Digital Commons Network^™

Fatty Acid Binding Protein Deletion Suppresses Inflammatory Pain Through Endocannabinoid/N-Acylethanolamine-Dependent Mechanisms, Martin Kaczocha, Sherrye T. Glaser, Thomas Maher, Brendan Clavin, John Hamilton, Joseph O’Rourke, Mario Rebecchi, Michelino Puopolo, Yuji Owada, Panayotis K. Thanos

Publications and Research

Background Fatty acid binding proteins (FABPs) serve as intracellular carriers that deliver endocannabinoids and N-acylethanolamines to their catabolic enzymes. Inhibition of FABPs reduces endocannabinoid transport and catabolism in cells and FABP inhibitors produce antinociceptive and anti-inflammatory effects in mice. Potential analgesic effects in mice lacking FABPs, however, have not been tested. Findings Mice lacking FABP5 and FABP7, which exhibit highest affinities for endocannabinoids, possessed elevated levels of the endocannabinoid anandamide and the related N-acylethanolamines palmitoylethanolamide and oleoylethanolamide. There were no compensatory changes in the expression of other FABPs or in endocannabinoid-related proteins in the brains of FABP5/7 knockout mice. These …

Ultrasonic Vocalizations Of Male Mice Differ Among Species And Females Show Assortative Preferences For Male Calls, Kerstin Musolf, Stefanie Meindl, Angela L. Larsen, Matina C. Kalcounis-Rueppell, Dustin J. Penn

Publications and Research

Male house mice (Mus musculus) emit ultrasonic vocalizations (USVs) during courtship, which attract females, and we aimed to test whether females use these vocalizations for species or subspecies recognition of potential mates. We recorded courtship USVs of males from different Mus species, Mus musculus subspecies, and populations (F1 offspring of wild-caught Mus musculus musculus, Mus musculus domesticus (and F1 hybrid crosses), and Mus spicilegus), and we conducted playback experiments to measure female preferences for male USVs. Male vocalizations contained at least seven distinct syllable types, whose frequency of occurrence varied among species, subspecies, and populations. Detailed analyses of multiple common …

Phylogenetic Co-Occurrence Of Exor, Exos, And Chvi, Components Of The Rsi Bacterial Invasion Switch, Suggests A Key Adaptive Mechanism Regulating The Transition Between Free-Living And Host-Invading Phases In Rhizobiales, Mary Ellen Heavner, Wei-Gang Qiu, Hai-Ping Cheng

Publications and Research

Both bacterial symbionts and pathogens rely on their host-sensing mechanisms to activate the biosynthetic pathways necessary for their invasion into host cells. The Gram-negative bacterium Sinorhizobium meliloti relies on its RSI (ExoR-ExoS-ChvI) Invasion Switch to turn on the production of succinoglycan, an exopolysaccharide required for its host invasion. Recent whole-genome sequencing efforts have uncovered putative components of RSI-like invasion switches in many other symbiotic and pathogenic bacteria. To explore the possibility of the existence of a common invasion switch, we have conducted a phylogenomic survey of orthologous ExoR, ExoS, and ChvI tripartite sets in more than ninety proteobacterial genomes. Our …

The Evolutionarily Conserved Lim Homeodomain Protein Lim-4/Lhx6 Specifies The Terminal Identity Of A Cholinergic And Peptidergic C. Elegans Sensory/Inter/Motor Neuron-Type, Jinmahn Kim, Jihye Yeon, Seong-Kyoon Choi, Yang Hoon Huh, Zi Fang, Seo Jin Park, Myoung Ok Kim, Zae Young Ryoo, Kyeongjin Kang, Hee-Seok Kweon, Won Bae Jeon, Chris Li, Kyuhyung Kim

Publications and Research

The expression of specific transcription factors determines the differentiated features of postmitotic neurons. However, the mechanism by which specific molecules determine neuronal cell fate and the extent to which the functions of transcription factors are conserved in evolution are not fully understood. In C. elegans, the cholinergic and peptidergic SMB sensory/inter/motor neurons innervate muscle quadrants in the head and control the amplitude of sinusoidal movement. Here we show that the LIM homeobox protein LIM-4 determines neuronal characteristics of the SMB neurons. In lim-4 mutant animals, expression of terminal differentiation genes, such as the cholinergic gene battery and the flp-12 neuropeptide …

The Dual Role Of Inos In Cancer☆, Frederica Vanini, Khosrow Kashfi, Niharika Nath

Publications and Research

Nitric oxide (NO) is one of the 10 smallest molecules found in nature. It is a simple gaseous free radical whose predominant functions is that of a messenger through cGMP. In mammals, NO is synthesized by the enzyme nitric oxide synthase (NOS) of which there are three isoforms. Neuronal (nNOS, NOS1) and endothelial (eNOS, NOS3) are constitutive calcium-dependent forms of the enzyme that regulate neural and vascular function respectively. The third isoform (iNOS, NOS2), is calcium-independent and is inducible. In many tumors, iNOS expression is high, however, the role of iNOS during tumor development is very complex and quite perplexing, …

Hydrogen Sulfide-Releasing Naproxen Suppresses Colon Cancer Cell Growth And Inhibits Nf-Κb Signaling, Ravinder Kodela, Niharika Nath, Mitali Chattopadhyay, Diandra E. Nesbitt, Carlos A. Velázquez-Martínez, Khosrow Kashfi

Publications and Research

Colorectal cancer (CRC) is the second leading cause of death due to cancer and the third most common cancer in men and women in the USA. Nuclear factor kappa B (NF-κB) is known to be activated in CRC and is strongly implicated in its development and progression. Therefore, activated NF-κB constitutes a bona fide target for drug development in this type of malignancy. Many epidemiological and interventional studies have established nonsteroidal anti-inflammatory drugs (NSAIDs) as a viable chemopreventive strategy against CRC. Our previous studies have shown that several novel hydrogen sulfide-releasing NSAIDs are promising anticancer agents and are safer derivatives …

Elevated Hba1c Levels And The Accumulation Of Differentiated T Cells In Cmv+ Individuals, Jerrald L. Rector, G. Neil Thomas, Victoria E. Burns, Jennifer B. Dowd, Raphael M. Herr, Paul A. Moss, Marc N. Jarczok, Kristina Hoffman, Joachim E. Fischer, Jos A. Bosch

Publications and Research

Aims/hypothesis Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27−CD45RA+/−; or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV+ and CMV− individuals. Methods A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) …

Positional Isomerism Markedly Affects The Growth Inhibition Of Colon Cancer Cells By Nosh-Aspirin: Cox Inhibition And Modeling☆, Federica Vannini, Mitali Chattopadhyay, Ravinder Kodela, Praveen P.N. Rao, Khosrow Kashfi

Publications and Research

We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon cancer cells, belonging to the same histological subtype, but with different expression of cyclooxygenase (COX) enzymes; HT-29 express both COX-1 and COX-2, whereas HCT 15 …

Outcome Prediction In Mathematical Models Of Immune Response To Infection, Manuel Mai, Kun Wang, Greg Huber, Michael Kirby, Mark D. Shattuck, Corey S. O’Hern

Publications and Research

Clinicians need to predict patient outcomes with high accuracy as early as possible after disease inception. In this manuscript, we show that patient-to-patient variability sets a fundamental limit on outcome prediction accuracy for a general class of mathematical models for the immune response to infection. However, accuracy can be increased at the expense of delayed prognosis. We investigate several systems of ordinary differential equations (ODEs) that model the host immune response to a pathogen load. Advantages of systems of ODEs for investigating the immune response to infection include the ability to collect data on large numbers of ‘virtual patients’, each …

Dichotomy In The Epigenetic Mark Lysine Acetylation Is Critical For The Proliferation Of Prostate Cancer Cells, Ravi Pathak, Marc Philizaire, Shiraz Mujtaba

Publications and Research

The dynamics of lysine cetylation serve as a major epigenetic mark, which regulates cellular response to inflammation, DNA damage and hormonal changes. Microarray assays reveal changes in gene expression, but cannot predict regulation of a protein function by epigenetic modifications. The present study employs computational tools to inclusively analyze microarray data to understand the potential role of acetylation during development of androgen-independent PCa. The data revealed that the androgen receptor interacts with 333 proteins, out of which at least 92 proteins were acetylated. Notably, the number of cellular proteins undergoing acetylation in the androgen-dependent PCa was more as compared to …

Development Of A Clickable Bimodal Fluorescent/Pet Probe For In Vivo Imaging, Andreas Paulus, Pooja Desai, Brandon Carney, Giuseppe Carlucci, Thomas Reiner, Christian Brand, Wolfgang A. Weber

Publications and Research

Background Fluorescent imaging agents are becoming evermore important in preclinical and clinical research. They do, however, suffer from poor tissue penetration, which makes optical fluorescence imaging incompatible with whole-body imaging techniques. The design of novel bimodal PET active and fluorescent tracers could therefore combine the benefits of optical imaging with radioactively labeled imaging probes. Herein, we report the synthesis and evaluation of a clickable 18F-labeled fluorescent dye. Methods An azide-modified BODIPY-Fl dye could be successfully radio-labeled with 18F using an 18F/19F exchange reaction of the boron-fluoride core of the BODIPY dye to yield a clickable bimodal PET/fluorescent imaging tool. In …

Papio Cranium From The Hominin-Bearing Site Of Malapa: Implications For The Evolution Of Modern Baboon Cranial Morphology And South African Plio-Pleistocene Biochronology, Christopher C. Gilbert, Christine M. Steininger, Job M. Kibii, Lee R. Berger

Publications and Research

A new partial cranium (UW 88-886) of the Plio-Pleistocene baboon Papio angusticeps from Malapa is identified, described and discussed. UW 88-886 represents the only non-hominin primate yet recovered from Malapa and is important both in the context of baboon evolution as well as South African hominin site biochronology. The new specimen may represent the first appearance of modern baboon anatomy and coincides almost perfectly with molecular divergence date estimates for the origin of the modern P. hamadryas radiation. The fact that the Malapa specimen is dated between ~2.026–2.36 million years ago (Ma) also has implications for the biochronology of other …

Nosh-Sulindac (Avt-18a) Is A Novel Nitric Oxide- And Hydrogen Sulfide-Releasing Hybrid That Is Gastrointestinal Safe And Has Potent Anti-Inflammatory, Analgesic, Antipyretic, Anti-Platelet, And Anti-Cancer Properties, Khosrow Kashfi, Mitali Chattopadhyay, Ravinder Kodela

Publications and Research

Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac and NOSH-sulindac administered orally to rats at equimolar doses. Gastrointestinal safety: 6 h post-administration, number/size of hemorrhagic lesions in stomachs were counted. Tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1 h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5 h. Anti-pyretic: …

Exploring The Role Of Mkk7 In Excitotoxicity And Cerebral Ischemia: A Novel Pharmacological Strategy Against Brain Injury, A Vercelli, S Biggi, A Sclip, I E. Repetto, S Cimini, F Falleroni, S Tomasi, R Monti, N Tonna, F Morelli, V Grande, M Stravalaci, E Biasini, O Marin, F Bianco, D Di Marino, T Borsello

Publications and Research

Excitotoxicity following cerebral ischemia elicits a molecular cascade, which leads to neuronal death. c-Jun-N-terminal kinase (JNK) has a key role in excitotoxic cell death. We have previously shown that JNK inhibition by a specific cell-permeable peptide significantly reduces infarct size and neuronal death in an in vivo model of cerebral ischemia. However, systemic inhibition of JNK may have detrimental side effects, owing to blockade of its physiological function. Here we designed a new inhibitor peptide (growth arrest and DNA damage-inducible 45β (GADD45β-I)) targeting mitogen-activated protein kinase kinase 7 (MKK7), an upstream activator of JNK, which exclusively mediates JNK's pathological activation. …

Fruit And Vegetable Consumption And Cardiovascular Risk Factors In Older Chinese: The Guangzhou Biobank Cohort Study, Yangbo Sun, Chao Qiang Jiang, Kar Keung Cheng, Wei Sen Zhang, Gabriel M. Leung, Tai Hing Lam, Mary Schooling

Publications and Research

Objective
To examine the adjusted associations of fruit consumption and vegetable consumption with the Framingham score and its components in the non-Western setting of Southern China, considering health status.

Method
Linear regression was used to assess the cross-sectional associations of fruit and vegetable consumption with the Framingham score and its components, among 19,518 older Chinese (50 years) from the Guangzhou Biobank Cohort Study in Southern China (2003– 2006), and whether these differed by health status.

Results
The association of fruit consumption with the Framingham score varied by health status (P-value

Conclusion
This large study from a non-western setting found that …

Examining The Safety Of Respiratory And Intravenous Inoculation Of Bdellovibrio Bacteriovorus And Micavibrio Aeruginosavorus In A Mouse Model, Kenneth Shatzkes, Richard Chae, Chi Tang, Gregory C. Ramirez, Somdatta Mukherjee, Liana Tsenova, Nancy D. Connell, Daniel E. Kadouri

Publications and Research

Bdellovibrio spp. and Micavibrio spp. are Gram-negative predators that feed on other Gram-negative bacteria, making predatory bacteria potential alternatives to antibiotics for treating multi-drug resistant infections. While the ability of predatory bacteria to control bacterial infections in vitro is well documented, the in vivo effect of predators on a living host has yet to be extensively examined. In this study, respiratory and intravenous inoculations were used to determine the effects of predatory bacteria in mice. We found no reduction in mouse viability after intranasal or intravenous inoculation of B. bacteriovorus 109J, HD100 or M. aeruginosavorus. Introducing predators into the respiratory …

Simulating And Animating The Spatial Dynamics Of Interacting Species Living On A Torus, Boyan Kostadinov

Publications and Research

The goal of this talk is to present a student research project in computational population biology, which aims at creating a computer simulation and animation of the spatial dynamics of interactions between two kinds of species living on a torus-shaped universe. The habitat for spatial interactions is modeled by a 2D lattice with periodic boundary conditions, which wrap the rectangular grid into a torus. The spatial interactions between the species have two components: 1. Population dynamics modeled by the classical Nicholson-Bailey two-parameter family of models for coupled interactions between species, extended to incorporate space and 2. Two-parameter migration dynamics, modeled …

Comparative Sorption Of Methylene Blue Onto Hydrophobic Clays, Alvaro D. Sponza, Natalia J. Fernandez, David Yang, Karla A. Ortiz, Abel E. Navarro

Publications and Research

Chemical modifications of clay to remove methylene blue (MB) from aqueous solutions at room temperature were compared. Natural bentonite (NC) was modified by cation exchange with hexadecyltrimethylammonium chloride (HC), bencyltriethylammonium chloride (BC), and tetramethylammonium chloride (TC) to reverse the surface polarity of the hydrophilic bentonite. The adsorption of MB was studied and fitted by the adsorption theories of Langmuir, Freundlich, Dubinin-Radushkevich, and Temkin. Equilibrium parameters were calculated, indicating that chemical modification did not improve the adsorption, due to the electrostatic adsorption mechanism. Specific surface area was determined, reporting the following trend: NC > TC > BC > HC. Isotherms show that TC is …

Polycations Xxii. Ru(Bpy)2l2 And Ru(Phen)2l2 Systems With Cationic 4,4’-Bipyridine Ligands: Syntheses, Characteristics, And Interactions With Dna, Jasmine Hatcher, Freida Zavurov, Leslie Babukutty, Thomas Strekas, Robert Engel

Publications and Research

Earlier efforts have been concerned with the association of Ruthenium octahedral complexes with DNA. Since the positively charged ruthenium species has been found to associate with the electron rich major groove of double-stranded DNA, it was proposed the addition of cationic sites on the ligands attached to ruthenium would facilitate such association. Thus, we have synthesized several series of octahedral ruthenium complexes bearing ligands having within themselves cationic sites. These have been investigated in their interaction with calf thymus DNA using fluorescence titration analysis. The introduction of the cationic ligands has been found to exhibit enhanced association of the ruthenium …

Tailored Delivery Of Analgesic Ziconotide Across A Blood Brain Barrier Model Using Viral Nanocontainers, Prachi Anand, Alison O’Neil, Emily Lin, Trevor Douglas, Mandë Holford

Publications and Research

The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics, and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity, and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid. Virus like particles (VLPs) …

Geospatial Resolution Of Human And Bacterial Diversity With City-Scale Metagenomics, Ebrahim Afshinnekoo, Cem Meydan, Shanin Chowdhury, Dyala Jaroudi, Collin Boyer, Nick Bernstein, Julia M. Maritz, Darryl Reeves, Jorge Gandara, Sagar Chhangawala, Sofia Ahsanuddin, Amber Simmons, Timothy Nessel, Bharathi Sundaresh, Elizabeth Pereira, Ellen Jorgensen, Sergios-Orestis Kolokotronis, Nell Kirchberger, Isaac Garcia, David Gandara, Sean Dhanraj, Tanzina Nawrin, Yogesh Saletore, Noah Alexander, Priyanka Vijay, Elizabeth M. Hénaff, Paul Zumbo, Michael Walsh, Gregory D. O'Mullan, Scott Tighe, Joel T. Dudley, Anya Dunaif, Sean Ennis, Eoghan O'Halloran, Tiago R. Magalhaes, Braden Boone, Angela L. Jones, Theodore R. Muth, Katie Schneider Paolantonio, Elizabeth Alter, Eric E. Schadt, Jeanne Garbarino, Robert J. Prill, Jane M. Carlton, Shawn Levy, Christopher E. Mason

Publications and Research

The panoply of microorganisms and other species present in our environment influence human health and disease, especially in cities, but have not been profiled with metagenomics at a city-wide scale. We sequenced DNA from surfaces across the entire New York City (NYC) subway system, the Gowanus Canal, and public parks. Nearly half of the DNA (48%) does not match any known organism; identified organisms spanned 1,688 bacterial, viral, archaeal, and eukaryotic taxa, which were enriched for harmless genera associated with skin (e.g., Acinetobacter). Predicted ancestry of human DNA left on subway surfaces can recapitulate U.S. Census demographic data, and bacterial …

The Phytoene Synthase Gene Family Of Apple (Malus X Domestica) And Its Role In Controlling Fruit Carotenoid Content, Charles Ampomah-Dwamena, Nicky Driedonks, David Lewis, Maria Shumskaya, Xiuyin Chen, Eleanore T. Wurtzel, Richard V. Espley, Andrew C. Allan

Publications and Research

Background Carotenoid compounds play essential roles in plants such as protecting the photosynthetic apparatus and in hormone signalling. Coloured carotenoids provide yellow, orange and red colour to plant tissues, as well as offering nutritional benefit to humans and animals. The enzyme phytoene synthase (PSY) catalyses the first committed step of the carotenoid biosynthetic pathway and has been associated with control of pathway flux. We characterised four PSY genes found in the apple genome to further understand their involvement in fruit carotenoid accumulation. Results The apple PSY gene family, containing six members, was predicted to have three functional members, PSY1, PSY2, …

Diagnostic Imaging Of Cervical Intraepithelial Neoplasia Based On Hematoxylin And Eosin Fluorescence, Mario R. Castellanos, Anita Szerszen, Stephen Gundry, Edyta C. Pirog, Mitchell Maiman, Sritha Rajupet, John Paul Gomez, Adi Davidov, Priya Ranjan Debata, Probal Banerjee, Jimmie E. Fata

Publications and Research

Background Pathological classification of cervical intraepithelial neoplasia (CIN) is problematic as it relies on subjective criteria. We developed an imaging method that uses spectroscopy to assess the fluorescent intensity of cervical biopsies derived directly from hematoxylin and eosin (H&E) stained tissues. Methods Archived H&E slides were identified containing normal cervical tissue, CIN I, and CIN III cases, from a Community Hospital and an Academic Medical Center. Cases were obtained by consensus review of at least 2 senior pathologists. Images from H&E slides were captured first with bright field illumination and then with fluorescent illumination. We used a Zeiss Axio Observer …

Population Genetic Structure Of The Dwarf Seahorse (Hippocampus Zosterae) In Florida, Nathan Fedrizzi, Melanie L. J. Stiassny, J. T. Boehm, Eric R. Dougherty, George Amato, Martin Mendez

Publications and Research

The dwarf seahorse (Hippocampus zosterae) is widely distributed throughout near-shore habitats of the Gulf of Mexico and is of commercial significance in Florida, where it is harvested for the aquarium and curio trades. Despite its regional importance, the genetic structure of dwarf seahorse populations remains largely unknown. As an aid to ongoing conservation efforts, we employed three commonly applied mtDNA markers (ND4, DLoop and CO1) to investigate the genetic structuring of H. zosterae in Florida using samples collected throughout its range in the state. A total of 1450 bp provided sufficient resolution to delineate four populations of dwarf seahorses, as …

Cdc6 Degradation Requires Phosphodegron Created By Gsk-3 And Cdk1 For Scfcdc4 Recognition In Saccharomyces Cerevisiae, Amr Al-Zain, Lea Schroeder, Alina Sheglov, Amy E. Ikui

Publications and Research

DNA replication has to be tightly regulated to ensure genome integrity such that DNA replication takes place only once per cell cycle. The Cdc6 sequential phosphorylation by GSK-3 and Cdk1 creates a binding site for Cdc4 ubiquitin ligase to promote Cdc6 degradation.

The 3’-Jα Region Of The Tcrα Locus Bears Gene Regulatory Activity In Thymic And Peripheral T Cells, Martina Kučerová-Levisohn, Stefan Knirr, Rosa I. Mejia, Benjamin D. Ortiz

Publications and Research

Much progress has been made in understanding the important cis-mediated controls on mouse TCRα gene function, including identification of the Eα enhancer and TCRα locus control region (LCR). Nevertheless, previous data have suggested that other cis-regulatory elements may reside in the locus outside of the Eα/LCR. Based on prior findings, we hypothesized the existence of gene regulatory elements in a 3.9-kb region 5’ of the Cα exons. Using DNase hypersensitivity assays and TCRα BAC reporter transgenes in mice, we detected gene regulatory activity within this 3.9-kb region. This region is active in both thymic and peripheral T cells, and selectively …

Common Cell Shape Evolution Of Two Nasopharyngeal Pathogens, Frédéric J. Veyrier, Nicolas Biais, Pablo Morales, Nouria Belkacem, Cyril Guilhen, Sylvia Ranjeva, Odile Sismeiro, Gérard Péhau-Arnaudet, Eduardo P. Rocha, Catherine Werts, Muhamed-Kheir Taha, Ivo G. Boneca

Publications and Research

Respiratory infectious diseases are the third cause of worldwide death. The nasopharynx is the portal of entry and the ecological niche of many microorganisms, of which some are pathogenic to humans, such as Neisseria meningitidis and Moraxella catarrhalis. These microbes possess several surface structures that interact with the actors of the innate immune system. In our attempt to understand the past evolution of these bacteria and their adaption to the nasopharynx, we first studied differences in cell wall structure, one of the strongest immune-modulators. We were able to show that a modification of peptidoglycan (PG) composition (increased proportion of pentapeptides) …

Nitric Oxide-Releasing Aspirin Suppresses Nf-Κb Signaling In Estrogen Receptor Negative Breast Cancer Cells In Vitro And In Vivo, Niharika Nath, Mitali Chattopadhyay, Deborah B. Rodes, Anna Nazarenko, Ravinder Kodela, Khosrow Kashfi

Publications and Research

Estrogen receptor negative (ER(−)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(−) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(−) breast cancers. Nitric oxide-releasing aspirin (NO-ASA) is a safer ASA where ASA is linked to an NO-releasing moiety through a spacer. In vitro, we investigated anti-proliferation effects of NO-ASA (para- and meta-isomers) against ER(−) breast cancer cells MDA-MB-231 and SK-BR-23, effects on NF-κB signaling, and reactive oxygen species by standard techniques. In vivo, effects of NO-ASA were evaluated in a mouse xenograft model …

Sugar-Induced Cephalic-Phase Insulin Release Is Mediated By A T1r2+T1r3-Independent Taste Transduction Pathway In Mice, John I. Glendinning, Sarah Stano, Marlena Holter, Tali Azenkot, Olivia Goldman, Robert F. Margolskee, Joseph R. Vasselli, Anthony Sclafani

Publications and Research

Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity …

Inferring Interaction Type In Gene Regulatory Networks Using Co-Expression Data, Pegah Khosravi, Vahid H. Gazestani, Leila Pirhaji, Brian Law, Mehdi Sadeghi, Bahram Goliaei, Gary D. Bader

Publications and Research

Background

Knowledge of interaction types in biological networks is important for understanding the functional organization of the cell. Currently information-based approaches are widely used for inferring gene regulatory interactions from genomics data, such as gene expression profiles; however, these approaches do not provide evidence about the regulation type (positive or negative sign) of the interaction.

Results

This paper describes a novel algorithm, “Signing of Regulatory Networks” (SIREN), which can infer the regulatory type of interactions in a known gene regulatory network (GRN) given corresponding genome-wide gene expression data. To assess our new approach, we applied it to three different benchmark …