Digital Commons Network^™

Unifying The Mathematical Modeling Of In Vivo And In Vitro Microdialysis, Peter M. Bungay, Rachita K. Sumbria, Ulrich Bickel

Pharmacy Faculty Articles and Research

A unifying approach is presented for developing mathematical models of microdialysis that are applicable to both in vitro and in vivo situations. Previous models for cylindrical probes have been limited by accommodating analyte diffusion through the surrounding medium in the radial direction only, i.e., perpendicular to the probe axis, or by incomplete incorporation of diffusion in the axial direction. Both radial and axial diffusion are included in the present work by employing two-dimensional finite element analysis. As in previous models, the nondimensional clearance modulus (Θ) represents the degree to which analyte clearance from the external medium influences diffusion through the …

Fluorine Substitutions In An Antigenic Peptide Selectively Modulate T Cell Receptor Binding In A Minimally Perturbing Manner, Kurt H. Piepenbrink, Oleg Y. Borbulevych, Ruth F. Sommese, John Clemens, Kathrynq M. Armstrong, Clare Desmond, Priscilla Do, Brian M. Baker

Food for Health: Publications

T cell receptor (TCR) recognition of antigenic peptides bound and presented by major histocompatibility complex (MHC) molecules forms the basis of the cellular immune response to pathogens and cancer. TCRs bind peptide/MHC molecules weakly and with fast kinetics, features which have hindered detailed biophysical studies of these interactions. Modified peptides resulting in enhanced TCR binding could help overcome these challenges. Further, there is considerable interest in using modified peptides with enhanced TCR binding as the basis for clinical vaccines. Here, we studied how fluorine substitutions in an antigenic peptide can selectively impact TCR recognition. Using a structure-guided design approach, we …

Comprehensive Gene-Based Association Study Of A Chromosome 20 Linked Region Implicates Novel Risk Loci For Depressive Symptoms In Psychotic Illness, T. Bernard Bigdeli, Brion S. Maher, Zhongming Zhao, Edwin J. C. G. Van Den Oord, Dawn L. Thiselton, Jingchun Sun, Bradley T. Webb, Richard L. Amdur, Brandon Wormley, Francis A. O'Neill, Dermot Walsh, Brien P. Riley, Kenneth S. Kendler, Ayman H. Fanous

Human and Molecular Genetics Publications

Background

Prior genomewide scans of schizophrenia support evidence of linkage to regions of chromosome 20. However, association analyses have yet to provide support for any etiologically relevant variants.

Methods

We analyzed 2988 LD-tagging single nucleotide polymorphisms (SNPs) in 327 genes on chromosome 20, to test for association with schizophrenia in 270 Irish high-density families (ISHDSF, N = 270 families, 1408 subjects). These SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Given a previous report of novel linkage with chromosome 20p using latent classes of psychotic illness in this sample, association analysis was also conducted …

Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin M. Rice, Bin Wang, Eric R. Blough

MIIR Faculty Research

Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, …

An Algorithm For Facial Expression Recognition To Assist Handicapped Individuals With Eating Disabilities, Anthony Rudolph De La Loza

Theses Digitization Project

The purpose of this thesis is to describe an algorithm and implement a software system based upon facial expression recognition that will accurately determine the specific need of a handicapped individual pertaining to the eating process. Then based upon that need, determine the appropriate action that should be executed. This thesis aims to present a solution to allow a special needs individual to eat more efficienty and foster independence, while providing a platform for further research in the area of feature detection to assist individuals with special needs.

Learning From Mistakes: Improving Initial Fingertip Force Scaling By Observing Lifting Errors, Gavin Buckingham, Minnie Tang, Paul Gribble, Melvyn A. Goodale

Psychology Presentations

• When lifting objects that are lighter or heaver than we expect them to be, individuals typically misapply forces in a way that reflects their prior expectations of heaviness.

• Because we lift in this predictive way, large and small cubes elicit these characteristic errors even when they are adjusted to have equal mass. Lifters will apply too much force to a large cube and substantially less force to a small cube – errors that are rapidly corrected with repeated lifts (Flanagan & Beltzner, 2000).

• When watching others lift objects, an observer’s motor system automatically reacts in a way …

Negative Associations Between Corpus Callosum Midsagittal Area And Iq In A Representative Sample Of Healthy Children And Adolescents., Hooman Ganjavi, John D Lewis, Pierre Bellec, Penny A Macdonald, Deborah P Waber, Alan C Evans, Sherif Karama, The Brain Development Cooperative Group

Brain and Mind Institute Researchers' Publications

Documented associations between corpus callosum size and cognitive ability have heretofore been inconsistent potentially owing to differences in sample characteristics, differing methodologies in measuring CC size, or the use of absolute versus relative measures. We investigated the relationship between CC size and intelligence quotient (IQ) in the NIH MRI Study of Normal Brain Development sample, a large cohort of healthy children and adolescents (aged six to 18, n = 198) recruited to be representative of the US population. CC midsagittal area was measured using an automated system that partitioned the CC into 25 subregions. IQ was measured using the Wechsler …

Tegument Protein Subcellular Localization Of Human Cytomegalovirus, John Paul Tomtishen Iii

Honors Theses

To determine the subcellular localization of the tegument proteins pp65, pp71, pp150, and pp28 as fusions to one of several fluorescent proteins. Since these tegument proteins play pivotal roles in several stages of the viral life cycle, knowledge of where and the mechanism of how these proteins localize upon release could result in a better understanding of their function during a lytic infection as well as assist in the development of an effective, novel antiviral treatment.

Functional Connectivity For Configural And Featural Face Processing In The Broad Autism Phenotype, Jonathan Darrell Clark

University of Kentucky Doctoral Dissertations

During normal development, face processing involves a gradual shift from a featurally oriented style to a mature configural style by adolescence. This shift may coincide with increased right hemispheric dominance for faces supporting configural processing. Previous studies suggest that individuals diagnosed with ASD continue to process faces using individual parts and features into adulthood. This continued bias may be due to deficits in configural processing abilities. The current study investigated measures of functional connectivity during featural and configural processing of faces in broad autism phenotype sibling (ASD-sibs) children compared to age, sex, and handedness matched normal developing (ND) controls and …

The Role Of The Pediatrican In The Effort To Prevent Congenital Malformations, Robert L. Brent Dr.

The Selected Works of Robert Brent

No

Evaluation Of Reproductive And Developmental Risks Of Caffeine, Robert L. Brent Dr.

The Selected Works of Robert Brent

No abstract provided.

The Professonal Responsibility Model Of Obstetrical Ethics: Avoiding The Perils Of Clashing Rights, Robert L. Brent, Frank A. Chervenak, Md, Laurence B. Mccullough, Phd

The Selected Works of Robert Brent

Obstetric ethics is sometimes represented by polarized views. One extreme asserts the rights of the fetus as the overwhelming ethical consideration. Both assertions are overly simplistic. Such oversimplification is called reductionism. This article explains the fallacy of rights-based reductionism and 2 models of obstetric ethics based on it and explains why the fetal rights reductionism model and the pregnant woman's rights reductionism model result in conceptual and clinical failure and therefore should be abandoned. The article argues for the professional responsibility model of obstetric ethics, which emphasizes the importance of medical science and compassionate clinical care of both the pregnant …

3-Substitued Indoles: One Pot Synthesis And Evaluation Of Anticancer And Src Kinase Inhibitory Activities, V. Kameshwara Rao, Bhupender S. Chhikara, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

An efficient and economical method was developed for the synthesis of 3-substituted indoles by one pot three-component coupling reaction of a substituted or unsubstituted benzaldehyde, N-methylaniline, and indole or N-methylindole using Yb(OTf)3-SiO2 as a catalyst. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. The 4-methylphenyl (4o and 4p) and 4-methoxyphenyl (4q) indole derivatives inhibited the cell proliferation of SK-OV-3 and HT-29 cells by 7077% at a concentration of 50 μM. The unsubstituted phenyl (4d) and 3-nitrophenyl (4l) derivatives showed the inhibition of c-Src kinase …

Click Chemistry Inspired One-Pot Synthesis Of 1, 4-Disubstituted 1, 2, 3-Triazoles And Their Src Kinase Inhibitory Activity, Dalip Kumar, V. Buchi Reddy, Anil Kumar, Deendayal Mandal, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Two classes of 1,4-disubstituted 1,2,3-triazoles were synthesized using one-pot reaction of α-tosyloxy ketones/α-halo ketones, sodium azide, and terminal alkynes in the presence of aq. PEG (1:1, v/v) using the click chemistry approach and evaluated for Src kinase inhibitory activity. Structure-activity relationship analysis demonstrated that insertion of C6H5- and 4-CH3C6H4- at position 4 for both classes and less bulkier aromatic group at position 1 in class 1 contribute critically to the modest Src inhibition activity (IC50 = 32-43 µM) of 1,4-disubstituted 1,2,3-triazoles.

Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus serotype (Ad5) is the most studied Ad. Ad1, 2, and 6 are also members of species C Ad and are presumed to have biologies similar to Ad5. In this work, we have compared the ability of Ad1, 2, 5, and 6 to infect liver and muscle after intravenous and intramuscular injection. We found that Ad6 was surprisingly the most potent at liver gene delivery and that Ad1 and Ad2 were markedly weaker than Ad5 and 6. To understand these differences, we sequenced the Ad6 genome. This revealed that the Ad6 fiber protein is surprisingly three shaft repeats shorter than …

The Evolution Of Host Specialization In The Vertebrate Gut Symbiont Lactobacillus Reuteri, Steven A. Frese, Andrew K. Benson, Gerald W. Tannock, Diane M. Loach, Jaehyoung Kim, Min Zhang, Phaik Lyn Oh, Nicholas C. K. Heng, Prabhu B. Patil, Nathalie Juge, Donald A. Mackenzie, Bruce M. Pearson, Alla Lapidus, Eileen Dalin, Hope Tice, Eugene Goltsman, Miriam Land, Loren Hauser, Natalia Ivanova, Nikos C. Kyrpides, Jens Walter

Jens Walter Publications

Recent research has provided mechanistic insight into the important contributions of the gut microbiota to vertebrate biology, but questions remain about the evolutionary processes that have shaped this symbiosis. In the present study, we showed in experiments with gnotobiotic mice that the evolution of Lactobacillus reuteri with rodents resulted in the emergence of host specialization. To identify genomic events marking adaptations to the murine host, we compared the genome of the rodent isolate L. reuteri 100-23 with that of the human isolate L. reuteri F275, and we identified hundreds of genes that were specific to each strain. In …

Inhibition Of Multi-Drug Resistant Hiv-1 Reverse Transcriptase By Nucleoside Beta-Triphosphates, Chandravanu Dash, Yousef Ahmadibeni, Michael J. Hanley, Jui Pandhare, Mathias Gotte, Stuart F. J. Le Grice, Keykavous Parang

Pharmacy Faculty Articles and Research

Despite the success of potent reverse transcriptase (RT) inhibitors against human immunodeficiency virus type 1 (HIV-1) in combination regimens, the development of drug resistant RTs constitutes a major hurdle for the long-term efficacy of current antiretroviral therapy. Nucleoside β-triphosphate analogs of adenosine and nucleoside reverse transcriptase inhibitors (NRTIs) (3′-azido-2′,3′-dideoxythymidine (AZT), 3′-fluoro-2′,3′-dideoxythymidine (FLT), and 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T)) were synthesized and their inhibitory activities were evaluated against wild-type and multidrug resistant HIV-1 RTs. Adenosine β-triphosphate (1) and AZT β-triphosphate (2) completely inhibited the DNA polymerase activity of wild type, the NRTI multi resistant, and nonnucleoside RT inhibitors (NNRTI) resistant HIV-1 RT at 10 …

Thiazolyl N-Benzyl-Substituted Acetamide Derivatives: Synthesis, Src Kinase Inhibitory And Anticancer Activities, Asal Fallah-Tafti, Alireza Foroumadi, Rakesh Tiwari, Amir Nasrolahi Shirazi, David G. Hangauer, Yahao Bu, Tahmineh Akbarzadeh, Keykavous Parang, Abbas Shafiee

Pharmacy Faculty Articles and Research

KX2-391 (KX-01/Kinex Pharmaceuticals), N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetamide, is a highly selective Src substrate binding site inhibitor. To understand better the role of pyridine ring and N-benzylsubstitution in KX2-391 and establish the structure-activity relationship, a number of N-benzyl substituted (2-morpholinoethoxy)phenyl)thiazol-4-yl)acetamide derivatives containing thiazole instead of pyridine were synthesized and evaluated for Src kinase inhibitory activities. The unsubstituted N-benzyl derivative (8a) showed the inhibition of c-Src kinase with GI50 values of 1.34 μM and 2.30 M in NIH3T3/c-Src527F and SYF/c-Src527F cells, respectively. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), breast carcinoma (BT-20), and leukemia (CCRF-CEM) cells. …

Altered Self-Assembly And Apatite Binding Of Amelogenin Induced By N-Terminal Proline Mutation, Li Zhu, Vuk Uskoković, Thuan Le, Pamela Denbesten, Yulei Huang, Stefan Habelitz, Wu Li

Pharmacy Faculty Articles and Research

Objective—A single Pro-70 to Thr (p.P70T) mutation of amelogenin is known to result in hypomineralized amelogenesis imperfecta (AI). This study aims to test the hypothesis that the given mutation affects the self-assembly of amelogenin molecules and impairs their ability to conduct the growth of apatite crystals.

Design—Recombinant human full-length wild-type (rh174) and p.P70T mutated amelogenins were analyzed using dynamic light scattering (DLS), protein quantification assay and atomic force microscopy (AFM) before and after the binding of amelogenins to hydroxyapatite crystals. The crystal growth modulated by both amelogenins in a dynamic titration system was observed using AFM.

Results—As …

Roles Of The 15-Kda Selenoprotein (Sep15) In Redox Homeostasis And Cataract Development Revealed By The Analysis Of Sep 15 Knockout Mice, Marina V. Kasaikina, Dmitri E. Fomenko, Vyacheslav M. Labunskyy, Salil A. Lachke, Wenya Qiu, Juliet A. Moncaster, Jie Zhang, Mark W. Wojnarowicz, Sathish Kumar Natarajan, Mikalai I. Malinouski, Ulrich Schweizer, Petra A. Tsuji, Bradley A. Carlson, Richard L. Maas, Marjorie F. Lou, Lee E. Goldstein, Dolph L. Hatfield, Vadim N. Gladyshev

School of Veterinary and Biomedical Sciences: Faculty Publications

The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteinerich UDP-glucose:glycoprotein glucosyltransferase-binding domain. These KO mice synthesized a mutant mRNA, but the shortened protein product could be detected neither in tissues nor in Sep15 KO embryonic fibroblasts. Sep15 KO mice were viable …

A Computational Framework For Proteome-Wide Pursuit And Prediction Of Metalloproteins Using Icp-Ms And Ms/Ms Data, W. Andrew Lancaster, Jeremy L. Praissman, Farris L. Poole, Aleksandar Cvetkovic, Angeli Lal Menon, Joseph W. Scott, Francis E. Jenney, Michael P. Thorgersen, Ewa Kalisiak, Junefredo V. Apon, Sunia A. Trauger, Gary Siuzdak, John A. Tainer, Michael W. W. Adams

PCOM Scholarly Works

BACKGROUND: Metal-containing proteins comprise a diverse and sizable category within the proteomes of organisms, ranging from proteins that use metals to catalyze reactions to proteins in which metals play key structural roles. Unfortunately, reliably predicting that a protein will contain a specific metal from its amino acid sequence is not currently possible. We recently developed a generally-applicable experimental technique for finding metalloproteins on a genome-wide scale. Applying this metal-directed protein purification approach (ICP-MS and MS/MS based) to the prototypical microbe Pyrococcus furiosus conclusively demonstrated the extent and diversity of the uncharacterized portion of microbial metalloproteomes since a majority of the …

Assessment Of The Left Atrial Longitudinal Myocardial Function By Assessment Of The Left Atrial Longitudinal Myocardial Function By The Strain And Strain Rate Echocardiography In Patients With Rheumatic Mitral Stenosis*, Enbi̇ya Aksakal, Serdar Sevi̇mli̇, Hanefi̇ Yekta Gürlertop, Mehmet Ali̇ Elbey, Muhammed Hakan Taş, Fuat Gündoğdu, Mustafa Kemal Erol, Şule Karakelleoğlu

Turkish Journal of Medical Sciences

To evaluate the regional left atrial (LA) myocardial functions and time to peak deformations by the longitudinal strain (S) and strain rate (Sr) echocardiography in isolated mitral stenosis (MS) patients for 3 LA periods (contractile, reservoir, and conduit periods). Materials and methods: Included in the study were 30 MS patients and 30 healthy controls. Longitudinal peak S and Sr indices, time to peak S and time to peak Sr, and systolic and diastolic velocities were measured from the color Doppler myocardial imaging data, for each LA period. Results: For all 3 periods, all of the segment S values and most …

Gabaergic Signaling To Adult-Generated Neurons In Hippocampus, Sean Markwardt

All ETDs from UAB

In the central nervous system of adult mammals, new neurons are produced throughout life in at least two regions, the subventricular zone and dentate gyrus of the hippocampus. New neurons in the SVZ migrate via the rostral migratory stream and eventually participate in adaptive olfactory processes. In the dentate gyrus, a variety of physiological functions for continued addition of neurons have been proposed, but its role in normal or pathological conditions remains largely unclear. Neurogenesis in the dentate gyrus consists of the stepwise process of generating fully functional granule cells (GCs) from adult neural stem cells. Regulation of neurogenesis can …

Killer Immunoglobulin-Like Receptors And Human Leukocyte Polymorphisms In Hiv-1 Pathogenesis, Aimee Marie Merino

All ETDs from UAB

Human leukocyte antigen (HLA) molecules influence the adaptive and innate immune responses through interactions with cytotoxic T lymphocytes and natural killer cells (NK). HLA influence the activation state of NK through direct binding to killer immunoglobulin-like receptors (KIR) and presentation of HLA-derived peptides to NKG2 receptors. Activated NK can kill HIV-infected cells through direct cytolysis and release cytokines that influence other aspects of the immune system. Variations in KIR gene content and allelic variants have been associated with autoimmunity, transplantation success, and infectious diseases such as hepatitis C and HIV/AIDS. We investigated the impact of KIR genes and potential KIR-HLA …

Structural And Mechanistic Studies On Er Upr Sensor Perk And Mitochondrial Translocon Element Tim44, Wenjun Cui

All ETDs from UAB

The unfolded protein response is one mechanism utilized by endoplasmic reticulum (ER) to maintain the homeostasis between ER protein folding machinery and ER proteins. UPR is induced by three ER transmembrane sensors: IRE1, ATF6 and PERK. PKR-like ER kinase (PERK) can sense the ER stress signal through its luminal domain to activate its cytoplasmic kinase domain catalytic activity. PERK kinase domain belongs to the eIF2α family. Members in this family are activated after being autophosphorylated at their activation loops and then specifically phosphorylate eIF2α at its Ser51 position. Phosphorylation of eIF2α can shutdown the cytosol protein translation from the initiation …

Functional Interplay Between Trans Factors And Cis-Elements That Govern Il17a&F Transcription, Sarah Kern Whitley

All ETDs from UAB

Protective immunity against a variety of infections depends on the amplification and differentiation of naïve antigen-specific CD4 T cells. T helper 17 (Th17) cells are important for defending mucosal barriers from invading extracellular bacterial pathogens. This effector CD4 lineage is characterized by production of the cytokines IL-17A, IL-17F, IL-21, and IL-22, which elicit influx of inflammatory cells to promote pathogen clearance. The cytokines IL-6 and TGF&beta are the principal factors that initiate Th17 lineage development, and the STAT3-inducing cytokines IL-21 and IL-23 assist and/or maintain the Th17 developmental program. Recently, an additional cytokine has been demonstrated to encourage Th17 differentiation: …

The Natural History Of Sivcpz Infection In Wild Living Chimpanzees, Rebecca Steele Rudicell

All ETDs from UAB

Simian immunodeficiency virus of chimpanzees (SIVcpz) is the immediate precursor to human immunodeficiency virus type 1 (HIV-1), but even the most basic aspects of SIVcpz infection in its natural host are unknown. Here, we present the first comprehensive analysis of the natural history of SIVcpz infection in wild living chimpanzees. Using non-invasive (feces and urine based) methods, we studied two unique chimpanzee populations in Tanzania: the famous chimpanzees of Gombe National Park and the savanna chimpanzees of Ugalla, located about 135 km southeast of Gombe. Gombe chimpanzees are endemically infected with SIVcpz, and the park's established research infrastructure provides a …

In Vivo Analysis Of The Natural Diversity Of The Igr Ires Family And Characterization Of The Role Of Ribosomal Protein S25 In Ires-Mediated Translation, Marla Ilene Hertz

All ETDs from UAB

Translation of the majority of eukaryotic mRNAs is initiated upon recognition of its 5' cap structure by translation initiation factors in so-called cap-dependent translation. Cap-dependent translation is repressed during cell stress and translation initiation by internal ribosome entry sites (IRESs) predominates. IRESs, located in the 5' untranslated region of specific mRNAs, recruit the ribosome independent of the 5' cap and are essential regulatory elements in many RNA viruses and cellular messages. The dysregulation of cellular IRESs has been linked to cancer because they regulate the expression of genes involved in growth, development and stress response. In comparison to cap-dependent translation, …

Biological Characterization Of Transmitted Human Immunodeficiency Virus Type-1, Tara Grant Edmonds

All ETDs from UAB

Heterosexual transmission of human immunodeficiency virus type&ndash1 (HIV&ndash1) accounts for the majority of infections worldwide, with women representing the larger percentage of infected individuals. The events leading to the transmission of HIV&ndash1 at mucosal surfaces are not well defined. Based on the observations that transmitted viruses nearly exclusively utilize the CCR5 coreceptor, and that in 80% of heterosexual transmissions a single virus variant establishes infection, there appears to be a selection mechanism that allows only a subset of viruses to be transmitted. This genetic bottleneck suggests that transmitted viruses may possess specific phenotypic and/or genotypic properties that allow for their …

Molecular Mechanisms Regulating Caenorhabditis Elegans Sperm Migration, Johnathan Wesley Edmonds

All ETDs from UAB

Fertilization is the process by which male and female gametes join to give rise to a new organism. Union of sperm and ova requires that sperm be able to successfully locate and migrate towards oocytes in the female reproductive tract. By analyzing the in vitro migration of sperm from diverse species and mapping the complex architecture of their female reproductive tracts, we can infer that sperm must respond to directional cues to seek out the mature oocyte. However, the internal fertilization schemes of most complex animals complicate the analysis of in vivo sperm migration. The transparent epidermis of the nematode …