Digital Commons Network^™

Immune Variation Across Different Contexts In Non-Model Systems, Kwanho Claudia Ki

All Graduate Theses and Dissertations, Fall 2023 to Present

The immune system is important to an animal’s survival against disease-causing agents and physical injuries. Accordingly, many resources are required to maintain and activate the immune system (such as energy). However, as these resources also need to be shared with other important systems of the body, the portion of resources that can be allotted to the immune system is variable. Thus, many different factors may alter how well the immune system operates. My dissertation sought to understand what sorts of factors can lead to changes in the immune system. Reptiles are known to have a very robust immune system. Therefore, …

From Pasture To Plate: Striking An Omega Balance Between Grass-Fed And Grain-Fed Beef Ribeyes - Fatty Acid Composition, Minerals, Soil, And Forage Analysis, Travis Earl Statham

All Graduate Theses and Dissertations, Fall 2023 to Present

Most beef cattle in the US are feedlot-finished where intensive feeding of grains is used to increase weight and yield; however, a minority are raised in grass-fed operations that use exclusive pasture, rangeland, and hay for feeding, possibly leading to benefits for the land, soil, ecosystems, forages, and the meat itself. These operations use a variety of methods, and the goal of this was to recognize differences in the soil and forage metrics to help understand the resulting meat fatty acid composition and mineral content. We collected these samples from 78 sets of farmers while testing 25 sets of grain-fed …

Are Universities Adequately Preparing Undergraduate Students For Careers As Professional Wildlife Biologists?, Trevon D. Strange

All Graduate Theses and Dissertations, Fall 2023 to Present

The demands for diversely skilled wildlife biologists and scientific researchers in the wildlife profession are projected to increase. Increasing urbanization has affected wildlife management, and the recruitment of future wildlife professionals. Thus, state and federal supervisors in agencies that hire wildlife professionals are concerned that recent graduates of university wildlife programs lack the necessary skill-sets to address these complex contemporary wildlife management issues. My research sought to identify where the educational performance gaps may exist between university wildlife programs, wildlife agencies, and student expectations. To conduct my research, I evaluated undergraduate wildlife curricula offered by 42 accredited universities listed on …

Adolescent Mental Health And Social Media: The Roles Of Psychosocial Development And Online Interaction, Mark L. Ferguson

All Graduate Theses and Dissertations, Fall 2023 to Present

Social media has become an integral part of adolescent life, and its effects on adolescents’ mental health has been studied for over twenty years. However, the research approaches used to discover connections between adolescent social media use and their mental health have been diverse, and findings have varied over time. This study sought to explore the potential relationships between adolescent social media use and mental health by including several different variables that aren’t typically accounted for in the same study, such as attachment to parents and peers, internal psychological development, emotional intensity towards social media use, and how adolescents feel …

Mathematical And Statistical Methods To Harness Limited Data In Models For Ecological Space Use Under Global Change, Sarah C. Bogen

All Graduate Theses and Dissertations, Fall 2023 to Present

The dynamics of how plants and animals use space in their habitats has important implications for the fields of ecology and conservation. However, understanding and responding to these spatial and temporal dynamics is often limited by data availability, financial resources and biases. As average global temperatures increase, suitable habitats shift poleward and require local populations to move with suitable habitat, adapt to the changing environment, or risk extinction. Capacity to persist without movement may be estimated by considering changes to a combination of habitat characteristics. Capacity to track suitable habitat may be modeled through synthesizing information on species demographic mechanisms …

Corrosion Behavior Of Laser Powder Bed Fusion Additive Manufacturing Produced Tini Alloy By Micro-Arc Oxidation, Xin Zhao, Yicheng Liu, Chenfan Jia, Hao Chang, Wei Zhang, Yun Bai, Shujun Li, Lai-Chang Zhang, Wei Yuan

Research outputs 2022 to 2026

To improve the corrosion resistance of TiNi alloy fabricated by laser powder bed fusion (LPBF), a porous oxidation layer was synthesized by micro-arc oxidation in a sodium aluminate and sodium silicate electrolyte. The influences of the applied voltage and the processing time on the morphology of oxidation layer were investigated, and the corrosion behavior of the oxidation layer in artificial saliva was evaluated and compared with that of the as-fabricated LPBF alloy. The results indicate that, as increasing the applied voltage and the processing time, the oxidation layer becomes uniform and integrated. The optimum parameters are with an applied voltage …

Environmental Dna Identifies Coastal Plant Community Shift 1,000 Years Ago In Torrens Island, South Australia, Nicole R. Foster, Alice R. Jones, Oscar Serrano, Anna Lafratta, Paul S. Lavery, Kor-Jent Van Dijk, Ed Biffin, Bronwyn M. Gillanders, Jennifer Young, Pere Masque, Patricia S. Gadd, Geraldine E. Jacobsen, Atun Zawadzki, Andria Greene, Michelle Waycott

Research outputs 2022 to 2026

Anthropogenic activities are causing detrimental changes to coastal plants– namely seagrass, mangrove, and tidal marshes. Looking beyond recent times to past vegetation dynamics is critical to assess the response and resilience of an environment to change. Here, we develop a high-resolution multi-proxy approach, providing a new evidence base to decipher long-term change in coastal plant communities. Combining targeted environmental DNA analysis with chemical analysis of soils, we reconstructed 4,000 years of change at a temperate wetland on Torrens Island South Australia and identified an ecosystem shift that occurred ~ 1000 years ago. What was once a subtidal seagrass system shifted …

Organ Pedalboard As A Rehabilitation Tool: A Qualitative Exploratory Study Of Healthcare Providers’ Perceptions And Recommendations, Mandy M.P. Kan, Wai Hang Kwok, Eric C. Fan, Fadi M. Al Zoubi

Research outputs 2022 to 2026

Objective This qualitative study explored healthcare providers’ perceptions and attitudes regarding the use of organ pedalboards as a rehabilitation tool, particularly for lower extremity conditions. The study also sought to identify the perceived barriers and facilitators to adopting organ pedalboards within rehabilitation settings, as well as gather healthcare providers’ recommendations for integrating this tool into clinical practice. Method Healthcare providers, including physiotherapists, occupational therapists, music therapists, and sports therapists, were recruited for focus group interviews using purposive and snowball sampling. At the outset of the interview, participants watched an organist playing musical notes on a pedalboard and had the opportunity …

What Journalism Feels Like: Considering The Body Of The Journalist, Mark Deuze, Laura Glitsos

Research outputs 2022 to 2026

All journalists have bodies. This commonsensical fact acquires more currency every day as the work of reporters and editors becomes automated, robotized, and taken over by (generative) artificial intelligence. The embodied nature of news work matters, not in the least because of the personal attachment practitioners have to what journalism is, or should be. However, in the rich history of journalism studies, bodily perspectives are remarkably absent—beyond descriptions of journalists as sociodemographic profiles. In this essay, we explore various theoretical frameworks to bring the body back into the study and practice of journalism. In our argument, we apply the insights …

Crosstalk Between Cytokines And Igg N-Glycosylation: Bidirectional Effects And Relevance To Clinical Innovation For Inflammatory Diseases, Zhixian Chen, Xiaojia Xu, Manshu Song, Ling Lin

Research outputs 2022 to 2026

The crosstalk between cytokines and immunoglobulin G (IgG) N-glycosylation forms a bidirectional regulatory network that significantly impacts inflammation and immune function. This review examines how various cytokines, both pro- and anti-inflammatory, modulate IgG N-glycosylation, shaping antibody activity and influencing inflammatory responses. In addition, we explore how altered IgG N-glycosylation patterns affect cytokine production and immune signaling, either promoting or reducing inflammation. Through a comprehensive analysis of current studies, this review underscores the dynamic relationship between cytokines and IgG N-glycosylation. These insights enhance our understanding of the mechanisms underlying inflammatory diseases and contribute to improved strategies for disease prevention, diagnosis, monitoring, …

Genome-Wide Cross-Disease Analyses Highlight Causality And Shared Biological Pathways Of Type 2 Diabetes With Gastrointestinal Disorders, Emmanuel O. Adewuyi, Tenielle Porter, Eleanor K. O’Brien, Oladapo Olaniru, Giuseppe Verdile, Simon M. Laws

Research outputs 2022 to 2026

Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess the genetic relationship between type 2 diabetes (T2D) and GI disorders. Our study demonstrates a significant positive global genetic correlation of T2D with peptic ulcer disease (PUD), irritable bowel syndrome (IBS), gastritis-duodenitis, gastroesophageal reflux disease (GERD), and diverticular disease, but not inflammatory bowel disease (IBD). We identify several positive local genetic correlations (negative for T2D – IBD) contributing to T2D’s relationship with GI disorders. Univariable and multivariable Mendelian randomisation analyses suggest causal effects of T2D on PUD and gastritis-duodenitis and …

Role Of N-Glycosylation In Gastrointestinal Cancers, Ruirui Xu, Lois Balmer, Gengzhen Chen, Manshu Song

Research outputs 2022 to 2026

Gastrointestinal cancers pose a significant global health challenge. N-glycosylation modulates various cellular processes, including key cancer-related mechanisms. Elucidating its involvement in the onset and advancement of these cancers can offer critical insights for enhancing diagnostic and therapeutic approaches. This review outlines the core process of protein N-glycosylation and highlights its contribution to the progression of gastrointestinal cancers, encompassing cell proliferation, survival, invasion, metastasis, and immune evasion, mainly through its impact on critical signaling pathways. Notably, aberrant N-glycosylation patterns have emerged as crucial biomarkers for the diagnosis and prognosis of various gastrointestinal cancers, providing the foundation for more personalized therapeutic approaches. …

Patterns Of Carbon And Nitrogen Accumulation In Seagrass (Posidonia Oceanica) Meadows Of The Eastern Mediterranean Sea, Eugenia T. Apostolaki, Paul S. Lavery, Victoria Litsi-Mizan, Eduard Serrano, Karina Inostroza, Vasilis Gerakaris, Thanos Dailianis, Julius Glampedakis, Tara Holitzki, Erik Johnson, Miguel A. Mateo, Oscar Serrano

Research outputs 2022 to 2026

The variability in stocks and accumulation rates of organic carbon (Corg), nitrogen (N), and carbonate (CaCO3) was studied in fifteen Posidonia oceanica meadows spread throughout the South Aegean Sea (Greece). In addition, the abiotic and biotic drivers determining the pattern of variability in the accumulation rates were assessed by exploring the influence of sediment characteristics, seagrass traits, and environmental settings. The meadows supported on average (±STDEV) 14.6 ± 5.0 kg Corg m−2, 0.47 ± 0.17 kg N m−2, and 249 ± 210 kg CaCO3 m−2 in the top meter of their sediments, with mean accumulation rates over the last 500 …

Oscillometry Changes Reflect Clinically Meaningful Improvement After Bronchial Thermoplasty For Uncontrolled Asthma: A Case Report, Niranjan Setty, Alice Crawford, Brooke Kyle, Dhaval Thakkar, Rajesh Thomas, John Blakey

Research outputs 2022 to 2026

Asthma is a highly prevalent but heterogenous condition. Uncontrolled disease is relatively common and may be due to ongoing inflammation and/or persisting bronchial hyper-reactivity. Bronchial thermoplasty has been in use for many years but optimal case selection and post-procedure assessment remain uncertain. We present a case of a gentleman in his 50s with lifelong asthma who experienced a persistent loss of control following influenza A in 2017. Despite multidisciplinary assessment and guideline-based escalation of therapy, he had persisting symptoms. In the context of his atopy, he was trialled unsuccessfully on dupilumab. Bronchial thermoplasty (BT) was undertaken with good clinical benefit. …

Predation Rates On Flatback Turtle Natator Depressus Eggs And Hatchlings At An Island Rookery, Casper Avenant, Sabrina Fossette, Scott Whiting, Glenn A. Hyndes

Research outputs 2022 to 2026

Predation can significantly threaten the vulnerable egg and hatchling stages of sea turtles, yet for most populations this remains poorly quantified for use in conservation. We provided the first quantified predation rates of flatback turtle eggs and hatchlings at Thevenard Island, a medium-sized rookery on the northwest coast of Australia, with a focus on ghost crabs as potential predators. Burrow densities were used as proxy for ghost crab densities, while start- and end-of-season nest inventories and infrared videography were used to quantify egg and hatchling predation, respectively. Inventories of 27 nests suggested a mean hatching success of 74.2 ± 4.6% …

Morphological And Physiological Changes Of Katuray (Sesbania Grandiflora) During Seed Maturation [Research Note], Alangelico San Pascual, Lucille Elna De Guzman, Maurice Gravidez, Elijah Estante

The Philippine Agricultural Scientist

Katuray (Sesbania grandiflora), whose flowers are consumed as steamed vegetables, is an important green manure crop in the Philippines. Understanding different processes leading to seed maturity can aid in determining S. grandiflora’s seed quality, preventing premature harvesting for seed increase, ensuring efficient propagation and production of seedlings, and breeding new varieties of this crop. Multiple flowers were tagged, and three to five pods were collected five days after anthesis (DAA) and at a five-day interval thereafter until 100% germination was achieved. Seed size, moisture content (MC), dry weight, germination percentage, and embryo development were observed and recorded. Seed length was …

Comparative Analysis Of Household Food And Nutrition Security In Selected Philippine Urban And Rural Households During The Covid-19 Pandemic, Jay-Al Reyes, Julieta Delosreyes

The Philippine Agricultural Scientist

This study analyzed the food and nutrition security of selected urban and rural households in Pili, Camarines Sur, Philippines during the COVID-19 pandemic. It determined the prevalence of food insecurity among the selected urban and rural households, analyzed the determinants of food insecurity in these households, determined the prevalence of malnutrition, and assessed the relationship between the households’ food security and nutrition security. Primary data from a survey of 185 urban and rural households and secondary data from the Electronic Operation Timbang Plus (e-OPT) Tool were used to determine the prevalence of food insecurity using the Food Insecurity Experience Scale …

Bioactivity And Synergism Of Tagpo (Ardisia Tomentosa) Molluscicidal Extracts, Darwin C. Gomez, Grechelle Socias, Rosemarie Galanza, Florlyn C. Gayas Ma., Fe T. Piedad, Brian John Sarno

The Philippine Agricultural Scientist

Population control of golden apple snails (GAS, Pomacea canaliculata) is beneficial in rice farming; however, the associated control measures can be expensive and time-consuming. Currently, farmers use synthetic molluscicides such as niclosamide to control GAS infestation, but this has some drawbacks. For example, niclosamide has broad toxicity to non-target organisms and negatively affects the growth of rice seedlings. Plant extracts with potent bioactivity and low toxicity to non-target organisms are attractive alternatives to synthetic molluscicides. In this study, the bioactivity of the crude fruit extract of tagpo (Ardisia tomentosa) was assessed against GAS and tilapia (Oreochromis niloticus) fries. The potential …

Field Assessment Of Fertilization, Nursery, And Crop Management Practices Among Tomato (Solanum Lycopersicum L.) Growers In The Ilocos Provinces, Philippines, Annalissa Aquino, Sancho Bon, Angelica Guanlao, Ann Mylalulex Magnaye, Filomena Sta Cruz, Pompe C. Sta. Cruz

The Philippine Agricultural Scientist

Growth and yield of many economically important vegetables like tomatoes are heavily influenced by crop management practices, particularly fertilizer application, irrigation scheme, and pest management. To attain maximum tomato yields and increase farmers’ profits, these crop production components must be optimized in local farm levels. Before optimization measures can be conducted, baseline information on prevailing practices needs to be evaluated. To assess the nutrient management and other crop production practices of tomato farmers in the Ilocos provinces, Philippines, on-farm surveys were conducted in 16 and 18 barangays planting fresh-type and processing-type tomatoes, respectively. The study involved a total of 88 …

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Rachel L Henson, Beau Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer's disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

METHODS: We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium-Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

Subcutaneous Ocrelizumab In Multiple Sclerosis: Results Of The Phase 1b Ocarina I Study, Scott D Newsome, Robert T Naismith, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Subcutaneous ocrelizumab is being developed to provide treatment flexibility and additional choice to patients with multiple sclerosis. OCARINA I (NCT03972306) is an open-label, multicenter, Phase 1b, dose-finding study to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of subcutaneous ocrelizumab and to select a dose for the Phase 3 OCARINA II study (NCT05232825).

METHODS: Patients with relapsing or primary progressive multiple sclerosis (aged 18-65 years; Expanded Disability Status Scale score 0.0-6.5) were enrolled into two groups: previously treated with intravenous ocrelizumab (Group A) or naïve to ocrelizumab (Group B). Patients received single ascending doses of subcutaneous ocrelizumab up to 1200 …

Quantifying Brain Development In The Healthy Brain And Child Development (Hbcd) Study: The Magnetic Resonance Imaging And Spectroscopy Protocol, Douglas C Dean 3rd, Chad M Sylvester, Michael P Harms, Christopher D Smyser, Et Al.

2020-Current year OA Pubs

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition …

Inflammation, Physical Activity, And Disease-Free Survival In Stage Iii Colon Cancer: Cancer And Leukemia Group B-Southwest Oncology Group 80702 (Alliance), Justin C Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M Goldberg, Eileen M O'Reilly, Anthony F Shields, Jeffrey A Meyerhardt

2020-Current year OA Pubs

BACKGROUND: Inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown.

METHODS: This cohort study was nested within the Cancer and Leukemia Group B (now part of the Alliance for Clinical Trials in Oncology) and Southwest Oncology Group randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free …

Development And Validation Of A Prechiasmatic Mouse Model Of Subarachnoid Hemorrhage To Measure Long-Term Cognitive Deficits, Deepti Diwan, Jogender Mehla, James W Nelson, James D Quirk, Sheng-Kwei Song, Sarah Cao, Benjamin Meron, Aminah Mostofa, Gregory J Zipfel

2020-Current year OA Pubs

Controllable and reproducible animal models of aneurysmal subarachnoid hemorrhage (SAH) are crucial for the systematic study of the pathophysiology and treatment of this debilitating condition. However, current animal models have not been successful in replicating the pathology and disabilities seen in SAH patients, especially the long-term neurocognitive deficits that affect the survivor's quality of life. Therefore, there is an unmet need to develop experimental models that reliably replicate the long-term clinical ramifications of SAH - especially in mice where genetic manipulations are straightforward and readily available. To address this need, a standardized mouse SAH model is developed that reproducibly produced …

Dysfunctional Alpha Modulation As A Mechanism Of Working Memory Impairment In Serious Mental Illness, Molly A Erickson, Megan A Boudewyn, Kurt Winsler, Charlotte Li, Deanna M Barch, Cameron S Carter, Michael J Frank, James M Gold, Angus W Macdonald 3rd, John D Ragland, Steven M Silverstein, Andrew Yonelinas, Steven J Luck

2020-Current year OA Pubs

BACKGROUND: People with psychosis and mood disorders experience disruptions in working memory; however, the underlying mechanism remains unknown. We focused on 2 potential mechanisms: poor attentional engagement should be associated with elevated levels of prestimulus alpha-band activity within the electroencephalogram (EEG), whereas impaired working memory encoding should be associated with reduced poststimulus alpha suppression.

METHODS: We collected EEG data from 68 people with schizophrenia, 43 people with bipolar disorder with a history of psychosis, 53 people with major depressive disorder, and 90 healthy comparison subjects while they completed a spatial working memory task. We quantified attention lapsing, memory precision, and …

Personality Dynamics Turn Positive And Negative Mood Into Creativity, Ronald Bledow, Jana Kuhnel, Julius Kuhl

Research Collection Lee Kong Chian School Of Business

Introduction: Research on the link between affect and creativity rests on the assumption that creativity unfolds as a stimulus-driven response to affective states. We challenge this assumption and examine whether personality dynamics moderate the relationship of positive and negative mood with creativity. Theoretical Model: According to our model, personality dynamics that generate and maintain positive affect and down-regulate negative affect energize creativity. Based on this model, we expect high creativity in response to negative mood if people engage in self-motivation and achieve a reduction in negative mood. We further derive that individual differences in action versus state orientation moderate the …

On Neutrosophic Pδs-Irresolute Functions In Neutrosophic Topological Spaces, Bishnupada Debnath, Anjan Mukherjee

Neutrosophic Systems with Applications

In general topology the notion of pds-irresolute and aδs-irresolute functions were introduced by Beceren and Noiri. In the present paper, these concepts of pδs-irresolute (briefly, Npδs-irresolute) and aδs-irresolute (briefly, Naδs-irresolute) functions are explored for the first time in neutrosophic topological spaces (NTS) as generalized version. We proved that every Naδs-irresolute function is Npδs-irresolute function but not conversely. Some characterizations, counter examples, and fundamental features are also presented. By neutrosophic pre-open, neutrosophic δ-open, and neutrosophic δ-semi-open sets, some new fundamental properties of such functions are provided. Furthermore, under Npδs-irresolute functions, the behavior of neutrosophic semi-connected, neutrosophic pre-connected, neutrosophic pre-T2, neutrosophic δ-semi-T2, …

Chronic Β3-Ar Stimulation Activates Distinct Thermogenic Mechanisms In Brown And White Adipose Tissue And Improves Systemic Metabolism In Aged Mice, Duraipandy Natarajan, Bhuvana Plakkot, Kritika Tiwari, Shoba Ekambaram, Weidong Wang, Michael Rudolph, Mahmoud A Mohammad, Shaji K Chacko, Madhan Subramanian, Stefano Tarantini, Andriy Yabluchanskiy, Zoltan Ungvari, Anna Csiszar, Priya Balasubramanian

Faculty, Staff and Students Publications

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle-aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age-related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3-adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18-month-old) C57BL/6JN mice. Sustained β3-AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a …

Exploring Fibroblast Interactions On Nanocrystalline Surfaces In Physiological Environments Through A Phenomenological Lens, R D K Misra, Aladin M Boriek

Faculty, Staff and Students Publications

The cytological behaviour and functional dynamics (adhesion, spreading, synthesis of proteins) of fibroblasts when interacting with biomedical surfaces are intricately influenced by the inherent nature of surface (nanocrystalline or microcrystalline), where the nanocrystalline (NC) surface is preferred in relation to the microcrystalline (MC) surface. This preference is a direct consequence of the distinct differences in physical and chemical characteristics between NC and MC surfaces, which include crystal boundary bio-physical attributes, electron work function, surface energy, and charge carrier density. The observed variances in cytological behaviour at the interfaces of NC and MC bio-surfaces can be attributed to these fundamental differences, …

Template-Assisted Covalent Modification Underlies Activity Of Covalent Molecular Glues, Yen-Der Li, Michelle W Ma, Muhammad Murtaza Hassan, Moritz Hunkeler, Mingxing Teng, Kedar Puvar, Justine C Rutter, Ryan J Lumpkin, Brittany Sandoval, Cyrus Y Jin, Anna M Schmoker, Scott B Ficarro, Hakyung Cheong, Rebecca J Metivier, Michelle Y Wang, Shawn Xu, Woong Sub Byun, Brian J Groendyke, Inchul You, Logan H Sigua, Isidoro Tavares, Charles Zou, Jonathan M Tsai, Paul M C Park, Hojong Yoon, Felix C Majewski, Haniya T Sperling, Jarrod A Marto, Jun Qi, Radosław P Nowak, Katherine A Donovan, Mikołaj Słabicki, Nathanael S Gray, Eric S Fischer, Benjamin L Ebert

Faculty, Staff and Students Publications

Molecular glues are proximity-inducing small molecules that have emerged as an attractive therapeutic approach. However, developing molecular glues remains challenging, requiring innovative mechanistic strategies to stabilize neoprotein interfaces and expedite discovery. Here we unveil a trans-labeling covalent molecular glue mechanism, termed ‘template-assisted covalent modification’. We identified a new series of BRD4 molecular glue degraders that recruit CUL4DCAF16 ligase to the second bromodomain of BRD4 (BRD4BD2). Through comprehensive biochemical, structural and mutagenesis analyses, we elucidated how pre-existing structural complementarity between DCAF16 and BRD4BD2 serves as a template to optimally orient the degrader for covalent modification of DCAF16Cys58. This process stabilizes …