Genetics Commons^™

United States Regulation Of Stem Cell Research: Recasting Government's Role And Questions To Be Resolved, Owen C. B. Hughes, Alan L. Jakimo, Michael J. Malinowski

Journal Articles

This article directly addresses the stem cell controversy, but also the broader history and norms regarding the roles of federal and state government in U.S. science research funding.

Comparative Functional Analysis Of Aquaporins/Glyceroporins In Mammals And Anurans, Carissa M. Krane, David L. Goldstein

Biology Faculty Publications

Maintenance of fluid homeostasis is critical to establishing and maintaining normal physiology. The landmark discovery of membrane water channels (aquaporins; AQPs) ushered in a new area in osmoregulatory biology that has drawn from and contributed to diverse branches of biology, from molecular biology and genomics to systems biology and evolution, and from microbial and plant biology to animal and translational physiology. As a result, the study of AQPs provides a unique and integrated backdrop for exploring the relationships between genes and genome systems, the regulation of gene expression, and the physiologic consequences of genetic variation. The wide species distribution of …

Optimization Of Cutaneous Electrically Mediated Plasmid Dna Delivery Using Novel Electrode, L. C. Heller, M. J. Jaroszeski, D. Coppola, A. N. Mccray, J. Hickey, R. Heller

Bioelectrics Publications

The easy accessibility of skin makes it an excellent target for gene transfer protocols. To take advantage of skin as a target for gene transfer, it is important to establish an efficient and reproducible delivery system. Electroporation is an established technique for enhancing plasmid delivery to many tissues in vivo. A critical component of this technique is the electrode configuration. Electroporation parameters were optimized for transgene expression with minimal tissue damage with a novel electrode. The highest transgene expression and efficiency of individual cell transformation with minimal damage was produced with eight 150 ms pulses at field strength of …

Potential For Stimulating Host Anti-Tumor Immune Response Via Rnai-Mediated Local Foxp3 Knockdown, N. Klaiber

Chemistry & Biochemistry Faculty Publications

Neoplastic growths represent a unique challenge for the host immune system. As they are indeed derived from self, many of the same mechanisms operating to prevent autoimmunity also provide an umbrella beneath which malignant cells are free to proliferate.1 Central among these immune regulatory boundaries are an influential subset of lymphocytes known as T regs. Hypothesized to exist decades ago, yet eluding definitive characterization until relatively recently, T regs have been demonstrated to play a crucial role in the proper functioning of the immune system as a whole. They may also, however, represent one of the primary obstacles to successful …

Sensory Genes And Mate Choice: Evidence That Duplications, Mutations, And Adaptive Evolution Alter Variation In Mating Cue Genes And Their Receptors, Lisa Horth

Biological Sciences Faculty Publications

Fascinating new data, revealed through gene sequencing, comparative genomics, and genetic engineering, precisely establish which genes are involved in mate choice and mating activity—behaviors that are surprisingly understudied from a genetic perspective. Discussed here are some of the recently identified visual and chemosensory genes that are involved in mate choice and mating behavior. These genes’ products are involved in the production, transmission, and receipt of crucial sensory mate-choice cues that affect fitness. This review exposes newfound evidence that alternative splicing, gene-expression pattern changes, and molecular genetic variation in sensory genes are crucial for both intra- and interspecific mate choice and …

The Fat Cadherin Acts Through The Hippo Tumor-Suppressor Pathway To Regulate Tissue Size, Maria Willecke, Fisun Hamaratoglu, Madhuri Kango-Singh, Ryan Udan, Chiao-Lin Chen, Chunyao Tao, Xinwei Zhang, Georg Halder

Biology Faculty Publications

Background: The Hippo tumor-suppressor pathway has emerged as a key signaling pathway that controls tissue size in Drosophila. Merlin, the Drosophila homolog of the human Neurofibromatosis type-2 (NF2) tumor-suppressor gene, and the related protein Expanded are the most upstream components of the Hippo pathway identified so far. However, components acting upstream of Expanded and Merlin, such as transmembrane receptors, have not yet been identified.

Results: Here, we report that the protocadherin Fat acts as an upstream component in the Hippo pathway. Fat is a known tumor-suppressor gene in Drosophila, and fat mutants have severely overgrown imaginal discs. We …

Lobe And Serrate Are Required For Cell Survival During Early Eye Development In Drosophila, Amit Singh, Xiao Shi, Kwang-Wook Choi

Biology Faculty Publications

Organogenesis involves an initial surge of cell proliferation, leading to differentiation. This is followed by cell death in order to remove extra cells. During early development, there is little or no cell death. However, there is a lack of information concerning the genes required for survival during the early cell-proliferation phase. Here, we show that Lobe (L) and the Notch (N) ligand Serrate (Ser), which are both involved in ventral eye growth, are required for cell survival in the early eye disc. We observed that the loss-of-ventral-eye phenotype in L or Ser mutants is due to …

Expression Of The Primary Carbohydrate Component Of The Bordetella Bronchiseptica Biofilm Matrix Is Dependent On Growth Phase But Independent Of Bvg Regulation, Yasuhiko Irie, Andrew Preston, Ming H. Yuk

Biology Faculty Publications

We previously showed that the Bvg virulence control system regulates biofilm formation in Bordetella bronchiseptica (Y. Irie, S. Mattoo, and M. H. Yuk, J. Bacteriol. 186:5692-5698, 2004). Analyses of the extracellular components of B. bronchiseptica biofilm matrix revealed that the major sugar component in the matrix was xylose, and linkage analysis indicated a majority of it to be in a 4-linked polymeric form. The production of xylose was independent of Bvg regulation but instead was dependent on bacterial growth phase. In addition, N-acetyl-glucosamine in the matrix was found to be important for the initial development of the biofilm. These …

Saccharomyces Cerevisiae-Based Molecular Tool Kit For Manipulation Of Genes From Gram-Negative Bacteria, Robert M. Q. Shanks, Nicky C. Caiazza, Shannon M. Hinsa, Christine M. Toutain, George A. O'Toole

Dartmouth Scholarship

A tool kit of vectors was designed to manipulate and express genes from a wide range of gram-negative species by using in vivo recombination. Saccharomyces cerevisiae can use its native recombination proteins to combine several amplicons in a single transformation step with high efficiency. We show that this technology is particularly useful for vector design. Shuttle, suicide, and expression vectors useful in a diverse group of bacteria are described and utilized. This report describes the use of these vectors to mutate clpX and clpP of the opportunistic pathogen Pseudomonas aeruginosa and to explore their roles in biofilm formation and surface …

Evaluation Of Toxicity Following Electrically Mediated Interleukin-12 Gene Delivery In A B16 Mouse Melanoma Model, Loree Heller, Kathleen Merkler, Jeffrey Westover, Yolmari Cruz, Domenico Coppola, Kaaron Benson, Adil Daud, Richard Heller

Bioelectrics Publications

PURPOSE: Interleukin-12 (IL-12) has potential as an immunotherapeutic agent for the treatment of cancer but is unfortunately associated with toxicity. Delivery of a plasmid encoding IL-12 with electroporation induces an antitumor effect in the B16 mouse melanoma model without serious side effects. To translate this observation to the clinic, an evaluation of toxicity was done in the mouse model.

EXPERIMENTAL DESIGN: Weight change, tumor response, blood chemistry and hematology values, and serum IL-12 levels were evaluated. Multiple tissues were analyzed histopathologically.

RESULTS: A pronounced reduction in tumor volume, including a large percentage of complete regressions, was observed after electrically mediated …

Eye Development At The Houston "Fly Meeting", Amit Singh

Biology Faculty Publications

Meeting report: The 47th Annual Drosophila Research Conference or "Fly Meeting" took place at Houston, Texas, USA from March 29th- April 2nd, 2006, under the aegis of the Genetics Society of America. The Fly Meeting provides an excellent opportunity for fly researchers to present their work and to get a snapshot of recent developments and upcoming trends in their research field. The fruit fly, Drosophila melanogaster, is a very versatile model to study growth, patterning, neural development, evolution, systemetics and various other facets of biomedical science. The topics presented in the meeting covered a very broad spectrum of fly research. …

Empirical Analysis Of The Str Profiles Resulting From Conceptual Mixtures, David R. Paoletti, Travis E. Doom, Carissa M. Krane, Michael L. Raymer, Dan E. Krane

Biology Faculty Publications

Samples containing DNA from two or more individuals can be difficult to interpret. Even ascertaining the number of contributors can be challenging and associated uncertainties can have dramatic effects on the interpretation of testing results. Using an FBI genotypes dataset, containing complete genotype information from the 13 Combined DNA Index System (CODIS) loci for 959 individuals, all possible mixtures of three individuals were exhaustively and empirically computed. Allele sharing between pairs of individuals in the original dataset, a randomized dataset and datasets of generated cousins and siblings was evaluated as were the number of loci that were necessary to reliably …

Atypical Pkciota Contributes To Poor Prognosis Through Loss Of Apical-Basal Polarity And Cyclin E Overexpression In Ovarian Cancer, Astrid M. Eder, Xiaomei Sui, Daniel G. Rosen, Laura K. Nolden, Kwai Wa Cheng, John P. Lahad, Madhuri Kango-Singh, Karen H. Lu, Carla L. Warneke, Edward N. Atkinson, Isabelle Bedrosian, Khandan Keyomarsi, Wen-Lin Kuo, Joe W. Gray, Jerry C. P. Yin, Jinsong Liu, Georg Halder, Gordon B. Mills

Biology Faculty Publications

We show that atypical PKCι, which plays a critical role in the establishment and maintenance of epithelial cell polarity, is genomically amplified and overexpressed in serous epithelial ovarian cancers. Furthermore, PKCι protein is markedly increased or mislocalized in all serous ovarian cancers. An increased PKCι DNA copy number is associated with decreased progression-free survival in serous epithelial ovarian cancers. In a Drosophila in vivo epithelial tissue model, overexpression of persistently active atypical PKC results in defects in apical-basal polarity, increased Cyclin E protein expression, and increased proliferation. Similar to the Drosophila model, increased PKCι proteins levels are associated with …

Metaheuristic Applications And Their Solutions Quality, Dr. Zahid Hussain

International Conference on Information and Communication Technologies

Over the past few decades, a wide variety of classes of combinatorial problems (e.g. the assignment problem, the knapsack problem, the vehicle routing problem, etc.) have emerged - from such areas as management science, telecommunication, AI, VLSI design and many others. Many large combinatorial problems are NP-hard problems because of the combinatorial growth of their solution search space with the problem size. Such problems are commonly solved by some version of a prominent metaheuristic (e.g. Genetic Algorithms, Tabu Search, Simulated Annealing and etc.). These heuristics seek good but approximate solutions at a reasonable computational cost. These heuristics are of stochastic …

Group 13 Hox Proteins Interact With The Mh2 Domain Of R-Smads And Modulate Smad Transcriptional Activation Functions Independent Of Hox Dna Binding Capability, Thomas M. Williams, Melissa E. Williams, Joanne H. Heaton, Thomas D. Gelehrter, Jeffrey W. Innis

Biology Faculty Publications

Interactions with co-factors provide a means by which HOX proteins exert specificity. To identify candidate protein interactors of HOXA13, we created and screened an E11.5–E12.5, distal limb bud yeast two-hybrid prey library. Among the interactors, we isolated the BMP-signaling effector Smad5, which interacted with the paralogous HOXD13 but not with HOXA11 or HOXA9, revealing unique interaction capabilities of the AbdB-like HOX proteins. Using deletion mutants, we determined that the MH2 domain of Smad5 is necessary for HOXA13 interaction.

This is the first report demonstrating an interaction between HOX proteins and the MH2 domain of Smad proteins. HOXA13 and HOXD13 …

On Thacker's Biomedia (2004), Nicholas Ruiz Iii

Reconstruction: Studies in Contemporary Culture

[First paragraph]

Only we could have done it. The Code (DNA and its analogs, etc.) that we perhaps only narrate, never forgetting all of the fictions that narration portends, today consciously edits the text that evolution has edited unconsciously for eons. Thacker considers how humans -- perhaps little more than interactive Code, manipulate the Code -- with the technology of the Code. No other faction of Code has yet to make such heady ‘gains.’ Where posthumanity was always a literary endeavor, a literary bypass, out of instrumental science and into fictive states, it now is a technical endeavor, encompassing a …

The Bvg Virulence Control System Regulates Biofilm Formation In Bordetella Bronchiseptica, Yasuhiko Irie, Seema Mattoo, Ming H. Yuk

Biology Faculty Publications

Bordetella species utilize the BvgAS (Bordetella virulence gene) two-component signal transduction system to sense the environment and regulate gene expression among at least three phases: a virulent Bvg⁺ phase, a nonvirulent Bvg⁻ phase, and an intermediate Bvgⁱ phase. Genes expressed in the Bvg⁺ phase encode known virulence factors, including adhesins such as filamentous hemagglutinin (FHA) and fimbriae, as well as toxins such as the bifunctional adenylate cyclase/hemolysin (ACY). Previous studies showed that in the Bvgⁱ phase, FHA and fimbriae continue to be expressed, but ACY expression is significantly downregulated. In this report, we determine …

Drosophila As An Emerging Model To Study Metastasis, Madhuri Kango-Singh, Georg Halder

Biology Faculty Publications

Metastasis is the primary cause of human cancer-related deaths. Two recent studies describe a system for testing how multiple genetic events synergize to promote neoplastic growth and metastasis in Drosophila, paving the way for systematic approaches to understanding metastasis using the powerful tools of Drosophila genetics.

Morphological Characteristics And Species Separation Of Hawaiian Postlarval Amphidromous Fishes, M. Eric Benbow, Albert J. Burky, Carl M. Way

Biology Faculty Publications

There are five Hawaiian amphidromous fishes (Gobiidae: Lentipes concolor, Awaous guamensis, Sicyopterus stimpsoni, Stenogobius hawaiiensis; Eleotridae: Eleotris sandwicensis). Amphidromous adults deposit eggs on the stream bottom. After hatching, larvae drift to the ocean for growth followed by postlarval migration back into the streams. Postlarvae were collected to construct a dichotomous identification key based on 12 morphological measures and ray counts from four fins. Overall, the presense of fused pelvic fins, standard length (SL), and fin ray numbers were the most useful in species separation. Gobies were separated from the eleotrid by the former having fused …

Initial State Of The Drosophila Eye Before Dorsoventral Specification Is Equivalent To Ventral, Amit Singh, Kwang-Wook Choi

Biology Faculty Publications

Dorsoventral (DV) patterning is crucial for eye development in invertebrates and higher animals. DV lineage restriction is the primary event in undifferentiated early eye primordia of Drosophila. InDrosophila eye disc, a dorsal-specific GATA family transcription factor pannier (pnr) controls Iroquois-Complex (Iro-C) genes to establish the dorsal eye fate whereas Lobe (L), which is involved in controlling a Notch ligand Serrate (Ser), is specifically required for ventral growth. However, fate of eye disc cells before the onset of dorsal expression of pnr and Iro-C is not known. We show that L/Ser …

Life Cycle Of A Torrenticolous Hawaiian Chironomid (Telmatogeton Torrenticola): Stream Flow And Microhabitat Effects, M. Eric Benbow, Albert J. Burky, Carl M. Way

Biology Faculty Publications

In this study we documented the instar densities and life cycle of Telmatogeton torrenticola Terry (Chironomidae : Telmatogetoninae) from Kinihapai Stream, Maui, Hawaii. Greatest larval densities of this midge are found on substrates of high velocity, shallow flows of cascades, and splash zones of waterfalls, with lower densities in riffles. In the summer of 1994 we compared the effects of two microhabitats (termed optimal and suboptimal) on inter-instar density and relative abundance. In a second year (1995), we evaluated the effect of long-term reduced stream flow on these variables only in optimal microhabitats. A significant reduction in stream flow from …

Comparison Of Methods For Dna Isolation From Food Samples For Detection Of Shiga Toxin-Producing Escherichia Coli By Real-Time Pcr, Loree C. Heller, Carisa R. Davis, K. Kealy Peak, David Wingfield, Andrew C. Cannons, Philip T. Amuso, Jacqueline Cattani

Bioelectrics Publications

In this study, food samples were intentionally contaminated with Escherichia coli O157:H7, and then DNA was isolated by using four commercial kits. The isolated DNA samples were compared by using real-time PCR detection of the Shiga toxin genes. The four kits tested worked similarly.

Shar-Pei Mediates Cell Proliferation Arrest During Imaginal Disc Growth In Drosophila, Madhuri Kango-Singh, Riitta Nolo, Chunyao Tao, Patrik Verstreken, P. Robin Hiesinger, Hugo J. Bellen, Georg Halder

Biology Faculty Publications

During animal development, organ size is determined primarily by the amount of cell proliferation, which must be tightly regulated to ensure the generation of properly proportioned organs. However, little is known about the molecular pathways that direct cells to stop proliferating when an organ has attained its proper size. We have identified mutations in a novel gene, shar-pei, that is required for proper termination of cell proliferation during Drosophila imaginal disc development. Clones of shar-pei mutant cells in imaginal discs produce enlarged tissues containing more cells of normal size. We show that this phenotype is the result of both …

Electrically Mediated Delivery Of Vector Plasmid Dna Elicits An Antitumor Effect, L. Heller, D. Coppola

Bioelectrics Publications

In vivo electroporation is an efficient means of increasing plasmid DNA delivery to normal tissues, such as skin and muscle, as well as directly to tumors. In the experiments described here, plasmid DNA was delivered by in vivo electroporation to B16 mouse melanomas using two very different pulsing protocols. Reporter expression increased 21- or 42-fold, respectively with electroporation over injection alone. The growth of experimental melanomas with an approximate diameter of 4 mm on the day of treatment was monitored after electroporation delivery of reporter plasmid DNA. Remarkably, short-term complete regressions using one of these pulsing protocols occurred in up …

Eye Suppression, A Novel Function Of Teashirt, Requires Wingless Signaling, Amit Singh, Madhuri Kango-Singh, Y. Henry Sun

Biology Faculty Publications

Teashirt (tsh) encodes a Drosophila zinc-finger protein. Misexpression of tsh has been shown to induce ectopic eye formation in the antenna. We report that tsh can suppress eye development. This novel function of tsh is due to the induction of homothorax (hth), a known repressor of eye development, and requires Wingless (WG) signaling. Interestingly, tsh has different functions in the dorsal and ventral eye, suppressing eye development close to the ventral margin, while promoting eye development near the dorsal margin. It affects both growth of eye disc and retinal cell differentiation.

Effect Of Electrically Mediated Intratumor And Intramuscular Delivery Of A Plasmid Encoding Ifn Α On Visible B16 Mouse Melanomas, Loree C. Heller, Stephanie F. Ingram, M. Lee Lucas, Richard A. Gilbert, Richard Heller

Bioelectrics Publications

Interferon α may be used as a single agent therapy for metastatic malignant melanoma or as an adjuvant to chemotherapy. Delivery of interferon α by gene therapy offers an alternative to recombinant protein therapy. Electrically mediated delivery enhances plasmid expression in a number of tissues, for instance skin, liver, muscle and tumors including melanomas. Here we compare the effect of delivery of a plasmid encoding mouse interferon α on growth of visible B16 mouse melanomas following electrically mediated delivery to muscle or directly to the tumor. Intratumoral delivery of interferon α plasmid not only slows melanoma growth, but induces complete, …

Il-12 Plasmid Delivery By In Vivo Electroporation For The Successful Treatment Of Established Subcutaneous B16.F10 Melanoma, M. Lee Lucus, Loree Heller, Domenico Coppola, Richard Heller

Bioelectrics Publications

Interleukin-12 (IL-12) has been used in numerous immunotherapy protocols against melanoma. However, delivery of IL-12 in the form of recombinant protein can result in severe toxicity, and gene therapy has had limited success against B16.F10 murine melanoma. The purpose of this study was to examine the effectiveness of in vivo electroporation for the delivery of plasmid DNA encoding IL-12 as an antitumor agent against B16.F10 melanoma. We treated mice bearing established B16.F10 melanoma tumors with intratumoral (i.t.) or intramuscular (i.m.) injections of a plasmid encoding IL-12, followed by in vivo electroporation. For i.t. treatments, we used an applicator containing six …

Functional Requirement Of Aquaporin-5 In Plasma Membranes Of Sweat Glands, Lene N. Nejsum, Tae-Hwan Kwon, Uffe B. Jensen, Ornella Fumagalli, Jørgen Frøkiaer, Carissa M. Krane, Anil G. Menon, Landon S. King, Peter C. Agre, Søren Nielsen

Biology Faculty Publications

The distribution and function of aquaporins (AQPs) have not previously been defined in sweat glands. In this study, AQP1, AQP3, and AQP5 mRNA were demonstrated in rat paw by reverse transcription (RT)–PCR, but AQP2 and AQP4 were not. AQP1, AQP3, and AQP5 protein were confirmed in these tissues by immunoblotting. AQP1 was identified in capillary endothelial cells by immunohistochemical labeling, but not in sweat glands or epidermis. Abundant AQP3 expression was seen in basal levels of epidermis, but not in sweat glands. AQP2 and AQP4 were not observed in either skin or sweat glands. Immunohistochemical labeling revealed abundant AQP5 in …

Genetic Variability Studies In A Selected Population Of Azadirachta Excelsa (Sentang) With Aflp Marker Technology, Chiew Foan Chin

Student Works (2000-2009)

A maternal half-s/b population of Azadirachta excelsa was established from seeds in a randomised complete block design with three replicates. 100 to 200 seeds were collected from each of the 13 selected mother trees. The mother trees were categorised into three groups i.e. large, medium and small according to their girth sizes. 50 progeny seedlings from each scedlot per replicate were planted in the experimental field. Genetic studies on phenotypic measurements and molecular marker analysis were carried out on the established A. excelsa population. Measurements of quantitative traits including diameter breast height (Dbh) and total height were made. Mean Dbh …

A Note On Cascade Climbing Of Migrating Goby And Shrimp Postlarvae In Two Maui Streams, M. Eric Benbow, Leslie Luchar Orzetti, Mollie D. Mcintosh, Albert J. Burky

Biology Faculty Publications

In this study, we documented cascade climbing rates of 133 and 230 postlarvae of Lentipes concolor (O‘opu alamo‘o) and Atyoida bisulcata (Opae kahaole), respectively, from two streams on the island of Maui, Hawaii. Climbing measurements and observations were made of postlarvae at the water-substrate interface in cascade habitats of constricted water flow. Both species were observed to move in short bursts of forward progression within or above the pulsing water-substrate interface. Goby postlarval climbing rates ranged from 0.04 – 1.50 cm s–1 and were slower than shrimp rates which ranged from 0.30 – 3.06 cm s–1. The high variability is …