Medicine and Health Sciences Commons^™

Synthesis Of Novel Ciprofloxacin Analogues And Evaluation Of Their Anti-Proliferative Effect On Human Cancer Cell Lines, Narva Suresh, Hunsur Nagendra Nagesh, Kondapalli Venkata Govri Chandra Sekhar, Anil Kumar, Amir Nasrolahi Shirazi, Keykavous Parang

Pharmacy Faculty Articles and Research

A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substitutedpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized (1H NMR, 13C NMR and LCMS) and evaluated for their inhibitory activity on the proliferation of human caucasian acute lymphoblastic leukemiacells (CCRF-CEM), breast adenocarcinoma cells (MDA-MB-468) and human colon carcinoma cells (HCT-116). Among all the synthesized ciprofloxacin analogues 3t at 50 µM showed comparable potency to doxorubicin (10mol) in all three cell lines and 3j inhibited proliferation of MDA-MB-468 up to 35% selectively over other two cell lines. Cancer is a leading cause of death worldwide. It is a group of diseases characterized by uncontrolled growth. Cancer …

Stress And Reproductive Hormones In Grizzly Bears Reflect Nutritional Benefits And Social Consequences Of A Salmon Foraging Niche, Heather M. Bryan, Chris T. Darimont, Paul C. Paquet, Katherine E. Wynne-Edwards, Judit E. G. Smits

Physiology Collection

Physiological indicators of social and nutritional stress can provide insight into the responses of species to changes in food availability. In coastal British Columbia, Canada, grizzly bears evolved with spawning salmon as an abundant but spatially and temporally constrained food source. Recent and dramatic declines in salmon might have negative consequences on bear health and ultimately fitness. To examine broadly the chronic endocrine effects of a salmon niche, we compared cortisol, progesterone, and testosterone levels in hair from salmon-eating bears from coastal BC (n = 75) with the levels in a reference population from interior BC lacking access to salmon …

Mice With Deficient Bk Channel Function Show Impaired Prepulse Inhibition And Spatial Learning, But Normal Working And Spatial Reference Memory, Marei Typlt, Magdalena Mirkowski, Erin Azzopardi, Lukas Ruettiger, Peter Ruth, Susanne Schmid

Anatomy and Cell Biology Publications

Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains.

We first evaluated hearing and motor function to establish the suitability of this …

Predeliberation Activity In Prefrontal Cortex And Striatum And The Prediction Of Subsequent Value Judgment, Uri Maoz, Ueli Rutishauser, Soyoun Kim, Xinying Cai, Christof Koch

Psychology Faculty Articles and Research

Rational, value-based decision-making mandates selecting the option with highest subjective expected value after appropriate deliberation. We examined activity in the dorsolateral prefrontal cortex (DLPFC) and striatum of monkeys deciding between smaller, immediate rewards and larger, delayed ones. We previously found neurons that modulated their activity in this task according to the animal's choice, while it deliberated (choice neurons). Here we found neurons whose spiking activities were predictive of the spatial location of the selected target (spatial-bias neurons) or the size of the chosen reward (reward-bias neurons) before the onset of the cue presenting the decision-alternatives, and thus before rational deliberation …

X-Linked Mtmr8 Diversity And Evolutionary History Of Sub-Saharan Populations, Damian Labuda, Vania Yotova, Jean-François Lefebvre, Claudia Moreau, Gerd Utermann, Scott M. Williams

Dartmouth Scholarship

The genetic diversity within an 11 kb segment of the MTMR8 gene in a sample of 111 sub-Saharan and 49 non-African X chromosomes was investigated to assess the early evolutionary history of sub-Saharan Africans and the out-of-Africa expansion. The analyses revealed a complex genetic structure of the Africans that contributed to the emergence of modern humans. We observed partitioning of two thirds of old lineages among southern, west/central and east African populations indicating ancient population stratification predating the out of Africa migration. Age estimates of these lineages, older than coalescence times of uniparentally inherited markers, raise the question whether contemporary …

Cell-Based Multi-Parametric Model Of Cleft Progression During Submandibular Salivary Gland Branching Morphogenesis, Shayoni Ray, Daniel Yuan, Nimit Dhulekar, Basak Oztan, Bu¨Lent Bu¨Lent Yener, Melinda Larsen

Biological Sciences Faculty Scholarship

Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ. Previous experimental studies indicated requirements for several epithelial cellular processes, such as proliferation, migration, cell-cell adhesion, cell-extracellular matrix (matrix) adhesion, and cellular contraction in cleft formation; however, the relative contribution of each of these processes is not fully understood since it is not possible to experimentally manipulate each factor independently. We present here a comprehensive analysis of several cellular parameters regulating cleft progression during branching morphogenesis in the epithelial tissue of an early embryonic salivary gland at a …

From (Un)Willingness To Involvement: Development Of A Successful Study Brand For Recruitment Of Diverse Msm To A Longitudinal Hiv Research, Paula M. Frew, Victoria A. Williams, Eve T. Shapiro, Travis Sanchez, Eli S. Rosenberg, Vincent L. Fenimore, Patrick S. Sullivan

Environmental & Occupational Health Faculty Publications

Background. HIV continues to be a major concern among MSM, yet Black MSM have not been enrolled in HIV research studies in proportionate numbers to White MSM. We developed an HIV prevention research brand strategy for MSM. Methods. Questionnaires and focus groups were conducted with 54 participants. Descriptive statistics and chi-square analyses were performed and qualitative data were transcribed and content analyzed to identify common themes. Results. Formative research results indicated that younger Black MSM (18–29 years) were less likely to think about joining prevention studies compared to older (≥30 years) Black MSM (, ). Qualitative and quantitative results indicate …

A Process Similar To Autophagy Is Associated With Cytocidal Chloroquine Resistance In Plasmodium Falciparum, David Gaviria, Michelle F. Paguio, Lindsey B. Turnbull, Asako Tan, Amila Siriwardana, Debasish Ghosh, Michael T. Ferdig, Anthony P. Sinai, Paul D. Roepe

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Resistance to the cytostatic activity of the antimalarial drug chloroquine (CQ) is becoming well understood, however, resistance to cytocidal effects of CQ is largely unexplored. We find that PfCRT mutations that almost fully recapitulate P. falciparum cytostatic CQ resistance (CQR(CS)) as quantified by CQ IC50 shift, account for only 10-20% of cytocidal CQR (CQR(CC)) as quantified by CQ LD50 shift. Quantitative trait loci (QTL) analysis of the progeny of a chloroquine sensitive (CQS; strain HB3)×chloroquine resistant (CQR; strain Dd2) genetic cross identifies distinct genetic architectures for CQR(CS) vs CQR(CC) phenotypes, including identification of novel interacting chromosomal loci that influence CQ …

Short Duration Waveforms Recorded Extracellularly From Freely Moving Rats Are Representative Of Axonal Activity, Ashlee A. Robbins, Steven E. Fox, Gregory L. Holmes, Rod C. Scott, Jeremy M. Barry

Dartmouth Scholarship

While extracellular somatic action potentials from freely moving rats have been well characterized, axonal activity has not. We report direct extracellular tetrode recordings of putative axons whose principal feature is a short duration waveform (SDW) with an average peak-trough length less than 179 μs. While SDW recordings using tetrodes have previously been treated as questionable or classified as cells, we hypothesize that they are representative of axonal activity. These waveforms have significantly shorter duration than somatic action potentials, are triphasic and are therefore similar to classic descriptions of microelectrode recordings in white matter and of in vitro action potential propagation …

A Novel Signal Processing Method For Intraoperative Neurophysiological Monitoring In Spinal Surgeries, Krishnatej Vedala

FIU Electronic Theses and Dissertations

Intraoperative neurophysiologic monitoring is an integral part of spinal surgeries and involves the recording of somatosensory evoked potentials (SSEP). However, clinical application of IONM still requires anywhere between 200 to 2000 trials to obtain an SSEP signal, which is excessive and introduces a significant delay during surgery to detect a possible neurological damage. The aim of this study is to develop a means to obtain the SSEP using a much less, twelve number of recordings. The preliminary step involved was to distinguish the SSEP with the ongoing brain activity. We first establish that the brain activity is indeed quasi-stationary whereas …

Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe …

Aspects Of The Innate Immune System In The Caribbean Octocoral Swiftia Exserta, Lorenzo P. Menzel

FIU Electronic Theses and Dissertations

The immune systems of cnidaria are important to study for two reasons: to gain a better understanding of the evolution of immune responses, and to provide a basis to partially redress the precipitous world-wide die-offs of reef corals, some of which have been attributed to diseases and stress. Many immune responses share ancient evolutionary origins and are common across many taxa.

Using Swiftia exserta, an azooxanthellate ahermatypic local octocoral, as a proxy model organism to study aspects of innate immunity in corals and cnidaria allows us to address both of the reasons listed above while not using endangered species. …

Reduced Expression Of The Vesicular Acetylcholine Transporter And Neurotransmitter Content Affects Synaptic Vesicle Distribution And Shape In Mouse Neuromuscular Junction, Hermann A. Rodrigues, Matheus De C. Fonseca, Wallace L. Camargo, Patricia M. A. Lima, Patricia M. Martinelli, Ligia A. Naves, Vania F. Prado, Marco A. M. Prado, Cristina Guatimosim

Anatomy and Cell Biology Publications

In vertebrates, nerve muscle communication is mediated by the release of the neurotransmitter acetylcholine packed inside synaptic vesicles by a specific vesicular acetylcholine transporter (VAChT). Here we used a mouse model (VAChT KDHOM) with 70% reduction in the expression of VAChT to investigate the morphological and functional consequences of a decreased acetylcholine uptake and release in neuromuscular synapses. Upon hypertonic stimulation, VAChT KDHOM mice presented a reduction in the amplitude and frequency of miniature endplate potentials, FM 1-43 staining intensity, total number of synaptic vesicles and altered distribution of vesicles within the synaptic terminal. In contrast, under electrical stimulation or …

Recurrent Tissue-Specific Mtdna Mutations Are Common In Humans, David C. Samuels, Chun Li, Bingshan Li, Zhuo Song, Eric Torstenson, Hayley Boyd Clay, Antonis Rokas, Tricia A. Thornton-Wells, Jason H. Moore, Tia M. Hughes, Robert D. Hoffman, Jonathan L. Haines, Deborah G. Murdock, Douglas P. Mortlock, Scott M. Williams

Dartmouth Scholarship

Mitochondrial DNA (mtDNA) variation can affect phenotypic variation; therefore, knowing its distribution within and among individuals is of importance to understanding many human diseases. Intra-individual mtDNA variation (heteroplasmy) has been generally assumed to be random. We used massively parallel sequencing to assess heteroplasmy across ten tissues and demonstrate that in unrelated individuals there are tissue-specific, recurrent mutations. Certain tissues, notably kidney, liver and skeletal muscle, displayed the identical recurrent mutations that were undetectable in other tissues in the same individuals. Using RFLP analyses we validated one of the tissue-specific mutations in the two sequenced individuals and replicated the patterns in …

Communication And Common Interest, Peter Godfrey-Smith, Manolo Martínez

Publications and Research

Explaining the maintenance of communicative behavior in the face of incentives to deceive, conceal information, or exaggerate is an important problem in behavioral biology. When the interests of agents diverge, some form of signal cost is often seen as essential to maintaining honesty. Here, novel computational methods are used to investigate the role of common interest between the sender and receiver of messages in maintaining cost-free informative signaling in a signaling game. Two measures of common interest are defined. These quantify the divergence between sender and receiver in their preference orderings over acts the receiver might perform in each state …

Food Sovereignty: An Alternative Paradigm For Poverty Reduction And Biodiversity Conservation In Latin America, M. Jahi Chappell, Hannah Wittman, Christopher M. Bacon, Bruce G. Ferguson, Luis García Barrios, Raúl García Barrios, Daniel Jaffee, Jefferson Lima, V. Ernesto Méndez, Helda Morales, Lorena Soto-Pinto, John Vandermeer, Ivette Perfecto

College of Agriculture and Life Sciences Faculty Publications

Strong feedback between global biodiversity loss and persistent, extreme rural poverty are major challenges in the face of concurrent food, energy, and environmental crises. This paper examines the role of industrial agricultural intensification and market integration as exogenous socio-ecological drivers of biodiversity loss and poverty traps in Latin America. We then analyze the potential of a food sovereignty framework, based on protecting the viability of a diverse agroecological matrix while supporting rural livelihoods and global food production. We review several successful examples of this approach, including ecological land reform in Brazil, agroforestry, milpa, and the uses of wild varieties in …

Taxis Toward Hydrogen Gas By Methanococcus Maripaludis, Kristen A. Brileya, James M. Connolly, Carey Downey, Robin Gerlach, Matthew W. Fields

Biology Faculty Publications and Presentations

Knowledge of taxis (directed swimming) in the Archaea is currently expanding through identification of novel receptors, effectors, and proteins involved in signal transduction to the flagellar motor. Although the ability for biological cells to sense and swim toward hydrogen gas has been hypothesized for many years, this capacity has yet to be observed and demonstrated. Here we show that the average swimming velocity increases in the direction of a source of hydrogen gas for the methanogen, Methanococcus maripaludis using a capillary assay with anoxic gas-phase control and time-lapse microscopy. The results indicate that a methanogen couples motility to hydrogen concentration …

Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to …

Regulation Of Stress-Inducible Phosphoprotein 1 Nuclear Retention By Protein Inhibitor Of Activated Stat Pias1, Iaci N. Soares, Fabiana A. Caetano, Jordan Pinder, Bruna Roz Rodrigues, Flavio H. Beraldo, Valeriy G. Ostapchenko, Chantal Durette, Grace Schenatto Pereira, Marilene H. Lopes, Nicolle Queiroz-Hazarbassanov, Isabela W. Cunha, Paulo I. Sanematsu, Sergio Suzuki, Luiz F. Bleggi-Torres, Caroline Schild-Poulter, Pierre Thibault, Graham Dellaire, Vilma R. Martins, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

Stress-inducible phosphoprotein 1 (STI1), a cochaperone for Hsp90, has been shown to regulate multiple pathways in astrocytes, but its contributions to cellular stress responses are not fully understood. We show that in response to irradiation-mediated DNA damage stress STI1 accumulates in the nucleus of astrocytes. Also, STI1 haploinsufficiency decreases astrocyte survival after irradiation. Using yeast two-hybrid screenings we identified several nuclear proteins as STI1 interactors. Overexpression of one of these interactors, PIAS1, seems to be specifically involved in STI1 nuclear retention and in directing STI1 and Hsp90 to specific sub-nuclear regions. PIAS1 and STI1 co-immunoprecipitate and PIAS1 can function as …

One-Day Treatment Of Small Molecule 8-Bromo-Cyclic Amp Analogue Induces Cell-Based Vegf Production For In Vitro Angiogenesis And Osteoblastic Differentiation, Kevin W.-H. Lo, Ho Man Kan, Keith A. Gagnon, Cato T. Laurencin

UCHC Articles - Research

Small molecule based regenerative engineering is emerging as a promising strategy for regenerating bone tissue. Small molecule cAMP analogues have been proposed as novel biofactors for bone repair and regeneration, and while promising, the effect that these small molecules have on angiogenesis, a critical requirement for successful bone regeneration, is still unclear. Our previous research demonstrated that the small molecule cAMP analogue 8-bromoadenosine-3’,5’-cyclic monophosphate (8-Br-cAMP) was able to promote initial osteoblast adhesion on a polymeric scaffold via cAMP signaling cascades. Here, we report that 8-Br-cAMP is capable of inducing in vitro cell-based VEGF production for angiogenesis promotion. We first demonstrated …

Incorporating New Technologies Into Toxicity Testing And Risk Assessment: Moving From 21st Century Vision To A Data-Driven Framework, Russell S. Thomas, Martin A. Philbert, Scott Auerbach, Barbara A. Wetmore, Michael J. Devito, Ila Cote, J. Craig Rowlands, Maurice Whelan, Sean M. Hays, Melvin E. Andersen, M.E. (Bette) Meek, Lawrence W. Reiter, Jason C. Lambert, Harvey J. Clewell Iii, Martin L. Stephens, Q. Jay Zhao, Scott C. Wesselkamper, Lynn Flowers, Edward W. Carney, Tim P. Pastoor, Dan D. Petersen, Carole L. Yauk, Andy Nong

in Vitro Research Models Collection

Based on existing data and previous work, a series of studies is proposed as a basis toward a pragmatic early step in transforming toxicity testing. These studies were assembled into a data-driven framework that invokes successive tiers of testing with margin of exposure (MOE) as the primary metric. The first tier of the framework integrates data from high-throughput in vitro assays, in vitro-to-in vivo extrapolation (IVIVE) pharmacokinetic modeling, and exposure modeling. The in vitro assays are used to separate chemicals based on their relative selectivity in interacting with biological targets and identify the concentration at which these interactions …

Insulin Responsiveness In Metabolic Syndrome After Eight Weeks Of Cycle Training, Charles A. Stuart, Mark A. South, Michelle L. Lee, Melanie P. Mccurry, Mary E. A. Howell, Michael W. Ramsey, Michael H. Stone

ETSU Faculty Works

Introduction Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome.

Methods Eighteen nondiabetic, sedentary subjects, 11 with the metabolic syndrome, participated in 8 wk of increasing intensity stationary cycle training.

Results Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (V˙O2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. The activated mammalian target of rapamycin was not …

Validity Of Boston Marathon Qualifying Times, Paul M. Vanderburgh

Health and Sport Science Faculty Publications

Purpose: To assess the validity of Boston Marathon qualifying (BMQ) standards for men and women. Methods: Percent differences between BMQ and current world records (WR) by sex and age group were computed. WR was chosen as the criterion comparison because it is not confounded by intensity, body composition, lifestyle, or environmental factors. A consistent difference across age groups would indicate an appropriate slope of the age-vs-BMQ curve. Inconsistent differences were corrected by adjusting BMQ standards to achieve a uniform percentage difference from WR. Results: BMQ standards for men were consistently ~50% slower than WR (mean 51.5% ± …

Oncology Section Task Force On Breast Cancer Outcomes: Scapular Assessment, Mary Insana Fisher, Pamela K. Levangie

Physical Therapy Faculty Publications

Background: Functional deficits and changes in scapular mechanics following breast cancer (BC) treatments have been documented. Scapular assessment is important when examining the shoulder in survivors of breast cancer to document the need for or effectiveness of physical therapy intervention. The Oncology Section Task Force on Breast Cancer Outcomes sought to identify scapular examination tools that can be recommended for routine use in individuals treated for BC.

Methods: A systematic review of the literature on scapular measures was conducted. Relevant studies were examined for psychometric properties and clinical usefulness. Each method was given a recommendation score based on the Breast …

Oncology Section Task Force On Breast Cancer Outcomes: An Introduction To The Edge Task Force And Clinical Measures Of Upper Extremity Function, Pamela K. Levangie, Mary Insana Fisher

Physical Therapy Faculty Publications

With the proliferation of outcome measures in the literature, many of which lack documentation of sufficient psychometric properties to justify use, it is difficult to document patient change or demonstrate effectiveness of interventions. The goal of the Section on Research’s EDGE (Evaluation Database to Guide Effectiveness) Task Force is to facilitate identification of valid and reliable tests and measures that reflect clinically important outcomes and are responsive to change for standard use across selected patient groups. This paper lays the groundwork for understanding the work of the Oncology Section’s Breast Cancer EDGE Task Force on clinical measures of shoulder function …

Modeling Acute Respiratory Illness During The 2007 San Diego Wildland Fires Using A Coupled Emissions-Transport System And General Additive Modeling, Brian Thelen, Nancy H. F. French, Benjamin W. Koziol, Michael Billmire, Robert Chris Owen, Jeffrey Johnson, Michele Ginsberg, Tatiana Loboda, Shiliang Wu

Michigan Tech Research Institute Publications

Background

A study of the impacts on respiratory health of the 2007 wildland fires in and around San Diego County, California is presented. This study helps to address the impact of fire emissions on human health by modeling the exposure potential of proximate populations to atmospheric particulate matter (PM) from vegetation fires. Currently, there is no standard methodology to model and forecast the potential respiratory health effects of PM plumes from wildland fires, and in part this is due to a lack of methodology for rigorously relating the two. The contribution in this research specifically targets that absence by modeling …

Prenatal Development: Annotated Bibliography, Victoria J. Molfese, Amanda Prokasky, Kathleen Moritz Rudasill, Ibrahim H. Acar, Xiaoqing Tu, Kate Sirota, Brian Keiser

Department of Child, Youth, and Family Studies: Faculty Publications

For decades, researchers have investigated how events in the prenatal period impact women and their infants. These studies, particularly by researchers in the medical, neuroscience, and behavioral science fields, led to discoveries of important information regarding the prenatal events that were strongly associated with mortality (or death) and morbidity (or incidences of injury, pathology and abnormalities/anomalies, and neurobehavioral sequelae) in the neonatal and infancy periods. Among the many common findings from early research studies, two are particularly noteworthy. First, maternal and fetal risk conditions arising in the prenatal period do not do so in isolation. Sameroff and Chandler characterized this …

The Biology And Taxonomy Of Head And Body Lice: Implications For Louse-Borne Disease Prevention, Denise L. Bonilla, Lance A. Durden, Marina E. Eremeeva, Gregory A. Dasch

Harold W. Manter Laboratory: Library Materials

Sucking lice (Phthiraptera: Anoplura) are obligate blood-feeding ectoparasites of placental mammals including humans. Worldwide, more than 550 species have been described and many are specific to a particular host species of mammal. Three taxa uniquely parasitize humans: the head louse, body louse, and crab (pubic) louse. The body louse, in particular, has epidemiological importance because it is a vector of the causative agents of three important human diseases: epidemic typhus, trench fever, and louse-borne relapsing fever. Since the advent of antibiotics and more effective body louse control measures in the 1940s, these diseases have markedly diminished in incidence. However, due …

Epigenetic Dominance Of Prion Conformers, Eri Saijo, Hae-Eun Kang, Jifeng Bian, Kristi G. Bowling, Shawn Browning, Sehun Kim, Nora Hunter, Glenn C. Telling

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Although they share certain biological properties with nucleic acid based infectious agents, prions, the causative agents of invariably fatal, transmissible neurodegenerative disorders such as bovine spongiform encephalopathy, sheep scrapie, and human Creutzfeldt Jakob disease, propagate by conformational templating of host encoded proteins. Once thought to be unique to these diseases, this mechanism is now recognized as a ubiquitous means of information transfer in biological systems, including other protein misfolding disorders such as those causing Alzheimer's and Parkinson's diseases. To address the poorly understood mechanism by which host prion protein (PrP) primary structures interact with distinct prion conformations to influence pathogenesis, …

Killerflip: A Novel Lytic Peptide Specifically Inducing Cancer Cell Death, B Pennarun, G. Gaidos, O Bucur, A Tinari

Dartmouth Scholarship

One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killer FLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using …