Biology subjects

Ernst, K.

Publications and source records attributed to Ernst, K..

7 recordsLinked to original sources

bioRxiv2026

Climate change and extreme weather events to intensify West Nile virus activity

Vector-borne zoonotic diseases pose a substantive risk to public health worldwide, yet predicting outbreaks at scales useful for public health response remains a critical challenge. Transmitted by Culex mosquitoes, West Nile virus is the leading cause of arboviral disease in the United States, progressing to neuroinvasive disease in approximately 1% of infections. Arizona's record-breaking 2021 outbreak, with 1,715 reported human cases and 127 deaths exemplifies this growing burden. Using a decade of mosquito surveillance data coupled with time-lagged weather patterns in a random forest framework, we developed spatial models predicting Culex abundance and West Nile virus occurrence across Arizona at weekly temporal and fine spatial resolution. Our weighted models classified viral occurrence with 98.9% accuracy and explained 65.3% of weekly variation in county-level human cases, with human cases lagging modeled activity by one week. Neither mosquito abundance nor viral occurrence declined at the extreme temperatures characteristic of Arizona summers, suggesting that thermal refugia sustain transmission. Drought-monsoon cycling, rather than temperature alone, emerged as the primary driver of West Nile activity, and projections through 2100 indicate intensifying activity under all climate change scenarios.

ecology↗

bioRxiv2025

Systematic investigation of Epstein-Barr virus transcriptional regulator interactions with the human genome

We systematically investigate interactions between Epstein-Barr virus (EBV) transcriptional regulators (vTRs) and the human genome. Starting with 16 known and candidate vTRs, we identify nine whose introduction into human cells results in substantial alterations to host gene expression. Genome-scale determination of vTR genomic binding events and alterations to chromatin accessibility reveals a detailed map of EBVs functional interactions with the human genome, including >100,000 vTR binding events impacting almost a quarter of all human genes. BMRF1 emerges as a potent regulator, impacting >7,000 genes and altering >37,000 chromatin regions. Our results provide new evidence that EBV RTA interacts with and stabilizes the binding of human RBPJ. Network analysis reveals that many human genes are targeted by multiple EBV vTRs, highlighting the vast coordinated impact of EBV on human gene expression. This study provides a valuable, extensive resource for examining EBV-induced alterations to human gene regulation, with data available on multiple platforms.

genomics↗

bioRxiv2024

Embracing native diversity to enhance maximum quantum efficiency of photosystem II in maize (Zea mays L.)

Sustainability of maize cultivation would benefit tremendously from early sowing but is hampered by low temperatures during early development in temperate climate. We show that allelic variation of subunit M of NADH-dehydrogenase-like (NDH) complex (ndhm1), discovered in a European maize landrace affects several quantitative traits relevant during early development in cold climates through NDH-mediated cyclic electron transport (CET) around photosystem I, a process crucial for photosynthesis. Starting from a genome-wide association study (GWAS) for maximum potential quantum yield of photosystem II in dark-adapted leaves (Fv/Fm) we capitalized on large phenotypic effects of a hAT transposon insertion in ndhm1 on quantitative traits early plant height (EPH), Fv/Fm, chlorophyll content and cold tolerance caused by reduced protein levels of NDHM and associated NDH components. Analysis of the native allelic series of ndhm1 revealed a rare allele of ndhm1 which is associated with small albeit significant effects on maximum potential quantum yield of photosystem II in dark- and light adapted leaves (Fv/Fm, {Phi}PSII) and early plant height compared to common alleles. Our work showcases the extraction of novel, favorable alleles from locally adapted landraces, offering an efficient strategy for broadening the genetic variation of elite germplasm by breeding or genome editing.

plant biology↗

bioRxiv2023

A root-specific NLR network confers resistance to plant parasitic nematodes

Nucleotide-binding domain and leucine-rich repeat immune receptors (NLRs) confer disease resistance to a multitude of foliar and root parasites of plants. However, the extent to which NLR immunity is expressed differentially between plant organs is poorly known. Here, we show that a large cluster of tomato genes, which encodes the cyst and root-knot nematode disease resistance proteins Hero and MeR1 as well as the NLR-helper NRC6, exhibits nearly exclusive expression in the roots. This root-specific gene cluster emerged in Solanum species about 21 million years ago through gene duplication from the ancient NRC network of asterid plants. NLR-sensors in this gene cluster exclusively signal through NRC6 helpers to trigger the hypersensitive cell death immune response. These findings indicate that the NRC6 gene cluster has sub-functionalized from the larger NRC network to specialize for resistance against root pathogens, including cyst and root-knot nematodes. We propose that NLR gene clusters and networks have evolved organ-specific gene expression as an adaptation to particular parasites and to reduce the risk of autoimmunity.

plant biology↗

bioRxiv2021

A connectivity signature for glioblastoma

Tumor cell extensions called tumor microtubes (TMs) in glioma resemble neurites during neurodevelopment and connect glioma cells to a network that has considerable relevance for tumor progression and therapy resistance. The determination of interconnectivity in individual tumors has been challenging and the impact of tumor cell connectivity on patient survival remained unresolved so far. Here, a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells was established and clinically validated. Thirty-four of 40 connectivity genes were related to neurogenesis, neural tube development or glioma progression, including the TM-network-relevant GAP43 gene. Astrocytic-like and mesenchymal-like GB cells had the highest connectivity signature scores in scRNA-Seq data of patient-derived xenografts and patient samples. In 230 human GBs, high connectivity correlated with the mesenchymal expression subtype, TP53 wildtype, and with dismal patient survival. CHI3L1 was identified as a robust molecular marker of connectivity. Thus, the connectivity signature allows novel insights into brain tumor biology, provides a proof-of-principle that tumor cell connectivity is relevant for patients prognosis, and serves as a robust biomarker that can be used for future clinical trials. Statement of significanceIntegration of GB cells into functional networks drives tumor progression and resistance. Here, we established and validated a novel connectivity gene expression signature of single GB cells and whole tumors that can be easily applied to clinical and preclinical samples. It is shown that connectivity is determining prognosis combining molecular, functional and clinical insights into the disease.

cancer biology↗

bioRxiv2020

Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo

Whooping cough is caused by Bordetella pertussis that releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein -subunits resulting in increased cAMP signaling. Here, the role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is characterized in detail. PTS1 specifically and directly interacts with chaperones in vitro and in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing cytosolic PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough.

pharmacology and toxicology↗

bioRxiv2018

Vertical transmission of Zika virus from orally infected Aedes aegypti produces infectious adult progeny.

Vertical transmission, or pathogen transfer from mother to offspring, can facilitate persistence of emerging arboviruses, such as Zika virus (ZIKV), in mosquito populations. Understanding vertical transmission and the different environmental and temporal conditions that affect it is important to assess whether new outbreaks could occur without reintroduction of the virus. To determine the rate of vertical transmission for ZIKV, Aedes aegypti females were fed on ZIKV infected blood, maintained under three temperature conditions (27{degrees}C, 30{degrees}C, and 33{degrees}C), and allowed to oviposit three times. Progeny were tested for virus presence at 3, 7, and 14 days after adult emergence. The overall vertical transmission rate was 6.5% (3.9 - 9.9). Vertical transmission was observed across all maternal temperature conditions and was detected in adult progeny as young as 3 days and as late as 14 days post-emergence. In total, 3.4% (1.6 - 6.2) of adult progeny produced saliva with detectable ZIKV, indicating their capacity to transmit ZIKV to humans. To our knowledge, this is the first evidence that vertical transmission occurs from orally-infected female Aedes aegypti to their adult progeny at a range of temperatures, and proof that Zika virus can persist in the saliva of those progeny throughout their lifetimes. These results suggest that the virus may be maintained in Ae. aegypti populations without a vertebrate host, allowing for human infections to occur without consistent re-introductions of ZIKV.\n\nAuthor SummaryIn 2015, Zika virus spread to over 50 countries. However, it is not known whether the virus persisted in the outbreak areas or became locally extinct. One way mosquito-borne viruses, like Zika, could become established is by transferring directly between mosquito generations rather than circulating between mosquitoes and humans. This is known as vertical transmission, and happens when the virus infects the developing eggs of infected maternal mosquitoes. As with other mosquito-borne diseases, like dengue, in order to infect humans the virus must be present in the saliva of infected mosquito progeny during blood feeding. We found vertical transmission occurred throughout the infected mothers reproductive lifetime and across a range of temperature conditions. Vertically infected progeny had Zika virus in their saliva as early as three days after adult emergence, implying that they could infect a person even during their first bloodmeal. Importantly, this work indicates that Zika virus could establish itself in the mosquito population even when human to mosquito transmission is not actively occurring.

epidemiology↗