Biology subjects

Erickson, J.

Publications and source records attributed to Erickson, J..

8 recordsLinked to original sources

bioRxiv2025

Leveraging Crop Wild Relatives and Ploidy Level for Climate-Resilient Annual Ryegrass

Leveraging crop wild relatives and chromosome manipulations are powerful tools for developing climate-resilient agroecosystems. Yet, the combined effects of polyploidy and diverse genetic makeup on plant responses to climate-induced stresses remain generally underexplored, particularly in annual ryegrass (Lolium multiflorum Lam.), a major cool-season forage species. In a two-year controlled environment study, we assessed phenotypic responses of a wildtype and the cultivar Marshall at diploid (2x = 14) and tetraploid (4x = 28) levels. Plants were grown under 540 and 800 ppm [CO2] and at full and 50% evapotranspiration regimes. Anatomical and physiological differences between populations and ploidy levels were limited. Despite genetic background, total biomass production increased by 44% from 540 to 800 ppm [CO2], driven by enhanced aboveground growth. While the 2x-wildtype showed a lower leaf-to-stem ratio (a proxy for forage quality) than 2x-Marshall, this gap diminished at the tetraploid condition. These differences, and the lack thereof, highlight the importance of considering both chromosome manipulation and the genetic sourcing of crop wild relatives to expand diversity in cultivated species. Our findings reveal that wild populations can achieve comparable productivity and efficiency to improved populations under climate-change induced environments, while contributing adaptive traits valuable for resilient cropping systems. HIGHLIGHTWildtype ryegrass matched improved high-yield cultivar under stress and elevated [CO2], suggesting the need for both local adaptation potential and for new breeding targets under climate change.

plant biology↗

bioRxiv2023

Nitric Oxide modulates spontaneous Ca2+ release and ventricular arrhythmias during β adrenergic signalling through S-nitrosylation of Calcium/Calmodulin dependent kinase II

RationaleNitric oxide (NO) has been identified as a signalling molecule generated during {beta}-adrenergic receptor (AR) stimulation in the heart. Furthermore, a role for NO in triggering spontaneous Ca2+ release via S-nitrosylation of Ca2+/calmodulin kinase II delta (CaMKII{delta}) is emerging. NO donors are routinely used clinically for their cardioprotective effects in the heart, but it is unknown how NO donors modulate the pro-arrhythmic CaMKII to alter cardiac arrhythmia incidence. ObjectiveWe test the role of S-nitrosylation of CaMKII{delta} at the Cys-273 inhibitory site and Cys-290 activating site in cardiac Ca2+ handling and arrhythmogenesis before and during {beta}-AR stimulation. Methods and ResultsWe measured Ca2+-handling in isolated cardiomyocytes from C57BL/6J wild-type (WT) mice and mice lacking CaMKII{delta} expression (CaMKII{delta}-KO) or with deletion of the S-nitrosylation site on CaMKII{delta} at Cys-273 or Cys-290 (CaMKII{delta}-C273S and -C290A knock-in mice). Cardiomyocytes were exposed to NO donors, S-nitrosoglutathione (GSNO; 150 M), sodium nitroprusside (SNP; 200 M) and/or {beta}-adrenergic agonist isoproterenol (ISO; 100 nM). WT and CaMKII{delta}-KO cardiomyocytes treated with GSNO showed no change in Ca2+ transient or spark properties under baseline conditions (0.5 Hz stimulation frequency). Both WT and CaMKII{delta}-KO cardiomyocytes responded to ISO with a full inotropic and lusitropic Ca2+ transient response as well as increased Ca2+ spark frequency. However, the increase in Ca2+ spark frequency was significantly attenuated in CaMKII{delta}-KO cardiomyocytes. The protection from ISO-induced Ca2+ sparks and waves was mimicked by GSNO pre-treatment in WT cardiomyocytes, but lost in CaMKII{delta}-C273S cardiomyocytes that displayed a robust increase in Ca2+ waves. This observation is consistent with CaMKII{delta}-C273 S-nitrosylation being critical in limiting ISO-induced arrhythmogenic sarcoplasmic reticulum Ca2+ leak. When GSNO was applied after ISO this protection was not observed in WT or CaMKII{delta}-C273S but was apparent in CaMKII{delta}-C290A. In Langendorff-perfused isolated hearts, GSNO pre-treatment limited ISO-induced arrhythmias in WT but not CaMKII{delta}-C273S hearts, while GSNO exposure after ISO sustained or exacerbated arrhythmic events. ConclusionsWe conclude that prior S-nitrosylation of CaMKII{delta} at Cys-273 can limit subsequent {beta}-AR induced arrhythmias, but that S-nitrosylation at Cys-290 might worsen or sustain {beta}-AR-induced arrhythmias. This has important implications for the administration of NO donors in the clinical setting.

physiology↗

bioRxiv2023

Stromule geometry allows optimal spatial regulation of organelle interactions in the quasi-2D cytoplasm

In plant cells, plastids form elongated extensions called stromules, the regulation and purposes of which remain unclear. Here we quantitatively explore how different stromule structures serve to enhance the ability of a plastid to interact with other organelles: increasing the effective space for interaction and biomolecular exchange between organelles. Strikingly, electron microscopy and confocal imaging showed that the cytoplasm in Arabidopsis thaliana and Nicotiana benthamiana epidermal cells is extremely thin (around 100 nm in regions without organelles), meaning that inter-organelle interactions effectively take place in 2D. We combine these imaging modalities with mathematical modelling and new in planta experiments to demonstrate how different the elongation of stromules (single or multiple, linear or branching) could be employed to optimise different aspects of inter-organelle interaction capacity in this 2D space. Stromule formation and branching is shown to provide a proportionally higher benefit to interaction capacity in 2D than in 3D. Additionally we find this benefit depends on optimal plastid spacing. We hypothesize that cells can promote the formation of different stromule architectures in the quasi-2D cytoplasm to optimise their interaction interface to meet specific requirements. These results provide new insight into the mechanisms underlying the transition from low to high stromule numbers during biotic stress, the consequences for interaction with smaller organelles, how plastid access and plastid to nucleus signalling is balanced, as well as the impact of plastid density on organelle interaction.

plant biology↗

bioRxiv2021

Validation of non-invasive body-surface gastric mapping for detecting electrophysiological biomarkers by simultaneous high-resolution serosal mapping in a porcine model

Gastric disorders are increasingly prevalent, but reliable clinical tools to objectively assess gastric function are lacking. Body-surface gastric mapping (BSGM) is a non-invasive method for the detection of gastric electrophysiological biomarkers including slow wave direction, which have correlated with symptoms in patients with gastroparesis and functional dyspepsia. However, no studies have validated the relationship between gastric slow waves and body surface activation profiles. This study aimed to comprehensively evaluate the relationship between gastric slow waves and body-surface recordings. High-resolution electrode arrays were placed to simultaneously capture slow waves from the gastric serosa (32x6 electrodes at 4 mm resolution) and abdominal surface (8x8 at 20 mm inter-electrode spacing) in a porcine model. BSGM signals were extracted based on a combination of wavelet and phase information analyses. A total of 1185 individual cycles of slow waves assessed, out of which 897 (76%) were normal antegrade waves, occurring in 10/14 (71%) subjects studied. BSGM accurately detected the underlying slow wave in terms of frequency (r = 0.99, p = 0.43) as well as the direction of propagation (p = 0.41, F-measure: 0.92). In addition, the cycle-by-cycle match between BSGM and transitions of gastric slow waves in terms either or both temporal and spatial abnormalities was demonstrated. These results validate BSGM as a suitable method for non-invasively and accurately detecting gastric slow wave activation profiles from the body surface. Single sentence summarySimultaneous recordings of the stomach using serosal and body-surface electrode arrays demonstrated reliable detection of frequency and classification of propagation.

physiology↗

bioRxiv2021

An ancient polymorphic regulatory region within the BDNF gene associated with obesity modulates anxiety-like behaviour in mice and humans.

Obesity and anxiety are morbidities notable for their increased impact on society during the recent COVID-19 pandemic. Understanding the mechanisms governing susceptibility to these conditions will increase quality of life and our resilience to future pandemics. In the current study we explored the function of a highly conserved regulatory region (BE5.1) within the BDNF gene that harbours a polymorphism strongly associated with obesity (rs10767664; p=4.69x10-26). Analysis in primary cells suggested that the major T-allele of BE5.1 was an enhancer whereas the obesity associated A-allele was not. However, CRISPR/CAS9 deletion of BE5.1 from the mouse genome (BE5.1KO) produced no significant effect on the expression of BDNF transcripts in the hypothalamus, no change in weight gain after 28 days and only a marginally significant increase in food intake. Nevertheless, transcripts were significantly increased in the amygdala of female mice and elevated zero maze and marble burying tests demonstrated a significant increase in anxiety-like behaviour that could be reversed by diazepam. Consistent with these observations, human GWAS cohort analysis demonstrated a significant association between rs10767664 and anxiousness in human populations. Intriguingly, interrogation of the human GTEx eQTL database demonstrated no effect on BDNF mRNA levels associated with rs10767664 but a highly significant effect on BDNF-antisense (BDNF-AS) gene expression and splicing suggesting a possible mechanism. We discuss our findings within the context of the known function and regulation of BDNF in obesity and anxiety whilst exploring the validity of interrogating GWAS data using comparative genomics and functional analysis using CRISPR genome editing in mice.

genetics↗

bioRxiv2021

Retroviral Infection of Human Neurospheres and Use of Stem Cell EVs to Repair Cellular Damage

HIV-1 remains an incurable infection that is associated with substantial economic and epidemiologic impacts. HIV-associated neurocognitive disorders (HAND) are commonly linked with HIV-1 infection; despite the development of combination antiretroviral therapy (cART), HAND is still reported to affect at least 50% of HIV-1 infected individuals. It is believed that the over-amplification of inflammatory pathways, along with release of toxic viral proteins from infected cells, are primarily responsible for the neurological damage that is observed in HAND; however, the underlying mechanisms are not well-defined. Therefore, there is an unmet need to develop more physiologically relevant and reliable platforms for studying these pathologies. In recent years, neurospheres derived from induced pluripotent stem cells (iPSCs) have been utilized to model the effects of different neurotropic viruses. Here, we report the generation of neurospheres from iPSC-derived neural progenitor cells (NPCs) and we show that these cultures are permissive to retroviral (e.g. HIV-1, HTLV-1) replication. In addition, we also examine the potential effects of stem cell derived extracellular vesicles (EVs) on HIV-1 damaged cells as there is abundant literature supporting the reparative and regenerative properties of stem cell EVs in the context of various CNS pathologies. Consistent with the literature, our data suggests that stem cell EVs may modulate neuroprotective and anti-inflammatory properties in damaged cells. Collectively, this study demonstrates the feasibility of NPC-derived neurospheres for modeling HIV-1 infection and, subsequently, highlights the potential of stem cell EVs for rescuing cellular damage induced by HIV-1 infection.

cell biology↗

bioRxiv2019

Progressive differentiation of memory CD8 T cells in the cervicovaginal tissue

Tissue-resident memory CD8 T cells (CD8 TRM) are critical for maintaining barrier immunity. CD8 TRM have been mainly studied in the skin and gut with recent studies suggesting that the signals that control tissue-residence and phenotype are highly tissue-dependent. We examined the T cell compartment in healthy human cervicovaginal tissue (CVT) and found that most CD8 T cells were granzyme B+ and TCF-1-. To address if this phenotype is driven by CVT tissue-residence, we used a mouse model to control for environmental factors. Using localized and systemic infection models, we found that CD8 TRM in the mouse CVT gradually acquired a granzyme B+, TCF-1- phenotype as seen in human CVT. In contrast to CD8 TRM in the gut, these CD8 TRM were not stably maintained regardless of the initial infection route, which led to reductions in local immunity. Our data show that residence in the CVT is sufficient to progressively shape the size and function of its CD8 TRM compartment. SummaryThe tissue-resident memory (TRM) CD8 T cell compartment in human and mouse cervicovaginal tissue (CVT) is remarkably similar. The CVT TRM compartment is maintained autonomously and does not reach phenoypical or numerical equilibrium. The numerical decline leads to impaired viral control in a secondary challenge.

immunology↗

bioRxiv2019

Validation of a CRISPR/cas9-based technology platform for examining specific immune gene functions in an experimental murine model of IBD

Inflammatory bowel diseases (IBD) are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. Association studies have identified hundreds of genes that are linked to IBD and potentially regulate its pathology. The further dissection of the genetic network underlining IBD pathogenesis and pathophysiology is hindered by the limited capacity to investigate the role of each GWAS association through functional studies, including the generation of knockout animal models for each of the associated genes. The CRISPR/Cas9 system represents a cutting edge technology which has the potential to transform the field of IBD research by facilitating the introduction of genetic alterations in an efficient and effective manner. Using the CD40-mediated-colitis model, our results demonstrate the validity of a CRISPR/Cas9-based platform as a tool for the validation of target genes or interference strategies in experimental IBD. The utilization of this discovery strategy will allow for the timely in vivo validation of therapeutic targets as the rapidly emerge from current genetic and genomics efforts with human disease tissue. As such, the CRISPR/Cas9-based platform can significantly shorten the time span between target identification and generation of proof of principle experiments for drug discovery.

immunology↗