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Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater 2018 University of Louisville

Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater

Posters-at-the-Capitol

Immunotherapy strategies are very promising treatments for cancer patients. Specifically, Immune checkpoint inhibitor therapy focusing on the PD-1/PD-L1 pathway shows long-lasting positive results in many cancer patients. Unfortunately, not all the patients can benefit from this highly effective treatment. Hence, there is a great need for predictive biomarkers. Immunohistochemical (IHC) staining has been used as a way of predicting patient response, yet shows many problems. For example, IHC utilizes an invasive biopsy and sample fixing, which creates an incomplete and delayed picture of the patient’s biochemistry and the tumor microenvironment, consequently ignoring metastases.

The purpose of this study ...


Computational Investigation Of The Interactions Between Bioactive Compounds And Biological Assemblies, Tye D. Martin 2018 University of New Mexico - Main Campus

Computational Investigation Of The Interactions Between Bioactive Compounds And Biological Assemblies, Tye D. Martin

Shared Knowledge Conference

Design of small molecules is an ongoing focus for developing agents against pathogenic viruses and bacteria that are threats to worldwide health. Viruses such as Zika feature assemblies of repeat peptide subunits or capsid proteins which are potential targets for antiviral compounds. Other protein assemblies are implicated in pathology of Alzheimer’s Disease (AD) and additional neurodegenerative diseases characterized by large assemblies of misfolded proteins such as amyloid-beta (Aβ) and tau. Recent studies on a class of conjugated polyelectrolytes (CPEs) with phenylene ethynylene moieties and charged functional groups have shown potential both as bioactive antimicrobials and theragnostic sensing agents for ...


L-Serine Reduces Reactive Oxygen Species Yield In Cisplatin Treated Zebrafish Utricles, Satya A. Moolani, Elvin Irihamye, Jerry D. Monroe, Michael E. Smith 2018 Western Kentucky University

L-Serine Reduces Reactive Oxygen Species Yield In Cisplatin Treated Zebrafish Utricles, Satya A. Moolani, Elvin Irihamye, Jerry D. Monroe, Michael E. Smith

Posters-at-the-Capitol

Cisplatin is a chemotherapy compound effective against a variety of cancers. However, it can act as an ototoxin and cause hearing loss by promoting reactive oxygen species (ROS) production in auditory tissues. The antioxidant amino acid, L-serine has been hypothesized to lower levels of cisplatin-mediated ROS. In this project, we investigated whether L-serine can reduce cisplatin-mediated ROS production in auditory tissue and potentially act as an otoprotectant during cisplatin chemotherapy. We used a zebrafish utricular tissue culture system and fluorescent ROS indicator dye to spectrophotometrically measure if L-serine could decrease reactive oxygen species levels in cisplatin-treated tissues. We found that ...


43 - Library Synthesis Of Antimicrobial Peptide Targeting Staphylococcus Aureus, Jonathan Bridges 2018 University of North Georgia

43 - Library Synthesis Of Antimicrobial Peptide Targeting Staphylococcus Aureus, Jonathan Bridges

Georgia Undergraduate Research Conference (GURC)

Library Synthesis of antimicrobial peptide targeting Staphylococcus aureus

Due to the overprescribing of antibiotics bacteria have adapted and developed mechanisms to combat the antimicrobial agents. One example is Staphylococcus aureus, which causes common skin infections, and can be easily treated. But amidst the abuse of antibiotics, S. aureus has become resistant to most known antibiotics; resistant strains are termed Methicillin-resistantStaphylococcus aureus (MRSA). This is a major concern in hospitals where the bacteria evolve under constant pressure developing multi-drug resistance. Thus significant efforts have been made to develop either stronger antibiotics or investigating alternate pathways to target the resistant strains ...


31 - The Critical Role Of Atad3a In The Estrogen Signaling Pathway In Breast Cancer Cells, Parth Thakkar 2018 Augusta University

31 - The Critical Role Of Atad3a In The Estrogen Signaling Pathway In Breast Cancer Cells, Parth Thakkar

Georgia Undergraduate Research Conference (GURC)

Abstract

Breast cancer is the leading malignancy and leading cause of cancer-related death in women globally. The greatest barrier to a treatment is the incomplete understanding of mechanisms underlying molecular regulators whose function is cellular adaptation to estrogen. One such enzyme, ATAD3A, a nuclear-encoded mitochondrial enzyme, has been brought under this lab’s scrutiny. The role of ATAD3A in breast cancer progression is largely unknown but it has been shown to be a crucial mediator in promoting cell cycle progression. The two objectives of this project were: to determine whether the ATAd3A is an Estrogen Receptor-α target (ERα) and to ...


38 - Stereochemical Synthesis Of Lugdunin – An Antimicrobial Cyclic Peptide, Shivam Patel 2018 University of North Georgia

38 - Stereochemical Synthesis Of Lugdunin – An Antimicrobial Cyclic Peptide, Shivam Patel

Georgia Undergraduate Research Conference (GURC)

Stereochemical synthesis of Lugdunin – An antimicrobial cyclic peptide

The consequence of overuse of antibiotics is that the bacteria have developed a various mechanism to overcome the effect of these molecules, which we now address as antibiotic resistance. In fact, antibiotic resistance has become a serious issue in hospitals where the local microbial flora has evolved under constant selection pressure from the various antibiotics in use. The Center for Disease Control has developed an extensive list of many multi-drug resistant bacteria. This includes many bacteria, which otherwise would be simple to treat, but because of acquired resistance have become a serious ...


Design, Synthesis, And Evaluation Of Amphiphilic Cyclic And Linear Peptides Composed Of Hydrophobic And Positively-Charged Amino Acids As Antibacterial Agents, Neda Riahifard, Saghar Mozaffari, Taibah Aldakhil, Francisco Nunez, Qamar Alshammari, Saud Alshammari, Jason Yamaki, Keykavous Parang, Rakesh Kumar Tiwari 2018 Chapman University

Design, Synthesis, And Evaluation Of Amphiphilic Cyclic And Linear Peptides Composed Of Hydrophobic And Positively-Charged Amino Acids As Antibacterial Agents, Neda Riahifard, Saghar Mozaffari, Taibah Aldakhil, Francisco Nunez, Qamar Alshammari, Saud Alshammari, Jason Yamaki, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Antimicrobial peptides (AMPs) contain amphipathic structures and are derived from natural resources. AMPs have been found to be effective in treating the infections caused by antibiotic-resistant bacteria (ARB), and thus, are potential lead compounds against ARB. AMPs’ physicochemical properties, such as cationic nature, amphiphilicity, and their size, will provide the opportunity to interact with membrane bilayers leading to damage and death of microorganisms. Herein, AMP analogs of [R4W4] were designed and synthesized by changing the hydrophobicity and cationic nature of the lead compound with other amino acids to provide insights into a structure-activity relationship against selected model ...


Interleukin-1 Receptor-Associated Kinase 4 (Irak4) Plays A Dual Role In Myddosome Formation And Toll-Like Receptor Signaling, Dominic De Nardo, Katherine R. Balka, Yamel Cardona Gloria, Vikram R. Rao, Eicke Latz, Seth L. Masters 2018 University of Melbourne

Interleukin-1 Receptor-Associated Kinase 4 (Irak4) Plays A Dual Role In Myddosome Formation And Toll-Like Receptor Signaling, Dominic De Nardo, Katherine R. Balka, Yamel Cardona Gloria, Vikram R. Rao, Eicke Latz, Seth L. Masters

Open Access Articles

Toll-like receptors (TLRs) form part of the host innate immune system, in which they act as sensors of microbial and endogenous danger signals. Upon TLR activation, the intracellular Toll/interleukin-1 receptor domains of TLR dimers initiate oligomerization of a multiprotein signaling platform comprising myeloid differentiation primary response 88 (MyD88) and members of the interleukin-1 receptor-associated kinase (IRAK) family. Formation of this myddosome complex initiates signal transduction pathways, leading to the activation of transcription factors and the production of inflammatory cytokines. To date, little is known about the assembly and disassembly of the myddosome and about the mechanisms by which these ...


All-In-One Adeno-Associated Virus Delivery And Genome Editing By Neisseria Meningitidis Cas9 In Vivo, Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani, Wen Xue, Erik J. Sontheimer 2018 University of Massachusetts Medical School

All-In-One Adeno-Associated Virus Delivery And Genome Editing By Neisseria Meningitidis Cas9 In Vivo, Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani, Wen Xue, Erik J. Sontheimer

RNA Therapeutics Institute Publications

BACKGROUND: Clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) have recently opened a new avenue for gene therapy. Cas9 nuclease guided by a single-guide RNA (sgRNA) has been extensively used for genome editing. Currently, three Cas9 orthologs have been adapted for in vivo genome engineering applications: Streptococcus pyogenes Cas9 (SpyCas9), Staphylococcus aureus Cas9 (SauCas9), and Campylobacter jejuni (CjeCas9). However, additional in vivo editing platforms are needed, in part to enable a greater range of sequences to be accessed via viral vectors, especially those in which Cas9 and sgRNA are combined into a single vector genome.

RESULTS: Here ...


One Group's Historical Reflections On Dna Vaccine Development, Ellen F. Fynan, Shan Lu, Harriet L. Robinson 2018 Worcester State College

One Group's Historical Reflections On Dna Vaccine Development, Ellen F. Fynan, Shan Lu, Harriet L. Robinson

Open Access Articles

DNA vaccines were pioneered by several groups in the early 1990s. This article presents the reflections of one of these groups on their work with retroviral vectors in chickens that contributed to the discovery and early development of DNA vaccines. Although the findings were initially met with skepticism, the work presented here combined with that of others founded a new method of vaccination: the direct inoculation of purified DNA encoding the target antigen.


Intestinal P-Glycoprotein Exports Endocannabinoids To Prevent Inflammation And Maintain Homeostasis, Rose L. Szabady, Christopher Louissaint, Anneke Lubben, Bailu Xie, Shaun Reeksting, Christine Tuohy, Zachary Demma, Sage Foley, Christina S. Faherty, Alejandro Llanos-Chea, Andrew J. Olive, Randall J. Mrsny, Beth A. McCormick 2018 University of Massachusetts Medical School

Intestinal P-Glycoprotein Exports Endocannabinoids To Prevent Inflammation And Maintain Homeostasis, Rose L. Szabady, Christopher Louissaint, Anneke Lubben, Bailu Xie, Shaun Reeksting, Christine Tuohy, Zachary Demma, Sage Foley, Christina S. Faherty, Alejandro Llanos-Chea, Andrew J. Olive, Randall J. Mrsny, Beth A. Mccormick

Open Access Articles

Neutrophil influx into the intestinal lumen is a critical response to infectious agents, but is also associated with severe intestinal damage observed in idiopathic inflammatory bowel disease. The chemoattractant hepoxilin A3, an eicosanoid secreted from intestinal epithelial cells by the apically restricted efflux pump multidrug resistance protein 2 (MRP2), mediates this neutrophil influx. Information about a possible counterbalance pathway that could signal the lack of or resolution of an apical inflammatory signal, however, has yet to be described. We now report a system with such hallmarks. Specifically, we identify endocannabinoids as the first known endogenous substrates of the apically restricted ...


Recombinant Human Proteoglycan-4 Reduces Phagocytosis Of Urate Crystals And Downstream Nuclear Factor Kappa B And Inflammasome Activation And Production Of Cytokines And Chemokines In Human And Murine Macrophages, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Wendy Wong, Anthony M. Reginato, Changqi Sun, Tannin A. Schmidt 2018 Chapman University

Recombinant Human Proteoglycan-4 Reduces Phagocytosis Of Urate Crystals And Downstream Nuclear Factor Kappa B And Inflammasome Activation And Production Of Cytokines And Chemokines In Human And Murine Macrophages, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Wendy Wong, Anthony M. Reginato, Changqi Sun, Tannin A. Schmidt

Pharmacy Faculty Articles and Research

Microbial biofilms are organized communities of cells that are associated with a wide spectrum of resistant and chronic infections that lead to the treatment failure. Accordingly, there is an urgent demand to create novel effective therapeutic drugs that can inhibit biofilm formation with new mechanisms of action to surmount the current escalating resistance. In this study, in silico hybrid model was utilized to develop three novel short linear peptides (4, 5, and 6) with potential biofilm inhibiting activities (scores > 1.0). The peptides were composed of cationic and hydrophobic residues. They were synthesized using solid-phase strategy. Synthesized peptides were purified ...


Select Gp120 V2 Domain Specific Antibodies Derived From Hiv And Siv Infection And Vaccination Inhibit Gp120 Binding To Alpha4beta7, Sakaorat Lertjuthaporn, Shan Lu, Yang Lou, Shixia Wang, James Arthos 2018 Mahidol University

Select Gp120 V2 Domain Specific Antibodies Derived From Hiv And Siv Infection And Vaccination Inhibit Gp120 Binding To Alpha4beta7, Sakaorat Lertjuthaporn, Shan Lu, Yang Lou, Shixia Wang, James Arthos

Open Access Articles

The GI tract is preferentially targeted during acute/early HIV-1 infection. Consequent damage to the gut plays a central role in HIV pathogenesis. The basis for preferential targeting of gut tissues is not well defined. Recombinant proteins and synthetic peptides derived from HIV and SIV gp120 bind directly to integrin alpha4beta7, a gut-homing receptor. Using both cell-surface expressed alpha4beta7 and a soluble alpha4beta7 heterodimer we demonstrate that its specific affinity for gp120 is similar to its affinity for MAdCAM (its natural ligand). The gp120 V2 domain preferentially engages extended forms of alpha4beta7 in a cation -sensitive manner and is inhibited ...


Allostatic Load Biomarker Associations With Depressive Symptoms Vary Among Us Black And White Women And Men, Ganga Bey, William M. Jesdale, Christine M. Ulbricht, Eric O. Mick, Sharina D. Person 2018 University of Massachusetts Medical School

Allostatic Load Biomarker Associations With Depressive Symptoms Vary Among Us Black And White Women And Men, Ganga Bey, William M. Jesdale, Christine M. Ulbricht, Eric O. Mick, Sharina D. Person

Open Access Articles

The prevalence and severity of depression differ in women and men and across racial groups. Psychosocial factors such as chronic stress have been proposed as contributors, but causes of this variation are not fully understood. Allostatic load, a measure of the physiological burden of chronic stress, is known to be associated with depression. Using data from the National Health and Nutrition Examination Survey 2005(-)2010, we examined the associations of nine allostatic load biomarkers with depression among US black and white adults aged 18(-)64 years (n = 6431). Depressive symptoms were assessed using the Patient Health Questionaire-9; logistic models estimated ...


Characterisation Of The Structure And Oligomerisation Of Islet Amyloid Polypeptides (Iapp): A Review Of Molecular Dynamics Simulation Studies, Sandra J Moore, Krushna Sonar, Prashant Bharadwaj, Evelyne Deplazes, Ricardo L Mancera 2018 Edith Cowan University

Characterisation Of The Structure And Oligomerisation Of Islet Amyloid Polypeptides (Iapp): A Review Of Molecular Dynamics Simulation Studies, Sandra J Moore, Krushna Sonar, Prashant Bharadwaj, Evelyne Deplazes, Ricardo L Mancera

ECU Publications Post 2013

Human islet amyloid polypeptide (hIAPP) is a naturally occurring, intrinsically disordered protein whose abnormal aggregation into amyloid fibrils is a pathological feature in type 2 diabetes, and its cross-aggregation with amyloid beta has been linked to an increased risk of Alzheimer's disease. The soluble, oligomeric forms of hIAPP are the most toxic to β-cells in the pancreas. However, the structure of these oligomeric forms is difficult to characterise because of their intrinsic disorder and their tendency to rapidly aggregate into insoluble fibrils. Experimental studies of hIAPP have generally used non-physiological conditions to prevent aggregation, and they have been unable ...


Herpes Icp8 Protein Stimulates Homologous Recombination In Human Cells, Melvys Valledor, Richard S. Myers, Paul C. Schiller 2018 University of Massachusetts Medical School

Herpes Icp8 Protein Stimulates Homologous Recombination In Human Cells, Melvys Valledor, Richard S. Myers, Paul C. Schiller

Open Access Articles

Recombineering has transformed functional genomic analysis. Genome modification by recombineering using the phage lambda Red homologous recombination protein Beta in Escherichia coli has approached 100% efficiency. While highly efficient in E. coli, recombineering using the Red Synaptase/Exonuclease pair (SynExo) in other organisms declines in efficiency roughly correlating with phylogenetic distance from E. coli. SynExo recombinases are common to double-stranded DNA viruses infecting a variety of organisms, including humans. Human Herpes virus 1 (HHV1) encodes a SynExo comprised of ICP8 synaptase and UL12 exonuclease. In a previous study, the Herpes SynExo was reconstituted in vitro and shown to catalyze a ...


Ripk1-Ripk3-Mlkl-Associated Necroptosis Drives Leishmania Infantum Killing In Neutrophils, Laiana A. Barbosa, Paloma P. Fiuza, Leticia J. Borges, Fellipe A. Rolim, Mayara B. Andrade, Nivea F. Luz, Graziele Quintela-Carvalho, Jonilson B. Lima, Roque P. Almeida, Francis Ka-Ming Chan, Marcelo T. Bozza, Valeria M. Borges, Deboraci B. Prates 2018 Federal University of Bahia

Ripk1-Ripk3-Mlkl-Associated Necroptosis Drives Leishmania Infantum Killing In Neutrophils, Laiana A. Barbosa, Paloma P. Fiuza, Leticia J. Borges, Fellipe A. Rolim, Mayara B. Andrade, Nivea F. Luz, Graziele Quintela-Carvalho, Jonilson B. Lima, Roque P. Almeida, Francis Ka-Ming Chan, Marcelo T. Bozza, Valeria M. Borges, Deboraci B. Prates

Open Access Articles

Necroptosis is a pro-inflammatory cell death, which happens in the context of caspase-8 inhibition, allowing activation of the receptor interacting protein kinase 1-receptor interacting protein kinase 3-mixed lineage kinase domain-like (RIPK1-RIPK3-MLKL) axis. Recently, necroptosis has emerged as a key component of resistance against pathogens including infected macrophage by Leishmania infantum, the ethiologic agent of Visceral leishmaniasis (VL). VL is the most severe form of Leishmaniasis, characterized by systemic inflammation and neutropenia. However, the role of neutrophil cell death in VL has not been characterized. Here, we showed that VL patients exhibited increased lactate dehydrogenase levels in the serum, a hallmark ...


Are Membranes Non-Apoptotic Compartments For Apoptotic Caspases, Andreas Bergmann 2018 University of Massachusetts Medical School

Are Membranes Non-Apoptotic Compartments For Apoptotic Caspases, Andreas Bergmann

Open Access Articles

Critical mediators of apoptotic cell death are caspases, a highly specialized class of Cys-proteases that cleave substrates after Asp residues. Under normal conditions, caspases are cytosolic proteins. After their activation, they cleave a large number of cytosolic proteins and execute apoptosis (Figure 1, left). However, in addition to their well-studied role in apoptosis, caspases also have many non-apoptotic functions [1, 2]. It is not very well understood how cells escape the potential harmful action of caspases when they perform nonapoptotic functions. In our recent work, we now show that epithelial cells may prevent apoptosis by sequestration of caspases at the ...


Targeting Neuropeptides To Bone Fractures For Accelerated Healing, Nicholas A. Young, Jeffery J. Nielsen, Philip S. Low 2018 Purdue University

Targeting Neuropeptides To Bone Fractures For Accelerated Healing, Nicholas A. Young, Jeffery J. Nielsen, Philip S. Low

The Summer Undergraduate Research Fellowship (SURF) Symposium

In patients over the age of 65 especially, bone fractures represent a significant disease burden. Non-invasive drug therapies are not available for bone fractures which represents a problem for this population. Vasoactive intestinal peptide (VIP) and Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP), two neuromodulator peptides in the glucagon superfamily, have demonstrated positive regulation of osteoblast proliferation and activity. Using acidic oligopeptides, we have developed ligands that target to and accumulate at fracture sites. These targeting ligands can be synthesized in sequence with bone anabolic peptides to minimize off target effects and increase potency at the fracture site to create safer and ...


Jnk Regulates Muscle Remodeling Via Myostatin/Smad Inhibition, Sarah J. Lessard, Tara L. MacDonald, Prerana Pathak, Myoung Souk Han, Vernon G. Coffey, Johann Edge, Donato A. Rivas, Michael F. Hirshman, Roger J. Davis, Laurie J. Goodyear 2018 Harvard Medical School

Jnk Regulates Muscle Remodeling Via Myostatin/Smad Inhibition, Sarah J. Lessard, Tara L. Macdonald, Prerana Pathak, Myoung Souk Han, Vernon G. Coffey, Johann Edge, Donato A. Rivas, Michael F. Hirshman, Roger J. Davis, Laurie J. Goodyear

Open Access Articles

Skeletal muscle has a remarkable plasticity to adapt and remodel in response to environmental cues, such as physical exercise. Endurance exercise stimulates improvements in muscle oxidative capacity, while resistance exercise induces muscle growth. Here we show that the c-Jun N-terminal kinase (JNK) is a molecular switch that when active, stimulates muscle fibers to grow, resulting in increased muscle mass. Conversely, when muscle JNK activation is suppressed, an alternative remodeling program is initiated, resulting in smaller, more oxidative muscle fibers, and enhanced aerobic fitness. When muscle is exposed to mechanical stress, JNK initiates muscle growth via phosphorylation of the transcription factor ...


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