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Achieving High Accuracy Prediction Of Minimotifs, Tian Mi, Sanguthevar Rajasekaran, Jerlin Camilus Merlin, Michael R. Gryk, Martin Schiller 2012 University of Connecticut - Storrs

Achieving High Accuracy Prediction Of Minimotifs, Tian Mi, Sanguthevar Rajasekaran, Jerlin Camilus Merlin, Michael R. Gryk, Martin Schiller

Life Sciences Faculty Research

The low complexity of minimotif patterns results in a high false-positive prediction rate, hampering protein function prediction. A multi-filter algorithm, trained and tested on a linear regression model, support vector machine model, and neural network model, using a large dataset of verified minimotifs, vastly improves minimotif prediction accuracy while generating few false positives. An optimal threshold for the best accuracy reaches an overall accuracy above 90%, while a stringent threshold for the best specificity generates less than 1% false positives or even no false positives and still produces more than 90% true positives for the linear regression and neural network …


Epidemiological Ins And Outs Of Helicobacter Pylori: A Review, Jibran Sualeh Muhammad, Syed Faisal Zaidi, Toshiro Sugiyama 2012 Aga Khan University

Epidemiological Ins And Outs Of Helicobacter Pylori: A Review, Jibran Sualeh Muhammad, Syed Faisal Zaidi, Toshiro Sugiyama

Department of Biological & Biomedical Sciences

Helicobacter pylori infection is now recognised as a worldwide problem. It is the most common cause of chronic gastritis, and is strongly linked to peptic ulcer disease and gastric cancer. A comprehensive understanding of epidemiological ins and outs of H. pylori infection is very important in solving the patho-physiological enigma and might help in leading towards better management and prognosis of infection. This article presents a review of the literature on the epidemiology of H. pylori infection from 2006 to 2011. The authors used Medical Subject Heading (MeSH) terms 'Helicobacter' with 'epidemiology,' 'transmission' or 'risk factor' to search PubMed database. …


Endogenous Inhibitor Proteins That Connect Ser/Thr Kinases And Phosphatases In Cell Signaling., Masumi Eto, David L Brautigan 2012 Thomas Jefferson University

Endogenous Inhibitor Proteins That Connect Ser/Thr Kinases And Phosphatases In Cell Signaling., Masumi Eto, David L Brautigan

Department of Molecular Physiology and Biophysics Faculty Papers

Protein phosphatase activity acts as a primary determinant of the extent and duration of phosphorylation of cellular proteins in response to physiological stimuli. Ser/Thr protein phosphatase-1 (PP1) belongs to the PPP superfamily, and is associated with regulatory subunits that confer substrate specificity, allosteric regulation, and subcellular compartmentalization. In addition, all eukaryotic cells contain multiple heat-stable proteins that originally were thought to inhibit phosphatase catalytic subunits released from the regulatory subunits, as a fail-safe mechanism. However, discovery of C-kinase-activated PP1 inhibitor, Mr of 17 kDa (CPI-17) required fresh thinking about the endogenous inhibitors as specific regulators of particular phosphatase complexes, acting …


Effect Of Egf-Receptor Tyrosine Kinase Inhibitor On Rab5 Function During Endocytosis, Ivan Jozic, Samar C. Saliba, M. Alejandro Barbieri 2012 Florida International University

Effect Of Egf-Receptor Tyrosine Kinase Inhibitor On Rab5 Function During Endocytosis, Ivan Jozic, Samar C. Saliba, M. Alejandro Barbieri

Biology Faculty Articles

Tyrosine autophosphorylation within the cytoplasmic tail of EGF-receptor is a key event, which in turn recruits several factors including Shc, Grb2 and Rin1 that are essential activities for receptor-mediated endocytosis and signaling. In this study, we demonstrated that treatment with AG1478, an EGF-receptor kinase inhibitor, blocked the formation of Rab5-positive endosomes as well as the activation of Rab5 upon addition of EGF. We also found that EGF-receptor catalytically inactive mutant failed to activate Rab5 upon EGF stimulation. Additionally, endosomal co-localization of Rab5 and EGF-receptor was inhibited by AG1478. Interestingly, AG1478 inhibitor did not block the formation of enlarged Rab5-positive endosomes …


Taking Aim At The Start Of Translation, Medha Raina, Michael Ibba 2012 The Ohio State University

Taking Aim At The Start Of Translation, Medha Raina, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

No abstract provided.


Role Of Sequence And Structure Of The Hendra Fusion Protein Fusion Peptide In Membrane Fusion, Everett Clinton Smith, Sonia M. Gregory, Lukas K. Tamm, Trevor P. Creamer, Rebecca Ellis Dutch 2012 University of Kentucky

Role Of Sequence And Structure Of The Hendra Fusion Protein Fusion Peptide In Membrane Fusion, Everett Clinton Smith, Sonia M. Gregory, Lukas K. Tamm, Trevor P. Creamer, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Viral fusion proteins are intriguing molecular machines that undergo drastic conformational changes to facilitate virus-cell membrane fusion. During fusion a hydrophobic region of the protein, termed the fusion peptide (FP), is inserted into the target host cell membrane, with subsequent conformational changes culminating in membrane merger. Class I fusion proteins contain FPs between 20 and 30 amino acids in length that are highly conserved within viral families but not between. To examine the sequence dependence of the Hendra virus (HeV) fusion (F) protein FP, the first eight amino acids were mutated first as double, then single, alanine mutants. Mutation of …


Sex Determination In Beetles: Production Of All Male Progeny By Parental Rnai Knockdown Of Transformer, Jayendra Nath Shukla, Subba Reddy Palli 2012 University of Kentucky

Sex Determination In Beetles: Production Of All Male Progeny By Parental Rnai Knockdown Of Transformer, Jayendra Nath Shukla, Subba Reddy Palli

Entomology Faculty Publications

Sex in insects is determined by a cascade of regulators ultimately controlling sex-specific splicing of a transcription factor, Doublesex (Dsx). We recently identified homolog of dsx in the red flour beetle, Tribolium castaneum (Tcdsx). Here, we report on the identification and characterization of a regulator of Tcdsx splicing in T. castaneum. Two male-specific and one female-specific isoforms of T. castaneum transformer (Tctra) were identified. RNA interference-aided knockdown of Tctra in pupa or adults caused a change in sex from females to males by diverting the splicing of Tcdsx pre-mRNA to male-specific isoform. All the pupa and adults developed from Tctra …


Differential Virus Host-Ranges Of The Fuselloviridae Of Hyperthermophilic Archaea: Implications For Evolution In Extreme Environments, Ruben Michael Ceballos, Caleb D. Marceau, Joshua O. Marceau, Steven Morris, Adam J. Clore, Kenneth M. Stedman 2012 University of Arkansas, Fayetteville

Differential Virus Host-Ranges Of The Fuselloviridae Of Hyperthermophilic Archaea: Implications For Evolution In Extreme Environments, Ruben Michael Ceballos, Caleb D. Marceau, Joshua O. Marceau, Steven Morris, Adam J. Clore, Kenneth M. Stedman

Biological Sciences Faculty Publications and Presentations

An emerging model for investigating virus-host interactions in hyperthermophilic Archaea is the Fusellovirus-Sulfolobus system. The host, Sulfolobus, is a hyperthermophilic acidophile endemic to sulfuric hot springs worldwide. The Fuselloviruses, also known as Sulfolobus Spindle-shaped Viruses (SSVs), are “lemon” or “spindle”-shaped double-stranded DNA viruses, which are also found worldwide. Although a few studies have addressed the host-range for the type virus, Sulfolobus Spindle-shaped Virus 1 (SSV1), using common Sulfolobus strains, a comprehensive host-range study for SSV-Sulfolobus systems has not been performed. Herein, we examine six bona fide SSV strains (SSV1, SSV2, SSV3, SSVL1, SSVK1, SSVRH) and their respective infection characteristics on …


Small-Molecule Inhibition Of Brdt For Male Contraception., Martin M. Matzuk, Michael R. McKeown, Panagis Filippakopoulos, Qinglei Li, Lang Ma, Julio E. Agno, Madeline E. Lemieux, Sarah Picaud, Richard M. Yu, Jun Qi, Stefan Knapp, James E. Bradner 2012 Baylor College of Medicine

Small-Molecule Inhibition Of Brdt For Male Contraception., Martin M. Matzuk, Michael R. Mckeown, Panagis Filippakopoulos, Qinglei Li, Lang Ma, Julio E. Agno, Madeline E. Lemieux, Sarah Picaud, Richard M. Yu, Jun Qi, Stefan Knapp, James E. Bradner

Biochemistry and Molecular Medicine Faculty Publications

A pharmacologic approach to male contraception remains a longstanding challenge in medicine. Toward this objective, we explored the spermatogenic effects of a selective small-molecule inhibitor (JQ1) of the bromodomain and extraterminal (BET) subfamily of epigenetic reader proteins. Here, we report potent inhibition of the testis-specific member BRDT, which is essential for chromatin remodeling during spermatogenesis. Biochemical and crystallographic studies confirm that occupancy of the BRDT acetyl-lysine binding pocket by JQ1 prevents recognition of acetylated histone H4. Treatment of mice with JQ1 reduced seminiferous tubule area, testis size, and spermatozoa number and motility without affecting hormone levels. Although JQ1-treated males mate …


Biochemical Evaluation Of Srh Analogs As Potential Luxs Inhibitors, richa gupta 2012 The University of San Francisco

Biochemical Evaluation Of Srh Analogs As Potential Luxs Inhibitors, Richa Gupta

Master's Theses

Quorum sensing in bacteria is a process of cell-to-cell communication facilitated by small molecules called autoinducers. Interspecies quorum sensing is facilitated by the autoinducer AI-2. The enzyme LuxS catalyzes the formation of AI-2 from S-ribosyl homocysteine (SRH) in a wide variety of bacterial species. Inhibition of LuxS would therefore inhibit interspecies quorum sensing. The goal of this project is to establish biochemical assays for the evaluation of small molecules as potential LuxS inhibitors. The first assay is a conventional colorimetric assay that utilizes Ellman’s reagent to quantify the homocysteine byproduct of DPD production by LuxS. For this assay purified …


Green Tea Extract Protects Against Fibrogenesis Associated With Nonalcoholic Fatty Liver Disease In Diet-Induced Obese Rats, Allyson M. Bower 2012 University of Connecticut - Storrs

Green Tea Extract Protects Against Fibrogenesis Associated With Nonalcoholic Fatty Liver Disease In Diet-Induced Obese Rats, Allyson M. Bower

Master's Theses

No abstract provided.


Breast Tumour Initiating Cell Fate Is Regulated By Microenvironmental Cues From An Extracellular Matrix, Sharmistha Saha, Pang-Kuo Lo, Xinrui Duan, Hexin Chen, Qian Wang 2012 University of South Carolina - Columbia

Breast Tumour Initiating Cell Fate Is Regulated By Microenvironmental Cues From An Extracellular Matrix, Sharmistha Saha, Pang-Kuo Lo, Xinrui Duan, Hexin Chen, Qian Wang

Faculty Publications

Cancer stem cells, also known as tumour-initiating cells (TICs), are identified as highly tumorigenic population within tumours and hypothesized to be main regulators in tumour growth, metastasis and relapse. Evidence also suggests that a tumour microenvironment plays a critical role in the development and progression of cancer, by constantly modulating cell–matrix interactions. Scientists have tried to characterize and identify the TIC population but the actual combination of extracellular components in deciphering the fate of TICs has not been explored. The basic unanswered question is the phenotypic stability of this TIC population in a tissue extracellular matrix setting. The in vivo …


Gas Phase Characterization Of Supramolecules Using Cross-Sectional Areas By Fticr And Sustained Off-Resonance Irradiation Collision Induced Dissociation Techniques In A Fourier Transform Ion Cyclotron Resonance Mass Spectrometer, Fan Yang 2012 Brigham Young University - Provo

Gas Phase Characterization Of Supramolecules Using Cross-Sectional Areas By Fticr And Sustained Off-Resonance Irradiation Collision Induced Dissociation Techniques In A Fourier Transform Ion Cyclotron Resonance Mass Spectrometer, Fan Yang

Theses and Dissertations

In my dissertation, I use a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICR-MS) to investigate supramolecules. Cross-sectional areas by Fourier transform ICR (CRAFTI), a novel technique for measurements of collision cross sections by FTICR, is demonstrated for the first time. The CRAFTI method measures the total "dephasing cross section" for removal of the ions from the coherent packet in the FTICR cell, including contributions not only from momentum transfer but also from reactive collisions including those leading to collisional dissociation. Experimental CRAFTI collision cross sections correlate linearly with theoretically computed results and with results obtained using ion mobility measurements. …


Flow Valve Diagnostics For Label-Free, Quantitative Biomarker Detection: Device Fabrication, Surface Modification, And Testing, Danielle Scarlet Mansfield 2012 Brigham Young University - Provo

Flow Valve Diagnostics For Label-Free, Quantitative Biomarker Detection: Device Fabrication, Surface Modification, And Testing, Danielle Scarlet Mansfield

Theses and Dissertations

Diseases are often diagnosed by detection of disease-specific biomarkers in fluid samples. However, many state-of-the-art detection methods require a lab with complex machinery, trained operators, and/or lengthy analysis time. In contrast, point-of-care (POC) devices are brought to the patient's location, they are easy to use, and results are obtained almost immediately. Many current POC devices are too difficult to be used without a skilled assistant, and although many are able to detect analytes above a threshold value, they give little or no quantitative information. This work presents the development of polymer-based microfluidic devices capable of sensing and quantifying biomarkers in …


Synthesis And Biological Evaluation Of Various Derivatives Of A Broad-Spectrum Anticancer Nucleoside, Jadd R. Shelton 2012 Brigham Young University - Provo

Synthesis And Biological Evaluation Of Various Derivatives Of A Broad-Spectrum Anticancer Nucleoside, Jadd R. Shelton

Theses and Dissertations

Recently the Peterson lab discovered a promising anticancer adenosine derivative-- 2´,3´-bis-O-tert-butyldimethylsilyl-5´-deoxy-5´-[N-(methylcarbamoyl)amino]-N6-(N-phenylcarbamoyl)adenosine. This compound showed selective toxicity against human colon cancer cells in vitro with LC50's = 6--10 µM. It was hypothesized that the lead compound exerted its cytotoxic effects by interacting with a protein kinase. A systematic Structure Activity Relationship (SAR) was undertaken in an attempt to increase the kinase-binding affinity of the lead compound. Many regions of the lead compound were examined: the N6-phenyl urea moiety, the 5´-N-methyl urea group, the 2´,3´-bis-O-TBS groups, the nucleobase, and the ribose sugar. Results of these studies produced some promising new derivatives. In …


Interactome-Wide Analysis Identifies End-Binding Protein 1 As A Crucial Component For The Speck-Like Particle Formation Of Activated Absence In Melanoma 2 (Aim2) Inflammasomes, Li-Jie Wang, Chia-Wei Hsu, Chiu-Chin Chen, Ying Liang, Lih-Chyang Chen, David M. Ojcius, Ngan-Ming Tsang, Chuen Hsueh, Chih-Ching Wu, Yu-Sun Chang 2012 Chang Gung University

Interactome-Wide Analysis Identifies End-Binding Protein 1 As A Crucial Component For The Speck-Like Particle Formation Of Activated Absence In Melanoma 2 (Aim2) Inflammasomes, Li-Jie Wang, Chia-Wei Hsu, Chiu-Chin Chen, Ying Liang, Lih-Chyang Chen, David M. Ojcius, Ngan-Ming Tsang, Chuen Hsueh, Chih-Ching Wu, Yu-Sun Chang

All Dugoni School of Dentistry Faculty Articles

Inflammasomes are cytoplasmic receptors that can recognize intracellular pathogens or danger signals and are critical for interleukin 1β production. Although several key components of inflammasome activation have been identified, there has not been a systematic analysis of the protein components found in the stimulated complex. In this study, we used the isobaric tags for relative and absolute quantification approach to systemically analyze the interactomes of the NLRP3, AIM2, and RIG-I inflammasomes in nasopharyngeal carcinoma cells treated with specific stimuli of these interactomes (H2O2, poly (dA:dT), and EBV noncoding RNA, respectively). We identified a number of proteins that appeared to be …


Sorafenib Enhances Pemetrexed-Induced Cytotoxicity Through And Autophagy-Dependent Mechanism In Cancer Cells, Bareford Mary 2012 Virginia Commonwealth University

Sorafenib Enhances Pemetrexed-Induced Cytotoxicity Through And Autophagy-Dependent Mechanism In Cancer Cells, Bareford Mary

Theses and Dissertations

Acquired cellular resistance to traditional chemotherapeutics is a common obstacle in the treatment of most cancer cell types. This resistance occurs as a result of changes in the underlying molecular mechanisms of disease progression. The development of novel chemotherapeutic approaches designed to enhance the efficacy of protypical anti-cancer drugs is important in order to overcome this issue. Such approaches will aid in understanding the biomolecular phenomena responsible for drug resistance and disease progression. Combining signaling pathway inhibitors has become an effective strategy for enhancing tumor cell death by targeting multiple pathways known to regulate cell survival. Pemetrexed, an FDA-approved anti-folate …


Physiologically-Based Pharmacokinetic Modeling Of Acetaminophen Metabolism And Toxicity, David M. Ng, Ali Navid 2012 San Jose State University

Physiologically-Based Pharmacokinetic Modeling Of Acetaminophen Metabolism And Toxicity, David M. Ng, Ali Navid

STAR Program Research Presentations

Acetaminophen is a common analgesic and antipyretic. Metabolism of acetaminophen and acetaminophen-induced liver necrosis are predicted using physiologically-based pharmacokinetic (PBPK) modeling. Pharmacokinetic means the model determines where the drug is distributed in the body over time. Physiologically-based means the anatomy and physiology of the human body is reflected in the structure and functioning of the model. Acetaminophen is usually safe and effective when taken as recommended, but consumption at higher levels may lead to liver damage. Additionally, other factors such as alcoholic liver disease, smoking, and malnutrition affect the maximum safe dose of acetaminophen.


Using Stable Isotope Analysis To Study Zooplankton Trophic Ecology In San Francisco Estuary, Steven C. Westbrook, Julien Moderan, Wim Kimmerer 2012 California State University - Chico

Using Stable Isotope Analysis To Study Zooplankton Trophic Ecology In San Francisco Estuary, Steven C. Westbrook, Julien Moderan, Wim Kimmerer

STAR Program Research Presentations

Zooplankton biomasses in estuaries are often high and represent an important food source for fish, like theendangered Delta Smelt. Human interferences (nitrates from crops, freshwater flow alteration, invasive species introduction…) have altered the structure of the San Francisco Estuary (SFE) ecosystem. We use stable isotope analysis to improve our knowledge of the planktonic food web in the SFE and gain insights into its evolution over the past decades. Every living thing has a specific isotopic signature. For example, in the plankton we study exists Carbon 13 and Carbon 12. Carbon 13 is different only because it has one extra neutron, …


Quantification And In Vitro Analysis Of Nanolipoproteins (Nlps) Containing Adjuvants, Purna Venkataraman, Craig Blanchette, Nicholas O. Fischer 2012 Lawrence Livermore National Laboratory

Quantification And In Vitro Analysis Of Nanolipoproteins (Nlps) Containing Adjuvants, Purna Venkataraman, Craig Blanchette, Nicholas O. Fischer

STAR Program Research Presentations

Nanolipoprotein particles (NLPs) self-assemble into nanoscale structures that can be used as vaccines or drug delivery agents. Due to the nature of the NLPs, a variety of immune stimulating compounds or adjuvants can be readily incorporated into NLPs: a characteristic difficult to engineer into most other nanoscale platforms. In light of this, a method for quantifying the amount adjuvant actually incorporated into NLPs is a question of high importance. Through the use of reverse phase High-Performance Liquid Chromatography (HPLC) and an Evaporative Light Scattering Detector (ELSD), standard curves can be constructed by analyzing mixtures of NLP components of known concentration, …


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