Biology subjects

Mercer, K.

Publications and source records attributed to Mercer, K..

7 recordsLinked to original sources

bioRxiv2026

Domestication, spread, and improvement have shaped biological nitrogen fixation traits in Zea taxa

Synthetic nitrogen fertilizers enhance maize (Zea mays ssp. mays) productivity but impose substantial environmental and economic costs. Some Mexican maize landraces support biological nitrogen fixation (BNF) in aerial root mucilage, raising the question of how much variation exists in this trait and how domestication, geographic spread, and improvement have shaped BNF-related traits across Zea in the Americas. We evaluated aerial root traits and BNF capacity across the maize domestication continuum using 60 Zea accessions grown in field experiments over two years under low-N conditions. Some accessions of wild Zea, landraces from Mexico and South America, and improved varieties had elevated nitrogen derived from the atmosphere (%Ndfa), ranging from 20 to 40%; some of these also had greater %Ndfa than typical improved varieties. Spread and improvement appear to have significantly reduced the number of aerial root-bearing nodes, with wild Zea and Mexican landraces consistently producing more. Nevertheless, the proportion of nitrogen derived from the atmosphere (%Ndfa) does not vary systematically across the domestication continuum. Thus, crop evolution shaped aerial root phenotypes more than associative BNF capacity. The persistence of substantial within-group variation indicates that the genetic potential for enhanced BNF remains within the Zea gene pool, providing opportunities to encourage and improve nitrogen use efficiency in maize cropping systems.

ecology↗

bioRxiv2026

Lineage-specific CK2α deletion reshapes the transcriptome of hematopoietic stem cells toward an immune-primed state

Casein Kinase 2 (CK2) is a constitutively active kinase regulating proliferation and immune signaling and is frequently dysregulated in cancer, including acute myeloid leukemia (AML), making it a therapeutic target. CK2 comprises two catalytic subunits, CK2 or CK2, with two regulatory {beta} subunits. The role of CK2, the predominant catalytic subunit and principal mediator of CK2 kinase activity in hematopoietic cells, in steady-state hematopoiesis remains undefined. To define how CK2 shapes hematopoietic cells, we used bone marrow and spleen tissue samples of wild type control and conditional knock out (KO) of CK2 (Csnk2a1) in the hematopoietic compartment of transgenic mice. Using single-cell RNA sequencing, we profiled the transcriptomic changes associated with CK2 loss. Although HSC abundance was comparable between the control and CK2-deficient samples, HSCs experienced the largest transcriptional response to CK2 loss among all cell types. CK2-deficient HSCs displayed transcriptional remodeling for inflammatory and immune-associated programs, interferon signaling, and antigen presentation. Expression of inflammatory genes such as S100a8 and S100a9, changed in opposite directions in bone marrow and spleen HSCs, demonstrating the transcriptional consequences of CK2 loss shaped by tissue context. Using a network-based approach, we identified immune-associated transcription factors Nfkb1, Rfx5, Hes1, and AP-1 family members as regulatory hubs driving these inflammatory transcriptional states in CK2-deficient HSCs. Cell-cell communication profiling revealed multiple gains and losses in ligand-receptor communication between the HSCs and their immune microenvironment in KO. Our findings identify CK2 as a regulator of immune transcriptional programs in HSCs and suggest that disruption of CK2 signaling influences stem cell behavior and immune activation in contexts relevant to hematologic malignancies and CK2-targeted cancer therapies. Statement of significanceThis study reveals that inhibiting the protein CK2 forces blood stem cells into a stressed, immune-primed state. These tissue-specific findings highlight potential side effects for cancer therapies targeting this essential regulatory kinase.

genomics↗

bioRxiv2025

CK2 inhibitor, CX-4945, enhances BH3 priming and promotes apoptosis of venetoclax-resistant AML by targeting antiapoptotic proteins

Acute myeloid leukemia (AML), the most common hematologic malignancy, generally has a poor prognosis. Despite initial favorable responses to the BCL2 inhibitor venetoclax (VEN), remission is transient, and AML is eventually fatal. Resistance to VEN is primarily due to the overexpression of anti-apoptotic proteins, including MCL-1, BCL2L1 (BCL-XL), and BCL2A1. Casein kinase II (CK2) is a serine-threonine kinase and a known suppressor of apoptosis. We and others have reported that protein kinase CK2 activity is high in leukemic stem cells (LSCs) and associated with resistance to chemotherapy. We have shown that the selective CK2 inhibitor, CX-4945, suppresses BCL-XL and has a significant anti-tumor effect in AML preclinical models. CK2 expression and activity are high in venetoclax-resistant AML (VR-AML) cell lines. Genetic and pharmacological inhibition of CK2 significantly altered VR-AML gene signature, decreased MCL-1 protein level, increased BH3 priming and sensitized VR-AML cells to apoptosis. More importantly, CX-4945 selectively targeted LSCs (CD34+CD38-) and chemoresistant (CD123+CD47+) subpopulation in VR-AML. CX-4945 combined with VEN decreased leukemia burden and prolonged the survival of VR-AML cell line-derived and patient-derived xenografts compared to either drug alone. The combinatorial treatment was well tolerated in mice without additional myelosuppression or organ toxicity. CX-4945 (silmitasertib) is being tested in several early-phase clinical trials against adult and pediatric cancers. These preclinical results support the use of CX-4945 in combination with VEN to overcome resistance to apoptosis and re-sensitize VR-AML to chemotherapy. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/696284v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@6a902forg.highwire.dtl.DTLVardef@2028f5org.highwire.dtl.DTLVardef@160fd4dorg.highwire.dtl.DTLVardef@95da53_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2023

Genomic signatures of adaptation to abiotic stress from a geographically diverse collection of chile peppers (Capsicum spp.) from Mexico

Extreme environmental variability requires the identification of genetic diversity that can help crops withstand difficult abiotic conditions. Understanding the genetic basis of adaptation to abiotic stress can provide tools for adapting agriculture to changing climates. Crop landraces and their wild ancestors from centers of domestication have often evolved across diverse environmental conditions and provide a unique opportunity to locate loci harboring alleles that could contribute to abiotic stress tolerance, among other traits. We collected chile peppers (Capsicum spp.) from farmers in southern Mexico along environmental transects crossing temperature, precipitation, and elevational gradients. Using 32,623 filtered SNPs generated from genotyping-by-sequencing (GBS), we conducted an environmental association analysis (EAA) combined with two outlier analyses, FST and spatial ancestry analyses to detect priority candidate loci associated with climate and soil phenotypes relevant to drought tolerance. Even though cultivated species may be shielded from some environmental selection by management practices (e.g., irrigation), we found fifteen priority loci whose genetic variation covaried with environmental variation in our EAA and were also allele frequency outliers (i.e., Fst and/or SPA). Thirty-three percent of the priority loci were validated with phenotype in response to water deficit. The haplotype blocks associated with these loci identify unique genetic variants worthy of conservation and harbor genes with abiotic stress-related functions. This work provides valuable information to explore quantitative trait loci (QTLs) underlying abiotic stress tolerance in chile pepper and is a new resource for improving plant breeding around the world. Article SummaryThe extreme environmental variability faced by crops requires the identification of potentially adaptive loci for abiotic stressors. We conducted an environmental association analysis (EAA) environments using chile peppers collected in southern Mexico along environmental transects crossing temperature, precipitation, and elevational gradients. We combined EAA with outlier analyses FST and spatial ancestry analysis to detect priority candidate loci associated with climate and soil phenotypes relevant to drought tolerance that may putatively contribute to abiotic stress adaptation.

genetics↗

bioRxiv2022

Capturing the distribution as it shifts: chile pepper (Capsicum annuum L.) domestication gradient meets geography.

AimDomestication is an ongoing well-described process. However, while many have studied the changes domestication causes in the genetic landscape, few have explored the way domestication changes the geographic landscape in which the plants exist. Therefore, the goal of this study was to understand how the domestication status changed the suitable geographic space of chile pepper in its center of origin. MethodsCapsicum annuum is a major crop species globally whose domestication center, Mexico, has been well studied. This provides a unique opportunity to explore the degree to which ranges of different domestication classes diverged and how these ranges might be altered by climate change. To this end, we created ecological niche models for four domestication classes (wild, semiwild, landrace, modern cultivar) based on present climate and future climate scenarios for 2050, 2070, and 2090. ResultsConsidering present environment, we found substantial overlap in the geographic niches of all the domestication gradient categories. Yet, there were also clear unique environmental and geographic aspects to the current ranges. Wild and commercial varieties were at ease in desert conditions as opposed to landraces. With projections into the future, habitat was lost asymmetrically, with wild, semiwild and landraces at far greater risk than modern cultivars. Further, we identified areas where future suitability overlap between landraces and wilds is expected to decouple. Main conclusionsWhile range expansion is widely associated with domestication, there is little support of a constant niche expansion (either in environmental or geographical space) throughout the domestication gradient. However, a shift to higher altitudes with cooler climate was identified for landraces. The clear differences in environmental adaptation, such as higher mean diurnal range and precipitation seasonality along the domestication gradient classes and their future potential range shifts show the need to increase conservation efforts, particularly to preserve landraces and semiwild genotypes.

evolutionary biology↗

bioRxiv2020

Rapid Development of Neutralizing and Diagnostic SARS-COV-2 Mouse Monoclonal Antibodies

The need for high-affinity, SARS-CoV-2-specific monoclonal antibodies (mAbs) is critical in the face of the global COVID-19 pandemic, as such reagents can have important diagnostic, research, and therapeutic applications. Of greatest interest is the ~300 amino acid receptor binding domain (RBD) within the S1 subunit of the spike protein because of its key interaction with the human angiotensin converting enzyme 2 (hACE2) receptor present on many cell types, especially lung epithelial cells. We report here the development and functional characterization of 29 nanomolar-affinity mouse SARS-CoV-2 mAbs created by an accelerated immunization and hybridoma screening process. Differing functions, including binding of diverse protein epitopes, viral neutralization, impact on RBD-hACE2 binding, and immunohistochemical staining of infected lung tissue, were correlated with variable gene usage and sequence.

immunology↗

bioRxiv2020

Germination response of diverse wild and landrace chile peppers (Capsicum spp.) under drought stress simulated with polyethylene glycol

Responses to drought within a single species may vary based on plant development stage, drought severity, and the avoidance or tolerance mechanisms employed. Early drought stress can restrict emergence and seedling growth. Thus, in areas where water availability is limited, rapid germination leading to early plant establishment may be beneficial. Alternatively, germination without sufficient water to support the seedling may lead to early senescence, so reduced germination under low moisture conditions may be adaptive at the level of the population. We studied the germination response to osmotic stress of diverse chile pepper germplasm collected in southern Mexico from varied ecozones, cultivation systems, and of named landraces. Drought stress was simulated using polyethylene glycol solutions. Overall, survival time analysis revealed delayed germination at the 20% concentration of PEG across all ecozones. The effect was most pronounced in the genotypes from hotter, drier ecozones. Additionally, accessions from wetter and cooler ecozones had the fastest rate of germination. Moreover, accessions of the landraces Costeno Rojo and Tusta germinated more slowly and incompletely if sourced from a drier ecozone than a wetter one, indicating that slower, reduced germination under drought stress may be an adaptive avoidance mechanism. Significant differences were also observed between named landraces, with more domesticated types from intensive cultivation systems nearly always germinating faster than small-fruited backyard- or wild-types, perhaps due to the fact that the smaller-fruited accessions have generally undergone less selection. Thus, we conclude that there is evidence of local adaptation to both ecozone of origin and source cultivation system in germination characteristics of diverse chile peppers.

evolutionary biology↗