, including code, in The American Phytopathological Society journals. Key areas such as diagnostic assays, experimental design, data sharing, and code deposition are explored in detail. This guidance aligns with that observed by other leading journals. We hope the information assembled in this paper will raise awareness of best practices and enable greater appraisal of the true effects of biological phenomena in plant pathology.

Picarbutrazox Effectiveness Added to a Seed Treatment Mixture for Management of Oomycetes that Impact Soybean in Ohio.

None of the current oomycota fungicides are effective towards all species of Phytophthora, Phytopythium, Globisporangium, and Pythium that affect soybean seed and seedlings in Ohio. Picarbutrazox is a new oomyceticide with a novel mode of action towards oomycete pathogens. Our objectives were to evaluate picarbutrazox to determine (i) baseline sensitivity (EC50) to 189 isolates of 29 species, (ii) the efficacy with a base seed treatment with three cultivars with different levels of resistance in 14 field environments; and (iii) if the rhizosphere microbiome was affected by the addition of the seed treatment on a moderately susceptible cultivar. The mycelial growth of all isolates was inhibited beginning at 0.001 µg, and the EC50 ranged from 0.0013 to 0.0483 µg of active ingredient (a.i.)/ml. The effect of seed treatment was significantly different for plant population and yield in eight of 14 and six of 12 environments, respectively. The addition of picarbutrazox at 1 and 2.5 g of a.i./100 kg seed to the base seed treatment compared to the base alone was associated with higher plant populations and yield in three and one environments, respectively. There was limited impact of the seed treatment mefenoxam 7.5 g of a.i. plus picarbutrazox 1 g of a.i./100 kg seed on the oomycetes detected in the rhizosphere of soybean seedlings collected at the V1 growth stage. Picarbutrazox has efficacy towards a wider range of oomycetes that cause disease on soybean, and this will be another oomyceticide tool to combat early season damping-off in areas where environmental conditions highly favor disease development.

Giant Starship Elements Mobilize Accessory Genes in Fungal Genomes.

Accessory genes are variably present among members of a species and are a reservoir of adaptive functions. In bacteria, differences in gene distributions among individuals largely result from mobile elements that acquire and disperse accessory genes as cargo. In contrast, the impact of cargo-carrying elements on eukaryotic evolution remains largely unknown. Here, we show that variation in genome content within multiple fungal species is facilitated by Starships, a newly discovered group of massive mobile elements that are 110 kb long on average, share conserved components, and carry diverse arrays of accessory genes. We identified hundreds of Starship-like regions across every major class of filamentous Ascomycetes, including 28 distinct Starships that range from 27 to 393 kb and last shared a common ancestor ca. 400 Ma. Using new long-read assemblies of the plant pathogen Macrophomina phaseolina, we characterize four additional Starships whose activities contribute to standing variation in genome structure and content. One of these elements, Voyager, inserts into 5S rDNA and contains a candidate virulence factor whose increasing copy number has contrasting associations with pathogenic and saprophytic growth, suggesting Voyager's activity underlies an ecological trade-off. We propose that Starships are eukaryotic analogs of bacterial integrative and conjugative elements based on parallels between their conserved components and may therefore represent the first dedicated agents of active gene transfer in eukaryotes. Our results suggest that Starships have shaped the content and structure of fungal genomes for millions of years and reveal a new concerted route for evolution throughout an entire eukaryotic phylum.

Female mice are protected from impaired parenchymal arteriolar TRPV4 function and impaired cognition in hypertension.

Hypertension is a leading modifiable risk factor for cerebral small vessel disease. Our laboratory has shown that endothelium-dependent dilation in cerebral parenchymal arterioles (PAs) is dependent on transient receptor potential vanilloid 4 (TRPV4) activation, and this pathway is impaired in hypertension. This impaired dilation is associated with cognitive deficits and neuroinflammation. Epidemiological evidence suggests that women with midlife hypertension have an increased dementia risk that does not exist in age-matched men, though the mechanisms responsible for this are unclear. This study aimed to determine the sex differences in young, hypertensive mice to serve as a foundation for future determination of sex differences at midlife. We tested the hypothesis that young hypertensive female mice would be protected from the impaired TRPV4-mediated PA dilation and cognitive dysfunction observed in male mice. Angiotensin II (ANG II)-filled osmotic minipumps (800 ng/kg/min, 4 wk) were implanted in 16- to 19-wk-old male C56BL/6 mice. Age-matched female mice received either 800 ng/kg/min or 1,200 ng/kg/min ANG II. Sham-operated mice served as controls. Systolic blood pressure was elevated in ANG II-treated male mice and in 1,200 ng ANG II-treated female mice versus sex-matched shams. PA dilation in response to the TRPV4 agonist GSK1016790A (10-9-10-5 M) was impaired in hypertensive male mice, which was associated with cognitive dysfunction and neuroinflammation, reproducing our previous findings. Hypertensive female mice exhibited normal TRPV4-mediated PA dilation and were cognitively intact. Female mice also showed fewer signs of neuroinflammation than male mice. Determining the sex differences in cerebrovascular health in hypertension is critical for developing effective therapeutic strategies for women.NEW & NOTEWORTHY Vascular dementia is a significant public health concern, and the effect of biological sex on dementia development is not well understood. TRPV4 channels are essential regulators of cerebral parenchymal arteriolar function and cognition. Hypertension impairs TRPV4-mediated dilation and memory in male rodents. Data presented here suggest female sex protects against impaired TRPV4 dilation and cognitive dysfunction during hypertension. These data advance our understanding of the influence of biological sex on cerebrovascular health in hypertension.

Interactions Among Heterodera glycines, Macrophomina phaseolina, and Soybean Genotype.

Heterodera glycines, the soybean cyst nematode (SCN), and fungal pathogen Macrophomina phaseolina are economically important soybean pathogens that may coinfest fields. Resistance remains the most effective management tactic for SCN, and the rhg1-b resistance allele derived from plant introduction 88788 is most commonly deployed in the northern United States. The concomitant effects of SCN and M. phaseolina on soybean performance, as well as the effect of the rhg1-b allele in two different genetic backgrounds, were evaluated in three environments (during 2013 to 2015) and a greenhouse bioassay. Within two soybean populations, half of the lines had the rhg1-b allele, and the other half had the susceptible allele in the backgrounds of the cultivars IA3023 and LD00-3309. Significant interactions between soybean rhg1-b allele and M. phaseolina-infested plots were observed in 2014. In all experiments, initial SCN populations (Pi) and M. phaseolina in roots were associated with reduced soybean yield. SCN reproduction factor (RF = final population/Pi) was affected by SCN Pi, rhg1-b, and genetic background. A background-by-genotype interaction on yield was observed only in 2015, with a stronger rhg1-b effect in the LD00-3309 background, which suggested that the susceptible parent 'IA3023' is tolerant to SCN. SCN female index from greenhouse experiments was compared with field RF, and Lin's concordance and Pearson's correlation coefficients decreased with increasing field SCN Pi in soil. In this study, both SCN and M. phaseolina reduced soybean yield asymptomatically, and the impact of SCN rhg1-b resistance was dependent on SCN virulence but also population density.

Chronic cerebral hypoperfusion in male rats results in sustained HPA activation and hyperinsulinemia.

Vascular contributions to cognitive impairment and dementia (VCID) is a spectrum of cognitive deficits caused by cerebrovascular disease, for which insulin resistance is a major risk factor. A major cause of VCID is chronic cerebral hypoperfusion (CCH). Under stress, sustained hypothalamic-pituitary-adrenal axis (HPA) activation can result in insulin resistance. Little is known about the effects of CCH on the HPA axis. We hypothesized that CCH causes sustained HPA activation and insulin resistance. Male rats were subjected to bilateral carotid artery stenosis (BCAS) for 12 wk to induce CCH and VCID. BCAS reduced cerebral blood flow and caused memory impairment. Plasma adrenocorticotropic hormone was increased in the BCAS rats (117.2 ± 9.6 vs. 88.29 ± 9.1 pg/mL, BCAS vs. sham, P = 0.0236), as was corticosterone (220 ± 21 vs. 146 ± 18 ng/g feces, BCAS vs. sham, P = 0.0083). BCAS rats were hypoglycemic (68.1 ± 6.1 vs. 76.5 ± 5.9 mg/dL, BCAS vs. sham, P = 0.0072), with increased fasting insulin (481.6 ± 242.6 vs. 97.94 ± 40.02 pmol/L, BCAS vs. sham, P = 0.0003) indicating that BCAS rats were insulin resistant [homeostasis model assessment of ß-cell function-insulin resistance (HOMA-IR): 11.71 ± 6.47 vs. 2.62 ± 0.93; BCAS vs. control, P = 0.0008]. Glucose tolerance tests revealed that BCAS rats had lower blood glucose areas under the curve (AUCs) than controls (250 ± 12 vs. 326 ± 20 mg/dL/h, BCAS vs. sham, P = 0.0075). These studies indicate that CCH causes sustained activation of the HPA and results in insulin resistance, a condition that is expected to worsen VCID.NEW & NOTEWORTHY Cerebrovascular disease and insulin resistance are two major risk factors for the development of dementia. Here, we demonstrate that chronic cerebral hypoperfusion results in glucocorticoid excess and hyperinsulinemia. This study indicates that chronic cerebral hypoperfusion, glucocorticoid excess, and insulin resistance participate in a detrimental cycle that could exacerbate cerebral vascular disease and dementia.

Pathotype Complexity and Genetic Characterization of Phytophthora sojae Populations in Illinois, Indiana, Kentucky, and Ohio.

Phytophthora sojae, the causal agent of Phytophthora root and stem rot of soybean, has been managed with single Rps genes since the 1960s but has subsequently adapted to many of these resistance genes, rendering them ineffective. The objective of this study was to examine the pathotype and genetic diversity of P. sojae from soil samples across Illinois, Indiana, Kentucky, and Ohio by assessing which Rps genes were still effective and identifying possible population clusters. There were 218 pathotypes identified from 473 P. sojae isolates with an average of 6.7 out of 15 differential soybean lines exhibiting a susceptible response for each isolate. Genetic characterization of 103 P. sojae isolates from across Illinois, Indiana, Kentucky, and Ohio with 19 simple sequence repeat markers identified 92 multilocus genotypes. There was a moderate level of population differentiation between these four states, with pairwise FST values ranging from 0.026 to 0.246. There were also moderate to high levels of differentiation between fields, with pairwise FST values ranging from 0.071 to 0.537. Additionally, cluster analysis detected the presence of P. sojae population structure across neighboring states. The level of pathotype and genetic diversity, in addition to the identification of population clusters, supports the hypothesis of occasional outcrossing events that allow an increase in diversity and the potential to select for a loss in avirulence to specific resistance genes within regions. The trend of suspected gene flow among neighboring fields is expected to be an ongoing issue with current agricultural practices.

Oxathiapiprolin Alone or Mixed with Metalaxyl Seed Treatment for Management of Soybean Seedling Diseases Caused by Species of Phytophthora, Phytopythium, and Pythium.

Species of Phytophthora, Phytopythium, and Pythium affect soybean seed and seedlings each year, primarily through reduced plant populations and yield. Oxathiapiprolin is effective at managing several foliar diseases caused by some oomycetes. The objectives of these studies were to evaluate oxathiapiprolin in a discriminatory dose assay in vitro; evaluate oxathiapiprolin as a soybean seed treatment on a moderately susceptible cultivar in 10 environments; compare the impact of seed treatment on plant populations and yields in environments with low and high precipitation; and compare a seed treatment mixture on cultivars with different levels of resistance in four environments. There was no reduction in growth in vitro among 13 species of Pythium at 0.1 µg ml-1. Soybean seed treated with the base fungicide plus oxathiapiprolin (12 and 24 µg a.i. seed-1) alone, oxathiapiprolin (12 µg a.i. seed-1) plus mefenoxam (6 µg a.i. seed-1), or oxathiapiprolin (24 µg a.i. seed-1) plus ethaboxam (12.1 µg a.i. seed-1) had greater yields in environments that received ≥50 mm of precipitation within 14 days after planting compared with those that received less. Early plant population and yield were significantly higher for seed treated with oxathiapiprolin (24 µg a.i. seed-1) + metalaxyl (13.2 µg a.i. seed-1) compared with nontreated for six of seven cultivars in at least one of four environments. Oxathiapiprolin combined with another Oomycota fungicide applied to seed has the potential to be used to protect soybean plant establishment and yield in regions prone to poor drainage after high levels of precipitation.

Soluble epoxide hydrolase inhibition improves cognitive function and parenchymal artery dilation in a hypertensive model of chronic cerebral hypoperfusion.

OBJECTIVE: Parenchymal arterioles (PAs) regulate perfusion of the cerebral microcirculation, and impaired PA endothelium-dependent dilation occurs in dementia models mimicking chronic cerebral hypoperfusion (CCH). Epoxyeicosatrienoic acids (EETs) are vasodilators; their actions are potentiated by soluble epoxide hydrolase (sEH) inhibition. We hypothesized that chronic sEH inhibition with trifluoromethoxyphenyl-3 (1-propionylpiperidin-4-yl) urea (TPPU) would prevent cognitive dysfunction and improve PA dilation in a hypertensive CCH model. METHODS: Bilateral carotid artery stenosis (BCAS) was used to induce CCH in twenty-week-old male stroke-prone spontaneously hypertensive rats (SHSRP) that were treated with vehicle or TPPU for 8 weeks. Cognitive function was assessed by novel object recognition. PA dilation and structure were assessed by pressure myography, and mRNA expression in brain tissue was assessed by qRT-PCR. RESULTS: TPPU did not enhance resting cerebral perfusion, but prevented CCH-induced memory deficits. TPPU improved PA endothelium-dependent dilation but reduced the sensitivity of PAs to a nitric oxide donor. TPPU treatment had no effect on PA structure or biomechanical properties. TPPU treatment increased brain mRNA expression of brain derived neurotrophic factor, doublecortin, tumor necrosis factor-alpha, sEH, and superoxide dismutase 3, CONCLUSIONS: These data suggest that sEH inhibitors may be viable treatments for cognitive impairments associated with hypertension and CCH.

Testing methods and statistical models of genomic prediction for quantitative disease resistance to Phytophthora sojae in soybean [Glycine max (L.) Merr] germplasm collections.

KEY MESSAGE: Genomic prediction of quantitative resistance toward Phytophthora sojae indicated that genomic selection may increase breeding efficiency. Statistical model and marker set had minimal effect on genomic prediction with > 1000 markers. Quantitative disease resistance (QDR) toward Phytophthora sojae in soybean is a complex trait controlled by many small-effect loci throughout the genome. Along with the technical and rate-limiting challenges of phenotyping resistance to a root pathogen, the trait complexity can limit breeding efficiency. However, the application of genomic prediction to traits with complex genetic architecture, such as QDR toward P. sojae, is likely to improve breeding efficiency. We provide a novel example of genomic prediction by measuring QDR to P. sojae in two diverse panels of more than 450 plant introductions (PIs) that had previously been genotyped with the SoySNP50K chip. This research was completed in a collection of diverse germplasm and contributes to both an initial assessment of genomic prediction performance and characterization of the soybean germplasm collection. We tested six statistical models used for genomic prediction including Bayesian Ridge Regression; Bayesian LASSO; Bayes A, B, C; and reproducing kernel Hilbert spaces. We also tested how the number and distribution of SNPs included in genomic prediction altered predictive ability by varying the number of markers from less than 50 to more than 34,000 SNPs, including SNPs based on sequential sampling, random sampling, or selections from association analyses. Predictive ability was relatively independent of statistical model and marker distribution, with a diminishing return when more than 1000 SNPs were included in genomic prediction. This work estimated relative efficiency per breeding cycle between 0.57 and 0.83, which may improve the genetic gain for P. sojae QDR in soybean breeding programs.

Auxin Profiling and GmPIN Expression in Phytophthora sojae-Soybean Root Interactions.

Auxin (indole-3-acetic acid, IAA) has been implicated as a susceptibility factor in both beneficial and pathogenic molecular plant-microbe interactions. Previous studies have identified a large number of auxin-related genes underlying quantitative disease resistance loci (QDRLs) for Phytophthora sojae. Thus, we hypothesized that auxin may be involved the P. sojae-soybean interaction. The levels of IAA and related metabolites were measured in mycelia and media supernatant as well as in mock and inoculated soybean roots in a time course assay. The expression of 11 soybean Pin-formed (GmPIN) auxin efflux transporter genes was also examined. Tryptophan, an auxin precursor, was detected in the P. sojae mycelia and media supernatant. During colonization of roots, levels of IAA and related metabolites were significantly higher in both moderately resistant Conrad and moderately susceptible Sloan inoculated roots compared with mock controls at 48 h postinoculation (hpi) in one experiment and at 72 hpi in a second, with Sloan accumulating higher levels of the auxin catabolite IAA-Ala than Conrad. Additionally, one GmPIN at 24 hpi, one at 48 hpi, and three at 72 hpi had higher expression in inoculated compared with the mock control roots in Conrad. The ability of resistant cultivars to cope with auxin accumulation may play an important role in quantitative disease resistance. Levels of jasmonic acid (JA), another plant hormone associated with defense responses, were also higher in inoculated roots at these same time points, suggesting that JA also plays a role during the later stages of infection.

Regulation of ion channels in the microcirculation by mineralocorticoid receptor activation.

The mineralocorticoid receptor (MR) has classically been studied in the renal epithelium for its role in regulating sodium and water balance and, subsequently, blood pressure. However, the MR also plays a critical role in the microvasculature by regulating ion channel expression and function. Activation of the MR by its endogenous agonist aldosterone results in translocation of the MR into the nucleus, where it can act as a transcription factor. Although most of the actions of the aldosterone can be attributed to its genomic activity though MR activation, it can also act by nongenomic mechanisms. Activation of this ubiquitous receptor increases the expression of epithelial sodium channels (ENaC) in both the endothelium and smooth muscle cells of peripheral and cerebral vessels. MR activation also regulates activity of calcium channels, calcium-activated potassium channels, and various transient receptor potential (TRP) channels. Modification of these ion channels results in a myriad of negative consequences, including impaired endothelium-dependent vasodilation, alterations in generation of myogenic tone, and increased inflammation and oxidative stress. Taken together, these studies demonstrate the importance of studying the impact of the MR on ion channel function in the vasculature. While research in this area has made advances in recent years, there are still many large gaps in knowledge that need to be filled. Crucial future directions of study include defining the molecular mechanisms involved in this interaction, as well as elucidating the potential sex differences that may exist, as these areas of understanding are currently lacking.

The Efficacy of Ethaboxam as a Soybean Seed Treatment Toward Phytophthora, Phytopythium, and Pythium in Ohio.

Phytophthora, Phytopythium, and Pythium species that cause early-season seed decay and pre-emergence and post-emergence damping off of soybean are most commonly managed with seed treatments. The phenylamide fungicides metalaxyl and mefenoxam, and ethaboxam are effective toward some but not all species. The primary objective of this study was to evaluate the efficacy of ethaboxam in fungicide mixtures and compare those with other fungicides as seed treatments to protect soybean against Pythium, Phytopythium, and Phytophthora species in both high-disease field environments and laboratory seed plate assays. The second objective was to evaluate these seed treatment mixtures on cultivars that have varying levels and combinations of resistance to these soilborne pathogens. Five of eight environments received adequate precipitation in the 14 days after planting for high levels of seedling disease development and treatment evaluations. Three environments had significantly greater stands, and three had significantly greater yield when ethaboxam was used in the seed treatment mixture compared with treatments containing metalaxyl or mefenoxam alone. Three fungicide formulations significantly reduced disease severity compared with nontreated in the seed plate assay for 17 species. However, the combination of ethaboxam plus metalaxyl in a mixture was more effective than either fungicide alone against some Pythium and Phytopythium species. Overall, our results indicate that the addition of ethaboxam to a fungicide seed treatment is effective in reducing seed rot caused by these pathogens commonly isolated from soybean in Ohio but that these effects can be masked when cultivars with resistance are planted.

Resistance of the SoyNAM Parents to Seed and Root Rot Caused by Four Pythium Species.

Some Pythium spp. cause damping off and root rot in soybeans and other crop species. One of the most effective management tools to reduce disease is host resistance; however, little is known about resistance in soybean to Pythium spp. The soybean nested associated mapping (SoyNAM) parent lines are a set of germplasms that were crossed to a single hub parent to create recombinant inbred line populations for the purpose of mapping agronomic traits. The SoyNAM parents were screened for resistance to Pythium lutarium, Pythium oopapillum, Pythium sylvaticum, and Pythium torulosum in separate assays to evaluate seed and root rot severity. Of the 40 SoyNAM parents, only 'Maverick' was resistant to the four species tested; however, 13 were resistant to three species. Other lines were resistant to two, one, or none of the species tested. Correlations between seed and root rot severity for the lines assessed were weak or insignificant. Results indicate that mechanisms of resistance to seed and root rot caused by Pythium spp. may not necessarily be the same.

Rs10230207 genotype confers changes in HDAC9 and TWIST1, but not FERD3L in lymphoblasts from patients with intracranial aneurysm.

Intracranial aneurysms (IA) are weakened outpouchings of the arterial wall in the cerebrovasculature. Rupture of an IA often leads to devastating consequences. The early identification of IA patients is crucial for management of their condition. A genetic variant at rs10230207, located nearby the HDAC9, TWIST1, and FERD3L genes, is associated with IA. HDAC9 is a class IIa histone deacetylase that mediates vascular smooth muscle cell dysfunction. TWIST1 is a mechanosensitive transcription factor and its expression is reduced in unstable carotid atherosclerotic plaques. In this study, the expression of the HDAC9, TWIST1, and FERD3L genes was characterized and associated with the presence of the rs10230207 genetic variant. Allelic discrimination and gene expression analysis were performed using lymphoblasts from 85 population controls and 109 IA patients. Subjects that were heterozygous (GT) within rs10230207 were 4.32 times more likely to have an IA than those that were homozygous for the reference allele (GG; 95%CI 1.23 to 14.16). Subjects that were homozygous (TT) were 8.27 times more likely to have an IA than those that were GG (95%CI 2.45 to 27.85). While the presence of the risk allele was not associated with changes in FERD3L gene expression, the risk allele was associated with increased HDAC9 and decrease in TWIST1 mRNA expression. The significant inverse correlation between HDAC9 and TWIST1 gene expression suggests that changes in the expression of both of genes may contribute to the formation of IAs.

Transient receptor potential vanilloid 4 channels are important regulators of parenchymal arteriole dilation and cognitive function.

OBJECTIVE: Hypertension-associated PA dysfunction reduces cerebral perfusion and impairs cognition. This is associated with impaired TRPV4-mediated PA dilation; therefore, we tested the hypothesis that TRPV4 channels are important regulators of cerebral perfusion, PA structure and dilation, and cognition. METHODS: Ten- to twelve-month-old male TRPV4 knockout (WKY-Trpv4em4Mcwi ) and age-matched control WKY rats were studied. Cerebral perfusion was measured by MRI with arterial spin labeling. PA structure and function were assessed using pressure myography and cognitive function using the novel object recognition test. RESULTS: Cerebral perfusion was reduced in the WKY-Trpv4em4Mcwi rats. This was not a result of PA remodeling because TRPV4 deletion did not change PA structure. TRPV4 deletion did not change PA myogenic tone development, but PAs from the WKY-Trpv4em4Mcwi rats had severely blunted endothelium-dependent dilation. The WKY-Trpv4em4Mcwi rats had impaired cognitive function and exhibited depressive-like behavior. The WKY-Trpv4em4Mcwi rats also had increased microglia activation, and increased mRNA expression of GFAP and tumor necrosis factor alpha suggesting increased inflammation. CONCLUSION: Our data indicate that TRPV4 channels play a critical role in cerebral perfusion, PA dilation, cognition, and inflammation. Impaired TRPV4 function in diseases such as hypertension may increase the risk of the development of vascular dementia.

Molecular characterization of genomic regions for resistance to Pythium ultimum var. ultimum in the soybean cultivar Magellan.

KEY MESSAGE: Two novel QTL for resistance to Pythium ultimum var. ultimum were identified in soybean using an Illumina SNP Chip and whole genome re-sequencing. Pythium ultimum var. ultimum is one of numerous Pythium spp. that causes severe pre- and post-emergence damping-off of seedlings and root rot of soybean [Glycine max (L.) Merr.]. The objective of this research was to identify quantitative trait loci (QTL) for resistance to P. ultimum var. ultimum in a recombinant inbred line population derived from a cross of 'Magellan' (moderately resistant) and PI 438489B (susceptible). Two different mapping approaches were utilized: the universal soybean linkage panel (USLP 1.0) and the bin map constructed from whole genome re-sequencing (WGRS) technology. Two genomic regions associated with variation in three disease-related parameters were detected using both approaches, with the bin map providing higher resolution. Using WGRS, the first QTL were mapped within a 350-kbp region on Chr. 6 and explained 7.5-13.5% of the phenotypic variance. The second QTL were positioned in a 260-kbp confidence interval on Chr. 8 and explained 6.3-16.8% of the phenotypic variation. Candidate genes potentially associated with disease resistance were proposed. High-resolution genetic linkage maps with a number of significant SNP markers could benefit marker-assisted breeding and dissection of the molecular mechanisms underlying soybean resistance to Pythium damping-off in 'Magellan.' Additionally, the outputs of this study may encourage more screening of diverse soybean germplasm and utilization of genome-wide association studies to understand the genetic basis of quantitative disease resistance.

Genetic Structure of Rhizoctonia solani AG-2-2IIIB from Soybean in Illinois, Ohio, and Ontario.

Rhizoctonia solani AG-2-2IIIB is an important seedling pathogen of soybean in North America and other soybean-growing regions around the world. There is no information regarding the population genetics of field populations of R. solani associated with soybean seedling disease. More specifically, information regarding genetic diversity, the mode of reproduction, and the evolutionary factors that shape different R. solani populations separated in time and space are lacking. We exploited genotyping by sequencing as a tool to assess the genetic structure of R. solani AG-2-2IIIB populations from Illinois, Ohio, and Ontario and investigate the reproductive mode of this subgroup. Our results revealed differences in genotypic diversity among three populations, with the Ontario population having greatest diversity. An overrepresentation of multilocus genotypes (MLGs) and a rejection of the null hypothesis of random mating in all three populations suggested clonality within each population. However, phylogenetic analysis revealed long terminal multifurcating branches for most members of the Ontario population, suggesting a mixed reproductive mode for this population. Analysis of molecular variance revealed low levels of population differentiation, and sharing of similar MLGs among populations highlights the role of genotype flow as an evolutionary force shaping population structure of this subgroup.