Biology subjects

Eskiw, C. H.

Publications and source records attributed to Eskiw, C. H..

7 recordsLinked to original sources

bioRxiv2026

A Locally Produced Bioinoculant (H-Start) Increases Field Pea (Pisum sativum) Yield Using Reduced Fertilizer: A Pilot Study with Implications for Low-Input Agriculture

Modern agriculture is an intensive process that disrupts the natural soil microbiome through the use of toxic chemicals such as fungicides. This reduces the soil's ability to support robust biomass production, lowering yields. Complex bioinoculants are heterogeneous mixtures of organisms from natural sources, such as compost, that can be added to soil to restore the natural soil microbiome. H-Start is one such bioinoculant (HumaTerra Regen Ag Inc.). Due to the lack of literature on complex bioinoculants, we aim to present a pilot study to identify potential effects of interest (alpha = 0.10) to inform future experimental designs. To achieve this, field pea (Pisum sativum cv. AAC Carver) was grown in Saskatchewan field soil in a growth chamber, with or without H-Start, at 75% or 100% of the recommended monoammonium phosphate (MAP) rate (n = 3 pots per treatment). By monitoring leaf size, leaf count, height, yield, and soil characteristics, we found that plants treated with H-Start were taller between days 21 and 28 (p = 0.089) and had a greater leaf size index (number of leaves x primary vein length2) over time (p = 0.002). H-Start at 75% MAP also produced the highest yield (p = 0.077). These results suggest H-Start influences the soil microbiome and the plants that depend on it. This is important because complex bioinoculants can be produced locally. Thus, bioinoculants may become increasingly relevant in low-income areas, which often lack the economic ability to sustain food imports and are the first to be affected by disruptions to the agri-chemical supply chain.

microbiology↗

bioRxiv2026

The Anaphase Promoting Complex targets the toxic protein Progerin for ubiquitin-dependent degradation via autophagy

The premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) results from the accumulation of progerin, a cytotoxic protein generated from a point mutation in the Lamin A/C gene, in the nuclear lamina. Upon the proper stimulation, cells degrade progerin, reversing cellular HGPS phenotypes; however, there is still a gap in our knowledge concerning which pathways are mediating progerin degradation. Previous data has demonstrated that the Anaphase Promoting Complex (APC), a multi-subunit ubiquitin ligase, tagets proteins for degradation, and that a decrease in APC function is linked with cellular aging. To determine if the APC is linked to HGPS disease phenotypes, we performed a meta-analysis of RNA-seq data from skin samples isolated from HGPS patients and identified dysregulation of several genes encoding subunits and substrates of the APC. Stimulation of APC activity decreased progerin protein levels and significantly decreased the number of cells with nuclear blebs. Proximity ligation assays (PLA) demonstrated that APC structure is compromised in HGPS cells and that APC stimulation increases proximity of the APC with progerin. Coimmunoprecipitation revealed that the APC co-activator, CDC20, physically interacted with nuclear lamina proteins. We further demonstrate that APC-mediated progerin degradation occurs through autophagy. Inhibition of the 26S proteasome enhanced progerin degradation, providing additional support for APC mediated-progerin degradation occurring independent of the proteasome. As such, we propose a previously unidentified interaction and mechanism by which cells remove progerin. This finding has impact on potential therapeutic strategies for HGPS, as well as providing further insight into linking the APC with both normal and premature aging.

cell biology↗

bioRxiv2025

Epigenetic Control of TERRA by FTSJ3 is Critical for Telomerase-Driven Cancers

Telomerase reverse transcriptase (hTERT) overexpression, a hallmark of most cancers, drives tumorigenesis by enabling limitless replicative potential. Direct targeting of hTERT is challenging, necessitating alternative strategies. Through genome-wide synthetic dosage lethality (SDL) screening in cancer models, including patient-derived organoids, we identify FTSJ3, an RNA 2-O-methyltransferase, as a critical vulnerability in hTERT-overexpressing cells. FTSJ3 methylates telomeric repeat-containing RNA (TERRA), a modification essential for recruiting SUV39H1 to telomeric ends to mediate H3K9 trimethylation and establish stable heterochromatin. Loss of FTSJ3 disrupts this cascade, impairing H3K9 trimethylation, HP1-alpha recruitment, and telomeric heterochromatin maintenance. Notably, this reveals an unexpected dependency on TERRA methylation for telomeric heterochromatin stability in hTERT-driven cancers. Non-malignant cells, lacking telomerase activity and de novo telomere repeat synthesis, are unaffected by FTSJ3 suppression. Our findings establish the FTSJ3/TERRA/SUV39H1 axis as a critical mechanism supporting telomeric heterochromatin stability in hTERT-driven cancers. This telomere-directed epigenetic strategy provides a robust framework for translational therapeutic innovation.

cancer biology↗

bioRxiv2021

Phenolic profiles and antioxidant activities of Saskatchewan (Canada) bred haskap (Lonicera caerulea) berries

Phenolic extracts from five Saskatoon, Saskatchewan, bred and grown haskap berry varieties (Aurora, Blizzard, Honey Bee, Indigo Gem, and Tundra) were characterized via liquid chromatography with photodiode array detection (HPLC-PDA) and mass spectrometry (HPLC-MS/MS). Tundra had the highest phenolic content (727.0 mg/100 g FW) while Indigo Gem had the highest anthocyanin content (447.8 mg/100 g FW). HPLC-MS/MS identified two previously unreported anthocyanins (Tundra variety): delphinidin-sambubioside and a peonidin-pentoside. Fruit extracts were fractionated to produce an anthocyanin rich (40% ethanol) and flavanol/flavonol rich (100% ethanol) fraction. This process affords the ability to isolate/concentrate specific subclasses for nutraceutical applications. High in vitro radical scavenging was observed for all haskap phenolic extracts. An extract from the Tundra variety delayed borage oil oxidation more effectively than commercial antioxidants (BHT and Rosamox). These results show the high phenolic content of these haskaps along with their capacity for radical scavenging/delaying lipid oxidation, indicating potential commercial value.

plant biology↗

bioRxiv2020

Anaphase Promoting Complex activity mediates clinical responsiveness to recurrent caninelymphoma

Like humans, canines spontaneously develop lymphomas that are treated by chemotherapy cocktails and frequently develop multiple drug resistance (MDR). Their shortened clinical timelines and tumor accessibility make them excellent models to study MDR mechanisms. We previously demonstrated that adjunct treatment of in vitro MDR cell lines with insulin-sensitizers effectively restored MDR chemosensitivity and prevented MDR development. This study extends the use of an insulin-sensitizer to clinical and tumor responses in vivo in volunteer canines with MDR lymphoma, including assessing changes in MDR protein biomarkers and global gene expression. Longitudinal tumor sampling and analysis of MDR cases throughout treatment allowed a correlation between in vivo molecular mechanisms and clinical responsiveness. We found reduced MDR biomarkers within all tumors, yet only one canine entered clinical remission. Analysis of tumor samples during remission and relapse allowed comparison of gene expression profiles. This revealed the Anaphase Promoting Complex (APC), a ubiquitin-E3 ligase regulating cell cycle progression, was impaired during chemoresistance/MDR and restored during remission. Validating in vitro tests restored MDR chemosensitivity upon APC activation, supporting the idea that APC activity is an important underlying cellular mechanism associated with treatment resistance, and a novel potential therapeutic target.

cancer biology↗

bioRxiv2018

Rapid nuclear exclusion of Hcm1 in aging Saccharomyces cerevisiae leads to vacuolar alkalization and replicative senescence

Yeast cells, like other higher eukaryotic cells, undergo a finite number of cell divisions before exiting the cell cycle due to the effects of aging. Here, we show that yeast aging begins with the nuclear exclusion of Hcm1 in young cells, resulting in loss of acidic vacuoles. Autophagy is required for healthy aging in yeast, with proteins targeted for turnover by autophagy directed to the vacuole. Consistent with this, vacuolar acidity is necessary for vacuolar function and yeast longevity. Using yeast genetics and immunofluorescence microscopy, we confirm that vacuolar acidity plays a critical role in cell health and lifespan, and is potentially maintained by a series of Forkhead Box (Fox) transcription factors. An interconnected transcriptional network involving the Fox proteins (Fkh1, Fkh2 and Hcm1) are required for transcription of v-ATPase subunits and vacuolar acidity. As cells age, Hcm1 is rapidly excluded from the nucleus in young cells, blocking the expression of Hcm1 targets (Fkh1 and Fkh2), leading to loss of v-ATPase gene expression, reduced vacuolar acidification, increased -syn-GFP vacuolar accumulation, and finally, diminished replicative lifespan (RLS). Loss of vacuolar acidity occurs about the same time as Hcm1 nuclear exclusion and is conserved; we have recently demonstrated that lysosomal alkalization similarly contributes to aging in C. elegans following a transition from progeny producing to post-reproductive life. Our data points to a molecular mechanism regulating vacuolar acidity that signals the end of RLS when acidification is lost.

genetics↗

bioRxiv2017

GrapHi-C: Graph-based visualization of Hi-C Datasets

BackgroundHi-C is a proximity-based ligation reaction used to detect regions of the genome that are close in 3D space (or \"interacting\"). Typically, results from Hi-C experiments (whole-genome contact maps) are visualized as heatmaps or Circos plots. While informative, these visualizations do not intuitively represent the complex organization and folding of the genome in 3D space, making the interpretation of the underlying 3D genomic organization difficult. Our objective was to utilize existing tools to generate a graph-based representation of a whole-genome contact map that leads to a more intuitive visualization.\n\nMethodologyWhole-genome contact maps were converted into graphs where each vertex represented a genomic region and each edge represented a detected or known interaction between two vertices. Three types of interactions were represented in the graph: linear, intra-chromosomal (cis-), and inter-chromosomal (trans-) interactions. Each edge had an associated weight related to the linear distance (Hi-C experimental resolution) or the associated interaction frequency from the contact map. Graphs were generated based on this representation scheme for whole-genome contact maps from a fission yeast dataset where yeast mutants were used to identify specific principles influencing genome organization (GEO accession: GSE56849). Graphs were visualized in Cytoscape with an edge-weighted spring embedded layout where vertices and linear interaction edges were coloured according to their corresponding chromosome.\n\nResultsThe graph-based visualizations (compared to the equivalent heatmaps) more intuitively represented the effects of the rad21 mutant on genome organization. Specifically, the graph based visualizations clearly highlighted the loss of structural globules and a greater intermingling of chromosomes in the mutant strain when compared to the wild-type. The graph-based representation and visualization protocol developed here will aid in understanding the complex organization and folding of the genome.

bioinformatics↗