Biology Commons^™

Force Sensitivity In Saccharomyces Cerevisiae Flocculins, Cho X. Chan, Sofiane El-Kirat-Chatel, Ivor G. Joseph, Desmond N. Jackson, Caleen B. Ramsook, Yves F. Dufrêne, Peter N. Lipke

Publications and Research

Many fungal adhesins have short, -aggregation-prone sequences that play important functional roles, and in the Candida albicans adhesin Als5p, these sequences cluster the adhesins after exposure to shear force. Here, we report that Saccharomyces cerevisiae flocculins Flo11p and Flo1p have similar -aggregation-prone sequences and are similarly stimulated by shear force, despite being nonhomologous. Shear from vortex mixing induced the formation of small flocs in cells expressing either adhesin. After the addition of Ca2, yeast cells from vortex-sheared populations showed greatly enhanced flocculation and displayed more pronounced thioflavin-bright surface nanodomains. At high concentrations, amyloidophilic dyes inhibited Flo1p- and Flo11p-mediated agar invasion …

Physical Separation From The Mate Diminishes Male’S Attentiveness Towards Other Females: A Study In Monogamous Prairie Voles Microtus Ochrogaster, Christine J. Delevan, Natalia A. Rodriguez, Karine M. Legzim, Fayeza Aliou, Jamie T. Parker, Maryam Bashad

Publications and Research

We tested whether continuous cohabitation in monogamous voles affects the mated male’s attentiveness to his breeding partner versus another female. Each male was housed in a 3-chamber apparatus with a Focal female (FF) and a Control female (CF) for 13 days then placed in a T-maze to assess his attentiveness to and memory of those females. The Distal male remained physically separated from both females, but received their distal cues. The Separate male cohabited with the FF for 3 days then remained physically separated from both females. The Disrupt male’s continuous cohabitation with the FF was disrupted by having him …

Odorant Receptors Can Mediate Axonal Identity And Gene Choice Via Campindependent Mechanisms, Kiavash Movahedi, Xavier Grosmaitre, Paul Feinstein

Publications and Research

Odorant receptors (ORs) control several aspects of cell fate in olfactory sensory neurons (OSNs), including singular gene choice and axonal identity. The mechanisms of OR-induced axon guidance have been suggested to principally rely on G-protein signalling. Here, we report that for a subset of OSNs, deleting G proteins or altering their levels of signalling does not affect axonal identity. Signalling-deficient ORs or surrogate receptors that are unable to couple to Gs/Golf still provide axons with distinct identities and the anterior–posterior targeting of axons does not correlate with the levels of cAMP produced by genetic modifications. In addition, we refine the …

Mousensor: A Versatile Genetic Platform To Create Super Sniffer Mice For Studying Human Odor Coding, Charlotte D'Hulst, Raena B. Mina, Zachary Gershon, Sophie Jamet, Antonio Cerullo, Delia Tomoiaga, Li Bai, Leonardo Belluscio, Matthew E. Rogers, Yevgeniy Sirotin, Paul Feinstein

Publications and Research

Typically, 0.1% of the total number of olfactory sensory neurons (OSNs) in the main olfactory epithelium express the same odorant receptor (OR) in a singular fashion and their axons coalesce into homotypic glomeruli in the olfactory bulb. Here, we have dramatically increased the total number of OSNs expressing specific cloned OR coding sequences by multimerizing a 21-bp sequence encompassing the predicted homeodomain binding site sequence, TAATGA, known to be essential in OR gene choice. Singular gene choice is maintained in these ‘‘MouSensors.’’ In vivo synaptopHluorin imaging of odor-induced responses by known M71 ligands shows functional glomerular activation in an M71 …

Machine Learning Meta-Analysis Of Large Metagenomic Datasets: Tools And Biological Insight, Edoardo Pasolli, Duy Tin Truong, Faizan Malik, Levi Waldron, Nicola Segata

Publications and Research

Shotgun metagenomic analysis of the human associated microbiome provides a rich set of microbial features for prediction and biomarker discovery in the context of human diseases and health conditions. However, the use of such high-resolution microbial features presents new challenges, and validated computational tools for learning tasks are lacking. Moreover, classification rules have scarcely been validated in independent studies, posing questions about the generality and generalization of disease-predictive models across cohorts. In this paper, we comprehensively assess approaches to metagenomics-based prediction tasks and for quantitative assessment of the strength of potential microbiome-phenotype associations. We develop a computational framework for prediction …

Small Packages, Big Returns: Uncovering The Venom Diversity Of Small Inverebrate Conoidean Snails, J. Gorson, M. Holford

Publications and Research

Venomous organisms used in research were historically chosen based on size and availability. This opportunity-driven strategy created a species bias in which snakes, scorpions, and spiders became the primary subjects of venom research. Increasing technological advancements have enabled interdisciplinary studies using genomics, transcriptomics, and proteomics to expand venom investigation to animals that produce small amounts of venom or lack traditional venom producing organs. One group of non-traditional venomous organisms that have benefitted from the rise of -omic technologies is the Conoideans. The Conoidean superfamily of venomous marine snails includes, the Terebridae, Turridae (s.l), and Conidae. Conoidea venom is used for …

Botanical Therapeutics In The Modern World, Vyacheslav Dushenkov, Brittany L. Graf, Mary Ann Lila

Publications and Research

Plants are the source of a broad spectrum of biologically active phytochemicals. For effective defense against pathogens and abiotic stress, plants have developed complicated chemical strategies with different mechanisms of action. By harnessing these phytochemicals, humans have used plants for medicinal purposes for over 30,000 years, and they remain a valuable source for the development of modern therapeutics. Plant-derived materials are utilized as pharmaceuticals, botanical drugs, dietary supplements (nutraceuticals), functional food ingredients, and cosmeceuticals. The Global Institute for Bioexploration (GIBEX), an international conglomerate of researchers, is involved in multiple botanical therapeutics discovery and development programs.

Mechanisms Of Immune Activation And Suppression By Parasitic Wasps Of Drosophila, Johnny R. Ramroop

Dissertations, Theses, and Capstone Projects

Drosophila melanogaster has served as an excellent model organism to study the molecular processes of innate immunity. Flies essentially lack adaptive immunity and the innate immune system is often divided into the humoral and cellular responses (Lemaitre and Hoffmann 2007). The humoral arm involves the production of antimicrobial peptides, secreted from the fat body, to combat bacterial and fungal infections. The cellular response involves the production of hemocytes (blood cells: crystal cells, plasmatocytes, and lamellocytes) in the larval lymph gland, in the sessile pools, and in circulation (Gold and Bruckner 2014). Microbial pathogens are phagocytosed by plasmatocytes whereas larger parasites …

Effect Of Cntf Derived Peptide, P021 On Cognition And Pathology In 3xtg-Ad Mouse Model Of Alzheimer's Disease, Narjes Baazaoui

Dissertations, Theses, and Capstone Projects

Studies described in this thesis deal with the preventive effects of a neurogenic/neurotropic peptidergic compound, P021, on neurogenesis and synaptic deficits, neurodegeneration, cognitive impairment, and Ab and tau pathologies in a 3xTg-AD mouse model of Alzheimer’s disease (AD).

Background: AD is a chronic progressive neurodegenerative disease. Its multifactorial nature and the heterogeneity make its treatment especially challenging. Although it is a major burden in society, at present there is no drug that can stop or slow down the progression of the disease. Currently, the only available treatments are symptomatic and for mild to severe stages. The development of a drug …

Mechanism Of Action And Applications Of Interleukin 24 In Immunotherapy, Leah Persaud, Dayenny De Jesus, Oliver Brannigan, Maria Richiez-Paredes, Jeannette Huaman, Giselle Alvarado, Linda Riker, Gissete Mendez, Jordan Dejoie, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is an important pleiotropic immunoregulatory cytokine, whose gene is located in human chromosome 1q32-33. IL-24’s signaling pathways have diverse biological functions related to cell differentiation, proliferation, development, apoptosis, and inflammation, placing it at the center of an active area of research. IL-24 is well known for its apoptotic effect in cancer cells while having no such effect on normal cells. IL-24 can also be secreted by both immune and non-immune cells. Downstream effects of IL-24, after binding to the IL-20 receptor, can occur dependently or independently of the JAK/STAT signal transduction pathway, which is classically involved in …

Study Of Alternative Functions Of The Mitochondrial Protein Bak, Ma Su Su Aung

Student Theses and Dissertations

Research in the past 15 years has established roles for the pro-apoptotic proteins Bax and Bak in release of death signaling molecules from mitochondria. The process involves relocation of cytoplasmic Bax into the mitochondrial outer membrane to form a giant pore, MAC. Another MAC component, Bak, is constitutively present in the outer membrane regardless of apoptotic stimulation. In this study we investigated the role of Bak in mitochondrial function outside the context of apoptosis. We examined the effects of Bak elimination on emission of reactive oxygen species from mitochondria. Our results indicate a disturbance of free-radical production both in cultured …

A Revisited Phylogeography Of Nautilus Pompilius, Lauren E. Vandepas, Frederick D. Dooley, Gregory J. Barord, Billie J. Swalla, Peter D. Ward

Publications and Research

The cephalopod genus Nautilus is considered a “living fossil” with a contested number of extant and extinct species, and a benthic lifestyle that limits movement of animals between isolated seamounts and landmasses in the Indo-Pacific. Nautiluses are fished for their shells, most heavily in the Philippines, and these fisheries have little monitoring or regulation. Here, we evaluate the hypothesis that multiple species of Nautilus (e.g., N. belauensis, N. repertus and N. stenomphalus) are in fact one species with a diverse phenotypic and geologic range. Using mitochondrial markers, we show that nautiluses from the Philippines, eastern Australia (Great Barrier Reef), Vanuatu, …

Innervation Of Gill Lateral Cells In The Bivalve Mollusc Crassostrea Virginica Affects Cellular Membrane Potential And Cilia Activity, Edward J. Catapane, Michael Nelson, Trevon Adams, Margaret A. Carroll

Publications and Research

Gill lateral cells of Crassostrea virginica are innervated by the branchial nerve, which contains serotonergic and dopaminergic fibers that regulate cilia beating rate. Terminal release of serotonin or dopamine results in an increase or decrease, respectively, of cilia beating rate in lateral gill cells. In this study we used the voltage sensitive fluorescent probe DiBAC4(3) to quantify changes in gill lateral cell membrane potential in response to electrical stimulation of the branchial nerve or to applications of serotonin and dopamine, and correlate these changes to cilia beating rates. Application of serotonin to gill lateral cells caused prolonged membrane depolarization, similar …

Epigenetic Profiles Signify Cell Fate Plasticity In Unipotent Spermatogonial Stem And Progenitor Cells, Ying Liu, Eugenia G. Giannopoulou, Duacheng Wen, Ilaria Falciatori, Oliver Elemento, C. David Allis, Shahin Rafii, Marco Seandel

Publications and Research

Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin. At enhancers, the core pluripotency circuitry is activated partially in SSCs and completely in MASCs, concomitant with loss of …

Molecular Self-Assembly Strategy For Generating Catalytic Hybrid Polypeptides, Yoshiaki Maeda, Justin Fang, Yasuhiro Ikezoe, Douglas H. Pike, Vikas Nanda, Hiroshi Matsui

Publications and Research

Recently, catalytic peptides were introduced that mimicked protease activities and showed promising selectivity of products even in organic solvents where protease cannot perform well. However, their catalytic efficiency was extremely low compared to natural enzyme counterparts presumably due to the lack of stable tertiary fold. We hypothesized that assembling these peptides along with simple hydrophobic pockets, mimicking enzyme active sites, could enhance the catalytic activity. Here we fused the sequence of catalytic peptide CP4, capable of protease and esterase-like activities, into a short amyloidogenic peptide fragment of Aβ. When the fused CP4-Aβ construct assembled into antiparallel β- sheets and amyloid …

From Mollusks To Medicine: A Venomics Approach For The Discovery And Characterization Of Therapeutics From Terebridae Peptide Toxins, Aida Verdes, Prachi Anand, Juliette Gorson, Stephen Jannetti, Patrick Kelly, Abba Leffler, Danny Simpson, Girish Ramrattan, Mandë Holford

Publications and Research

Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics …

Characterization Of The Ftsz C-Terminal Variable (Ctv) Region In Z-Ring Assembly And Interaction With The Z-Ring Stabilizer Zapd In E. Coli Cytokinesis, Kuo-Hsiang Huang, Aaron Mychack, Lukasz Tchorzewski, Anuradha Janakiraman

Publications and Research

Polymerization of a ring-like cytoskeletal structure, the Z-ring, at midcell is a highly conserved feature in virtually all bacteria. The Z-ring is composed of short protofilaments of the tubulin homolog FtsZ, randomly arranged and held together through lateral interactions. In vitro, lateral associations between FtsZ protofilaments are stabilized by crowding agents, high concentrations of divalent cations, or in some cases, low pH. In vivo, the last 4–10 amino acid residues at the C-terminus of FtsZ (the C-terminal variable region, CTV) have been implicated in mediating lateral associations between FtsZ protofilaments through charge shielding. Multiple Z-ring associated proteins (Zaps), also promote …

A Model Of Blood Pressure, Heart Rate, And Vaso-Vagal Responses Produced By Vestibulo-Sympathetic Activation, Theodore Raphan, Bernard Cohen, Yongqing Xiang, Sergei B. Yakushin

Publications and Research

Blood Pressure (BP), comprised of recurrent systoles and diastoles, is controlled by central mechanisms to maintain blood flow. Periodic behavior of BP was modeled to study how peak amplitudes and frequencies of the systoles are modulated by vestibular activation. The model was implemented as a relaxation oscillator, driven by a central signal related to Desired BP. Relaxation oscillations were maintained by a second order system comprising two integrators and a threshold element in the feedback loop. The output signal related to BP was generated as a nonlinear function of the derivative of the first state variable, which is a summation …

Controlled Microfluidics To Examine Growth-Factor Induced Migration Of Neural Progenitors In The Drosophila Visual System, Cade Beck, Tanya Singh, Angela Farooqi, Tadmiri Venkatesh, Maribel Vazquez

Publications and Research

BACKGROUND:

The developing visual system in Drosophila melanogaster provides an excellent model with which to examine the effects of changing microenvironments on neural cell migration via microfluidics, because the combined experimental system enables direct genetic manipulation, in vivo observation, and in vitro imaging of cells, post-embryo. Exogenous signaling from ligands such as fibroblast growth factor (FGF) is well-known to control glia differentiation, cell migration, and axonal wrapping central to vision.

NEW METHOD:

The current study employs a microfluidic device to examine how controlled concentration gradient fields of FGF are able to regulate the migration of vision-critical glia cells with and …

Characterization And Recombinant Expression Of Terebrid Venom Peptide From Terebra Guttata, John Moon, Juliette Gorson, Mary Elizabeth Wright, Laurel Yee, Samer Khawaja, Hye Young Shin, Yasmine Karma, Rajeeva Lochan Musunri, Michelle Yun, Mandë Holford

Publications and Research

Venom peptides found in terebrid snails expand the toolbox of active compounds that can be applied to investigate cellular physiology and can be further developed as future therapeutics. However, unlike other predatory organisms, such as snakes, terebrids produce very small quantities of venom, making it difficult to obtain sufficient amounts for biochemical characterization. Here, we describe the first recombinant expression and characterization of terebrid peptide, teretoxin Tgu6.1, from Terebra guttata. Tgu6.1 is a novel forty-four amino acid teretoxin peptide with a VI/VII cysteine framework (C–C–CC–C–C) similar to O, M and I conotoxin superfamilies. A ligation-independent cloning strategy with an ompT …

Engineered Protein Polymer-Gold Nanoparticle Hybrid Materials For Small Molecule Delivery, Min Dai, Ja Frezzo, E Sharma, R Chen, N Singh, C Yuvienco, E Caglar, S Xiao, A Saxena, Jk Montclare

Publications and Research

We have fabricated protein polymer-gold nanoparticle (P-GNP) nanocomposites that exhibit enhanced binding and delivery properties of the small hydrophobic molecule drug, curcumin, to the model breast cancer cell line, MCF-7. These hybrid biomaterials are constructed via in situ GNP templated-synthesis with genetically engineered histidine tags. The P-GNP nanocomposites exhibit enhanced small molecule loading, sustained release and increased uptake by MCF-7 cells. When compared to the proteins polymers alone, the P-GNPs demonstrate a greater than 7-fold increase in curcumin binding, a nearly 50% slower release profile and more than 2-fold increase in cellular uptake of curcumin. These results suggest that P-GNP …

Abnormal Tau Induces Cognitive Impairment Through Two Different Mechanisms: Synaptic Dysfunction And Neuronal Loss, J. Di, L. S. Cohen, C. P. Corbo, Greg R. Phillips, Abdeslem El Idrissi, Alejandra D. Alonso

Publications and Research

The hyperphosphorylated microtubule-associated protein tau is present in several neurodegenerative diseases, although the causal relationship remains elusive. Few mouse models used to study Alzheimerlike dementia target tau phosphorylation. We created an inducible pseudophosphorylated tau (Pathological Human Tau, PH-Tau) mouse model to study the effect of conformationally modified tau in vivo. Leaky expression resulted in two levels of PH-Tau: low basal level and higher upon induction (4% and 14% of the endogenous tau, respectively). Unexpectedly, low PH-Tau resulted in significant cognitive deficits, decrease in the number of synapses (seen by EM in the CA1 region), reduction of synaptic proteins, and localization …

Hydrodynamic Loading In Concomitance With Exogenous Cytokine Stimulation Modulates Differentiation Of Bovine Mesenchymal Stem Cells Towards Osteochondral Lineages, Stephen M. Goldman, Gilda A. Barabino

Publications and Research

Background: Mesenchymal stem cells (MSCs) are viewed as a having significant potential for tissue engineering and regenerative medicine therapies. Clinical implementation of MSCs, however, demands that their preparation be stable and reproducible. Given that environmental and bioprocessing parameters such as substrate stiffness, seeding densities, culture medium composition, and mechanical loading can result in undirected differentiation of the MSC population, the objective of this study was to systematically investigate how hydrodynamic loading influences the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) towards the osteochondral lineages both in the presence and absence of exogenous, inductive factors.

Methods: Expanded bovine MSCs were …

Chamber-Specific Patterns Of Epicardium Formation In Zebrafish, Sana Khan

Dissertations, Theses, and Capstone Projects

The outer cardiac layer, the epicardium, coordinates the final steps of vertebrate heart development. This cardiac tissue arises from cells in the proepicardial organ (PEO) that forms around the base of the inflow tract. Its general location is conserved across species despite morphological differences. Cellular mechanisms of migration differ across species. Three strategies of PEO migration are described: 1) The floating cyst model - PEO cells released into the pericardial cavity are directed by fluid movements to migrate onto the myocardium; 2) Villi transfer - cardiac contractions may mediate multicellular PEO villi contact to the myocardium; and 3) Tissue bridge-mediated …

Role Of Bec-1/Beclin 1 And Autophagy Genes In C.Elegans Germline Cell Proliferation, Kristina Ames

Dissertations, Theses, and Capstone Projects

Autophagy is an evolutionary conserved process involved in the cellular adaptation to stress and basal levels of autophagy are crucial for cellular metabolism and homeostasis. Cellular recycling by autophagy is characterized by the formation of distinctive double-membrane vesicles (autophagosomes) that engulf unnecessary cytoplasmic components, such as organelles and long-lived proteins. Failure to remove protein aggregates and/or damaged organelles, via autophagy, has been implicated in various medical conditions such as liver disease, neurodegenerative diseases and cancer. Autophagy may suppress or promote cellular proliferation in tumors, depending on the type and metabolic state of the cell, where autophagy is generally believed to …

The Implications Of Chromatin Remodelers' Acetylation In Ino1 Activation, Michelle M. Esposito

Dissertations, Theses, and Capstone Projects

It is known that histone acetylases (HATs) regulate gene expression, but only recently have new functional implications about remodelers’ acetylation emerged. For instance, the HAT, Gcn5p, is capable of acetylating the catalytic subunit of the nucleosome remodeling complex SWI/SNF, Snf2p, which results in the dissociation of the complex from chromatin. The implications of this acetylation and subsequent dissociation have yet to be explored with regard to transcriptional regulation and other possible mechanisms. To further understand the implications of remodeler acetylation, I used a yeast model system examining the expression of the inositol-3-phosphate synthase gene INO1. Through chromatin immunoprecipitation (ChIP) …

When Human-Leopard Conflict Turns Deadly: A Cross-Country Situational Analysis, Julie S. Viollaz

Dissertations, Theses, and Capstone Projects

Habitat destruction and pollution are two of the main causes for the decline of the planet’s biodiversity. Yet environmentalists are now recognizing that illegal wildlife killings, both poaching and retaliatory killings due to human-wildlife conflict, are perhaps the next major threat. Biologists have researched illegal killings and their effect on species conservation, but few researchers have applied criminological principles of crime reduction to them. This research will explore the situational factors that drive retaliatory leopard killings in parts of South Africa, Kenya, and India. These factors, human and environmental, include local expectations from wildlife, sensitivity to environmental issues, communication between …

The Human Disease-Associated Ab Amyloid Core Sequence Forms Functional Amyloids In A Fungal Adhesin, Rachele D. Rameau, Desmond N. Jackson, Audrey Beaussary, Yves F. Dufrêne, Peter N. Lipke

Publications and Research

There is increasing evidence that many amyloids in living cells have physiological functions. On the surfaces of fungal cells, amyloid core sequences in adhesins can aggregate into 100- to 1,000-nm-wide patches to form high-avidity adhesion nanodomains on the cell surface. The nanodomains form through interactions that have amyloid-like properties: binding of amyloid dyes, perturbation by antiamyloid agents, and interaction with homologous sequences. To test whether these functional interactions are mediated by typical amyloid interactions, we substituted an amyloid core sequence, LVFFA, from human A protein for the native sequence IVIVA in the 1,419-residue Candida albicans adhesin Als5p. The chimeric protein …

Site-Specifically Labeled Immunoconjugates For Molecular Imaging—Part 1: Cysteine Residues And Glycans, Pierre Adumeau, Sai Kiran Sharma, Colleen Brent, Brian M. Zeglis

Publications and Research

Due to their remarkable selectivity and specificity for cancer biomarkers, immunoconjugates have emerged as extremely promising vectors for the delivery of diagnostic radioisotopes and fluorophores to malignant tissues. Paradoxically, however, these tools for precision medicine are synthesized in a remarkably imprecise way. Indeed, the vast majority of immunoconjugates are created via the random conjugation of bifunctional probes (e.g., DOTA-NCS) to amino acids within the antibody (e.g., lysines). Yet antibodies have multiple copies of these residues throughout their macromolecular structure, making control over the location of the conjugation reaction impossible. This lack of site specificity can lead to the formation of …

Human Anatomy And Physiology Preparatory Course: Part 3 Of 4 (Interactive), Carlos Liachovitzky

Open Educational Resources

he overall purpose of these preparatory course set of learning objectives is to help students familiarize with some terms and some basic concepts they will find later in the Human Anatomy and Physiology I course.

These 40+ learning objectives to prepare for Human Anatomy and Physiology can be downloaded and played in a desktop, or laptop (windows exe file).

The entire course has four parts:

• Part 1
• Part 2
• Part 3
• Part 4

Each learning objective is followed by a set of multiple choice question similar to those found later in a Human Anatomy and Physiology course.