Research Methods in Life Sciences Commons^™

Modulation Of Hepatic Amyloid Precursor Protein And Lipoprotein Receptor-Related Protein 1 By Chronic Alcohol Intake: Potential Link Between Liver Steatosis And Amyloid-Β, Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter Van Der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Syndey M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting …

Prenatal Choline Supplementation During Maternal Obesity Alters Offspring Response To Western Diets, Hunter W. Korsmo

Dissertations, Theses, and Capstone Projects

Maternal obesity has led to an increase in adverse offspring developmental outcomes and a greater risk for long-term metabolic diseases. Choline, a semi-essential nutrient, can be incorporated into phosphatidylcholine (PC) as well as sphingomyelin (SM) and donate its labile methyl group for the remethylation of homocysteine after choline is oxidized to betaine. Prenatal choline insufficiency has been related to maternal obesity and metabolic diseases, such as metabolic associated fatty liver disease (MAFLD). Choline may interact with maternal obesity to influence the programming offspring.

Chapter 1 presents an introduction of choline and the various clinical outcomes associated with choline supplementation during …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Intestinal Microbiota Analysis Of Broiler Chickens Under Necrotic Enteritis Challenge And Tributyrin Supplementation, Taylor Nicole Mckinney

Graduate Theses and Dissertations

Poultry is a staple protein source for most of the planet. Until recently, antibiotic growth promoters (AGPs) were used to prevent illnesses in commercial chicken production. Currently, this is not possible due to regulations and consumer concern, but without such a preventative, diseases like necrotic enteritis (NE) have reemerged, posing a threat to bird health, and ultimately, our food source. Necrotic enteritis is a severe gastrointestinal disease caused by the gram-positive pathogen, Clostridium perfringens. Clinical features of this disease are diarrhea, intestinal lesions, and death, with a high transmission rate. In a subclinical form, growth performance is diminished and is …

The Role Of Temperature Variation On Macrophage Physiology And Function In Vitro In Mice, Chicken, And Fish, Intisar Abdullah Hassan

Graduate Theses and Dissertations

Fever is an essential component of the immune response. Baseline body temperatures vary in different species, and fever represents increased temperature over baseline. Fever initiates and enhances immune responses as well as creates an environment in which the body has advantages over pathogens. Macrophages are often the first line of cells that come in contact with pathogens, asthey reside in and traffic through tissues. They are important for their engulfment of pathogens that results in the digestion of the pathogen, and they also produce nitric oxide and cytokines that contribute to immune responses in a variety of ways, including initiating …

Ciliogenesis Mechanisms Mediated By Pak2-Arl13b Signaling In Brain Endothelial Cells Is Responsible For Vascular Stability, Karthikeyan Thirugnanam, Shubhangi Prabhudesai, Emma Van Why, Amy Pan, Ankan Gupta, Koji Foreman, Rahima Zennadi, Kevin R. Rarick, Surya M. Nauli, Sean P. Palacek, Ramani Ramchandran

Pharmacy Faculty Articles and Research

In the developing vasculature, cilia, microtubule-based organelles that project from the apical surface of endothelial cells (ECs), have been identified to function cell autonomously to promote vascular integrity and prevent hemorrhage. To date, the underlying mechanisms of endothelial cilia formation (ciliogenesis) are not fully understood. Understanding these mechanisms is likely to open new avenues for targeting EC-cilia to promote vascular stability. Here, we hypothesized that brain ECs ciliogenesis and the underlying mechanisms that control this process are critical for brain vascular stability. To investigate this hypothesis, we utilized multiple approaches including developmental zebrafish model system and primary cell culture systems. …

Effects Of Chronic Stress On Safety Processing And Physiology In The Medial Prefrontal-Amygdala-Basal Forebrain Circuit, Itamar S. Grunfeld

Dissertations, Theses, and Capstone Projects

Chronic stress increases generalization of fear to non-threatening cues, a key symptom in numerous psychiatric mood disorders. However, the mechanisms through which stress impacts safety learning remain poorly understood. To probe the relationship between stress and safety learning, this dissertation employed multiple behaviors, in conjunction with in-vivo multisite physiology during explicit safety and fear discrimination learning. In Chapter 1, I outline the role of chronic stress in driving neurological adaptations that result in generalized fear and highlight how this occurs because of impaired safety cue encoding. In Chapter 2, I show that chronic stress in the form of social defeat …

Full- Versus Sub-Regional Quantification Of Amyloid-Beta Load On Mouse Brain Sections, Yuu Ohno, Riley Murphy, Matthew Choi, Weijun Ou, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Extracellular accumulation of amyloid-beta (Aβ) plaques is one of the major pathological hallmarks of Alzheimer's disease (AD), and is the target of the only FDA-approved disease-modifying treatment for AD. Accordingly, the use of transgenic mouse models that overexpress the amyloid precursor protein and thereby accumulate cerebral Aβ plaques are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked immunosorbent assay (ELISA) and immunostaining, commonly measure the Aβ load in brain tissues derived from AD transgenic mice. Though the methods for Aβ detection and quantification have been well established and documented, the impact of the size of the …

The Role Of Calprotectin In T-Lymphocyte Driven Inflammation In A Mouse Model Of Psychological Trauma, Cassandra Moshfegh

Theses & Dissertations

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that affects nearly 45 million Americans. This mental disorder is characterized by behavioral symptoms such as learned helplessness, hyperarousal, withdrawal, and flashbacks. The deleterious effects of PTSD are far-reaching and go beyond behavioral dysfunction, as these individuals are at a three-fold higher risk of comorbid inflammatory diseases. Autonomic, metabolic, and cardiovascular diseases plague these individuals later in their lifetime, however, the mechanistic link connecting psychological trauma to this systemic peripheral immunological dysfunction remains elusive. T-lymphocyte-induced inflammation plays a significant role in all these disease pathologies. Previous work from our laboratory demonstrated …

Impact Forces And Patterns Of Axonal Injury Differ Between Two Models Of Tbi, Edward Lai, David M Devilbiss

Rowan-Virtua Research Day

Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum …

Effect Of Calcium Chloride And Isoflurane On Force Frequency Relationship In Canines, Harrison Patrizio, Lawrence Mulligan

Rowan-Virtua Research Day

Proper calcium cycling is critical for a optimally functioning heart.

Improper calcium cycling in humans can contribute to heart failure.

Human calcium cycling is difficult to study due to the risks of damaging the patient’s cardiac tissue.

Risk of further damaging cardiac tissue is substantially increased in a heart failure patient.

Past studies focus on studying the effects of changing calcium cycling in lab rats.

Current research shows limited alternative methods in studying relationships between calcium cycling and FFR in larger mammals.

This project analyzes data to determine the response of the canine force frequency relationship to calcium chloride and …

Characterizing The Roles Of Cannabinoid Receptor 1 & 2 In Zebrafish Behavior, Metabolism, And Seizure-Induced Activity, Kayci Kimmons

Honors Theses

Epileptic disorders like Dravet Syndrome require novel studies to determine the most ideal treatment. New research linking the endocannabinoid system (ECS) to epileptic disorders is arising, but there is still much to be discovered about the function and regulatory impact of the endocannabinoid system and its receptors in epilepsies like Dravet. In this study, knockout models of larval and adult zebrafish (Danio rerio) were used to investigate the roles of cannabinoid receptors 1 & 2 in behavior, brain mitochondrial metabolism, and seizure-induced activity following exposure to THC and CBD. Larval zebrafish which lacked cannabinoid receptor 1 exhibited increased …

Investigating Molecular Mechanisms Behind Bacterial Chondronecrosis With Osteomyelitis (Bco) Pathogenesis In Modern Broilers, Alison Ramser

Graduate Theses and Dissertations

Bacterial chondronecrosis with osteomyelitis (BCO), a leading cause of lameness in broiler chickens, is characterized by infection, inflammation, and bone attrition. There are currently no effective treatments and positive diagnosis is only possible through necropsy evaluations. Lameness is also a rising animal welfare and economic concern, making prevention and detection of BCO all the more critical. These challenges are exacerbated by a lack of mechanistic understanding of BCO’s etiology. The question I asked during my dissertation was how bacteria induce bone attrition in BCO pathology. My research has shown that mitochondrial dysfunction is characteristic of BCO conditions along with autophagy …

Evaluation Of The Effect Of A Lippia Organoides Essential Oil Extract On Clostridium Perfringens Proliferation In Vitro And Necrotic Enteritis In Broiler Chickens, Makenly E. Coles

Graduate Theses and Dissertations

The purpose of the present research was to assess the effects of essential oils derived from the plant Lippia organoides on performance parameters, intestinal integrity, and necrotic enteritis (NE) in broiler chickens. To do this, a previously established challenge model for NE was utilized which included challenging with Salmonella Typhimurium on day 0, Eimeria maxima on day 18, and Clostridium perfringens on days 22 and 23. Treatment groups included a 1) non-challenged, negative control, 2) challenged control, and 3) challenged, Lippia origanoides (37ppm in the diet). Group 1 (negative control) had significantly (P < 0.05) higher body weight gain from d8-25 and d0-25 compared to both challenged groups. Feed intake was significantly different for all three groups (P < 0.05) at 8-25 days and 0-25 days with group 1 having the highest feed intake for both time periods. Total mortality was greater in the positive control when compared to both the negative and treatment groups. NE lesion scores were significantly different between all groups with the positive control having the highest mean lesion scores and the negative control having a mean lesion score of 0. The positive control group had the highest FITC-d amounts detected in the sera, being statistically higher than both the treatment group and negative group which were both statistically different from each other. At the present inclusion rate for the essential oil (37 ppm), there was an overall reduction in the negative impact from the NE infection. Further studies should be conducted to reach more significant conclusions.

Author Correction: Short Amylin Receptor Antagonist Peptides Improve Memory Deficits In Alzheimer’S Disease Mouse Model, Rania Soudy, Ryoichi Kimura, Aarti Patel, Wen Fu, Kamaljit Kaur, David Westaway, Jing Yang, Jack Jhamandas

Pharmacy Faculty Articles and Research

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-47255-9, published online 29 July 2019

The original Article contained an error in Figure 1A where the control trace for both the HEK-AMY3 and HEKWT cells was duplicated...

The original Article has been corrected.

Quadruped Gait And Regulation Of Apoptotic Factors In Tibiofemoral Joints Following Intra-Articular Rhprg4 Injection In Prg4 Null Mice, Daniel S. Yang, Edward E. Dickerson, Ling X. Zhang, Holly Richendrfer, Padmini N. Karamchedu, Gary A. Badger, Tannin A. Schmidt, Alger M. Fredericks, Khaled A. Elsaid, Gregory D. Jay

Pharmacy Faculty Articles and Research

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome leads to diarthrodial joint arthropathy and is caused by the absence of lubricin (proteoglycan 4—PRG4), a surface-active mucinous glycoprotein responsible for lubricating articular cartilage. In this study, mice lacking the orthologous gene Prg4 served as a model that recapitulates the destructive arthrosis that involves biofouling of cartilage by serum proteins in lieu of Prg4. This study hypothesized that Prg4-deficient mice would demonstrate a quadruped gait change and decreased markers of mitochondrial dyscrasia, following intra-articular injection of both hindlimbs with recombinant human PRG4 (rhPRG4). Prg4^−/− (N = 44) mice of both sexes were injected with rhPRG4 …

Soy Formula Is Not Estrogenic And Does Not Result In Reproductive Toxicity In Male Piglets: Results From A Controlled Feeding Study, Martin J.J. Ronis, Horacio Gomez‐Acevedo, Kartik Shankar, Leah Hennings, Neha Sharma, Michael L. Blackburn, Isabelle Miousse, Harry Dawson, Celine Chen, Kelly E. Mercer, Thomas M. Badger

School of Graduate Studies Faculty Publications

Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White‐Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17‐beta‐estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21. …

Cilia Proteins Are Biomarkers Of Altered Flow In The Vasculature, Ankan Gupta, Karthikeyan Thirugnanam, Madhan Thamilarasan, Ashraf M. Mohieldin, Hadeel T. Zedan, Shubhangi Prabhudesai, Meghan R. Griffin, Andrew D. Spearman, Amy Pan, Sean P. Palecek, Huseyin C. Yalcin, Surya M. Nauli, Kevin R. Rarick, Rahima Zennadi, Ramani Ramchandran

Pharmacy Faculty Articles and Research

Cilia, microtubule-based organelles that project from the apical luminal surface of endothelial cells (ECs), are widely regarded as low-flow sensors. Previous reports suggest that upon high shear stress, cilia on the EC surface are lost, and more recent evidence suggests that deciliation—the physical removal of cilia from the cell surface—is a predominant mechanism for cilia loss in mammalian cells. Thus, we hypothesized that EC deciliation facilitated by changes in shear stress would manifest in increased abundance of cilia-related proteins in circulation. To test this hypothesis, we performed shear stress experiments that mimicked flow conditions from low to high shear stress …

A Semi-Physiological Three-Compartment Model Describes Brain Uptake Clearance And Efflux Of Sucrose And Mannitol After Iv Injection In Awake Mice, Behnam Noorani, Ekram Ahmed Chowdhury, Faleh Alqahtani, Md Sanaullah Sajib, Yeseul Ahn, Ehsan Nozohouri, Dhavalkumar Patel, Constantinos Mikelis, Reza Mehvar, Ulrich Bickel

Pharmacy Faculty Articles and Research

Purpose

To evaluate a three-compartmental semi-physiological model for analysis of uptake clearance and efflux from brain tissue of the hydrophilic markers sucrose and mannitol, compared to non-compartmental techniques presuming unidirectional uptake.

Methods

Stable isotope-labeled [¹³C]sucrose and [¹³C]mannitol (10 mg/kg each) were injected as IV bolus into the tail vein of awake young adult mice. Blood and brain samples were taken after different time intervals up to 8 h. Plasma and brain concentrations were quantified by UPLC-MS/MS. Brain uptake clearance (K_in) was analyzed using either the single-time point analysis, the multiple time point graphical method, …

Inhibition Of Interferon-Gamma-Stimulated Melanoma Progression By Targeting Neuronal Nitric Oxide Synthase (Nnos), Shirley Tong, Maris A. Cinelli, Naglaa Salem El-Sayed, He Huang, Anika Patel, Richard B. Silverman, Sun Yang

Pharmacy Faculty Articles and Research

Interferon-gamma (IFN-γ) is shown to stimulate melanoma development and progression. However, the underlying mechanism has not been completely defined. Our study aimed to determine the role of neuronal nitric oxide synthase (nNOS)-mediated signaling in IFN-γ-stimulated melanoma progression and the anti-melanoma effects of novel nNOS inhibitors. Our study shows that IFN-γ markedly induced the expression levels of nNOS in melanoma cells associated with increased intracellular nitric oxide (NO) levels. Co-treatment with novel nNOS inhibitors effectively alleviated IFN-γ-activated STAT1/3. Further, reverse phase protein array (RPPA) analysis demonstrated that IFN-γ induced the expression of HIF1α, c-Myc, and programmed death-ligand 1 (PD-L1), in contrast …

Barriers In Surgical Research: A Perspective From The Developing World, Nadeem Ahmed Siddiqui, Muhammad Aanish Raees, Rehan Nasir Khan, Farhan Zafar

Department of Surgery Docs

Research in surgery has led to significant advances over the last century in terms of how medicine is practised in and outside the operating rooms today. Surgical research in the developed countries is responsible for most of this advancement, but it is often inapplicable in resource-limited settings in the developing world. Lower- and middle-income countries are in a unique position to take this work further, but they are limited by certain barriers. These barriers could broadly be classified under social and cultural, infrastructure, financial, ethical, and personal categories. These barriers are often not fully realised, but can potentially be addressed …

Self-Conscious Emotions And The Right Fronto-Temporal And Right Temporal Parietal Junction, Adriana Lavarco, Nathira Ahmad, Qiana Archer, Matthew Pardillo, Ray Nunez Castaneda, Anthony Minervini, Julian Keenan

Department of Biology Faculty Scholarship and Creative Works

For more than two decades, research focusing on both clinical and non-clinical populations has suggested a key role for specific regions in the regulation of self-conscious emotions. It is speculated that both the expression and the interpretation of self-conscious emotions are critical in humans for action planning and response, communication, learning, parenting, and most social encounters. Empathy, Guilt, Jealousy, Shame, and Pride are all categorized as self-conscious emotions, all of which are crucial components to one’s sense of self. There has been an abundance of evidence pointing to the right Fronto-Temporal involvement in the integration of cognitive processes underlying the …

A Nationwide Virtual Research Education Program For Medical Students In Pakistan: Methodological Framework, Feasibility Testing, And Outcomes, Ali Aahil Noorali, Maha Inam, Hamna Shahbaz, Hareem Rauf, Faiqa Binte Aamir, Farah Khalid, Saadia Abbas, Abdullah Saeed, Muhammad Daniyal Musharraf, Asma Altaf Hussain Merchant, Babar Hasan, Muneera A. Rasheed, Fyezah Jehan, Muhammad Tariq, Adil Hussain Haider

Medical College Documents

Introduction: Equipping young medical trainees with fundamental research skills can be a promising strategy to address the need for professionals who can understand and responsibly communicate evolving scientific evidence during a pandemic. Despite an ardent interest to partake in research, most educational institutions in Pakistan and other low-middle income countries have not yet adopted a comprehensive strategy for research skills education. The authors aimed to design and assess the feasibility of implementing the first nation-wide virtual research workshop for medical students in Pakistan.
Methods: The course "Beginners Guide to Research," designed as a nation-wide virtual research workshop series, was conducted …

Comparison Of Percutaneous Vs Oral Infection Of Hamsters With The Hookworm Ancylostoma Ceylanicum: Parasite Development, Pathology And Primary Immune Response, Richard D. Bungiro, Lisa M. Harrison, Blaise Dondji, Michael Cappello

Biology Faculty Scholarship

Background

Hundreds of millions of people in poor countries continue to suffer from disease caused by bloodfeeding hookworms. While mice and rats are not reliably permissive hosts for any human hookworm species, adult Golden Syrian hamsters are fully permissive for the human and animal pathogen Ancylostoma ceylanicum. Similar to humans, hamsters may be infected with A. ceylanicum third-stage larvae orally or percutaneously. Oral infection typically leads to consistent worm yields in hamsters but may not accurately reflect the clinical and immunological manifestations of human infection resulting from skin penetration.

Methodology/Principal findings

In this study we compared host responses …

Biologic Tnf-Α Inhibitors Reduce Microgliosis, Neuronal Loss, And Tau Phosphorylation In A Transgenic Mouse Model Of Tauopathy, Weijun Ou, Joshua Yang, Juste Simanauskaite, Matthew Choi, Demi M. Castellanos, Rudy Chang, Jiahong Sun, Nataraj Jagadeesan, Karen D. Parfitt, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer’s disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of biologic TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the effects of biologic TNFIs on Aβ-independent tau pathology have not been reported. Existing biologic TNFIs do not cross the blood–brain barrier (BBB), therefore we engineered a BBB-penetrating biologic TNFI by fusing the extracellular domain of the type-II human TNF-α receptor (TNFR) to a transferrin receptor antibody (TfRMAb) that ferries the TNFR into the brain via …

Pets And Problems: Exploring Community Patterns In Calls For Animal Services, Paige Dejarnett

Sociology and Criminology Undergraduate Honors Theses

Pets have historically been viewed as family members, children, property, or economic resources. However, research surrounding animal maltreatment has expressed this issue as an individually-based problem, rather than a community-based phenomenon. Correlations have been found between animal cruelty, antisocial behaviors, and future interpersonal violence, whether this correlation be a predictive relationship, or a resultant relationship. Past research has also found correlations between animal treatment practices and the rural/urban differences of this behavior. However, there are many community-based indicators that have not been explored to understand the distribution of animal maltreatment. This study aims to explore these ideas by analyzing the …

Investigation Of Histomoniasis Prevention In Poultry, Lesleigh Beer

Graduate Theses and Dissertations

Histomonas meleagridis is the etiological agent of histomoniasis, also commonly known as blackhead disease. This protozoal disease of poultry is detrimental to turkeys with flock mortalities often reaching 80-100%, although other gallinaceous birds are susceptible. Since the voluntary removal of nitarsone in 2015, the poultry industry is suffering with no approved prophylactics, therapeutics, or vaccines for this disease. The objectives of this dissertation were to evaluate multiple methods for prevention or control of histomoniasis, including dietary chemoprophylaxis and vaccination. Specifically, this research evaluated quinine as a chemoprophylactic candidate (Chapter 3) or live-attenuated H. meleagridis as vaccine candidates (Chapter 4) in …

Arrhythmogenic Hearts In Pkd2 Mutant Mice Are Characterized By Cardiac Fibrosis, Systolic, And Diastolic Dysfunctions, Farideh Amirrad, Rajasekharreddy Pala, Kiumars Shamloo, Brian S. Muntean, Surya M. Nauli

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (PKD) is a hereditary disorder affecting multiple organs, including the heart. PKD has been associated with many cardiac abnormalities including the arrhythmogenic remodeling in clinical evaluations. In our current study, we hypothesized that Pkd2 gene mutation results in structural and functional defects in the myocardium. The structural and functional changes of Pkd2 mutant hearts were analyzed in the myocardial-specific Pkd2 knockout (KO) mouse. We further assessed a potential role of TGF-b₁ signaling in the pathology of Pkd2-KO hearts. Hearts from age-matched 6-month-old MyH6•Pkd2^wt/wt (control or wild-type) and MyH6 …

The Concentration Of Brain Homogenates With The Amicon Ultra Centrifugal Filters, Joshua Yang, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Accurately measuring the brain concentration of a neurotherapeutic is critical in determining its pharmacokinetic profile in vivo. Biologics are potential therapeutics for neurologic diseases and biologics fused to an antibody targeting a transcytosis receptor at the Blood-Brain Barrier, designated as antibody-biologic fusion proteins, are Blood-Brain Barrier penetrating neurotherapeutics. The use of sandwich immunosorbent assays to measure concentrations of antibody-biologic fusion proteins in brain homogenates has become increasingly popular. The raw brain homogenate contains many proteins and other macromolecules that can cause a matrix effect, potentially interfering with the limit of detection of such assays and reduce the overall sample …

Regulation Of Brain Primary Cilia Length By Mch Signaling: Evidence From Pharmacological, Genetic, Optogenetic, And Chemogenic Manipulations, Wedad Alhassen, Yuki Kobayashi, Jessica Su, Brianna Robbins, Henry Nguyen, Thant Myint, Micah Yu, Surya M. Nauli, Yumiko Saito, Amal Alachkar

Pharmacy Faculty Articles and Research

The melanin-concentrating hormone (MCH) system is involved in numerous functions, including energy homeostasis, food intake, sleep, stress, mood, aggression, reward, maternal behavior, social behavior, and cognition. In rodents, MCH acts on MCHR1, a G protein-coupled receptor, which is widely expressed in the brain and abundantly localized to neuronal primary cilia. Cilia act as cells’ antennas and play crucial roles in cell signaling to detect and transduce external stimuli to regulate cell differentiation and migration. Cilia are highly dynamic in terms of their length and morphology; however, it is not known if cilia length is causally regulated by MCH system activation …