Biology subjects

Young, S. L.

Publications and source records attributed to Young, S. L..

8 recordsLinked to original sources

bioRxiv2025

Integrated management of Canada thistle (Cirsium arvense) in the Great Plains and Intermountain West using a biocontrol agent (Puccinia suaveolens)

Canada thistle [Cirsium arvense (L.) Scop.] is an invasive perennial plant that threatens agricultural landscapes and natural ecosystems worldwide. The extensive regenerative root system of Canada thistle complicates control efforts, with current strategies having limited success. Puccinia suaveolens (Pers.) Rostr (syn. Puccinia punctiformis (F. Strauss) Rohl), an obligate biotrophic rust fungus, has shown potential as a biological control agent by systemically infecting the root system, reducing root mass and shoot growth, and limiting vegetative regeneration; however, its efficacy when integrated with other control methods remains unclear. We conducted experiments from 2020 to 2022 at two sites in Colorado and Utah to evaluate P. suaveolens efficacy when applied alone and in combination with mowing, tillage, and herbicide. Treatments were applied in Fall (2020 and 2021), with monitoring of thistle stem density, vegetative cover, as well as P. suaveolens incidence before and after treatments through 2022. While P. suaveolens alone contributed to a decrease in thistle density, it was less effective compared to herbicide treatments, and its impact when integrated with mowing or tillage was inconsistent. Herbicide application (alone and when combined with P. suaveolens) generated the greatest immediate reduction in thistle stem density and vegetative cover, although it resulted in the greatest amount of bare ground exposure. Grass coverage present within treated plots varied significantly between treatments, ranging from 0-75%, with the highest percentage observed in herbicide treatments compared to control and tillage in both years. Forb cover remained below 10% across treatments and years. Although P. suaveolens continues to show promise as a biological control agent, further research is needed to improve efficacy, and optimize integration with other control strategies.

ecology↗

bioRxiv2023

Scaling use of the rust fungus Puccinia punctiformis for biological control of Canada thistle (Cirsium arvense (L.) Scop.): First report on a U.S. statewide effort

Canada thistle (Cirsium arvense (L.) Scop., CT) is one of the worst weeds threatening temperate regions of the world. A host-specific rust fungus, Puccinia punctiformis (F. Strauss) Rohl., is known to cause systemic disease of CT, ultimately killing individuals and reducing stand densities. In 2013, it was demonstrated that fall inoculation of rosettes with coarsely ground leaves bearing P. punctiformis telia can successfully initiate epiphytotics. In the same year, a cooperative project between the Colorado Department of Agriculture and United States Department of Agriculture was initiated, in which CT patches across the state of Colorado (USA) were inoculated and tracked over subsequent years for changes in stem density. Here, we report our findings from 8 years (2014-2021) of monitoring effort. At most sites (N = 87), CT stem densities declined, from a mean ({+/-} SE) of 87.9 ({+/-} 6.5) stems to 44.7 ({+/-} 4.2). These declines however were spatially-autocorrelated, and likely attributable to local growing conditions, as mean annual daily maximum temperature and standard deviation of elevation, as well as climatic conditions around the times of both treatment and monitoring, were found to be important predictors of CT decline. Further, we observed that the amount of inoculum deployed, timing since last release, and method in which it was spread locally at a site were also associated with the magnitude of CT stem decline. These results are indicative of the value of P. punctiformis as a CT biological control agent. The name Cirsium arvense dieback (CADB) is proposed herein to describe the agriculturally important decline in CT stem densities attributable to this previously un-named systemic disease.

pathology↗

bioRxiv2022

The estrogen receptor α cistrome in human endometrium and epithelial organoids

ContextEndometrial health is impacted by molecular processes that underlie estrogen responses. ObjectiveTo define estrogen regulation of endometrial function by integrating the estrogen receptor alpha (ESR1) cistrome and transcriptome of endometrial biopsies taken from the proliferative and midsecretory phases of the menstrual cycle and hormonally stimulated endometrial epithelial organoids. DesignESR1 ChIPseq and RNAseq were performed on proliferative or mid-secretory endometrial biopsies and on hormone treated organoid cultures. SettingEndometrial samples were obtained from volunteers at outpatient research clinics for ChIPseq and for organoid culture. Patients or Other ParticipantsParticipants were fertile, reproductive aged women with normal cycle length, and without any history of infertility or irregular cycles. In total, 5 new endometrial biopsies obtained from 5 women were used in this study and were analyzed together with previously published cycle stage endometrial RNAseq data. Intervention(s)There were no interventions in this study. Main Outcome Measure(s)The cycle stage specific ESR1 binding sites and gene expression identification of human endometrium and organoid cultures were integrated with changes in gene expression. ResultsGenes with ESR1 binding in whole endometrium were enriched for chromatin modification and regulation of cell proliferation. The distribution of ESR1 binding sites in organoids was more distal to the gene promoter when compared to primary endometrium. Organoid estrogen/ESR1 candidate target genes impacted formation of cellular protrusions, and chromatin modification, ConclusionsAnalysis of the ESR1 cistromes and transcriptomes from endometrium and organoids provides important resources for understanding how estrogen impacts endometrial health and function.

genomics↗

bioRxiv2020

Endometrial epithelial ARID1A is critical for uterine gland function in early pregnancy establishment

Though endometriosis and infertility are clearly associated, the pathophysiological mechanism remains unclear. Previous work has linked endometrial ARID1A loss to endometriosis-related endometrial non-receptivity. Here, we show in mice that ARID1A binds and regulates transcription of the Foxa2 gene required for endometrial gland function. Uterine specific deletion of Arid1a compromises gland development and diminishes Foxa2 and Lif expression. Deletion of Arid1a with Ltf-iCre in the adult mouse endometrial epithelium preserves gland development while still compromising gland function. Mice lacking endometrial epithelial Arid1a are severely sub-fertile due to defects in implantation, decidualization, and endometrial receptivity from disruption of the LIF-STAT3-EGR1 pathway. FOXA2 is also reduced in the endometrium of women with endometriosis in correlation with diminished ARID1A, and both ARID1A and FOXA2 are reduced in non-human primates induced with endometriosis. Our findings describe a role for ARID1A in the endometrial epithelium supporting early pregnancy establishment through the maintenance of gland function.

physiology↗

bioRxiv2020

Sotagliflozin, a dual SGLT1/2 inhibitor, improves cardiac outcomes in a mouse model of early heart failure without diabetes

AimsSelective SGLT2 inhibition reduces the risk of worsening heart failure and cardiovascular death in patients with existing heart failure, irrespective of diabetic status. We aimed to investigate the effects of dual SGLT1/2 inhibition, using sotagliflozin, on cardiac outcomes in non-diabetic and diabetic mice with cardiac pressure overload. Methods and ResultsFive-week old male C57BL/6J mice were randomized to receive a high fat diet (HFD; 60% of calories from fat) to induce diabetes or remain on normal diet (ND) for 12 weeks. Transverse aortic constriction (TAC) was then employed to induce cardiac pressure-overload (50% increase in right:left carotid pressure versus sham surgery), resulting in features representative of heart failure with preserved ejection fraction. At five weeks into the dietary protocol, mice were treated for seven weeks by oral gavage once daily with sotagliflozin (10mg/kg body weight) or vehicle (0.1% tween 80). In ND non-diabetic mice, treatment with sotagliflozin attenuated cardiac hypertrophy and histological markers of cardiac fibrosis induced by TAC. These benefits were associated with profound diuresis and glucosuria, without shifts toward whole-body fatty acid utilisation nor increased cardiac ketolysis. In HFD diabetic mice, sotagliflozin did not attenuate cardiac injury induced by TAC. HFD mice had vacuolation of proximal tubular cells, associated with less profound diuresis and glucosuria, which may have compromised drug action and subsequent cardio-protection. ConclusionWe demonstrate the utility of dual SGLT1/2 inhibition in treating heart failure risk factors in the non-diabetic state. Its efficacy in high fat-induced diabetes with proximal tubular damage requires further study.

pharmacology and toxicology↗

bioRxiv2020

Identification of a Novel PP2A Regulator, WNK1, as Critical For Uterine Function

WNK1 is an atypical kinase protein ubiquitously expressed in humans and mice. A mutation in its encoding gene causes hypertension in humans which is associated with abnormal ion homeostasis. Our earlier findings demonstrated that WNK1 is critical for in vitro decidualization in human endometrial stromal cells – pointing towards an unrecognized role of WNK1 in female reproduction. Here, we employed a mouse model with conditional WNK1 ablation from the female reproductive tract to define its in vivo role in uterine biology. Loss of WNK1 altered uterine morphology, causing endometrial epithelial hyperplasia, adenomyosis and a delay in embryo implantation, ultimately resulting in compromised fertility. Combining transcriptomic, proteomic and interactomic analyses revealed a novel regulatory pathway whereby WNK1 represses AKT phosphorylation through the phosphatase PP2A in endometrial cells from both humans and mice. We show that WNK1 interacts with PPP2R1A, an isoform of the PP2A scaffold subunit. This interaction stabilizes the PP2A complex, which then dephosphorylates AKT. Therefore, loss of WNK1 reduced PP2A activity, causing AKT hypersignaling. Using FOXO1 as a readout of AKT activity, we demonstrate that there was escalated FOXO1 phosphorylation and nuclear exclusion, leading to a disruption in the regulation of genes that are crucial for embryo implantation.Competing Interest StatementThe authors have declared no competing interest.View Full Text

developmental biology↗

bioRxiv2019

Transcriptional and Progesterone Receptor Binding Profiles of the Human Endometrium Reveal Important Pathways and Regulators in the Epithelium During the Window of Implantation

ContextPoor uterine receptivity is one major factor leading to pregnancy loss and infertility. Understanding the molecular events governing successful implantation is hence critical in combating infertility.\n\nObjectiveTo define PGR-regulated molecular mechanisms and epithelial roles in receptivity.\n\nDesignRNA-seq and PGR-ChIP-seq were conducted in parallel to identify PGR-regulated pathways during the WOI in endometrium of fertile women.\n\nSettingEndometrial biopsies from the proliferative and mid-secretory phases were analyzed.\n\nPatients or Other ParticipantsParticipants were fertile, reproductive aged (18-37) women with normal cycle length; and without any history of dysmenorrhea, infertility, or irregular cycles. In total, 42 endometrial biopsies obtained from 42 women were analyzed in this study.\n\nInterventionsThere were no interventions during this study.\n\nMain Outcome MeasuresHere we measured the alterations in gene expression and PGR occupancy in the genome during the WOI, based on the hypothesis that PGR binds uterine chromatin cycle-dependently to regulate genes involved in uterine cell differentiation and function.\n\nResults653 genes were identified with regulated PGR binding and differential expression during the WOI. These were involved in regulating inflammatory response, xenobiotic metabolism, EMT, cell death, interleukin/STAT signaling, estrogen response, and MTORC1 response. Transcriptome of the epithelium identified 3,052 DEGs, of which 658 were uniquely regulated. Transcription factors IRF8 and MEF2C were found to be regulated in the epithelium during the WOI at the protein level, suggesting potentially important functions that are previously unrecognized.\n\nConclusionPGR binds the genomic regions of genes regulating critical processes in uterine receptivity and function.\n\nPrecisUsing a combination of RNA-seq and PGR ChIP-seq, novel signaling pathways and epithelial regulators were identified in the endometrium of fertile women during the window of implantation.

developmental biology↗

bioRxiv2018

A Novel Household Water Insecurity Scale: Procedures and Psychometric Analysis among Postpartum Women in Western Kenya

Our ability to measure household-level food insecurity has revealed its critical role in a range of physical, psychosocial, and health outcomes. Currently, there is no analogous, standardized instrument for quantifying household-level water insecurity, which prevents us from understanding both its prevalence and consequences. Therefore, our objectives were to develop and validate a household water insecurity scale appropriate for use in our cohort in western Kenya. We used a range of qualitative techniques to develop a preliminary set of 29 household water insecurity questions, and administered those questions at 15 and 18 months postpartum, concurrent with a suite of other survey modules. These data were complemented by data on quantity of water used and stored, and microbiological quality. Inter-item and item-total correlations were performed to reduce scale items to 20. Exploratory factor and parallel analyses were used to determine the latent factor structure; a unidimensional scale was hypothesized and tested using confirmatory factor and bifactor analyses, along with multiple statistical fit indices. Reliability was assessed using Cronbachs alpha and the coefficient of stability, which produced a coefficient alpha of 0.97 at 15 and 18 months postpartum and a coefficient of stability of 0.62. Predictive, convergent and discriminant validity of the final household water insecurity scale were supported, based on relationships with food insecurity, perceived stress, per capita household water use, and time and money spent acquiring water. The resultant scale is a valid and reliable instrument. It can be used in this setting to test a range of hypotheses about the role of household water insecurity in numerous physical and psychosocial health outcomes, to identify the households most vulnerable to water insecurity, and to evaluate the effects of water-related interventions. To extend its applicability, we encourage efforts to develop a cross-culturally valid scale using robust qualitative and quantitative techniques.

epidemiology↗