Scale-dependence in elk habitat selection for a reintroduced population in Wisconsin, USA.

Habitat selection is a critical aspect of a species' ecology, requiring complex decision-making that is both hierarchical and scale-dependent, since factors that influence selection may be nested or unequal across scales. Elk (Cervus canadensis) ranged widely across diverse ecoregions in North America prior to European settlement and subsequent eastern extirpation. Most habitat selection studies have occurred within their contemporary western range, even after eastern reintroductions began. As habitat selection can vary by geographic location, available cover, season, and diel period, it is important to understand how a non-migratory, reintroduced population in northern Wisconsin, USA, is limited by the lack of variation in topography, elevation, and vegetation. We tested scale-dependent habitat selection on 79 adult elk from 2017 to 2020 using resource selection functions across temporal (i.e., seasonal) and spatial scales (i.e., landscape and home range). We found that selection varied both spatially and temporally, and elk selected areas with the greatest potential to influence fitness at larger scales, meaning elk selected areas closer to escape cover and further from "risky" features (e.g., annual wolf territory centers, county roads, and highways). We found stronger avoidance of annual wolf territory centers during spring, suggesting elk were selecting safer habitats during calving season. Elk selected habitats with less canopy cover across both spatial scales and all seasons, suggesting that elk selected areas with better access to forage as early seral stage stands have greater forage biomass than closed-canopy forests and direct solar radiation to provide warmth in the cooler seasons. This study provides insight into the complexity of hierarchical decision-making, such as how risky habitat features and land cover type influence habitat selection differently across seasons and spatial scales, influencing the decision-making of elk. Scale-dependent behavior is crucial to understand within specific geographic regions, as these decisions scale up to influence population dynamics.

Bison, Elk, and Other Captive Wildlife Species Humoral Immune Responses against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has been found to infect various domestic and wild animal species. In this study, convenience serum samples from 575 bison, 180 elk, and 147 samples from various wildlife species collected between 2020 and 2023 from several regions in the United States were analyzed for the presence of SARS-CoV-2-specific antibodies. Two commercial ELISA assays based on the inhibition of the SARS-CoV-2 receptor-binding domain (sVNT) or the nucleocapsid protein (N-ELISA) of SARS-CoV-2 were used. Positive samples from the sVNT were additionally evaluated using a conventional virus neutralization test (VNT). Our results indicated that 1.2% of bison, 2.2% of elk, and 4.1% of the other wildlife species serum samples were seropositive in the sVNT, whereas 4.2% of bison, 3.3% of elk, and 1.4% of the other captive wildlife species serum samples tested positive by the N-ELISA. Among the sVNT serum samples, two samples from bison, one sample from elk, and five serum samples from other wildlife species (one cheetah, one gorilla, two lions, and one hippopotamus) had neutralizing antibody titers in the VNT, indicating these species are susceptible to SARS-CoV-2 infection. These findings highlight the importance of broad surveillance efforts for the effective monitoring of SARS-CoV-2 in non-human hosts.

Elevated expression of ELK1 promotes breast cancer cell growth and correlates with poor prognosis of breast cancer patients.

Background: Breast cancer is the most common tumor in women and poses a serious threat to women's physical and mental health. The ETS-like gene 1 (ELK1), upregulated in various malignancies, serves as a transcription regulatory factor. This study primarily investigates the biological functions and prognostic significance of ELK1 in breast cancer. Materials and methods: The authors conducted an analysis of ELK1 expression in breast cancer and adjacent tissues using data from The Cancer Genome Atlas (TCGA), and validated these findings with clinical specimens. Additionally, the authors employed siRNA transfection, proliferation and apoptosis assays to elucidate the roles of ELK1 in breast cancer cells. Furthermore, we assessed the correlations between ELK1 expression and the tumor microenvironment, as well as tumor-infiltrating immune cells (TIICs), utilizing the ESTIMATE and CIBERSORT algorithms. Finally, we used Kaplan-Meier plots and COX regressions to identify prognostic factors, and developed a predictive alignment diagram to evaluate the prognostic significance of ELK1 in breast cancer. Results: A marked increase in ELK1 expression is evident in breast cancer tissues (P<0.01). Experimental findings demonstrate that silencing ELK1 suppresses proliferation and promotes apoptosis in breast cancer cells. ELK1 plays a pivotal role in regulating the immune microenvironment of breast cancer. Furthermore, the alignment diagram indicates that ELK1 may serve as an independent prognostic factor for breast cancer patients. Conclusion: The authors' study reveals that ELK1 exhibits a high expression level in breast cancer tissues and is associated with disease progression and poor prognosis.

ELK4 targets CHMP6 to inhibit ferroptosis and enhance malignant properties of skin cutaneous melanoma cells.

Ferroptosis, a key factor in tumor progression, is poorly understood at the molecular level. This study investigates how ELK4 and CHMP6 regulate skin cutaneous melanoma (SKCM) cell proliferation and ferroptosis. Analysis of TCGA data reveals high expression of ELK4 and CHMP6 in SKCM. Overexpression of ELK4 or CHMP6 enhances cell proliferation, invasion, and migration while reducing ROS and Fe2 + levels. It also increases GPX4 and xCT expression and decreases ACSL4 levels in SKCM cells. The opposite effects are observed with ELK4 or CHMP6 knockdown. ELK4 binds to the CHMP6 promoter, promoting CHMP6 transcription. Knockdown of CHMP6 reverses the oncogenic effects of ELK4 overexpression. In conclusion, ELK4 enhances proliferation, invasion, and migration while inhibiting ferroptosis in SKCM cells by upregulating CHMP6 transcription. This study sheds light on the intricate mechanisms involved in SKCM progression and identifies potential therapeutic targets in melanoma treatment.

Friends because of foes: synchronous movement within predator-prey domains.

For prey, movement synchrony represents a potent antipredator strategy. Prey, however, must balance the costs and benefits of using conspecifics to mediate risk. Thus, the emergent patterns of risk-driven sociality depend on variation in space and in the predators and prey themselves. We applied the concept of predator-prey habitat domain, the space in which animals acquire food resources, to test the conditions under which individuals synchronize their movements relative to predator and prey habitat domains. We tested the response of movement synchrony of prey to predator-prey domains in two populations of ungulates that vary in their gregariousness and predator community: (i) elk, which are preyed on by wolves; and (ii) caribou, which are preyed on by coyotes and black bears. Prey in both communities responded to cursorial predators by increasing synchrony during seasons of greater predation pressure. Elk moved more synchronously in the wolf habitat domain during winter and caribou moved more synchronously in the coyote habitat domains during spring. In the winter, caribou increased movement synchrony when coyote and caribou domains overlapped. By integrating habitat domains with movement ecology, we provide a compelling argument for social behaviours and collective movement as an antipredator response. This article is part of the theme issue 'The spatial-social interface: A theoretical and empirical integration'.

"Luck Be a Lady": Retrospective Study of Disease-Associated Prion (PrPSc) Distribution and Lesions in Captive, Environmentally Exposed Female Rocky Mountain Elk (Cervus canadensis nelsoni) with 132LL Genotype.

Chronic wasting disease (CWD) is a fatal neurodegenerative disease of cervids caused by an infectious misfolded protein (prion). Several members of the Cervidae, including Rocky Mountain elk (Cervus canadensis nelsoni), are susceptible to CWD. There is no evidence of complete genetic resistance to CWD; the M132L polymorphism in the elk prion protein gene influences the incubation period: longest in 132LL, intermediate in 132ML, and shortest in 132MM elk. We retrospectively analyzed six female 132LL elk housed in an environment heavily contaminated with prions to 1) document clinical outcomes and incubation periods, 2) describe PrPSc distribution and extent in tissues, and 3) characterize their histologic lesions. In five of six elk, PrPSc was detected postmortem, with a distribution pattern distinct from that of 132MM and 132ML elk; time to clinical CWD onset CWD ranged from 73 to 117 mo (6.1-9.8 yr). Although the remaining animal was observed for 220 mo (18.3 yr), PrPSc was not detected in its tissues postmortem. This study suggests that 132LL elk infected via natural exposure may live even longer with CWD than previously thought, but ultimately remain susceptible. We also report a distinct distribution of PrPSc in 132LL genotypes and highlight unusual histologic findings. Understanding the relationship between cervid genetics and CWD is of increasing importance, especially given the growing interest in leveraging genetics that delay disease onset despite not preventing infection.

ELK4 ameliorates cognitive impairment and neuroinflammation induced by obstructive sleep apnea.

Intermittent hypoxia (IH) in patients with obstructive sleep apnea (OSA) syndrome elicited neuron injury (especially in the hippocampus and cortex), contributing to cognitive dysfunction. This study investigated the effects and clarified the mechanisms of ETS domain-containing protein Elk-4 (ELK4) on the cognitive function and neuroinflammation of mice with IH. Mouse microglia BV2 cells were induced with IH by exposure to fluctuating O2 concentrations (alternating from 5 % to 21 % every 30 min), and mice with OSA were developed and subjected to lentivirus-mediated gene intervention. ELK4 expression was significantly reduced in IH-induced microglia and brain tissues of mice with OSA. Overexpression of ELK4 attenuated oxidative stress, decreased the pro-inflammatory factors IL-1ß, IL-6, and TNF-α, and increased the level of the anti-inflammatory factors IL-10 and TGF-ß1, as well as the neuroprotective factor BDNF. ELK4 promoted the transcription of fibronectin type III domain-containing protein 5 (FNDC5) by binding to the promoter of FNDC5. Knockdown of FNDC5 in IH-induced microglia and animals reversed the protective effects of ELK4 on OSA-associated neuroinflammation and cognitive dysfunction. Overall, the results demonstrated that ELK4 overexpression repressed microglial activation by inducing the transcription of FNDC5, thus attenuating neuroinflammation and cognitive dysfunction induced by OSA.

Comparison of Butorphanol-Azaperone-Medetomidine and Nalbuphine-Medetomidine-Azaperone in Free-Ranging Elk (Cervus canadensis) in Pennsylvania, USA.

Chemical immobilization is commonly used to capture and handle free-ranging elk (Cervus canadensis). Butorphanol-azaperone-medetomidine (BAM) and nalbuphine-medetomidine-azaperone (NalMed-A) are compounded drug combinations that are lower-scheduled in the US than drugs historically used for elk immobilizations. We compared BAM and NalMed-A for immobilization of free-ranging elk using free-darting and Clover trapping. From January 2020 to April 2022, 196 female elk were immobilized in Pennsylvania, USA. We report vital rates, induction and recovery times, and the need for supplemental drugs. We built mixed-effects logistic regression models to describe differences between drug choice based on induction and recovery times, capture method, and individual variation. Several models were competing, including our null model, which suggests that BAM and NalMed-A are comparable based on the parameters we evaluated. Supplemental drug administration was more frequently needed in NalMed-A immobilizations (21.2%) than in BAM immobilizations (9.0%). Overall, we found minor differences between BAM and NalMed-A, both of which appear to be effective for immobilizing elk in both free-darting and Clover trapping scenarios when performing moderately invasive, minimally painful procedures on free-ranging elk.

Real-Time Visualization and Analysis Architecture for Data Integration Processes at Cologne University Hospital's Medical Data Integration Center.

This paper presents an implementation of an architecture based on open-source solutions using ELK Stack - Elasticsearch, Logstash, and Kibana - for real-time data analysis and visualizations in the Medical Data Integration Center, University Hospital Cologne, Germany. The architecture addresses challenges in handling diverse data sources, ensuring standardized access, and facilitating seamless analysis in real-time, ultimately enhancing the precision, speed, and quality of monitoring processes within the medical informatics domain.

A fine-scale examination of parturition timing in temperate ungulates.

Parturition timing has long been a topic of interest in ungulate research. However, few studies have examined parturition timing at fine scale (e.g., <1 day). Predator activity and environmental conditions can vary considerably with diel timing, which may result in selective pressure for parturition to occur during diel times that maximize the likelihood of neonate survival. We monitored parturition events and early-life survival of elk (Cervus canadensis) and mule deer (Odocoileus hemionus) in Utah, USA to better understand diel timing of parturition in temperate ungulates. Diel timing of parturition was moderately synchronous among conspecifics and influenced by environmental variables on the date of parturition. For elk, parturition events were most common during the morning crepuscular period and generally occurred later (i.e., closer to 12:00) when a relatively large proportion of the moon was illuminated. For mule deer, parturition events were most common during the diurnal period and generally occurred later (i.e., closer to 15:00) on cold, wet dates. Diel timing of parturition did not influence neonate survival, but larger datasets may be required to verify the apparent lack of influence. Although additional work could evaluate alternative variables that might affect parturition timing, our data provide an improved and finer scale understanding of reproductive ecology and phenology in ungulates.

Isotope hydrology of the intermontane Elk Valley, British Columbia: an assessment of water resources around coal mining operations.

This study aimed to synthesise and interpret stable isotopic data (δ2H and δ18O) from various sources to understand the isotope hydrology around coal mine operations in Elk Valley, B.C., Canada. The data, including precipitation, groundwaters, seeps, and mine rock drains, were used to construct a local meteoric water line (LMWL) for the Elk Valley, evaluate the spatiotemporal isotopic composition of its groundwater, and assess mine seepage and mine rock drain discharge. The study revealed a robust LMWL relation (δ2H = 7.4 ± 0.2 · δ18O - 4.3 ± 4.1). The groundwater and seep data indicated a winter season bias and a north-south latitudinal gradient, suggesting rapid near-surface groundwater flow without significant post-precipitation evaporation. Porewater isotope samples from unsaturated mine rock piles (MRPs) showed site-specific evaporation patterns, potentially due to convective air flows or exothermic sulphide oxidation. This research revealed the influence of groundwater and meltwater on rock drain discharge. Based on evaporative mass balance calculations, MRPs seasonally contributed ca. 5 %(December base flow) and 22 % (snowmelt) to drain discharge. The findings underscore the value of stable isotope data collections in the Elk Valley to help better define and quantify the hydrology-hydrogeology, including a better understanding of evaporative conditions in MRPs.

CircNUP98 promotes the malignant behavior of glioma cells through the miR-520f-3p/ELK4 axis.

Glioma, a formidable form of brain cancer, poses significant challenges in terms of treatment and prognosis. Circular RNA nucleoporin 98 (circNUP98) has emerged as a potential regulator in various cancers, yet its role in glioma remains unclear. Here, we elucidate the functional role of circNUP98 in glioma cell proliferation, invasion, and migration, shedding light on its therapeutic implications. Glioma cells were subjected to si-NUP98 transfection, followed by assessments of cell viability, proliferation, invasion, and migration. Subcellular localization of circNUP98 was determined, and its downstream targets were identified. We delineated the binding relationships between circNUP98 and microRNA (miR)-520f-3p, as well as between miR-520f-3p and ETS transcription factor ELK4 (ELK4). The expression levels of circNUP98/miR-520f-3p/ELK4 were quantified. Our findings demonstrated that circNUP98 was upregulated in glioma cells, and its inhibition significantly attenuated glioma cell proliferation, invasion, and migration. Mechanistically, circNUP98 functioned as a sponge for miR-520f-3p, thereby relieving the inhibitory effect of miR-520f-3p on ELK4. Moreover, inhibition of miR-520f-3p or overexpression of ELK4 partially rescued the suppressive effect of circNUP98 knockdown on glioma cell behaviors. In summary, our study unveils that circNUP98 promotes glioma cell progression via the miR-520f-3p/ELK4 axis, offering novel insights into the therapeutic targeting of circNUP98 in glioma treatment.

Baicalein Inhibits Metastasis of Oral Squamous Cell Carcinoma Cells by Regulating ERK/ELK-1/Snail Signaling.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is associated with high recurrence and poor prognosis. Baicalin has multiple pharmacological effects, including anti-inflammatory and anti-proliferative activities. Here, we examine the effect of baicalein on OSCC metastasis and its potential mechanism of action. METHODS: SCC-4 and CAL-27 cells were treated with different concentrations of baicalein. The proliferation of OSCC cells was evaluated by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. As for migration and metastasis, baicalein-treated OSCC cells were used for wound healing assay and Transwell assay. The levels of epithelial-mesenchymal transition-related proteins (E-cadherin, N-cadherin, vimentin) and extracellular regulated protein kinases (ERK)/ETS Transcription Factor ELK1 (ELK-1)/Snail signaling pathway-related proteins in baicalein-treated OSCC cells were evaluated by western blotting. RESULTS: The rates of cell proliferation and migration, along with the metastatic potential, of baicalein-treated cells were significantly lower than those of the control (p < 0.05), and the effects were concentration-dependent. Furthermore, compared to the control, baicalein significantly decreased the levels of N-cadherin and vimentin in SCC-4 and CAL-27 cells, and increased the E-cadherin level (p < 0.05). Mechanistically, baicalein downregulated the levels of p-ERK1/2, phospho-ETS Transcription Factor ELK1 (p-ELK-1), and Snail (p < 0.05). Finally, the ERK/ELK-1/Snail pathway inhibitor (U0126) promoted the effect of baicalein in inhibiting the migration and invasion of OSCC cells (p < 0.05). CONCLUSION: Baicalein abates the migration, invasion, and metastasis of OSCC cells through the ERK/ELK-1/Snail signaling pathway. This study provides a basis for the development of baicalein as a compound for the treatment of OSCC.

Mountaintop Removal Coal Mining Contaminates Snowpack across a Broad Region.

Mountaintop removal coal mining is a source of downstream pollution. Here, we show that mountaintop removal coal mining also pollutes ecosystems downwind. We sampled regional snowpack near the end of winter along a transect of sites located 3-60 km downwind of coal mining in the Elk River valley of British Columbia, Canada. Vast quantities of polycyclic aromatic compounds (PACs), a toxic class of organic contaminants, are emitted and transported atmospherically far from emission sources. Summed PAC (ΣPAC) snowpack concentrations ranged from 29-94,866 ng/L. Snowpack ΣPAC loads, which account for variable snowpack depth, ranged from <10 µg/m2 at sites >50 km southeast of the mines to >1000 µg/m2 at sites in the Elk River valley near mining operations, with one site >15,000 µg/m2. Outside of the Elk River valley, snowpack ΣPAC loads exhibited a clear spatial pattern decreasing away from the mines. The compositional fingerprint of this PAC pollution matches closely with Elk River valley coal. Beyond our study region, modeling results suggest a depositional footprint extending across western Canada and the northwestern United States. These findings carry important implications for receiving ecosystems and for communities located close to mountaintop removal coal mines exposed to air pollution elevated in PACs.

Serum Response Factor Expression in Excess Permits a Dual Contractile-Proliferative Phenotype of Airway Smooth Muscle.

The transcription factors (TFs) MyoCD (myocardin) and Elk-1 (ETS Like-1 protein) competitively bind to SRF (serum response factor) and control myogenic- and mitogenic-related gene expression in smooth muscle, respectively. Their functions are therefore mutually inhibitory, which results in a contractile-versus-proliferative phenotype dichotomy. Airway smooth muscle cell (ASMC) phenotype alterations occur in various inflammatory airway diseases, promoting pathological remodeling and contributing to airflow obstruction. We characterized MyoCD and Elk-1 interactions and their roles in phenotype determination in human ASMCs. MyoCD overexpression in ASMCs increased smooth muscle gene expression, force generation, and partially restored the loss of smooth muscle protein associated with prolonged culturing while inhibiting Elk-1 transcriptional activities and proliferation induced by EGF (epidermal growth factor). However, MyoCD overexpression failed to suppress these responses induced by FBS, as FBS also upregulated SRF expression to a degree that allowed unopposed function of both TFs. Inhibition of the RhoA pathway reversed said SRF changes, allowing inhibition of Elk-1 by MyoCD overexpression and suppressing FBS-mediated contractile protein gene upregulation. Our study confirmed that MyoCD in increased abundance can competitively inhibit Elk-1 function. However, SRF upregulation permits a dual contractile-proliferative ASMC phenotype that is anticipated to exacerbate pathological alterations, whereas therapies targeting SRF may inhibit pathological ASMC proliferation and contractile protein gene expression.

The Mediator Med23 controls a transcriptional switch for muscle stem cell proliferation and differentiation in muscle regeneration.

Muscle stem cells (MuSCs) contribute to a robust muscle regeneration process after injury, which is highly orchestrated by the sequential expression of multiple key transcription factors. However, it remains unclear how key transcription factors and cofactors such as the Mediator complex cooperate to regulate myogenesis. Here, we show that the Mediator Med23 is critically important for MuSC-mediated muscle regeneration. Med23 is increasingly expressed in activated/proliferating MuSCs on isolated myofibers or in response to muscle injury. Med23 deficiency reduced MuSC proliferation and enhanced its precocious differentiation, ultimately compromising muscle regeneration. Integrative analysis revealed that Med23 oppositely impacts Ternary complex factor (TCF)-targeted MuSC proliferation genes and myocardin-related transcription factor (MRTF)-targeted myogenic differentiation genes. Consistently, Med23 deficiency decreases the ETS-like transcription factor 1 (Elk1)/serum response factor (SRF) binding at proliferation gene promoters but promotes MRTF-A/SRF binding at myogenic gene promoters. Overall, our study reveals the important transcriptional control mechanism of Med23 in balancing MuSC proliferation and differentiation in muscle regeneration.

Discovery of novel treponemes associated with pododermatitis in elk (Cervus canadensis).

Pododermatitis, also known as treponeme-associated hoof disease (TAHD), presents a significant challenge to elk (Cervus canadensis) populations in the northwestern USA, with Treponema spp. consistently implicated in the lesion development. However, identifying species-specific Treponema strains from these lesions is hindered by its culture recalcitrance and limited genomic information. This study utilized shotgun sequencing, in silico genome reconstruction, and comparative genomics as a culture-independent approach to identify metagenome-assembled Treponema genomes (MATGs) from skin scraping samples collected from captive elk experimentally challenged with TAHD. The genomic analysis revealed 10 new MATGs, with 6 representing novel genomospecies associated with pododermatitis in elk and 4 corresponding to previously identified species-Treponema pedis and Treponema phagedenis. Importantly, genomic signatures of novel genomospecies identified in this study were consistently detected in biopsy samples of free-ranging elk diagnosed with TAHD, indicating a potential etiologic association. Comparative metabolic profiling of the MATGs against other Treponema genomes showed a distinct metabolic profile, suggesting potential host adaptation or geographic uniqueness of these newly identified genomospecies. The discovery of novel Treponema genomospecies enhances our understanding of the pathogenesis of pododermatitis and lays the foundation for the development of improved molecular surveillance tools to monitor and manage the disease in free-ranging elk.IMPORTANCETreponema spp. play an important role in the development of pododermatitis in free-ranging elk; however, the species-specific detection of Treponema from pododermatitis lesions is challenging due to culture recalcitrance and limited genomic information. The study utilized shotgun sequencing and in silico genome reconstruction to identify novel Treponema genomospecies from elk with pododermatitis. The discovery of the novel Treponema species opens new avenues to develop molecular diagnostic and epidemiologic tools for the surveillance of pododermatitis in elk. These findings significantly enhance our understanding of the genomic landscape of the Treponemataceae consortium while offering valuable insights into the etiology and pathogenesis of emerging pododermatitis in elk populations.

Corrigendum: Fecal and vaginal microbiota of vaccinated and non-vaccinated pregnant elk challenged with Brucella abortus.

[This corrects the article DOI: 10.3389/fvets.2024.1334858.].

Construction of gastric cancer prognostic signature based on the E26 transcription factor and the identification of novel oncogene ELK3.

The aim of the present study was to investigate the function of 29 E26 (ETS) transcription factor families in gastric cancer (GC) and determine their association with prognosis. Our analysis of the expression of the ETS family revealed that 28 genes were dysregulated in GC, and that their expression was associated with multiple clinicopathological features (P<0.05). Based on the expression signature of the ETS family, consensus clustering was performed to generate two gastric cancer subtypes. These subtypes exhibited differences in overall survival (OS, P = 0.161), disease-free survival (DFS, P<0.05) and GC grade (P<0.01). Functional enrichment analysis of the target genes associated with the ETS family indicated that these genes primarily contribute to functions that facilitate tumor progression. A systematic statistical analysis was used to construct a prognostic model related to OS and DFS in association with the ETS family. This model demonstrated that the maximum area under the curve (AUC) values for predicting OS and DFS were 0.729 and 0.670, respectively, establishing ETS as an independent prognostic factor for GC Furthermore, a nomogram was created from the prognostic signature, and its predictive accuracy was confirmed by a calibration curve. Finally, the expression and prognostic significance of the six genes comprising the model were also examined. Among these, ELK3 was found to be significantly overexpressed in GC clinical samples. Subsequent in vitro and in vivo studies verified that ELK3 regulates GC proliferation and metastasis, highlighting its potential as a therapeutic target for gastric cancer.

Correlation of lesion severity with bacterial changes in Treponeme-Associated Hoof Disease from free-roaming wild elk (Cervus canadensis).

BACKGROUND: Treponeme-Associated Hoof Disease (TAHD) is a polybacterial, multifactorial disease affecting free-ranging wild elk (Cervus canadensis) in the Pacific Northwest. Previous studies have indicated a bacterial etiology similar to digital dermatitis in livestock, including isolation of Treponema species from lesions. The lesions appear to progress rapidly from ulcerative areas in the interdigital space or along the coronary band to severe, ulcerative, necrotic, proliferative lesions under-running the hoof wall, perforating the sole, and contributing to hoof elongation, deformity, and overgrowth. Eventually the lesions undermine the laminal structure leading to sloughing of the hoof horn capsule. The objective of this study was to characterize the bacterial communities associated with hoof lesions, which were categorized into 5 stages or disease grade severities, with 0 being unaffected tissue and 4 being sloughed hoof capsule. We also wanted to determine if the etiology of TAHD through morphological changes was dominated by Treponema, as observed in hoof diseases in livestock. RESULTS: The bacterial 16S rRNA gene was sequenced from 66 hoof skin biopsy samples representing 5 lesion grades from samples collected by Washington Department of Fish and Wildlife as part of a voluntary hunter program. Analysis of the relative abundance of bacterial sequences showed that lesions were dominated by members of the bacterial phyla Proteobacteria, Firmicutes, Spirochaetes, Bacteroidetes and Actinobacteria. In lesion samples, members of the genus Treponema, Porphyromonas, and Mycoplasma increased with lesion severity. Association analysis indicated frequent identification of Treponema with Porphyromonas, Bacteroides and other anaerobic Gram-positive cocci. CONCLUSIONS: The bacterial 16S rRNA gene sequencing confirmed the presence of Treponema species at all stages of TAHD lesions, treponeme specie-specific PCR and histopathology, indicating that the morphological changes are a continual progression of disease severity with similar bacterial communities. Association and abundance of these other pathogenic genera within lesions may mean synergistic role with Treponema in hoof disease pathogenesis. Characterizing bacteria involved in lesion development, and their persistence during disease progression, provides evidence for science-based management decisions in TAHD infected elk populations.