Life Sciences Commons^™

The Effects Of Sex Hormones On The Size Of Intestinal Lipoproteins, Andromeda M. Nauli, Ann Phan, Patrick Tso, Surya M. Nauli

Pharmacy Faculty Articles and Research

Larger intestinal lipoproteins are more likely to be retained longer in the intestinal wall, allowing more time for their fat to be hydrolyzed and subsequently taken up by the abdominal viscera. Since men generally accumulate more abdominal visceral fat than women, we sought to determine if males produce larger intestinal lipoproteins compared to females. Using the conscious lymph fistula mouse model, we discovered that the male mice indeed produced larger intestinal lipoproteins than the female mice when they were intraduodenally infused with lipid emulsion. We then employed our differentiated Caco-2 cell model with semipermeable membrane system to determine the effects …

Mutational Analysis Of The Nitrogenase Carbon Monoxide Protective Protein Cown Reveals That A Conserved C‑Terminal Glutamic Acid Residue Is Necessary For Its Activity, Dustin L. Willard, Joshuah J. Arellano, Mitch Underdahl, Terrence M. Lee, Avinash S. Ramaswamy, Gabriella Fumes, Agatha Kliman, Emily Y. Wong, Cedric P. Owens

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN’s protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work …

Analyzing Functional Interactions Of Designed Peptides By Nmr Spectroscopy, Wonsuk Choi

Pharmaceutical Sciences (MS) Theses

The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic …

Computational Molecular Docking Studies Of Small Molecule Inhibitors With The Sars-Cov-2 Spike Protein Variants: In-Silico Drug Discovery Using Virtual Screening And Drug Repurposing Approaches, Grace Gupta

Computational and Data Sciences (MS) Theses

The pandemic caused by the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has caused a global public health crisis of nearly unprecedented scale. In the years following the outbreak, the scientific community has mobilized to develop several vaccines and treatments. Drug repurposing as a strategy for drug development has produced many of the current therapeutic options. The greatest challenge to designing a therapeutic inhibitor of SARS-CoV-2 is the shifting mutational landscape of the virus as it evolves. In this study, we focus on the spike protein as a target for potential inhibitors. We explore two …

The Psychology Of The Stage: Intersections Of Cognitive Science And Theatre, Ariya Selvakumar

Student Scholar Symposium Abstracts and Posters

By engaging audiences in a stranger’s story, theatre often depends on emotional contagion and empathetic responses to strike interest and investment in characters and their circumstances. Mirror neuron systems are those highly tied to the activation of empathy. These neurons are brain cells that activate when we perform an action and witness an action being performed. For example, when someone is crying, a subset of neurons that fire when we cry will also fire in response to seeing this action, thus often leading to emotional contagion. With an understanding of cognitive science, we can closely examine the perspective-taking and emotion-prediction …

Multi-Omics Reveals Largely Distinct Transcript- And Protein-Level Responses To The Environment In An Intertidal Mussel, Lani U. Gleason, Florian J. Fekete, Richelle L. Tanner, W. Wesley Dowd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Organismal responses to stressful environments are influenced by numerous transcript- and protein-level mechanisms, and the relationships between expression changes at these levels are not always straightforward. Here, we used paired transcriptomic and proteomic datasets from two previous studies from gill of the California mussel, Mytilus californianus, to explore how simultaneous transcript and protein abundance patterns may diverge under different environmental scenarios. Field-acclimatized mussels were sampled from two disparate intertidal sites; individuals from one site were subjected to three further treatments (common garden, low-intertidal or high-intertidal outplant) that vary in temperature and feeding time. Assessing 1519 genes shared between …

Exploring Pathways To Food Science Careers In Southern California: A Case Study In Food Science Career Development, Jeremy L. Hsu, Sarah Ahles, Lilian W. Senger, Anuradha Prakash

Food Science Faculty Articles and Research

Southern California is a diverse region that is home to a high concentration of food science companies, with an increasing demand for additional food scientists and technologists to join this workforce. Despite this abundance of food science companies and the high demand for jobs, there is currently a shortage in the number of qualified food scientists and technologists in the region. This shortage is also observed within higher education, with declining enrollments in the food science graduate and undergraduate programs across Southern California. Here, we conduct a case study to explore the factors that influence students from Southern California to …

A Novel Machine-Learning Framework Based On A Hierarchy Of Dispute Models For The Identification Of Fish Species Using Multi-Mode Spectroscopy, Mitchell Sueker, Amirreza Daghighi, Alireza Akhbardeh, Nicholas Mackinnon, Gregory Bearman, Insuck Baek, Chansong Hwang, Jianwei Qin, Amanda M. Tabb, Jiahleen Roungchun, Rosalee S. Hellberg, Fartash Vasefi, Moon Kim, Kouhyar Tavakolian, Hossein Kashini Zadeh

Food Science Faculty Articles and Research

Seafood mislabeling rates of approximately 20% have been reported globally. Traditional methods for fish species identification, such as DNA analysis and polymerase chain reaction (PCR), are expensive and time-consuming, and require skilled technicians and specialized equipment. The combination of spectroscopy and machine learning presents a promising approach to overcome these challenges. In our study, we took a comprehensive approach by considering a total of 43 different fish species and employing three modes of spectroscopy: fluorescence (Fluor), and reflectance in the visible near-infrared (VNIR) and short-wave near-infrared (SWIR). To achieve higher accuracies, we developed a novel machine-learning framework, where groups of …

Brain Microvascular Endothelial Cells Possess A Second Cilium That Arises From The Daughter Centriole, Karthikeyan Thirugnanam, Ankan Gupta, Francisco Nunez, Shubhangi Prabhudesai, Amy Y. Pan, Surya M. Nauli, Ramani Ramchandran

Pharmacy Faculty Articles and Research

Primary cilia from the brain microvascular endothelial cells (ECs) are specialized cell-surface organelles involved in mediating sensory perception, cell signaling, and vascular stability. Immunofluorescence (IF) analysis of human primary brain microvascular ECs reveals two cilia per cell. To confirm the in vitro observation of the two-cilia phenotype in human primary brain ECs, ECs isolated from mouse brain were cultured and stained for cilium. Indeed, brain ECs from a ciliopathic mouse (polycystic kidney disease or Pkd2−/−) also possess more than one cilium. Primary cilium emerges from the mother centriole. Centriole analysis by IF suggests that in brain ECs, markers …

Volcanic Diffuse Volatile Emissions Tracked By Plant Responses Detectable From Space, Robert R. Bogue, Peter M. J. Douglas, Joshua B. Fisher, John Stix

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Volcanic volatile emissions provide information about volcanic unrest but are difficult to detect with satellites. Volcanic degassing affects plants by elevating local CO2 and H2O concentrations, which may increase photosynthesis. Satellites can detect plant health, or a reaction to photosynthesis, through a Normalized Difference Vegetation Index (NDVI). This can act as a potential proxy for detecting changes in volcanic volatile emissions from space. We tested this method by analyzing 185 Landsat 5 and 8 images of the Tern Lake thermal area (TLTA) in northeast Yellowstone caldera from 1984 to 2022. We compared the NDVI values of the thermal area with …

Comparison Of Dna Extraction Methods For The Detection Of Canned Tuna Species With Dna Mini-Barcoding, Aubrey J. Emmi, Biola Fatusin, Rosalee S. Hellberg

Food Science Faculty Articles and Research

Tuna is susceptible to species mislabeling due to its high demand, quick rate of production, and wide range of price points. DNA barcoding, a sequencing-based technique, allows for the detection of species mislabeling by targeting a standardized region of DNA. A mitochondrial control region (CR) DNA barcode has been found to be capable of species discrimination for tuna, but it is challenging to recover the entire DNA fragment from canned tuna. While a short fragment of CR, referred to as a “mini-barcode,” has shown some success with canned tuna species identification, more research is needed to improve identification rates. The …

Diabetes-Associated Hyperglycemia Causes Rapid-Onset Ocular Surface Damage, Judy Weng, Christopher Ross, Jacob Baker, Saleh Alfuraih, Kiumars Shamloo, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose: The metabolic alterations due to chronic hyperglycemia are well-known to cause diabetes-associated complications. Short-term hyperglycemia has also been shown to cause many acute changes, including hemodynamic alterations and osmotic, oxidative, and inflammatory stress. The present study was designed to investigate whether diabetes-associated hyperglycemia can cause rapid-onset detrimental effects on the tear film, goblet cells, and glycocalyx and can lead to activation of an inflammatory cascade or cellular stress response in the cornea.

Methods: Mouse models of type 1 and type 2 diabetes were used. Tear film volume, goblet cell number, and corneal glycocalyx area were measured on …

Multiple Light Signaling Pathways Control Solar Tracking In Sunflowers, Christopher J. Brooks, Hagop S. Atamian, Stacey L. Harmer

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Sunflowers are famous for their ability to track the sun throughout the day and then reorient at night to face east the following morning. This occurs by differential growth patterns, with the east sides of stems growing more during the day and the west sides of stems growing more at night. This process, termed heliotropism, is generally believed to be a specialized form of phototropism; however, the underlying mechanism is unknown. To better understand heliotropism, we compared gene expression patterns in plants undergoing phototropism in a controlled environment and in plants initiating and maintaining heliotropic growth in the field. We …

Untargeted Metabolomics Analysis On Kidney Tissues From Mice Reveals Potential Hypoxia Biomarkers, Muhammad Imran Sajid, Francisco J. Nunez, Farideh Amirrad, Moom Rahman Roosan, Tom Vojtko, Scott Mcculloch, Amal Alachkar, Surya M. Nauli

Pharmacy Faculty Articles and Research

Chronic hypoxia may have a huge impact on the cardiovascular and renal systems. Advancements in microscopy, metabolomics, and bioinformatics provide opportunities to identify new biomarkers. In this study, we aimed at elucidating the metabolic alterations in kidney tissues induced by chronic hypoxia using untargeted metabolomic analyses. Reverse phase ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy (RP–UPLC–MS/MS) and hydrophilic interaction liquid chromatography (HILIC)–UPLC–MS/MS methods with positive and negative ion mode electrospray ionization were used for metabolic profiling. The metabolomic profiling revealed an increase in metabolites related to carnitine synthesis and purine metabolism. Additionally, there was a notable increase in bilirubin. Heme, N-acetyl-L-aspartic …

Investigating The Influence Of Assessment Question Framing On Undergraduate Biology Student Preference And Affect, Jeremy L. Hsu, Noelle Clark, Kate Hill, Melissa Rowland-Goldsmith

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nearly all undergraduate biology courses rely on quizzes and exams. Despite their prevalence, very little work has been done to explore how the framing of assessment questions may influence student performance and affect. Here, we conduct a quasi-random experimental study where students in different sections of the same course were given isomorphic questions that varied in their framing of experimental scenarios. One section was provided a description using the self-referential term “you”, placing the student in the experiment; another section received the same scenario that used classmate names; while a third section's scenario integrated counterstereotypical scientist names. Our results demonstrate …

Homogenization And Thermal Processing Reduce The Concentration Of Extracellular Vesicles In Bovine Milk, Anna P. Colella, Anuradha Prakash, John Miklavcic

Food Science Faculty Articles and Research

Extracellular vesicles (EVs) in bovine milk confer beneficial physiologic effects to consumers. Industrial processing treatments may affect the amount or bioactivity of EVs intrinsic to bovine milk. We investigated how the content and concentration of EVs were affected by homogenization and thermal processing of raw bovine milk. Raw milk was processed by homogenization, low-temperature (LT) heat, or pasteurization [high-temperature short-time (HTST) and ultra-high-temperature (UHT)] in a pilot processing facility. EVs were isolated from the raw and processed bovine milk using differential ultracentrifugation and quantified using a nanoparticle tracking analyzer. Bovine milk EVs were assessed for total miRNA and protein concentrations …

An Inquiry-Based Approach For Teaching Type Iii Functional Responses In Ecology, Jeremy L. Hsu

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Maize (also known as corn) has played an important role in human agriculture ever since its domestication by indigenous peoples of Mexico some 10,000 years ago. The crop is now planted across the world, including in China. However, several invasive pests, including the fall armyworm Spodoptera frugiperda, have threatened this crop and lowered yield. Eupeodes corollae, an endemic syrphid hoverfly, has been proposed as a biological control agent. Here, students will explore the antagonistic relationship between S. frugiperda and E. corollae, with both species feeding on larvae of the other species, and learn about type III functional …

What Is Microbial Dormancy?, Mark D. Mcdonald, Carlos Owusu-Ansah, Jared B. Ellenbogen, Zachary D. Malone, Michael P. Ricketts, Steve E. Frolking, Jessica Gilman Ernakovich, Michael Ibba, Sarah C. Bagby, J. L. Weissman

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Life can be stressful. One way to deal with stress is to simply wait it out. Microbes do this by entering a state of reduced activity and increased resistance commonly called ‘dormancy’. But what is dormancy? Different scientific disciplines emphasize distinct traits and phenotypic ranges in defining dormancy for their microbial species and system-specific questions of interest. Here, we propose a unified definition of microbial dormancy, using a broad framework to place earlier discipline-specific definitions in a new context. We then discuss how this new definition and framework may improve our ability to investigate dormancy using multi-omics tools. Finally, we …

Usa: Wolf Connection And Inclusive, Safe Spaces For All, Patrick Fuery, Kelli Fuery

CCI Books and Book Chapters

"Wolf Connection is a wolf sanctuary located on the outskirts of a rural town, Acton, California, nestled in the Angeles National Forest. The sanctuary consists of 165 acres of stunning woodland and high desert mountains, including a year-round stream. It is located within a one-hour drive from Los Angeles. Wolf Connection runs a series of programmes based around issues of mental health, addressing social and economic inequality, and providing strategies for resilience and well-being. Wolf Connection identifies the following as its core business activities: Providing Animal Rescue and Wildlife Preservation; At-Risk Youth Education and Empowerment; Community Empowerment; and Environmental Awareness …

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Computational Analysis Of Antibody Binding Mechanisms To The Omicron Rbd Of Sars-Cov-2 Spike Protein: Identification Of Epitopes And Hotspots For Developing Effective Therapeutic Strategies, Mohammed Alshahrani

Computational and Data Sciences (PhD) Dissertations

The advent of the Omicron strain of SARS-CoV-2 has elicited apprehension regarding its potential influence on the effectiveness of current vaccines and antibody treatments. The present investigation involved the implementation of mutational scanning analyses to examine the impact of Omicron mutations on the binding affinity of four categories of antibodies that target the Omicron receptor binding domain (RBD) of the Spike protein. The study demonstrates that the Omicron variant harbors 23 unique mutations across the RBD regions I, II, III, and IV. Of these mutations, seven are shared between RBD regions I and II, while three are shared among RBD …

Neutral Theory And Beyond: A Systematic Review Of Molecular Evolution Education, Desiree Forsythe, Jeremy L. Hsu

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Molecular evolution—including the neutral theory of molecular evolution—is a major sub-discipline of evolution and is widely taught in undergraduate evolution courses. However, despite its ubiquity, there have not been any previous attempts to compile and review the molecular evolution education literature. Here, we draw upon the framework proposed in a past literature review examining the broader evolution education landscape to conduct a literature review of papers related to molecular evolution education, classifying the contributions of such papers to evolution pedagogy as well as evolution education research. We find that there remains very limited coverage of molecular evolution in the education …

Α7 Nicotinic Acetylcholine Receptor Interaction With G Proteins In Breast Cancer Cell Proliferation, Motility, And Calcium Signaling, Murat Oz, Justin R. King, Keun-Hang Susan Yang, Sarah Khushaish, Yulia Tchugunova, Maitham A. Khajah, Yunus A. Luqmani, Nadine Kabbani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Chronic smoking is a primary risk factor for breast cancer due to the presence of various toxins and carcinogens within tobacco products. Nicotine is the primary addictive component of tobacco products and has been shown to promote breast cancer cell proliferation and metastases. Nicotine activates nicotinic acetylcholine receptors (nAChRs) that are expressed in cancer cell lines. Here, we examine the role of the α7 nAChR in coupling to heterotrimeric G proteins within breast cancer MCF-7 cells. Pharmacological activation of the α7 nAChR using choline or nicotine was found to increase proliferation, motility, and calcium signaling in MCF-7 cells. This effect …

The Structural Characterization And Bioactivity Assessment Of Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Caraway (Carum Carvi) Seeds, Taibah Aldakhil, Saud O. Alshammari, Bushra Siraj, Bishoy El-Aarag, Shamshad Zarina, David Salehi, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Carum carvi (caraway) of the Apiaceae family has been used in many cultures as a cooking spice and part of the folk medicine. Previous reports primarily focus on the medicinal properties of caraway seed essential oil and the whole seeds extract. However, no effort has been made to study caraway proteins and their potential pharmacological properties, including nonspecific lipid transfer protein (nsLTP), necessitating further research. The current study aimed to characterize nonspecific lipid transfer protein 1 (nsLTP1) from caraway seed, determine its three-dimensional structure, and analyze protein–ligand complex interactions through docking studies. We also evaluated nsLTP1 in vitro cytotoxic …

Science Communication Training Imparts Confidence And Influences Public Engagement Activity, Christina M. Swords, Jerlym S. Porter, Amy J. Hawkins, Edwin Li, Melissa Rowland-Goldsmith, Matthew D. Koci, John F. Tansey, Nicole C. Woitowich

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The impacts of science are felt across all socio-ecological levels, ranging from the individual to societal. In order to adapt or respond to scientific discoveries, novel technologies, or biomedical or environmental challenges, a fundamental understanding of science is necessary. However, antiscientific rhetoric, mistrust in science, and the dissemination of misinformation hinder the promotion of science as a necessary and beneficial component of our world. Scientists can promote scientific literacy by establishing dialogues with nonexperts, but they may find a lack of formal training as a barrier to public engagement. To address this, the American Society for Biochemistry and Molecular Biology …

Hydrolysis Of Chlorogenic Acid In Sunflower Flour Increases Consumer Acceptability Of Sunflower Flour Cookies By Improving Cookie Color, Christine Lo Verde, Criselda Toto Pacioles, Natalie Paterson, Jamie Chin, Cedric P. Owens, Lilian W. Senger

Food Science Faculty Articles and Research

Sunflower meal, a byproduct of sunflower oil pressing, is not commonly used in alkaline baking applications. This is because chlorogenic acid, the main phenolic antioxidant in sunflower seeds, reacts with protein, giving the baked product a green discoloration. Our group previously demonstrated that a chlorogenic acid esterase from Lactobacillus helveticus hydrolyzes chlorogenic acid in sunflower dough cookie formulations, resulting in cookies that were brown instead of green. This study presents a sensory analysis to determine the acceptability of enzymatically upcycled sunflower meal as an alternative protein source for those allergic to meals from legumes or tree nuts. We hypothesized that …

Skeletal Anatomy Of The Pectoral Fin In Mudskipper Species From Terrestrial And Aquatic Habitats, Haodong Zhou, Cassandra M. Donatelli, Odette Laneuville, Emily M. Standen

Engineering Faculty Articles and Research

Mudskippers are a group of amphibious fishes in the family Oxudercidae, whose species inhabit a range of habitats from mostly aquatic to mostly terrestrial. Most of our understanding about habitat preference comes from natural history observations, particularly where they are collected (i.e., low intertidal vs. high intertidal regions). Mudskippers have undergone several morphological changes to accommodate a terrestrial life, including major changes to the pectoral and pelvic girdles. These changes result in a novel crutching gait, which mudskippers use to move over land. Though the appendicular morphology and crutching gait of mudskippers have been described in some species, few …

Mapping California Rice Using Optical And Sar Data Fusion With Phenological Features In Google Earth Engine, Li Wenzhao, Hesham El-Askary, Daniele C. Struppa

Mathematics, Physics, and Computer Science Faculty Articles and Research

California, known for its diverse agriculture, is also a major producer of rice, especially in its northern regions in Sacramento River Valley. Traditional methods, predominantly reliant on optical-based satellite imagery, encounter limitations due to atmospheric interference and sensor resolution. The ability of Synthetic Aperture Radar (SAR) to penetrate atmospheric distortions and exhibit high sensitivity to vegetation structure presents a distinct advantage over optical-based methods. Utilizing Optical and SAR data fusion, this study advances the enhanced pixel-based phenological feature composite (Eppf) method using SVM classification algorithm, which can track phenological changes and patterns, providing valuable insights for agricultural planning and management. …

The Pros Of Changing Trna Identity, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The notion that errors in protein synthesis are universally harmful to the cell has been questioned by findings that suggest such mistakes may sometimes be beneficial. However, how often these beneficial mistakes arise from programmed changes in gene expression as opposed to reduced accuracy of the translation machinery is still unclear. A new study published in JBC shows that some bacteria have beneficially evolved the ability to mistranslate specific parts of the genetic code, a trait that allows improved antibiotic resistance.