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Utilizing Earth's Microbiology To Develop The Framework For A Manufactured Martian Nitrogen Cycle, Kyle Valgardson 2020 Utah State University

Utilizing Earth's Microbiology To Develop The Framework For A Manufactured Martian Nitrogen Cycle, Kyle Valgardson

All Graduate Theses and Dissertations

History has shown us that space travel is a complicated activity not to be taken lightly. Extended missions such as those that would accompany a manned mission to Mars are guaranteed to have increased complexity and require creative solutions to problems we likely take for granted. One such issue is how to supply the necessary amount of nitrogen to the astronauts to keep them alive. Nitrogen is an essential component to life on Earth as most biological molecules, such as protein and DNA, contain a significant amount of it. Most organisms have to get it from what they eat, but ...


Effects Of Oxidative Modifications On The Structure And Non-Canonical Functions Of Cytochrome C Studied By Mass Spectrometry, Victor Yin 2020 The University of Western Ontario

Effects Of Oxidative Modifications On The Structure And Non-Canonical Functions Of Cytochrome C Studied By Mass Spectrometry, Victor Yin

Electronic Thesis and Dissertation Repository

The peroxidase activity of the mitochondrial protein cytochrome c (cyt c) plays a critical role in triggering programmed cell death, or apoptosis. However, the native structure of cyt c should render this activity impossible due to the lack of open iron coordination sites at its heme cofactor. Despite its key biological importance, the molecular mechanisms underlying this structure-function mismatch remain enigmatic. The work detailed in this dissertation fills this knowledge gap by using mass spectrometry (MS) to decipher the central role that protein oxidative modifications and their associated structural changes play in activating the peroxidase function of cyt c.

Chapter ...


Algal Biomarkers As A Proxy For Pco2: Constraints From Late Quaternary Sapropels In The Eastern Mediterranean, Caitlyn R. Witkowski, Marcel T.J. van der Meer, Brian Blais, Jaap S. Sinninghe Damsté, Stefan Schouten 2020 Royal Netherlands Institute for Sea Research

Algal Biomarkers As A Proxy For Pco2: Constraints From Late Quaternary Sapropels In The Eastern Mediterranean, Caitlyn R. Witkowski, Marcel T.J. Van Der Meer, Brian Blais, Jaap S. Sinninghe Damsté, Stefan Schouten

Science and Technology Faculty Journal Articles

Records of carbon dioxide concentrations (partial pressure expressed as pCO2) over Earth’s history provide trends that are critical to understand our changing world. To better constrain pCO2 estimations, here we test organic pCO2 proxies against the direct measurements of pCO2 recorded in ice cores. Based on the concept of stable carbon isotopic fractionation due to photosynthetic CO2 fixation (Ɛp), we use the stable carbon isotopic composition (δ13C) of the recently proposed biomarker phytol (from all photoautotrophs), as well as the conventionally used alkenone biomarkers (from specific species) for comparison, to reconstruct pCO2 over several ...


Rethinking Fda Regulation Of Complex Products, Philip E. Alford 2020 University of Minnesota Law School

Rethinking Fda Regulation Of Complex Products, Philip E. Alford

Minnesota Journal of Law, Science & Technology

No abstract provided.


Atom Identifiers Generated By A Neighborhood-Specific Graph Coloring Method Enable Compound Harmonization Across Metabolic Databases, Huan Jin, Joshua M. Mitchell, Hunter N. B. Moseley 2020 University of Kentucky

Atom Identifiers Generated By A Neighborhood-Specific Graph Coloring Method Enable Compound Harmonization Across Metabolic Databases, Huan Jin, Joshua M. Mitchell, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Metabolic flux analysis requires both a reliable metabolic model and reliable metabolic profiles in characterizing metabolic reprogramming. Advances in analytic methodologies enable production of high-quality metabolomics datasets capturing isotopic flux. However, useful metabolic models can be difficult to derive due to the lack of relatively complete atom-resolved metabolic networks for a variety of organisms, including human. Here, we developed a neighborhood-specific graph coloring method that creates unique identifiers for each atom in a compound facilitating construction of an atom-resolved metabolic network. What is more, this method is guaranteed to generate the same identifier for symmetric atoms, enabling automatic identification of ...


The Influence Of The Cellular Environment On Z-Dna Formation, Amanda Hange 2020 State University of New York College at Brockport

The Influence Of The Cellular Environment On Z-Dna Formation, Amanda Hange

Senior Honors Theses

In the cell, chemically diverse solutes known as osmolytes accumulate in response to environmental stresses. To add to the understanding of how the environment inside a cell affects nucleic acid folding and function, we investigated the influence of cosolutes on the transition from B-DNA to Z-DNA in model DNA duplexes. Distinct from the familiar right-handed BDNA helical conformation, Z-DNA is a left-handed double helical structure with its phosphodiester backbone arranged in a zig-zag pattern that is unique to Z-DNA. Moreover, due to the correlation between Z-DNA formation potential and regions of active transcription, ZDNA is believed to serve a vital ...


Current Scenario Of Covid-19 With Epidemiological And Phylogenetic Analysis Of Pakistani Coronavirus: A Review, Asma Altaf, Wafa Iqbal, Sidra Younis, Farah Deeba 2020 Department of Biochemistry and Biotechnology, The Women University, Multan, Pakistan

Current Scenario Of Covid-19 With Epidemiological And Phylogenetic Analysis Of Pakistani Coronavirus: A Review, Asma Altaf, Wafa Iqbal, Sidra Younis, Farah Deeba

Journal of Bioresource Management

A novel corona virus named as 2019 n-CoV was identified to be the actual cause of an outbreak of respiratory illness in Wuhan, China beginning in late December 2019. This respiratory disease was named as COVID-19 by WHO. There are many countries affected by COVID-19 including Pakistan. In this review we have provided a brief introduction of COVID-19 and discussed epidemiological and phylogenetic analysis of Pakistani novel corona virus strain. Our epidemiological analysis of data till 16th May 2020 showed rapidly increasing number of new cases, while at the same time a higher recovery rate than number of deaths ...


Estimating Partial Body Ionizing Radiation Exposure By Automated Cytogenetic Biodosimetry, Peter Rogan 2020 The University of Western Ontario

Estimating Partial Body Ionizing Radiation Exposure By Automated Cytogenetic Biodosimetry, Peter Rogan

Biochemistry Publications

Purpose: Inhomogeneous exposures to ionizing radiation can be detected and quantified with the Dicentric Chromosome Assay (DCA) of metaphase cells. Complete automation of interpretation of the DCA for whole body irradiation has significantly improved throughput without compromising accuracy, however low levels of residual false positive dicentric chromosomes (DCs) have confounded its application for partial body exposure determination.

Materials and Methods: We describe a method of estimating and correcting for false positive DCs in digitally processed images of metaphase cells. Nearly all DCs detected in unirradiated calibration samples are introduced by digital image processing. DC frequencies of irradiated calibration samples and ...


Weak Binding To The A2re Rna Rigidifies Hnrnpa2 Rrms And Reduces Liquid–Liquid Phase Separation And Aggregation, Veronica H. Ryan, Scott Watters, Joshua Amaya, Balabhadra Khatiwada, Vincenzo Venditti, Mandar T. Naik, Nicolas L. Fawzi 2020 Brown University

Weak Binding To The A2re Rna Rigidifies Hnrnpa2 Rrms And Reduces Liquid–Liquid Phase Separation And Aggregation, Veronica H. Ryan, Scott Watters, Joshua Amaya, Balabhadra Khatiwada, Vincenzo Venditti, Mandar T. Naik, Nicolas L. Fawzi

Chemistry Publications

hnRNPA2 is a major component of mRNA transport granules in oligodendrocytes and neurons. However, the structural details of how hnRNPA2 binds the A2 recognition element (A2RE) and if this sequence stimulates granule formation by enhancing phase separation of hnRNPA2 has not yet been studied. Using solution NMR and biophysical studies, we find that each of the two individual RRMs retain the domain structure observed in complex with RNA but are not rigidly confined (i.e. they move independently) in solution in the absence of RNA. hnRNPA2 RRMs bind the minimal rA2RE11 weakly but at least, and most likely, two hnRNPA2 ...


The Bromodomains Of The Mammalian Swi/Snf (Mswi/Snf) Atpases Brahma (Brm) And Brahma Related Gene 1 (Brg1) Promote Chromatin Interaction And Are Critical For Skeletal Muscle Differentiation, Anthony N. Imbalzano, Hanna Witwicka, Tapan Sharma 2020 University of Massachusetts Medical School

The Bromodomains Of The Mammalian Swi/Snf (Mswi/Snf) Atpases Brahma (Brm) And Brahma Related Gene 1 (Brg1) Promote Chromatin Interaction And Are Critical For Skeletal Muscle Differentiation, Anthony N. Imbalzano, Hanna Witwicka, Tapan Sharma

University of Massachusetts Medical School Faculty Publications

Skeletal muscle differentiation induces changes in the epigenome of myoblasts as they proceed towards a myogenic phenotype. mSWI/SNF chromatin remodeling enzymes coordinate with lineage-determining transcription factors and are key regulators of differentiation. Three mSWI/SNF proteins, the mutually exclusive ATPases, BRG1 and BRM, and the BAF180 protein (Polybromo1, PBRM1) contain bromodomains belonging to the same structural subfamily. Bromodomains bind to acetylated lysines on histone N-terminal tails and on other proteins. Pharmacological inhibition of mSWI/SNF bromodomain function using the selective inhibitor PFI-3 reduced differentiation, decreased expression of myogenic genes, and increased the expression of cell cycle-related genes and the ...


Genome Scan Detection Of Selective Sweeps Among Biotypes Of The Soybean Aphid, Aphis Glycines, With Differing Virulence To Resistance To A. Glycines (Rag) Traits In Soybean, Glycine Max, Brad S. Coates, Jessica D. Hohenstein, Rosanna Giordano, Ravi Kiran Donthu, Andrew P. Michel, Erin W. Hodgson, Matthew E. O'Neal 2020 U.S. Department of Agriculture

Genome Scan Detection Of Selective Sweeps Among Biotypes Of The Soybean Aphid, Aphis Glycines, With Differing Virulence To Resistance To A. Glycines (Rag) Traits In Soybean, Glycine Max, Brad S. Coates, Jessica D. Hohenstein, Rosanna Giordano, Ravi Kiran Donthu, Andrew P. Michel, Erin W. Hodgson, Matthew E. O'Neal

Entomology Publications

Multiple biotypes of soybean aphid, Aphis glycines, occur in North America adapted for survival (virulence) on soybean, Glycine max, with one or more different resistance to A. glycines (Rag) traits. The degree of genome-wide variance between biotypes and the basis of virulence remains unknown, but the latter is hypothesized to involve secreted effector proteins. Between 167,249 and 217,750 single nucleotide polymorphisms (SNPs) were predicted from whole genome re-sequencing of A. glycines avirulent biotype 1 (B1) and virulent B2, B3 and B4 colony-derived iso-female lines when compared to the draft B1 genome assembly, Ag_bt1_v6.0. Differences in nucleotide diversity ...


Machine Learning Applications For Drug Repurposing, Hansaim Lim 2020 The Graduate Center, City University of New York

Machine Learning Applications For Drug Repurposing, Hansaim Lim

Dissertations, Theses, and Capstone Projects

The cost of bringing a drug to market is astounding and the failure rate is intimidating. Drug discovery has been of limited success under the conventional reductionist model of one-drug-one-gene-one-disease paradigm, where a single disease-associated gene is identified and a molecular binder to the specific target is subsequently designed. Under the simplistic paradigm of drug discovery, a drug molecule is assumed to interact only with the intended on-target. However, small molecular drugs often interact with multiple targets, and those off-target interactions are not considered under the conventional paradigm. As a result, drug-induced side effects and adverse reactions are often neglected ...


Investigating Photosynthetic Stability: Relation Between Thylakoid Lipid Content And The Stability Of The Cytochrome B6f Complex, Marina Mehling 2020 Purdue University

Investigating Photosynthetic Stability: Relation Between Thylakoid Lipid Content And The Stability Of The Cytochrome B6f Complex, Marina Mehling

The Journal of Purdue Undergraduate Research

The cytochrome b6f complex is an enzyme found in plants, cyanobacteria, and green algae that catalyzes the transport of electrons in the rate-limiting step of oxygenic photosynthesis. This dimeric complex has an extensive lipid architecture that is primarily composed of five distinct lipid classes: monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG), phosphatidyl glycerol (PG), monoglucosyl diacylglycerol (GlcDG), and sulfoquinovosyl diacylglycerol (SQDG). While these lipid classes have been identified, their precise role in the function of the cytochrome complex are only beginning to be understood. Mechanisms describing the relation between thylakoid lipid content on the stability of the b6 ...


Calcineurin, Trevor P. Creamer 2020 University of Kentucky

Calcineurin, Trevor P. Creamer

Molecular and Cellular Biochemistry Faculty Publications

The serine/threonine phosphatase calcineurin acts as a crucial connection between calcium signaling the phosphorylation states of numerous important substrates. These substrates include, but are not limited to, transcription factors, receptors and channels, proteins associated with mitochondria, and proteins associated with microtubules. Calcineurin is activated by increases in intracellular calcium concentrations, a process that requires the calcium sensing protein calmodulin binding to an intrinsically disordered regulatory domain in the phosphatase. Despite having been studied for around four decades, the activation of calcineurin is not fully understood. This review largely focuses on what is known about the activation process and highlights ...


The Role Of The Leucine-Rich (Leur) Domain Of Rho Guanine Nucleotide Exchange Factor (Rgnef) In The Regulation Of Amyotrophic Lateral Sclerosis (Als) Associated Protein Tar Dna-Binding Protein Of 43 Kda (Tdp-43), Hind Amzil 2020 The University of Western Ontario

The Role Of The Leucine-Rich (Leur) Domain Of Rho Guanine Nucleotide Exchange Factor (Rgnef) In The Regulation Of Amyotrophic Lateral Sclerosis (Als) Associated Protein Tar Dna-Binding Protein Of 43 Kda (Tdp-43), Hind Amzil

Electronic Thesis and Dissertation Repository

The presence of neuronal cytoplasmic inclusions (NCIs) composed of RNA-binding proteins (RBPs) and neurofilaments is considered to be ALS’s neuropathological hallmark. RGNEF has been previously shown to interact with TDP-43 and to have a regulatory effect on the expression levels of NEFL mRNA and NFL protein in vitro. Here, I examined the mechanism of the RGNEF N-terminus, leucine-rich domain (LeuR) domain’s interaction with TDP-43. I observed that the minimal domain required is 110 amino acids (LeuR110), that the Ankyrin domain adjacent to LeuR110 does not participate, and that LeuR110 forms of a high molecular weight complex with TDP-43 ...


Genome-Wide Mapping Of Human Dna Replication By Optical Replication Mapping Supports A Stochastic Model Of Eukaryotic Replication Timing, Weitao Wang, Kyle Klein, Karel Proesmans, Northwestern University, Claire Marchal, Xiaopeng Zhu, Tyler M. Borrman, Alex Hastie, Zhiping Weng, Simon Fraser University, Paris Sciences et Lettres University, Florida State University, Nicholas R. Rhind 2020 Paris Sciences et Lettres University

Genome-Wide Mapping Of Human Dna Replication By Optical Replication Mapping Supports A Stochastic Model Of Eukaryotic Replication Timing, Weitao Wang, Kyle Klein, Karel Proesmans, Northwestern University, Claire Marchal, Xiaopeng Zhu, Tyler M. Borrman, Alex Hastie, Zhiping Weng, Simon Fraser University, Paris Sciences Et Lettres University, Florida State University, Nicholas R. Rhind

University of Massachusetts Medical School Faculty Publications

DNA replication is regulated by the location and timing of replication initiation. Therefore, much effort has been invested in identifying and analyzing the sites of human replication initiation. However, the heterogeneous nature of eukaryotic replication kinetics and the low efficiency of individual initiation site utilization in metazoans has made mapping the location and timing of replication initiation in human cells difficult. A potential solution to the problem of human replication mapping is single-molecule analysis. However, current approaches do not provide the throughput required for genome-wide experiments. To address this challenge, we have developed Optical Replication Mapping (ORM), a high-throughput single-molecule ...


A Cross-Reactive Human Iga Monoclonal Antibody Blocks Sars-Cov-2 Spike-Ace2 Interaction, Ejemel Monir, Qi Li, Shurong Hou, Zachary Schiller, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Chandrashekar Ganesa, Lisa Cavacini, Mark S. Klempner, Celia A. Schiffer, Yan Wang 2020 University of Massachusetts Medical School

A Cross-Reactive Human Iga Monoclonal Antibody Blocks Sars-Cov-2 Spike-Ace2 Interaction, Ejemel Monir, Qi Li, Shurong Hou, Zachary Schiller, Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty, Chandrashekar Ganesa, Lisa Cavacini, Mark S. Klempner, Celia A. Schiffer, Yan Wang

COVID-19 Publications by UMMS Authors

COVID-19 caused by SARS-CoV-2 has become a global pandemic requiring the development of interventions for the prevention or treatment to curtail mortality and morbidity. No vaccine to boost mucosal immunity, or as a therapeutic, has yet been developed to SARS-CoV-2. In this study, we discover and characterize a cross-reactive human IgA monoclonal antibody, MAb362. MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2. When converted to secretory IgA, MAb326 also neutralizes authentic SARS-CoV-2 ...


Broad Host Range Of Sars-Cov-2 Predicted By Comparative And Structural Analysis Of Ace2 In Vertebrates, Joana Damas, Elinor K. Karlsson, Harris A. Lewin 2020 University of California, Davis

Broad Host Range Of Sars-Cov-2 Predicted By Comparative And Structural Analysis Of Ace2 In Vertebrates, Joana Damas, Elinor K. Karlsson, Harris A. Lewin

COVID-19 Publications by UMMS Authors

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike ...


Sampling Performance Of Multiple Independent Molecular Dynamics Simulations Of An Rna Aptamer, Shuting Yan, Jason M. Peck, Muslum Ilgu, Marit Nilsen-Hamilton, Monica H. Lamm 2020 Iowa State University

Sampling Performance Of Multiple Independent Molecular Dynamics Simulations Of An Rna Aptamer, Shuting Yan, Jason M. Peck, Muslum Ilgu, Marit Nilsen-Hamilton, Monica H. Lamm

Chemical and Biological Engineering Publications

Using multiple independent simulations instead of one long simulation has been shown to improve the sampling performance attained with the molecular dynamics (MD) simulation method. However, it is generally not known how long each independent simulation should be, how many independent simulations should be used, or to what extent either of these factors affects the overall sampling performance achieved for a given system. The goal of the present study was to assess the sampling performance of multiple independent MD simulations, where each independent simulation begins from a different initial molecular conformation. For this purpose, we used an RNA aptamer that ...


Uprmt Scales Mitochondrial Network Expansion With Protein Synthesis Via Mitochondrial Import, Tomer Shpilka, Yunguang Du, Qiyuan Yang, Andrew Melber, Nandhitha Uma Naresh, Joshua Lavelle, Pengpeng Liu, Hilla Weidberg, Rui Li, Jun Yu, Lihua Julie Zhu, Lara Strittmatter, Cole M. Haynes 2020 University of Massachusetts Medical School

Uprmt Scales Mitochondrial Network Expansion With Protein Synthesis Via Mitochondrial Import, Tomer Shpilka, Yunguang Du, Qiyuan Yang, Andrew Melber, Nandhitha Uma Naresh, Joshua Lavelle, Pengpeng Liu, Hilla Weidberg, Rui Li, Jun Yu, Lihua Julie Zhu, Lara Strittmatter, Cole M. Haynes

University of Massachusetts Medical School Faculty Publications

As organisms develop, individual cells generate mitochondria to fulfill physiologic requirements. However, it remains unknown how mitochondrial network expansion is scaled to cell growth and impacted by environmental cues. The mitochondrial unfolded protein response (UPRmt) is a signaling pathway mediated by the transcription factor ATFS-1 which harbors a mitochondrial targeting sequence (MTS)1. Here, we demonstrate that ATFS-1 mediates an adaptable mitochondrial expansion program that is active throughout normal development. Developmental mitochondrial network expansion required the relatively inefficient MTS2 in ATFS-1, which allowed the transcription factor to be responsive to parameters that impact protein import capacity of the ...


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