Biology Commons^™

Fibronectin And Androgen Receptor Expression Data In Prostate Cancer Obtained From A Rna-Sequencing Bioinformatics Analysis, Dibash K. Das, Thahmina Ali, Konstantinos Krampis, Olorunseun O. Ogunwobi

Publications and Research

Prostate cancer is the second most commonly diagnosed male cancer in the world. The molecular mechanisms underlying its development and progression are still unclear. Here we show analysis of a prostate cancer RNA-sequencing dataset that was originally generated by Ren et al. [3] from the prostate tumor and adjacent normal tissues of 14 patients. The data presented here was analyzed using our RNA-sequencing bioinformatics analysis pipeline implemented on the bioinformatics web platform, Galaxy. The relative expression of fibronectin (FN1) and the androgen receptor (AR) were calculated in fragments per kilobase of transcript per million mapped reads, and represented in FPKM …

Post-Transcriptional Regulation Of The Drosophila Anterior Determinant, Bicoid, John Mclaughlin

Dissertations, Theses, and Capstone Projects

In a wide variety of biological contexts, messenger RNA (mRNA) is known to have a complex and dynamic life cycle. In particular, the localization and translational control of mRNA are essential for proper development in eukaryotes. The fly Drosophila melanogaster is an excellent model for studying these processes. During D. melanogaster oogenesis, several mRNAs are trafficked and localized within the developing egg chamber, and regulated at the translational level to enable embryo patterning. One such mRNA, bicoid, is localized at the anterior of the oocyte and translated in the early embryo, where its encoded protein directs formation of the fly's …

Physical Mechanisms And Biological Consequences Of Voltage-Gated Sodium Channel Modulation By Fhf Proteins, Yue Liu

Dissertations, Theses, and Capstone Projects

Purpose: FHFs are cytosolic proteins that bind to voltage-gated sodium channels (Na_Vs) and modulate their functions to control membrane excitability. FHFs raise the voltage dependence of Na_V fast inactivation to promote excitability, while A isoforms FHF (A-FHFs) also capture open sodium channels into a long-term inactivated (LTI) state to limit excitability. My research has addressed how FHFs balance membrane excitability as it relates to normal and pathological brain functions. Part of this work stemmed from the discovery of a missense FHF1 mutation in patients with severe early onset epilepsy. Methods and Results: Wild-type FHF1A and FHF1B were …

Identification, Validation, And Targeting Of The Mutant P53- Parp-Mcm Chromatin Axis In Triple Negative Breast Cancer, Wei-Gang Qiu, Alla Polotskaia, Gu Xiao, Lia Di, Yuhan Zhao, Wenwei Hu, John Philip, Ronald C. Hendrickson, Jill Bargonetti

Publications and Research

Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous …

The Paucity Of Frugivores In Madagascar May Not Be Due To Unpredictable Temperatures Or Fruit Resources, Sarah Federman, Miranda Sinnott-Armstrong, Andrea L. Baden, Colin A. Chapman, Douglas C. Daly, Alison R. Richard, Kim Valenta, Michael J. Donoghue

Publications and Research

The evolution of ecological idiosyncrasies in Madagascar has often been attributed to selective pressures stemming from extreme unpredictability in climate and resource availability compared to other tropical areas. With the exception of rainfall, few studies have investigated these assumptions. To assess the hypothesis that Madagascar's paucity of frugivores is due to unreliability in fruiting resources, we use statistical modeling to analyze phenology datasets and their environmental correlates from two tropical wet forests, the Réserve Naturelle Intégrale Betampona in Madagascar, and Kibale National Park in Uganda. At each site we found that temperature is a good environmental predictor of fruit availability. …

Defining The Relationship Between Maternal Care Behavior And Hearing Development In Wistar Rats, Jingyun Qiu

Dissertations and Theses

Previous studies in rodents have demonstrated the profound effects that variations in maternal care play during the postnatal development of the brain. However, much less is known about how maternal care affects hearing development. Recently, manipulations of maternal care have been investigated to accelerate hearing onset. We hypothesized that accelerated hearing development results from changes in maternal care behavior. To test this hypothesis, we used a selection model in which natural variations in maternal care were identified in a large cohort of dams by measuring the frequency of different behaviors including LG followed by selection of dams with LG scores …

The Replication Initiator Of The Cholera Pathogen’S Second Chromosome Shows Structural Similarity To Plasmid Initiators, Natalia Orlova, Matthew Gerding, Olha Ivashkiv, Paul Dominic B. Olinares, Brian T. Chait, Matthew K. Waldor, David Jeruzalmi

Publications and Research

The conserved DnaA-oriC system is used to initiate replication of primary chromosomes throughout the bacterial kingdom; however, bacteria with multipartite genomes evolved distinct systems to initiate replication of secondary chromosomes. In the cholera pathogen, Vibrio cholerae, and in related species, secondary chromosome replication requires the RctB initiator protein. Here, we show that RctB consists of four domains. The structure of its central two domains resembles that of several plasmid replication initiators. RctB contains at least three DNA binding winged-helix-turn-helix motifs, and mutations within any of these severely compromise biological activity. In the structure, RctB adopts a headto- head dimeric configuration …

Bioremoval Of Phenol From Aqueous Solutions Using Native Caribbean Seaweed, Abel E. Navarro, Anibal Hernandez-Vega, Md Emran Masud, Loretta M. Roberson, Liz M. Diaz-Vázquez

Publications and Research

Among several Puerto Rican algae, Sargassum sp. (SG) and Chaetomorpha (CM) showed the highest phenol adsorption capacity from aqueous solutions and were used in optimized adsorption batch experiments at room temperature. The effects of pH, adsorbent dose, phenol concentration, salinity and presence of interfering substances were evaluated. Initial solution pH exhibited a strong effect, mainly on the phenol aqueous chemistry; showing the maximum adsorption at pH 10. Sorption isotherm results were modelled according to the Langmuir, Tempkin and Freundlich equations. Isotherm modelling indicated a maximum adsorption capacity (qmax) of 82.10 and 17.7 mg of phenol per gram of SG and …

A Mineralized Alga And Acritarch Dominated Microbiota From The Tully Formation (Givetian) Of Pennsylvania, Usa, John A. Chamberlain Jr., Rebecca B. Chamberlain, James O. Brown

Publications and Research

Sphaeromorphic algal cysts, most probably of the prasinophyte Tasmanites, and acanthomorphic acritarch vesicles, most probably Solisphaeridium, occur in a single 20 cm thick bed of micritic limestone in the lower part of the Middle Devonian (Givetian) Tully Formation near Lock Haven, Pennsylvania. Specimens are composed of authigenic calcite and pyrite crystals about 5–10 µm in length. Some specimens are completely calcitic; some contain both pyrite and calcite; and many are composed totally of pyrite. The microfossils are about 80 to 150 µm in diameter. Many show signs of originally containing a flexible wall composed of at least two layers. Some …

The Vibrio Cholerae Minor Pilin Tcpb Initiates Assembly And Retraction Of The Toxin- Coregulated Pilus, Dixon Ng, Tony Harn, Tuba Altindal, Subramania Kolappan, Jarrad M. Marles, Rajan Lala, Ingrid Spielman, Yang Gao, Caitlyn A. Hauke, Gabriela Kovacikova, Zia Verjee, Ronald K. Taylor, Nicolas Biais, Lisa Craig

Publications and Research

Type IV pilus (T4P) systems are complex molecular machines that polymerize major pilin proteins into thin filaments displayed on bacterial surfaces. Pilus functions require rapid extension and depolymerization of the pilus, powered by the assembly and retraction ATPases, respectively. A set of low abundance minor pilins influences pilus dynamics by unknown mechanisms. The Vibrio cholerae toxin-coregulated pilus (TCP) is among the simplest of the T4P systems, having a single minor pilin TcpB and lacking a retraction ATPase. Here we show that TcpB, like its homolog CofB, initiates pilus assembly. TcpB co-localizes with the pili but at extremely low levels, equivalent …

Efficient Method For Transfer Of Microinjected Eggs To Mouse Ampulla For Generating Transgenic Mice, Guang Wen, Jin Di, Qian Li, Jianling Chen, Ling Jin, Cheng Wang, Sanqing Xu

Publications and Research

Background: The new method described here is highly efficient in transferring microinjected mouse eggs (MEs) through the bursa membrane of a surrogate mother mouse to the ampulla of the oviduct without damaging the blood vessels on the bursa membrane.

Results: This method causes no loss of blood, and it produces newborn pups/founders from approximately 70% of the transferred MEs, because only a small hole is made on the blood vessel–free area of the bursa membrane and ampulla of the surrogate mother mouse. The infundibulum remains intact. The small hole on the bursa membrane/ ampulla may already heal up before the …

The Power Of Associative Learning And The Ontogeny Of Optimal Behaviour, Magnus Enquist, Johan Lind, Stefano Ghirlanda

Publications and Research

Behaving efficiently (optimally or near-optimally) is central to animals’ adaptation to their environment. Much evolutionary biology assumes, implicitly or explicitly, that optimal behavioural strategies are genetically inherited, yet the behaviour of many animals depends crucially on learning. The question of how learning contributes to optimal behaviour is largely open. Here we propose an associative learning model that can learn optimal behaviour in a wide variety of ecologically relevant circumstances. The model learns through chaining, a term introduced by Skinner to indicate learning of behaviour sequences by linking together shorter sequences or single behaviours. Our model formalizes the concept of conditioned …

Statistical Learning In Songbirds: From Self-Tutoring To Song Culture, Olga Fehér, Iva Ljubičić, Kenta Suzuki, Kazuo Okanoya, Ofer Tchernichovski

Publications and Research

At the onset of vocal development, both songbirds and humans produce variable vocal babbling with broadly distributed acoustic features. Over development, these vocalizations differentiate into the well-defined, categorical signals that characterize adult vocal behaviour. A broadly distributed signal is ideal for vocal exploration, that is, for matching vocal production to the statistics of the sensory input. The developmental transition to categorical signals is a gradual process during which the vocal output becomes differentiated and stable. But does it require categorical input?We trained juvenile zebra finches with playbacks of their own developing song, produced just a few moments earlier, updated continuously …

Hiv Glycoprotein Gp120 Impairs Fast Axonal Transport By Activating Tak1 Signaling Pathways, Sarah H. Berth, Nichole Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria Sapar, Gerardo Morfini, Scott T. Brady

Publications and Research

Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment. Significantly, we found that gp120 severely impaired both anterograde and retrograde FAT. Providing a …

Cooperative Stimulation Of Megakaryocytic Differentiation By Gfi1b Gene Targets Kindlin3 And Talin1, Divya Singh, Ghanshyam Upadhyay, Ananya Sengupta, Mohammed A. Biplob, Shaleen Chakyayil, Tiji George, Shireen Saleque

Publications and Research

Understanding the production and differentiation of megakaryocytes from progenitors is crucial for realizing the biology and functions of these vital cells. Previous gene ablation studies demonstrated the essential role of the transcriptional repressor Gfi1b (growth factor independence 1b) in the generation of both erythroid and megakaryocytic cells. However, our recent work has demonstrated the down-regulation of this factor during megakaryocytic differentiation. In this study we identify two new gene targets of Gfi1b, the cytoskeletal proteins Kindlin3 and Talin1, and demonstrate the inverse expression and functions of these cytoskeletal targets relative to Gfi1b, during megakaryocytic differentiation. Both kindlin3 and talin1 promoters …

The Evolution Of Line-1 In Vertebrates, Stephane Boissinot, Akash Sookdeo

Publications and Research

The abundance and diversity of the LINE-1 (L1) retrotransposon differ greatly among vertebrates. Mammalian genomes contain hundreds of thousands L1s that have accumulated since the origin of mammals. A single group of very similar elements is active at a time in mammals, thus a single lineage of active families has evolved in this group. In contrast, non-mammalian genomes (fish, amphibians, reptiles) harbor a large diversity of concurrently transposing families, which are all represented by very small number of recently inserted copies. Why the pattern of diversity and abundance of L1 is so different among vertebrates remains unknown. To address this …

Large-Scale Off-Target Identification Using Fast And Accurate Dual Regularized One- Class Collaborative Filtering And Its Application To Drug Repurposing, Hansaim Lim, Aleksandar Poleksic, Yuan Yao, Hanghang Tong, Di He, Luke Zhuang, Patrick Meng, Lei Xie

Publications and Research

Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting …

Electro-Chemotactic Fields Induce Cooperative Movement Of Cns Cells, Shawn Mishra, Stephen Redenti, Maribel Vazquez

Publications and Research

Vision loss in adults with Age Related Macular Degeneration (AMD) is attributed to damage of retinal photoreceptor cells that initiate vision by absorbing light. Mouse models have suggested that transplantation of precursor cells may be a novel approach to restore vision. This project uses a combination of electrotactic and chemotactic stimuli to promote and guide CNS cell migration within a microdevice model.

The Effect Of Protein Import On Membrane Potential, Ruth Hartke

Student Theses and Dissertations

Mitochondria are essential organelles often referred to as the “power plants” of eukaryotic cells. Energy conversion in mitochondria relies on oxidation of metabolite intermediates by protein components of the electron transport chain and establishment of an electrochemical gradient across the inner membrane. Some of the proteins involved are encoded by mitochondrial DNA, but the vast majority, over 98%, has to be imported from the cytosol. Protein import complexes form pores in the outer and inner membranes to mediate the process. However, opening of these pores would in theory jeopardize formation of the electrochemical gradient. In this study we examined this …

Evolutionary Interpretations Of Mycobacteriophage Biodiversity And Host-Range Through The Analysis Of Codon Usage Bias, Laura A. Esposito, Swati Gupta, Fraida Streiter, Ashley Prasad, John J. Dennehy

Publications and Research

In an genomics course sponsored by the Howard Hughes Medical Institute (HHMI), undergraduate students have isolated and sequenced the genomes of more than 1,150 mycobacteriophages, creating the largest database of sequenced bacteriophages able to infect a single host, Mycobacterium smegmatis, a soil bacterium. Genomic analysis indicates that these mycobacteriophages can be grouped into 26 clusters based on genetic similarity. These clusters span a continuum of genetic diversity, with extensive genomic mosaicism among phages in different clusters. However, little is known regarding the primary hosts of these mycobacteriophages in their natural habitats, nor of their broader host ranges. As such, it …

Comparative Population Genomics And Speciation Of Snakes Across The North American Deserts, Edward A. Myers

Dissertations, Theses, and Capstone Projects

Understanding the process of speciation is of central interest to evolutionary biologists. Speciation can be studied using a phylogeographic approach, by identifying regions that promote lineage divergence, addressing whether speciation has occurred with gene flow, and when extended to multiple taxa, addressing if the same patterns of speciation are shared across codistributed groups with different ecologies. Here I examine the comparative phylogeographic histories and population genomics of thirteen snake taxa that are widely distributed and co-occur across the arid southwest of North America. I first quantify the degree to which these species groups have a shared history of population divergence …

Computerized Classification Of Surface Spikes In Three-Dimensional Electron Microscopic Reconstructions Of Viruses, Younes Benkarroum

Dissertations, Theses, and Capstone Projects

The purpose of this research is to develop computer techniques for improved three-dimensional (3D) reconstruction of viruses from electron microscopic images of them and for the subsequent improved classification of the surface spikes in the resulting reconstruction. The broader impact of such work is the following.

Influenza is an infectious disease caused by rapidly-changing viruses that appear seasonally in the human population. New strains of influenza viruses appear every year, with the potential to cause a serious global pandemic. Two kinds of spikes – hemagglutinin (HA) and neuraminidase (NA) – decorate the surface of the virus particles and these proteins …

The Regulation Of The Phosphatidate Phosphatase Gene Pah1 And Its Regulatory Role On Cell Homeostasis, Goldie Libby Sherr

Dissertations, Theses, and Capstone Projects

The Saccharomyces cerevisiae gene, PAH1, encodes a phosphatidate (PA) phosphatase that plays a fundamental role in lipid metabolism. PA phosphatases are key enzymes that catalyze the PA dephosphorylation reaction to form diacylglycerides, the first step in the synthesis of triacylglycerols. Pah1p, one of the main PA phosphatases in yeast, has not only emerged as a key player in lipid biosynthetic pathways, but also acts as an important regulator of nuclear membrane biogenesis, the transcriptional regulation of many inositol-sensitive upstream activating sequence (UAS_INO)containing genes needed for phospholipid synthesis, vacuole homeostasis, and lipid droplet formation. Due to its …

Fhf-Independent Conduction Of Action Potentials Along The Leak-Resistant Cerebellar Granule Cell Axon, Katarzyna Dover, Christopher Marra, Sergio Solinas, Marko Popovic, Sathyaa Subramaniyam, Dejan Zecevic, Egidio D'Angelo, Mitchell Goldfarb

Publications and Research

Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell’s unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Nav inactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials. In addition, leak conductance density along the distal axon is estimated as o1% that of somatodendritic membrane. The faster …

Ifn-G Induces Histone 3 Lysine 27 Trimethylation In A Small Subset Of Promoters To Stably Silence Gene Expression In Human Macrophages, Yu Qiao, Kyuho Kang, Eugenia Giannopoulou, Celeste Fang, Lionel B. Ivashkiv

Publications and Research

The mechanisms by which IFN-g activates expression of interferon-stimulated genes that have inflammatory and host defense functions are well understood. In contrast, little is known about how IFN-g represses gene expression. By using transcriptomic and epigenomic analysis, we found that stable repression of a small group of genes by IFN-g is associated with recruitment of the histone methyltransferase EZH2 and deposition of the negative mark histone 3 lysine 27 trimethylation (H3K27me3) at their promoters. Repressed genes included MERTK, PPARG, and RANK, which have anti-inflammatory functions and promote osteoclast differentiation. Gene repression and H3K27me3 persisted after IFN-g signaling was terminated, and …

Receptor-Type Guanylyl Cyclase At 76c (Gyc76c) Regulates De Novo Lumen Formation During Drosophila Tracheal Development, Monn Monn Myat, Unisha Patel

Publications and Research

Lumen formation and maintenance are important for the development and function of essential organs such as the lung, kidney and vasculature. In the Drosophila embryonic trachea, lumena formde novo to connect the different tracheal branches into an interconnected network of tubes. Here, we identify a novel role for the receptor type guanylyl cyclase at 76C (Gyc76C) in de novo lumen formation in the Drosophila trachea.We show that in embryosmutant for gyc76C or its downsteam effector protein kinase G (PKG) 1, tracheal lumena are disconnected. Dorsal trunk (DT) cells of gyc76C mutant embryos migrate to contact each other and complete the …

Temporal Regularity Increases With Repertoire Complexity In The Australian Pied Butcherbird’S Song, Eathan Janney, Hollis Taylor, Constance Scharff, David Rothenberg, Lucas C. Parra, Ofer Tchernichovski

Publications and Research

Music maintains a characteristic balance between repetition and novelty. Here, we report a similar balance in singing performances of free-living Australian pied butcherbirds. Their songs include many phrase types. The more phrase types in a bird’s repertoire, the more diverse the singing performance can be. However, without sufficient temporal organization, avian listeners may find diverse singing performances difficult to perceive and memorize. We tested for a correlation between the complexity of song repertoire and the temporal regularity of singing performance. We found that different phrase types often share motifs (notes or stereotyped groups of notes). These shared motifs reappeared in …

A Species-Level Phylogeny Of Extant Snakes With Description Of A New Colubrid Subfamily And Genus, Alex Figueroa, Alexander D. Mckelvy, L. Lee Grismer, Charles D. Bell, Simon P. Lailvaux

Publications and Research

Background With over 3,500 species encompassing a diverse range of morphologies and ecologies, snakes make up 36% of squamate diversity. Despite several attempts at estimating higherlevel snake relationships and numerous assessments of generic- or species-level phylogenies, a large-scale species-level phylogeny solely focusing on snakes has not been completed. Here, we provide the largest-yet estimate of the snake tree of life using maximum likelihood on a supermatrix of 1745 taxa (1652 snake species + 7 outgroup taxa) and 9,523 base pairs from 10 loci (5 nuclear, 5 mitochondrial), including previously unsequenced genera (2) and species (61).

Results Increased taxon sampling resulted …

Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran

Publications and Research

Syndecans (SDC, SYND) comprise a group of four structurally related type 1 transmembrane heparan sulfate proteoglycans (HSPGs) that play important roles in tumorigenic processes. SDCs exert signaling via their protein cores and their conserved transmembrane and cytoplasmic domains or by forming complexes with growth factors (GFs). In classical Hodgkin's lymphoma (cHL), a lymphoid neoplasm of predominantly B cell origin, SDC1 and SDC4 are the active SDCs, and a number of GF (vascular endothelial growth factor, fibroblast growth factor, etc.) signaling pathways have been studied. However, despite extensive pre-clinical and clinical research on SDC-mediated GF signaling in many cancer types, there …

Molecular Basis For Strain Variation In The Saccharomyces Cerevisiae Adhesin Flo11p, Subit Barua, Li Li, Peter N. Lipke, Anne M. Dranginis

Publications and Research

FLO11 encodes a yeast cell wall flocculin that mediates a variety of adhesive phenotypes in Saccharomyces cerevisiae. Flo11p is implicated in many developmental processes, including flocculation, formation of pseudohyphae, agar invasion, and formation of microbial mats and biofilms. However, Flo11p mediates different processes in different yeast strains. To investigate the mechanisms by which FLO11 determines these differences in colony morphology, flocculation, and invasion, we studied gene structure, function, and expression levels. Nonflocculent Saccharomyces cerevisiae 1278b cells exhibited significantly higher FLO11 mRNA expression, especially in the stationary phase, than highly flocculent S. cerevisiae var. diastaticus. The two strains varied in cell …