Digital Commons Network^™

Impact Of Co-Mutations And Transcriptional Signatures In Non-Small Cell Lung Cancer Patients Treated With Adagrasib In The Krystal-1 Trial, Marcelo V Negrao, Alvaro G Paula, David Molkentine, Laura Hover, Monique Nilsson, Natalie Vokes, Lars Engstrom, Andrew Calinisan, David M Briere, Laura Waters, Jill Hallin, Lixia Diao, Mehmet Altan, George R Blumenschein, Ferdinandos Skoulidis, Jing Wang, Scott E Kopetz, David S Hong, Don L Gibbons, Peter Olson, James G Christensen, John V Heymach

Faculty, Staff and Student Publications

Purpose: KRAS inhibitors are revolutionizing the treatment of non-small cell lung cancer (NSCLC), but clinico-genomic determinants of treatment efficacy warrant continued exploration.

Experimental design: Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib [KRYSTAL-1 (NCT03785249)] were included in the analysis. Pretreatment next-generation sequencing data were collected per protocol. HTG EdgeSeq Transcriptome Panel was used for gene expression profiling. Clinical endpoints included objective response, progression-free survival (PFS), and overall survival (OS). KRASG12C-mutant NSCLC cell lines and xenograft models were used for sensitivity analyses and combination drug screens.

Results: KEAP1 MUT and STK11MUT were associated with shorter survival to adagrasib [KEAP1: …

Phase I Trial Of Tti-101, A First-In-Class Oral Inhibitor Of Stat3, In Patients With Advanced Solid Tumors, Apostolia M Tsimberidou, David J Vining, Sukeshi P Arora, Sofia De Achaval, Jeffrey Larson, John Kauh, Carrie Cartwright, Rony Avritscher, Imran Alibhai, David J Tweardy, Ahmed O Kaseb

Faculty, Staff and Student Publications

Purpose: Signal transducer and activator of transcription 3 is a transcription factor that is essential for the survival and immune sequestration of cancer cells. We conducted a phase I study of TTI-101, a first-in-class, selective small-molecule inhibitor of signal transducer and activator of transcription 3, in patients with advanced metastatic cancer.

Patients and methods: Patients were treated with TTI-101 orally twice daily in 28-day cycles at four dose levels (DL): 3.2 (DL1), 6.4 (DL2), 12.8 (DL3), and 25.6 (DL4) mg/kg/day ("3+3" design). Three TTI-101 formulations were used in a stepwise manner (NCT03195699).

Results: Sixty-four patients were treated (median …

Neural Correlates Of Opioid-Induced Risk-Taking Behavior In The Prelimbic Prefrontal Cortex, Cana B Quave, Andres M Vasquez, Guillermo Aquino-Miranda, Milagros Marín, Esha P Bora, Chinenye L Chidomere, Xu O Zhang, Douglas S Engelke, Fabricio H Do-Monte

Faculty, Staff and Student Publications

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

Ca-125 As A Biomarker In Renal Medullary Carcinoma: Integrated Molecular Profiling, Functional Characterization, And Prospective Clinical Validation, Sandra L Grimm, Menuka Karki, Kyle A Blum, Jean-Philippe Bertocchio, Rong He, Durga N Tripathi, Niki M Zacharias, Justin M Lebenthal, Rahul A Sheth, Priya Rao, Giannicola Genovese, Zhen Lu, Robert C Bast, Davis R Ingram, Rossana Lazcano, Khalida M Wani, Wei-Lien Wang, Alexander J Lazar, Nizar M Tannir, Cheryl L Walker, Cristian Coarfa, Pavlos Msaouel

Faculty, Staff and Student Publications

Purpose: Renal medullary carcinoma (RMC) is a highly aggressive malignancy defined by the loss of the SMARCB1 tumor suppressor. It mainly affects young individuals of African descent with sickle cell trait, and it is resistant to conventional therapies used for other renal cell carcinomas. This study aimed to identify potential biomarkers for early detection and disease monitoring of RMC.

Experimental design: Integrated profiling of primary untreated RMC tumor tissues and paired adjacent kidney controls was performed using RNA sequencing and histone chromatin immunoprecipitation sequencing. The expression of serum cancer antigen 125 (CA-125), was prospectively evaluated in 47 patients with RMC. …

Exploring The Therapeutic Potential Of Trigonella Foenum-Graecum Extract-Loaded Transferosomal Gel In Freund's Complete Adjuvant-Induced Rat Models., Vandana Singh Ms., Hema Arya Ms., Bhavana Singh Dr., Koushal Dhamija Mr., Preeti Singh Dr., Gautam Kumar Dr.

Chulalongkorn Medical Journal

Abstract:

Background: Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by inflammation and joint damage.

Objective: This study aimed to evaluate the antiarthritic activity of Trigonella foenum-graecum (TFG) Transferosomal gel in a Freund’s adjuvant-induced arthritic rat model and compare it with Diclofenac gel, a standard anti-inflammatory drug.

Methods: Arthritis was induced in rats by injecting a 0.1 mL (1mg/ml) CFA suspension into the left hind foot in the subplantar region, allowing them to develop arthritis for 21 days.

Results: Arthritis induction led to a significant increase in paw volume, indicative of inflammation. Treatment with both TFG-transferosomal gel and Diclofenac …

Fighting Instinct: The Brain, Emotions And Decision-Making In The Water, Jill Nash, Sam Hills

International Journal of Aquatic Research and Education

This conceptual paper explores the complex interplay among the human brain, emotions, and decision-making processes, particularly in aquatic environments. Integrating insights from neuroscience, psychology, and behavioural economics, we investigate how instinctual responses and emotional states influence our decisions during water-related activities. By analysing both biological and psychological factors, the paper aims to illuminate the intricacies of human behaviour in various aquatic settings and highlights significant gaps in the research on emotional decision-making that warrant further investigation. Additionally, the paper suggests interventions, including plausible communication strategies, to mitigate the impact of instinctual responses and improve safety and decision-making efficiency.

Superior Preclinical Efficacy Of Co-Treatment With Brg1/Brm And Flt3 Inhibitor Against Aml Cells With Flt3 Mutations, Warren Fiskus, Christopher P Mill, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Tapan M Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Patrick K Reville, Lauren B Flores, Sanam Loghavi, Xiaoping Su, Courtney D Dinardo, Kapil N Bhalla

Faculty, Staff and Student Publications

Although treatment with standard frontline therapies, including a FLT3 inhibitor (FLT3i) reduces AML burden and achieves clinical remissions, most patients with AML with FLT3 mutation relapse due to therapy-resistant stem/progenitor cells. The core ATPases, BRG1 (SMARCA4) and BRM (SMARCA2) of the canonical (c) BAF (BRG1/BRM-associated factor) complex is a dependency in AML cells, including those harboring FLT3 mutations. We have previously reported that treatment with FHD-286, a BRG1/BRM ATPases inhibitor, induces differentiation and loss of viability of AML stem/progenitor cells. Findings of present studies demonstrate that treatment with FHD-286 induces lethality in AML cells, regardless of sensitivity or resistance to …

Empowering Young Innovators Through School-Based Agricultural Education: Insights From A Nigerian Secondary School Teacher, Mary O. Olumide-Oyaniyi

National Collaborative for Research on Food, Energy, and Water Education (NC-FEW)

Nigeria faces challenges like food insecurity and economic instability, worsened by a growing youth population. School-Based Agricultural Education (SBAE) engages youth in agricultural innovations. This study implemented SBAE principles in a Nigerian school, combining poultry farming and aquaculture. Students managed a poultry farm, using chicken droppings to breed maggots as feed for catfish in rainwater-filled tanks. The project enhanced students' skills, improved local food production, and engaged the community. Despite funding and management challenges, the initiative demonstrated SBAE's potential to empower youth and advance agricultural practices, offering a model for similar projects in other regions.

Integrating The Few-Nexus Into An Agricultural Issues Course, Christopher M. Estepp, Hannah Scherer

National Collaborative for Research on Food, Energy, and Water Education (NC-FEW)

To address the global challenges facing the agricultural industry, graduates of agricultural degree programs must learn to utilize systems thinking skills, which can help them view the interconnectedness among issues and design holistic solutions. The Food-Energy-Water (FEW)-Nexus is an interdisciplinary framework that can support undergraduate student achievement of sustainability education competencies, including systems thinking. This project utilized the FEW-Nexus framework in an agricultural issues course to help students improve their systems thinking. Students were given lectures on various agricultural issues by experts in those areas. Two assignments, agricultural issue concept maps and critical reflections over each speaker’s session were completed …

Physical And Biological Effects On Moths’ Navigation Performance, Yiftach Golov, Roi Gurka, Alexander Liberzon, Ally Harari

Physics and Engineering Science

In a chemosensing system, the local olfactory environment experienced by a foraging organism is defined as an odorscape. Using the nocturnal pink bollworm moth (Pectinophora gossypiella), we tested the combined effect of three biophysical aspects in its immediate odorscape to shed light on the coupling effects of biotic and abiotic factors on navigation performances of a nocturnal forager: i) the quality of the pheromone source, ii) the pheromone availability, and iii) the airflow characteristics. The navigation performance of the males was investigated using a wind tunnel assay equipped with 3D infrared high-speed cameras. The navigation performance of the males was …

Strategies To Improve Antibody-Mediated Protection Against Herpes Simplex Virus Infections, Matthew D. Slein

Dartmouth College Ph.D Dissertations

No efficacious vaccine exists for herpes simplex virus and the global burden of disease remains high. Antibodies can serve as potent therapeutics to protect high risk populations such as neonates. Although rare, neonatal HSV (nHSV) infections can result in significant mortality and lifelong neurological morbidity even with antiviral therapy. While HSV-specific maternally derived antibodies significantly reduce the risk of neonatal disease in humans, the mechanisms by which they mediate protection have yet to be described. Using a mouse model of neonatal HSV (nHSV) infections we aimed to determine the mechanisms of antibody-mediated protection using monoclonal antibodies (mAbs) targeting two of …

The Sustainability Stones: Culturally Embedded Conservation Strategies And Their Vulnerability In Maupiti, French Polynesia, Russell Fielding, Fiona Gimenez

Honors College Faculty Publications

This paper explores culturally embedded conservation strategies through the lens of the traditional agroforestry and fisheries cycles in Maupiti, French Polynesia. By pairing certain breadfruit cultivars with specific fish species, the island’s community created a culinary system that regulates the seasonal consumption of marine resources, making the sustainable use of those resources more likely. While modern pressures such as reduced breadfruit diversity, competition with imported foods, and climate change have weakened these traditional practices, they remain an example of local ecological knowledge guiding conservation. The study highlights the threat of losing sustainable resource-use practices and biodiversity as both biodiversity and …

Juvenile And Adult Survival Estimates Of American Kestrels Throughout The Full Annual Cycle In Eastern North America, Mercy Melo, Joseph M. Kolowski, Rebecca A. Mccabe, John A. Smallwood, Allison Cornell, David King, Jean François Therrien

Department of Biology Faculty Scholarship and Creative Works

Measuring survival in a declining species provides the foundation for continued research, demographic modeling, and informed conservation strategies. Although American Kestrel (Falco sparverius) populations have continued to decline since the 1970s, little is known about their survival throughout the full annual cycle, making it difficult to identify factors responsible for these declines. We used radio telemetry to provide the first known-fate estimates of adult kestrel survival, and we present data across breeding stages, and between resident and migratory wintering individuals, in addition to separately modeling fledgling survival. Temporal and spatial stratification of study sites allowed for the investigation of different …

Sustainable Sediment Management In Jordanian Dams: Feasibility, Economic Viability, And Agricultural Reuse Potential, Ahmed Al-Taani, Nazem El Radaideh, Wesam Al Kateeb, Fares Howari, Yousef Nazzal, Jibran Iqbal, Abeer Al Bsoul

All Works

Jordan has long faced severe water scarcity, which has significant implications for agriculture, industry, and domestic consumption. This crisis is further exacerbated by climate change, population growth, regional conflicts, and unsustainable water use. In response, Jordan has focused heavily on dam construction to secure water supplies, despite the high financial and environmental costs. However, rapid sedimentation threatens dam storage capacity and operational efficiency, reducing their lifespan and long-term sustainability. This study evaluates the feasibility of sediment removal as an alternative to constructing new dams, considering environmental, technical, agricultural, and economic factors. The research is based on case studies from King …

Tunneling Nanotube-Like Structures Regulate Distant Cellular Interactions During Heart Formation, Lianjie Miao, Yangyang Lu, Anika Nusrat, Guizhen Fan, Shaohua Zhang, Luqi Zhao, Chia-Ling Wu, Hongyan Guo, Trang Le Nu Huyen, Yi Zheng, Zhen-Chuan Fan, Weinian Shou, Robert J Schwartz, Yu Liu, Ashok Kumar, Haixin Sui, Irina I Serysheva, Alan R Burns, Leo Q Wan, Bin Zhou, Sylvia M Evans, Mingfu Wu

Faculty, Staff and Student Publications

In the developing mammalian heart, the endocardium and the myocardium are separated by so-called cardiac jelly. Communication between the endocardium and the myocardium is essential for cardiac morphogenesis. How membrane-localized receptors and ligands achieve interaction across the cardiac jelly is not understood. Working in developing mouse cardiac morphogenesis models, we used a variety of cellular, imaging, and genetic approaches to elucidate this question. We found that myocardium and endocardium interacted directly through microstructures termed tunneling nanotube-like structures (TNTLs). TNTLs extended from cardiomyocytes (CMs) to contact endocardial cells (ECs) directly. TNTLs transported cytoplasmic proteins, transduced signals between CMs and ECs, and …

Exploration Of Working Memory Retrieval Stage For Mild Cognitive Impairment: Time-Varying Causality Analysis Of Electroencephalogram Based On Dynamic Brain Networks, Yi Jiang, Zhiwei Guo, Xiaobo Zhou, Ning Jiang, Jiayuan He

Faculty, Staff and Student Publications

Background: Mild Cognitive Impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and Alzheimer's disease (AD). Its management is crucial for it helps intervene and slow the progression of cognitive decline to AD. However, the understanding of the MCI mechanism is not completely clear. As working memory (WM) damage is a common symptom of MCI, this study focused on the core stage of WM, i.e., the memory retrieval stage, to investigate information processing and the causality relationships among brain regions based on electroencephalogram (EEG) signals.

Method: 21 MCI and 20 normal cognitive control (NC) participants …

More Choosy For Minor Foods: Diet, Seasonality And Food Selection In Sympatric Frugivorous And Folivorous Lemurs, Mitchell Irwin, Vololonirina Rahalinarivo, Bruno Ramorasata, Jean-Luc Raharison, Jean-Freddy Ranaivoarisoa, Chloé Gherardi, Jessica Rothman

Faculty Articles, Papers, and Other Scholarship

Despite traditional dietary categories common in primatology (folivore, frugivore, insectivore), most primates use one or more food types beyond their primary one. Among lemurs, folivores tend to have a complicated, long gastrointestinal tract with an enlarged cecum, shearing teeth, and microbiome adaptations to foliage, while frugivores have simple teeth and guts and fast gut passage. Yet frugivores often eat some leaves, and folivores eat some fruit, and little is known about the selection rules they follow within each food type. We quantified diet and food chemistry for two sympatric rainforest lemurs: a cathemeral frugivore (brown lemur, Eulemur fulvus) and a …

Salmon As An Ecological Pathway Of Contaminants Into Alaskan Food Webs, Miranda Brohman, Gretchen Roffler, Dimitri G. Giarikos, David Kerstetter, Amy C. Hirons

SECLER Data

Salmon are important fish taxa for humans and animals in hemiboreal and subarctic ecosystems. Trace elements and their marine food web bioaccumulation raises biomagnification and potential human health risk concerns. Sixteen trace element concentrations and their health risk assessments were determined in seven different tissues of two Southeast Alaska salmon species (chum, Oncorhynchus keta and pink, Oncorhynchus gorbuscha). Chum tissues had overall higher trace element concentrations compared to pink, which may be attributed to a difference of diets, generally longer-lived and spending more time in the open ocean. All kidney and liver samples exceeded the tolerable daily intake for …

Cranial Radiation Disrupts Dopaminergic Signaling And Connectivity In The Mammalian Brain, Die Zhang, Riya Thomas, Thanh Thai Lam, Ines Veselinovic, David R Grosshans

Faculty, Staff and Student Publications

Cognitive impairment is a common and challenging side effect of cranial radiation therapy for brain tumors, though its precise mechanisms remain unclear. The mesocortical dopaminergic pathway, known to play a key role in cognitive function, is implicated in several neuropsychiatric disorders, yet its involvement in radiation-induced cognitive dysfunction is unexplored. Here, with using in vivo multi-electrode array recordings of both anesthetized and free-moving rats to monitor the firing activities of dopamine neurons in the ventral tegmental area (VTA) and local field potentials in both the prefrontal cortex (PFC) and VTA, as well as the immunofluorescence assays and western blotting, we …

Closing Ceremony Speech, S. Ray Smith

IGC Proceedings (1977-2023)

No abstract provided.

Strategies Of Fertilizer Nitrogen Applications To Grassland For Beef: Effects On Production And Soil Mineral Nitrogen, N M. Titchen, R J. Wilkins, L Philipps, D Scholefield

IGC Proceedings (1977-2023)

Experiments in Britain have shown beef production increases with fertilizer-N application to grazed grassland up to at least 300 kg N/ha (Wilkins et al., 1987; Baker and Mayne, 1988). However in view of the small offtake of N in the animal products (c.30 kg/ha) there is increased concern on the fate of the applied N, particularly in relation to loss of nitrate by leaching (Garwood and Ryden, 1986). This paper reports a 3-year experiment which examined the impact on production and on N movements of different strategies of fertilizer-N appli­cation and of the effects of removing grazing livestock at the …

F.A.O Design K*B*P Trials In The Mid-Altitude Zone Of Yunnan Province, Southern China, J Bruce-Smith, Yang Guo-Rong, Huang Bi-Zhi, Li Ji-Xin

IGC Proceedings (1977-2023)

The Project is investigating the development of « improved pastures » as a practical way to increase ruminant livestock production. Some preliminary results of fertilizer requirements, indicated that K and B may be required as well as P (Wang el al., 1985) for the establishment of such pastures in this mid-alti­tude (2,000 m) transitional sub-tropic-temperate zone of Yunnan. The objective of this paper is to present some experiences from applying the Hauser (1971) truncated fac­torial design trials (widely used by FAO to obtain N, P, K, fert­ilizer recommendations for cereal crops) to a pasture establish­ment situation where P. K and …

Effect Of Nitrogen Fertilization In Combination With Potassium And Phosphorus And Cutting Frequency On The Yield Of Brachiaria Ruzizensis In Adamawa, Cameroon, E T. Pamo, D Pieper

IGC Proceedings (1977-2023)

Fertilizers have been shown to increase forage yields under some conditions (Owensby and Smith, 1975), but has very little effect under other conditions (Stoddart et al., 1975). Thus in recent years a great deal of attention has been focussed on the ways and possibilities of increasing forage production by fertil­ization. Various experiments have been conducted on the response of Brarhiaria ruziziensis Germain and Evrad, one of the best perennial forage grasses of the region, to fertilization at Wakwa Animal Research Station. Yonkeu et al., (1986) indicated that application of phosphorus did not lead to improved yield of the forage on …

The Influence Of Cow Manure On Forage Yields Of King Grass In A Ferrasol In Cuba, G Crespo, M Oduardo

IGC Proceedings (1977-2023)

Experiments conducted in sandy and brown soils in Cuba demonstrated the beneficial effect of manure for accelerating the establishment of forage plants, and the possibility of dimi­nishing up to 50 % the dosage of N fertilizer requirements to obtain maximum forage yield (Crespo and Diez 1978; Crespo and Arteaga 1984). The aims of the present experiments were: a) to determine the best time of application of cow manure and b) to learn the influence of manure and nitrogenous fertilizer on forage yield of king grass in a ferrasol soil.

Continuous Exposure To An Aversive Mixture: A Means Of Maintaining Aversion In Sheep Averted To Geigeria Ornativa O. Hoffm. (Vermeerbos) - An Assessment, Leendert D. Snyman

Poisonous Plant Research (PPR)

Establishing aversion to Geigeria ornativa only lasts for some time, after which the induced aversion disappears and sheep start eating G. ornativa again. This behavior is aggravated by the social influence of non-averted sheep in mixed grazing situations. Exposing sheep continuously to a so-called “aversive mixture”, containing an aversive substance (lithium chloride) and the sensory characteristics of the plant (hexane extract of G. ornativa) mixed with a tasty meal (maize meal), following an initial aversion treatment, resulted in sustained aversion to G. ornativa in the field. This method proved to be applicable to mixed grazing situations with averted and …

2025 Nebraska Farmland Values And Cash Rental Rates, Jim Jansen

Cornhusker Economics

The market value of agricultural land in Nebraska declined by 2% over the prior year to an average of $3,935 per acre, according to the 2025 Nebraska Farm Real Estate Market Survey. This marks the first decline in the market value of agricultural land in Nebraska since reaching the record non-inflation-adjusted statewide land value in the survey's 46-year history in 2024.

The University of Nebraska-Lincoln’s Department of Agricultural Economics annually surveys land industry professionals across Nebraska, including appraisers, farm and ranch managers, agricultural bankers, and related industry professionals. Results from the survey are divided by land class and summarized by …

The Expression Profile Of The Rank/Rankl/Opg Pathway In Breast Cancer Stem Cells Isolated From Breast Cancer Cell Lines, Mohamed M. Kamal, Hassnaa H. Elgohary, Sherine Maher Rizk, Nadine H. Maurice

Pharmacy

The RANK/RANKL/OPG signaling pathway plays a crucial role in breast cancer progression and metastasis. However, its expression patterns and potential implications in breast cancer stem cells remain poorly understood. This study aimed to characterize the expression profile of this pathway in breast cancer stem cells isolated from two distinct breast cancer cell lines: MDA‐MB‐231 and MCF‐7. Mammospheres (MS), representing breast cancer stem cells, were generated using agar‐coated 6 well tissue culture plates in suitable mammospheres culture conditions. Flow cytometric analysis showed enrichment of the CD44+/ CD24− subpopulations in the mammospheres cultures, with MDA‐MB‐231 exhibiting a higher percentage compared to MCF‐7. …

General Biology 2 Laboratory Manual: In Person Edition, Dmitry Y. Brogun, Azure N. Faucette, Farshad Tamari, Kristin Polizzotto

Open Educational Resources

The completed project is an in-person teaching version of the General Biology II OER (Open Educational Resource) lab manual. This lab manual was initially written by the four of us during the pandemic when all courses were online, but it is now has been adapted for in-person lab activities. We also ensured it aligns with UDL (Universal Design for Learning) and accessibility principles. This adaptation aims to make the lab manual suitable for traditional classroom settings while incorporating diverse teaching practices to accommodate diverse learners.

Influence Of Inselbergs On Bat Diversity In Afrotropical Ecosystems, Amanda Lee Grunwald

Dissertations and Theses

Humans are altering biological communities on local to global scales, driving profound changes in biodiversity and ecosystem functioning. However, significant gaps and biases in biodiversity data hinder our understanding of ecosystem interactions, making it challenging to develop effective, data-driven policies to protect remaining biodiversity. Bats, the second most species-rich groups of mammals, have a global distribution, and perform a broad array of vital ecosystem functions. Their diversity peaks in the tropics, where they often constitute more than 50% of mammal species diversity. The Afrotropics host substantial bat diversity, yet have historically been perceived as having lower species richness compared to …

Control Of Clostridioides Difficile Virulence And Physiology By The Flagellin Homeostasis Checkpoint Flic-Fliw-Csra In The Absence Of Motility, Duolong Zhu, Katherine J Wozniak, Firas Midani, Shaohui Wang, Xingmin Sun, Robert A Britton

Faculty, Staff and Students Publications

Mutations affecting Clostridioides difficile flagellin (FliC) have been shown to be hypervirulent in animal models and display increased toxin production and alterations in central metabolism. The regulation of flagellin levels in bacteria is governed by a tripartite regulatory network involving fliC, fliW, and csrA, which creates a feedback system to regulate flagella production. Through genomic analysis of C. difficile clade 5 strains (non-motile), we identified they have jettisoned many of the genes required for flagellum biosynthesis yet retain the major flagellin gene fliC and regulatory gene fliW. We therefore investigated the roles of fliC, fliW …