Life Sciences Commons^™

The Role Of Slu7 In Spliceosome Function In Saccharomyces Cerevisiae, Sovira A. Chaudhry

Theses and Dissertations

The removal of introns from pre-messenger RNA via splicing in the nucleus is an essential step in gene expression. In recent decades, significant effort has been made to understand the chemical mechanisms of splicing reactions and the composition of the spliceosome that catalyzes them. Yet very little is known about the exact function of many splicing factors and small proteins within the spliceosome. Slu7, a pre-mRNA splicing factor, is essential during the second catalytic step of splicing because it interacts with several proteins and stabilizes the active site conformation. It has been found that Slu7 is involved in 3' splice …

Using Image To Assist Students In Construct Searching Concepts And Framing Research Questions, Junli Diao

Open Educational Resources

No abstract provided.

Assembly Mechanism Of Early Hsp90-Cdc37-Kinase Complexes, Dimitra Keramisanou, M.V. Vasantha Kumar, Nicole Boose, Rinat R. Abzalimov, Ioannis Gelis

Advanced Science Research Center

Molecular chaperones have an essential role for the maintenance of a balanced protein homeostasis. Here, we investigate how protein kinases are recruited and loaded to the Hsp90-Cdc37 complex, the first step during Hsp90-mediated chaperoning that leads to enhanced client kinase stability and activation. We show that conformational dynamics of all partners is a critical feature of the underlying loading mechanism. The kinome co-chaperone Cdc37 exists primarily in a dynamic extended conformation but samples a low-populated, well-defined compact structure. Exchange between these two states is maintained in an assembled Hsp90-Cdc37 complex and is necessary for substrate loading. Breathing motions at the …

Protein Charge Parameters That Influence Stability And Cellular Internalization Of Polyelectrolyte Complex Micelles, Rachel A. Kapelner, Rachel S. Fisher, Shana Elbaum-Garfinkle, Allie C. Obermeyer

Advanced Science Research Center

Proteins are an important class of biologics, but there are several recurring challenges to address when designing protein-based therapeutics. These challenges include: the propensity of proteins to aggregate during formulation, relatively low loading in traditional hydrophobic delivery vehicles, and inefficient cellular uptake. This last criterion is particularly challenging for anionic proteins as they cannot cross the anionic plasma membrane. Here we investigated the complex coacervation of anionic proteins with a block copolymer of opposite charge to form polyelectrolyte complex (PEC) micelles for use as a protein delivery vehicle. Using genetically modified variants of the model protein green fluorescent protein (GFP), …

Tracking Cryptic Sars-Cov-2 Lineages Detected In Nyc Wastewater, Davida S. Smyth, Monica Trujillo, Devon A. Gregory, Kristen Cheung, Anna Gao, Maddie Graham, Yue Guan, Caitlyn Guldenpfennig, Irene Hoxie, Sherin Kannoly, Nanami Kubota, Terri D. Lyddon, Michelle Markman, Clayton Rushford, Kaung Myat San, Geena Sompanya, Fabrizio Spagnolo, Reinier Suarez, Emma Teixeiro, Mark Daniels, Marc C. Johnson, John J. Dennehy

Publications and Research

Tracking SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may lead to the emergence of novel variants resistant to naturally acquired or vaccine-induced immunity. To monitor New York City (NYC) for the presence of novel variants, we deep sequence most of the receptor binding domain coding sequence of the S protein of SARS-CoV-2 isolated from the New York City wastewater. Here we report detecting increasing frequencies of novel cryptic SARS-CoV-2 lineages not recognized in GISAID’s EpiCoV database. These lineages contain mutations that had been rarely observed in clinical samples, including Q493K, Q498Y, E484A, and T572N and share many mutations …

Importin-Mediated Pathological Tau Nuclear Translocation Causes Disruption Of The Nuclear Lamina, Tdp-43 Mislocalization And Cell Death, Robert F. Candia, Leah S. Cohen, Viktoriya Morozova, Christopher Corbo, Alejandra D. Alonso

Publications and Research

Tau is a cytosolic protein that has also been observed in the nucleus, where it has multiple proposed functions that are regulated by phosphorylation. However, the mechanism underlying the nuclear import of tau is unclear, as is the contribution of nuclear tau to the pathology of tauopathies. We have previously generated a pathological form of tau, PH-tau (pseudophosphorylation mutants S199E, T212E, T231E, and S262E) that mimics AD pathological behavior in cells, Drosophila, and a mouse model. Here, we demonstrated that PH-tau translocates into the nucleus of transiently transfected HEK-293 cells, but wildtype tau does not. We identified a putative …

The Role Of Rna Helicase Rhau In Immunoglobulin Class Switch Recombination, Sabine Jean Guillaume

Dissertations and Theses

B cells alter the expression of immunoglobulin isotypes through a process known as class switch recombination (CSR). In these cells, activation induced cytidine deaminase (AID) binds Gquadruplex (G4) switch transcripts, which serve as guide RNAs to target AID to the immunoglobulin heavy chain switch (S) regions in the DNA for CSR. Sequence alignment revealed homology between the AID G4 binding domain and the RNA helicase associated with AU-rich element (RHAU) specific motif (RSM), which allows RHAU binding to G4 RNAs and subsequent unwinding of G4 RNA into single-stranded transcripts. We hypothesize that RHAU functions in CSR by binding G4 S …

Neural Processing Of Semantic Content In Movies, Maximilian Nentwich

Dissertations and Theses

Naturalistic stimuli, such as movies, contain interacting, multimodal and semantic features and allow for free exploration through eye movements. The full extent of neural responses to features such as motion, film cuts and eye movement behavior has not been established. The main hypothesis of this thesis is that complex multimodal and semantic stimuli in naturalistic movies engage a widespread ensemble of locations across the entire brain. To address this question I analyzed simultaneous intracranial and eyetracking data from over 6,000 electrodes across 23 patients with intractable epilepsy. Responses to fast eye movements – saccades – and film cuts are widespread …

Population Structure Of The Lizard Ecpleopus Gaudichaudii Coincides With A Biogeographic Barrier - The Doce River, Alexander J. Garretson

Dissertations and Theses

Intraspecific genetic variation is an integral component of diversification and the accumulation of biodiversity. The degree to which isolated populations of the same species are genetically structured in geographical space is impacted by a variety of mechanisms. In this study, I document patterns and discuss possible drivers of genetic structure within Ecpleopus gaudichaudii, a lizard species endemic to the Atlantic Forest of Brazil. For that, I assembled ddRadseq sequences from 48 individuals across much of the range of the E. gaudichaudii and analyzed its population structure. I created an intraspecific phylogeny for this group utilizing RAxML and conducted a …

Exosome- And Microrna-Based Therapeutic Approach For Tendinopathy, Angela Wang Ilaltdinov

Dissertations and Theses

Tendinopathy, characterized by degeneration and chronic inflammation, is a significant clinical burden. Current treatments focus on symptom management but do not sufficiently address its underlying pathology; however, stem cell-based approaches aimed at repairing diseased tissues may overcome this limitation. Therapeutic effects of stem cells may be due in part to paracrine actions, including some mediated by exosomes – extracellular vesicles secreted by cells that play a role in cell communication. MicroRNA (miRNA), small non-coding RNA carried by exosomes, are likely responsible for many exosome effects. Exosomes and miRNA therapies show promise in treating diseases such as cancer and arthritis, but …

Cryo-Em Structure Of Transmembrane Aaa+ Protease Ftsh In The Adp State, Wu Liu, Martien Schoonen, Tong Wang, Sean Mcsweeney, Qun Liu

Advanced Science Research Center

AAA+ proteases regulate numerous physiological and cellular processes through tightly regulated proteolytic cleavage of protein substrates driven by ATP hydrolysis. FtsH is the only known family of membrane-anchored AAA+ proteases essential for membrane protein quality control. Although a spiral staircase rotation mechanism for substrate translocation across the FtsH pore has been proposed, the detailed conformational changes among various states have not been clear due to absence of FtsH structures in these states. We report here the cryo-EM structure for Thermotoga maritima FtsH (TmFtsH) in a fully ADP-bound symmetric state. Comparisons of the ADP-state structure with its apo-state and a substrate-engaged …

Evaluating A Test For Shedding Propensity Using Tape Lifts From Different Skin Locations, Xiao M. Chen

Student Theses

The shedding propensity of a person can assist data interpretation in casework when assessing the possibility of passive transfer for DNA analysis. Past studies on shedding propensity evaluated palmar skin (washed and unwashed) deposits. This study compared different skin locations with respect to shedding propensity, and explored the potential of tape-lifts as a skin surface collection method. Eight different skin types and samples were collected with adhesive tape disks from 28 participants over three non-consecutive days; the washed and unwashed fingers from both hands, toe, and arm, neck below ear, and nape. Samples were extracted, quantified, amplified, genotyped, and evaluated …

Reproducibility Of Individual Dna Deposits Detected Through Cellular Fluorescence, Natalee Small-Davidson

Student Theses

Contact traces are an important part of DNA casework, but the probative value of any identified associations depends on the possibility of passive transfer. There is known individual variation in DNA left behind during contact, this DNA shedding propensity has an effect on whose DNA is detected. This study evaluated this variability using a cell staining approach. Volunteers were asked to deposit a fingerprint on a clean glass slide, then wash their hands and deposit a second fingerprint after a 30-minute wait without touching anything. Three sets of samples were collected over three consecutive weeks. Fingerprints were stained with a …

High-Resolution Cryo-Electron Microscopy Structure Of Photosystem Ii From The Mesophilic Cyanobacterium, Synechocystis Sp. Pcc 6803, Christopher J. Gisriel, Jimin Wang, Jinchan Liu, David A. Flesher, Krystle M. Reiss, Hao-Li Huang, Ke R. Yang, William H. Armstrong, M. R. Gunner, Victor S. Batista, Richard J. Debus, Gary W. Brudvig

Publications and Research

Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a highresolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the …

Cryptococcus Neoformans Melanization Incorporates Multiple Catecholamines To Produce Polytypic Melanin, Rosanna P. Baker, Christine Chrissian, Ruth E. Stark, Arturo Casadevall

Publications and Research

Melanin is a major virulence factor in pathogenic fungi that enhances the ability of fungal cells to resist immune clearance. Cryptococcus neoformans is an important human pathogenic fungus that synthesizes melanin from exogenous tissue catecholamine precursors during infection, but the type of melanin made in cryptococcal meningoencephalitis is unknown. We analyzed the efficacy of various catecholamines found in brain tissue in supporting melanization using animal brain tissue and synthetic catecholamine mixtures reflecting brain tissue proportions. Solid-state NMR spectra of the melanin pigment produced from such mixtures yielded more melanin than expected if only the preferred constituent dopamine had been incorporated, …

Behavioral Patterns Of Goldfish (Carassius Auratus) Exploring A “Fish Tower”, Sasha Prasad-Shreckengast

Theses and Dissertations

Fish are held in captivity at some of the highest numbers of any taxa, but their curiosity is rarely studied. With this study, we set the groundwork to investigate the presence and nature of curiosity in goldfish (Carassius auratus) via novel free-choice exploration opportunities by creating a “fish tower."

Who Pays To Clean Up What A Dying Industry Leaves Behind?, Audrey Carleton

Capstones

As the birthplace of oil and gas, Pennsylvania is home to the highest number of orphaned abandoned oil and gas wells in the country — an estimated 300,000 to 500,000 dot the Keystone State, all remnants of a dying industry. These wells emit methane, a potent greenhouse gas, and have, for decades, caused alarm to hundreds of residents, documents obtained in a months-long capstone investigation show. The state is currently plugging 10 to 12 abandoned wells per year, on average, out of hundreds of thousands, in part because it has not collected enough in cleanup funds from producers to fund …

Pushing It To The Limit: Determining Asian Elephant (Elephas Maximus) Olfactory Sensitivity And Discrimination Through A Behavioral Choice Task, Matthew S. Rudolph

Theses and Dissertations

Elephants have shown remarkable olfactory capabilities. Their sense of smell impacts their foraging choices, behavior, and ultimately, survival. Being able to detect a target odor can allow elephants to locate specific resources, identify threats, and find receptive conspecifics. Previous studies have shown that elephants can consistently detect target odors, but have not identified the limits of this detection. Thus, to investigate the extent of elephants’ odor detection capabilities, we tested Asian elephants in a two-step odor discrimination task. First, we investigated whether elephants could detect odors at varying levels of dilution after a training procedure, and then whether they could …

Dolphins In Ny? Researchers Turn To Boat Tours For Sightings, Aaron K. Tremper

Capstones

Before 2009, coastal bottlenose dolphins were a rare sight north of New Jersey. According to local researchers, large pods of bottlenose dolphins made their way that spring/summer along Long Island. While dolphin population data by state and federal wildlife regulators are spotty, studies by local scientists suggest more dolphins have been flocking to New York since 2009. Many researchers are turning to whale-watching ventures to learn more about what dolphins are up to in the Big Apple.

https://jkt711.github.io/capstone/

Lost At Sea, Anny Oberlink

Capstones

At the end of World War I and World War II, in a new era of peace, nations confronted an unprecedented logistical problem: millions of tons of unexploded ordnance—once a wartime boon—had become a peacetime burden. Faced with a mandate to dispose of excess munitions, militaries turned to dumping their stockpiles into the sea. But now a complex and urgent issue is emerging. Increasingly, as industry looks to build offshore—wind power turbines, internet cables, oil pipelines—they are facing a potential peril: millions of tons of unexploded bombs and ammunition that are lying on the ocean floor can explode or leak …

Elevated Growth And Biomass Along Temperate Forest Edges, Luca L. Morreale, Jonathan R. Thompson, Xiaojing Tang, Andrew B. Reinmann, Lucy R. Hutyra

Publications and Research

Fragmentation transforms the environment along forest edges. The prevailing narrative, driven by research in tropical systems, suggests that edge environments increase tree mortality and structural degradation resulting in net decreases in ecosystem productivity. We show that, in contrast to tropical systems, temperate forest edges exhibit increased forest growth and biomass with no change in total mortality relative to the forest interior. We analyze > 48,000 forest inventory plots across the north-eastern US using a quasi- experimental matching design. At forest edges adjacent to anthropogenic land covers, we report increases of 36.3% and 24.1% in forest growth and biomass, respectively. Inclusion of …

Inter-Subject Correlation While Listening To Minimalist Music: A Study Of Electrophysiological And Behavioral Responses To Steve Reich’S Piano Phase, Tysen Dauer, Duc T. Nguyen, Nick Gang, Jacek P. Dmochowski, Jonathan Berger, Blair Kaneshiro

Publications and Research

Musical minimalism utilizes the temporal manipulation of restricted collections of rhythmic, melodic, and/or harmonic materials. One example, Steve Reich’s Piano Phase, offers listeners readily audible formal structure with unpredictable events at the local level. For example, pattern recurrences may generate strong expectations which are violated by small temporal and pitch deviations. A hyper-detailed listening strategy prompted by these minute deviations stands in contrast to the type of listening engagement typically cultivated around functional tonal Western music. Recent research has suggested that the inter-subject correlation (ISC) of electroencephalographic (EEG) responses to natural audio-visual stimuli objectively indexes a state of “engagement,” demonstrating …

Closely Related Gull Species Show Contrasting Foraging Strategies In An Urban Environment, K. A. Lato, D. J. Madigan, R. R. Veit, L. H. Thorne

Publications and Research

The expansion of urban landscapes has both negative and positive effects on wildlife. Understanding how different species respond to urbanization is key to assessing how urban landscapes influence regional wildlife behavior and ecosystem structure. Gulls are often described as strong urban adapters, but few studies have explored species-specific differences in habitat use. Here, we use GPS tracking in conjunction with stable isotope analysis (SIA) to quantify the habitat use and trophic ecology of great black-backed gulls (Larus marinus) and herring gulls (L. argentatus) in an urbanized area. Non-Metric Multidimensional Scaling (NMDS) of foraging locations revealed significant differences in the habitat …

Discovery Of Phosphotyrosine-Binding Oligopeptides With Supramolecular Target Selectivity, Ana S. Pina, Leonor Morgado, Krystyna L. Duncan, Sara Carvalho, Henrique F. Carvalho, Armenio J. M. Barbosa, Beatriz De P. Mariz, Ines P. Moreira, Daniela Kalafatovic, Bruno M. Morais Faustino, Vishal Narang, Tong Wang, Charalampos G. Pappas, Isabel Ferreira, A. Cecılia A. Roque, Rein V. Ulijn

Advanced Science Research Center

We demonstrate phage-display screening on self-assembled ligands that enables the identification of oligopeptides that selectively bind dynamic supramolecular targets over their unassembled counterparts. The concept is demonstrated through panning of a phage-display oligopeptide library against supramolecular tyrosine-phosphate ligands using 9-fluorenylmethoxycarbonyl-phenylalanine-tyrosine-phosphate (Fmoc-FpY) micellar aggregates as targets. The 14 selected peptides showed no sequence consensus but were enriched in cationic and proline residues. The lead peptide, KVYFSIPWRVPM-NH2 (P7) was found to bind to the Fmoc-FpY ligand exclusively in its self-assembled state with KD = 74 ± 3 μM. Circular dichroism, NMR and molecular dynamics simulations revealed that the peptide interacts with Fmoc-FpY …

Genomic Epidemiology Of Clostridium Difficile Colonization And Transmission In An Intensive Care Unit Cohort, Brianne Ciferri

Dissertations and Theses

Abstract

Genomic epidemiology of Clostridium difficile colonization and transmission in an intensive care unit cohort

by Brianne Ciferri, MPH

Advisor: C. Mary Schooling, PhD

Introduction: Clostridiodes difficile (C. difficile) is a leading cause of healthcare associated infections (HAI) in the United States and responsible for an estimated incidence of 223,900 cases and 12,800 deaths per year^1,2. C. difficile can cause gastrointestinal illness with symptoms ranging from mild diarrheal illness to a life-threatening condition. C. difficile is an opportunistic pathogen in which spores can live in an undisturbed dormant state within the intestinal tract and become …

A Preliminary Investigation Into The Effects Of Lucilia Sericata (Meigen) Blow Fly Larval Feeding On Sharp Force Trauma (Sft) Wound Patterns In Decomposing Bones Of Sus Scrofa Domesticus, Erica L. Klafehn

Student Theses

An important aspect of forensic investigations involves the characterization and analysis of bone related trauma as this can provide valuable information regarding the manner and circumstances of death. Bone trauma can be classified into three main categories, which include Sharp Force Trauma (SFT), Blunt Force Trauma (BFT), and Gunshot Trauma. Previous experiments have explored SFT on flesh and bones, specifically made with knives or saws, coupled with various microscopic analytical methods. Minimal research has been done integrating both a forensic entomology and forensic anthropology approach, so it is imperative to understand previous literature detailing the behaviors of insects (blow flies), …

Exploration Of Dark Chemical Genomics Space Via Portal Learning: Applied To Targeting The Undruggable Genome And Covid-19 Anti-Infective Polypharmacology, Tian Cai, Li Xie, Muge Chen, Yang Liu, Di He, Shuo Zhang, Cameron Mura, Philip Boume, Lei Xie

Publications and Research

Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones—a common dilemma in scientific inquiry. We have developed a new deep learning framework, called Portal Learning , to explore dark chemical and biological space. Three key, novel components of our approach include: (i) end-to-end, step-wise transfer learning, in recognition of biology’s sequence-structure-function paradigm, (ii) out-of-cluster meta-learning, and (iii) stress model selection. Portal Learning provides a practical solution to the out-of-distribution (OOD) …

Development And Validation Of A Method For The Determination Of Designer Benzodiazepines In Hair By Liquid Chromatography Tandem Mass Spectrometry (Lc-Ms/Ms), Laura C. Defreitas

Student Theses

In recent years, new designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogues of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been associated with overdoses and deaths. As a result, there has been a surge in efforts to develop ways to accurately test for these compounds in different biological matrices. This study focused to develop and validate a method for determining 17 new designer benzodiazepines in hair by liquid chromatography tandem mass spectrometry (LC-MS/MS). Hair samples were decontaminated, pulverized, and 20 mg of the sample was incubated in …

Impact Of Blood Collection Tubes In Cannabinoid Quantitative Analysis, Tega E. Obruche-Akponah

Student Theses

In forensic toxicological cases, sample stability and storage are pivotal for obtaining adequate analytical results. Currently, limited information is available about the impact of different preservatives and anticoagulants present in the blood tubes used in the collection of blood samples containing cannabinoids. This study investigated the impact of sodium fluoride (gray top) and sodium citrate (blue top) blood collection tubes on the concentrations of tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and 5 THC metabolites (THC-OH, THC-COOH, THC-diOH, THC-glucuronide, THCCOOH-glucuronide) in whole blood samples, stored at room temperature, 4ºC and -20ºC for up to 3.5 months. The samples were extracted using …

Living With A Giant, Flowering Parasite: Metabolic Differences Between Tetrastigma Loheri Gagnep. (Vitaceae) Shoots Uninfected And Infected With Rafflesia (Rafflesiaceae) And Potential Applications For Propagation, Jeanmaire Molina, Dejan Nikolic, Jashvanth Raaj Jeevarathanam, Rinat Abzalimov, Eun‑Jung Park, Ronniel Pedales, Elmer‑Rico E. Mojica, Danilo Tandang, William Mclaughlin, Kyle Wallick, James Adams, Ari Novy, Susan K. Pell, Richard B. Van Breemen, John M. Pezzuto

Advanced Science Research Center

Main conclusion: Metabolites in Rafflesia-infected and non-infected Tetrastigma were compared which may have applications in Rafflesia propagation. Benzylisoquinoline alkaloids, here reported for the first time in Vitaceae, were abundant in non-infected shoots and may be a form of defense. In Rafflesia-infected shoots, oxylipins, which mediate immune response, were elevated.

Endemic to the forests of Southeast Asia, Rafflesia (Rafflesiaceae) is a genus of holoparasitic plants producing the largest flowers in the world, yet completely dependent on its host, the tropical grape vine, Tetrastigma. Rafflesia species are threatened with extinction, making them an iconic symbol of plant conservation. Thus …