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Biowill - Characterising Willow Bark Bio-Actives For Skin Therapies, Arnold Marisa 2022 Department of Biological and Pharmaceutical Sciences, Munster Technological University, Kerry, Ireland

Biowill - Characterising Willow Bark Bio-Actives For Skin Therapies, Arnold Marisa

ORBioM (Open Research BioSciences Meeting)

Willow bark is considered as a disposable by-product when processing willow for biomass. Willow (Salix) is known to contain high value bioactive compounds which include salicin and its derivatives, and other phytochemicals of interest such as polyphenols and flavonoids. The plant is historically known as the primary source of salicylates to which the well-known drug aspirin is derived from. The work forms part of the Interreg project BioWILL, which is focused on integrated “Zero Waste” biorefinery utilising all fractions of willow feedstock for the production of biochemicals and renewable energy. This project aims to investigate the crude and processed bark ...


Determining The Genomic Localization And Binding Partners Of Zinc Finger Protein 410, Mariko Locke 2022 Liberty University

Determining The Genomic Localization And Binding Partners Of Zinc Finger Protein 410, Mariko Locke

Senior Honors Theses

The results of a folate deficiency study affecting cognition in mice suggested the altered genes may be controlled by a transcription factor known as Zinc Finger Protein 410 (Zfp410). Due to a lack of literature on Zfp410’s interacting proteins and DNA-binding location, our study aims to further elucidate the role Zfp410 plays in affecting cognition. A custom antibody was used to determine the Zfp410 isoforms present in mouse and rat brains. Moreover, the antibody was used to determine the binding partners of Zfp410 in the brain and locate specific genomic regions/sequences with which it associates in vivo. These ...


Discovering The Role Of Repeat Sequences In Regulation Of The Phaz Gene In Streptomyces Sp. Sfb5a, Harrison Senter, Stephen Baron 2022 Bridgewater College

Discovering The Role Of Repeat Sequences In Regulation Of The Phaz Gene In Streptomyces Sp. Sfb5a, Harrison Senter, Stephen Baron

Honors Projects

Streptomyces sp. SFB5A is an actinomycete (filamentous bacterium) that degrades PHB using an extracellular PHB depolymerase. PHB depolymerase synthesis is induced by growth on PHB and repressed by glucose (or other preferred carbon sources)2, which suggests that there is transcriptional regulation of its corresponding gene, phaZ. Binding sites are suspected to be the repeat sequences found in the phaZ gene. There are 3 different sets of primers that can be made in order to emphasize specific functional repeats while disrupting the functionality of others. The goal of the project is to transform Streptomyces sp. 5A with constructs containing a ...


Factorbook: An Updated Catalog Of Transcription Factor Motifs And Candidate Regulatory Motif Sites, Henry E. Pratt, Gregory Andrews, Nishigandha Phalke, Michael J. Purcaro, Arjan van der Velde, Jill E. Moore, Zhiping Weng 2022 University of Massachusetts Medical School

Factorbook: An Updated Catalog Of Transcription Factor Motifs And Candidate Regulatory Motif Sites, Henry E. Pratt, Gregory Andrews, Nishigandha Phalke, Michael J. Purcaro, Arjan Van Der Velde, Jill E. Moore, Zhiping Weng

UMass Chan Medical School Faculty Publications

The human genome contains approximately 2000 transcriptional regulatory proteins, including approximately 1600 DNA-binding transcription factors (TFs) recognizing characteristic sequence motifs to exert regulatory effects on gene expression. The binding specificities of these factors have been profiled both in vitro, using techniques such as HT-SELEX, and in vivo, using techniques including ChIP-seq. We previously developed Factorbook, a TF-centric database of annotations, motifs, and integrative analyses based on ChIP-seq data from Phase II of the ENCODE Project. Here we present an update to Factorbook which significantly expands the breadth of cell type and TF coverage. The update includes an expanded motif catalog ...


Modified Ysk12-Mend-Sirna In Dendritic Cells For Cancer Immunotherapy, Syed S. Alam 2022 Virginia Commonwealth University

Modified Ysk12-Mend-Sirna In Dendritic Cells For Cancer Immunotherapy, Syed S. Alam

Undergraduate Research Posters

Tumors may induce tolerogenesis through signaling dendritic cells to produce tolerogenic molecules, such as indoleamine 2, 3-dioxygenase 1 (IDO1). Tumor-associated immunosuppression is associated with higher mortality in patients. Small interfering RNA (siRNA) has been shown to silence specific target genes in the target cell. The siRNA associated with these genes could support a gene knockdown of these immunosuppressors and reduce mortality. Delivery of these therapeutic nucleic acids is difficult in vivo because siRNA is easily broken down inside the cell and the bloodstream through present nucleases. Use of liposome polymers has been reviewed extensively in literature. YSK12-C4, a lipid nanoparticle ...


Comparative Route Of Administration Studies Using Therapeutic Sirnas Show Widespread Gene Modulation In Dorset Sheep, Chantal M. Ferguson, Bruno M. D. C. Godinho, Julia F. Alterman, Andrew H. Coles, Matthew R. Hassler, Dimas Echeverria, James W. Gilbert, Emily G. Knox, Jillian Caiazzi, Reka A. Haraszti, Robert M. King, Toloo Taghian, Ajit S. Puri, Richard P. Moser, Matthew J. Gounis, Neil Aronin, Heather L. Gray-Edwards, Anastasia Khvorova 2021 University of Massachusetts Medical School

Comparative Route Of Administration Studies Using Therapeutic Sirnas Show Widespread Gene Modulation In Dorset Sheep, Chantal M. Ferguson, Bruno M. D. C. Godinho, Julia F. Alterman, Andrew H. Coles, Matthew R. Hassler, Dimas Echeverria, James W. Gilbert, Emily G. Knox, Jillian Caiazzi, Reka A. Haraszti, Robert M. King, Toloo Taghian, Ajit S. Puri, Richard P. Moser, Matthew J. Gounis, Neil Aronin, Heather L. Gray-Edwards, Anastasia Khvorova

Radiology Publications

siRNAs comprise a class of drugs that can be programmed to silence any target gene. Chemical engineering efforts resulted in development of divalent siRNAs (di-siRNAs), which support robust and long-term efficacy in rodent and nonhuman primate brains upon direct cerebrospinal fluid (CSF) administration. Oligonucleotide distribution in the CNS is nonuniform, limiting clinical applications. The contribution of CSF infusion placement and dosing regimen on relative accumulation, specifically in the context of large animals, is not well characterized. To our knowledge, we report the first systemic, comparative study investigating the effects of 3 routes of administration - intrastriatal (i.s.), i.c.v ...


Saf-A Mutants Disrupt Chromatin Structure Through Dominant Negative Effects On Rnas Associated With Chromatin, Heather J. Kolpa, Kevin M. Creamer, Lisa L. Hall, Jeanne B. Lawrence 2021 University of Massachusetts Medical School

Saf-A Mutants Disrupt Chromatin Structure Through Dominant Negative Effects On Rnas Associated With Chromatin, Heather J. Kolpa, Kevin M. Creamer, Lisa L. Hall, Jeanne B. Lawrence

UMass Chan Medical School Faculty Publications

Here we provide a brief review of relevant background before presenting results of our investigation into the interplay between scaffold attachment factor A (SAF-A), chromatin-associated RNAs, and DNA condensation. SAF-A, also termed heterogenous nuclear protein U (hnRNP U), is a ubiquitous nuclear scaffold protein that was implicated in XIST RNA localization to the inactive X-chromosome (Xi) but also reported to maintain open DNA packaging in euchromatin. Here we use several means to perturb SAF-A and examine potential impacts on the broad association of RNAs on euchromatin, and on chromatin compaction. SAF-A has an N-terminal DNA binding domain and C-terminal RNA ...


Wormcat 2.0 Defines Characteristics And Conservation Of Poorly Annotated Genes In Caenorhabditis Elegans [Preprint], Daniel P. Higgins, Caroline M. Weisman, Dominique Lui, Frank A. D’Agostino, Amy K. Walker 2021 UMass Chan Medical School

Wormcat 2.0 Defines Characteristics And Conservation Of Poorly Annotated Genes In Caenorhabditis Elegans [Preprint], Daniel P. Higgins, Caroline M. Weisman, Dominique Lui, Frank A. D’Agostino, Amy K. Walker

UMass Chan Medical School Faculty Publications

Genome-wide measurement of mRNA or protein levels provides broad data sets for biological discovery. However, subsequent computational methods are essential for uncovering the functional implications of the data as well as intuitively visualizing the findings. Current computational tools are biased toward well-described pathways, limiting their utility for novel discovery. Recently, we developed an annotation and category enrichment tool for Caenorhabditis elegans genomic data, WormCat, that provides an intuitive visualization output. Unlike GO, which excludes genes with no annotation information, WormCat 2.0 retains these genes as a special UNASSIGNED category. Here, we show that the UNASSIGNED gene category enrichment exhibits ...


An Rnai Therapeutic Targeting Hepatic Dgat2 In A Genetically Obese Mouse Model Of Nonalcoholic Steatohepatitis, Batuhan Yenilmez, Nicole Wetoska, Mark Kelly, Dimas Echeverria, Kyounghee Min, Lawrence M. Lifshitz, Julia F. Alterman, Matthew R. Hassler, Samuel R. Hildebrand, Chloe DiMarzio, Nicholas McHugh, Lorenc Vangjeli, Jacquelyn Sousa, Michael A. Brehm, Anastasia Khvorova, Michael P. Czech 2021 University of Massachusetts Medical School

An Rnai Therapeutic Targeting Hepatic Dgat2 In A Genetically Obese Mouse Model Of Nonalcoholic Steatohepatitis, Batuhan Yenilmez, Nicole Wetoska, Mark Kelly, Dimas Echeverria, Kyounghee Min, Lawrence M. Lifshitz, Julia F. Alterman, Matthew R. Hassler, Samuel R. Hildebrand, Chloe Dimarzio, Nicholas Mchugh, Lorenc Vangjeli, Jacquelyn Sousa, Michael A. Brehm, Anastasia Khvorova, Michael P. Czech

UMass Center for Clinical and Translational Science Supported Publications

Nonalcoholic steatohepatitis (NASH) is a severe liver disorder characterized by triglyceride accumulation, severe inflammation, and fibrosis. With the recent increase in prevalence, NASH is now the leading cause of liver transplant, with no approved therapeutics available. Although the exact molecular mechanism of NASH progression is not well understood, a widely held hypothesis is that fat accumulation is the primary driver of the disease. Therefore, diacylglycerol O-acyltransferase 2 (DGAT2), a key enzyme in triglyceride synthesis, has been explored as a NASH target. RNAi-based therapeutics is revolutionizing the treatment of liver diseases, with recent chemical advances supporting long-term gene silencing with single ...


Synergistic Anticancer Response Of Curcumin And Piperine Loaded Lignin-G-P (Nipam-Co-Dmaema) Gold Nanogels Against Glioblastoma Multiforme, Xinyi Zhao, Bilal Javad, Daxing Cui, James Curtin, Furong Tian 2021 Technological University Dublin

Synergistic Anticancer Response Of Curcumin And Piperine Loaded Lignin-G-P (Nipam-Co-Dmaema) Gold Nanogels Against Glioblastoma Multiforme, Xinyi Zhao, Bilal Javad, Daxing Cui, James Curtin, Furong Tian

Articles

Glioblastoma multiforme (GBM) is the most aggressive and commonly diag- 11 nosed brain cancer and presents a strong resistance to routine chemotherapeutic drugs. 12 The present study involves the synthesis of Lignin-g- p (NIPAM-co-DMAEMA) gold 13 nanogel, loaded with curcumin and piperine to treat GBM. The application has three 14 functions: (1) overcome the limitations of biodistribution, (2) enhance the toxicity of an- 15 ticancer drugs against GBM, (3) identify the uptake pathway. Atom transfer radical 16 polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with 17 the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and ...


Dcp2 C-Terminal Cis-Binding Elements Control Selective Targeting Of The Decapping Enzyme By Forming Distinct Decapping Complexes [Preprint], Feng He, Chan Wu, Allan S. Jacobson 2021 University of Massachusetts Medical School

Dcp2 C-Terminal Cis-Binding Elements Control Selective Targeting Of The Decapping Enzyme By Forming Distinct Decapping Complexes [Preprint], Feng He, Chan Wu, Allan S. Jacobson

UMass Chan Medical School Faculty Publications

A single Dcp1-Dcp2 decapping enzyme targets diverse classes of yeast mRNAs for decapping-dependent 5’ to 3’ decay, but the molecular mechanisms controlling selective mRNA targeting by the enzyme remain elusive. Through extensive genetic analyses we uncover cis-regulatory elements in the Dcp2 C-terminal domain that control selective targeting of the decapping enzyme by forming distinct decapping complexes. Two Upf1-binding motifs target the decapping enzyme to NMD substrates, and a single Edc3-binding motif targets both Edc3 and Dhh1 substrates. Pat1-binding leucine-rich motifs target Edc3 and Dhh1 substrates under selective conditions. Although it functions as a unique targeting component of specific complexes ...


Factors Regulating The Activity Of Line1 Retrotransposons, Maria Sergeevna Protasova, Tatiana Vladimirovna Andreeva, Evgeny I. Rogaev 2021 Russian Academy of Sciences

Factors Regulating The Activity Of Line1 Retrotransposons, Maria Sergeevna Protasova, Tatiana Vladimirovna Andreeva, Evgeny I. Rogaev

Open Access Publications by UMass Chan Authors

LINE-1 (L1) is a class of autonomous mobile genetic elements that form somatic mosaicisms in various tissues of the organism. The activity of L1 retrotransposons is strictly controlled by many factors in somatic and germ cells at all stages of ontogenesis. Alteration of L1 activity was noted in a number of diseases: in neuropsychiatric and autoimmune diseases, as well as in various forms of cancer. Altered activity of L1 retrotransposons for some pathologies is associated with epigenetic changes and defects in the genes involved in their repression. This review discusses the molecular genetic mechanisms of the retrotransposition and regulation of ...


Cues From Mrna Splicing Prevent Default Argonaute Silencing In C. Elegans, Yekaterina V. Makeyeva, Masaki Shirayama, Craig C. Mello 2021 University of Massachusetts Medical School

Cues From Mrna Splicing Prevent Default Argonaute Silencing In C. Elegans, Yekaterina V. Makeyeva, Masaki Shirayama, Craig C. Mello

Open Access Publications by UMass Chan Authors

In animals, Argonaute small-RNA pathways scan germline transcripts to silence self-replicating genetic elements. However, little is known about how endogenous gene expression is recognized and licensed. Here, we show that the presence of introns and, by inference, the process of mRNA splicing prevents default Argonaute-mediated silencing in the C. elegans germline. The silencing of intronless genes is initiated independently of the piRNA pathway but nevertheless engages multiple components of the downstream amplification and maintenance mechanisms that mediate transgenerational silencing, including both nuclear and cytoplasmic members of the worm-specific Argonaute gene family (WAGOs). Small RNAs amplified from intronless mRNAs can trans-silence ...


Stability And Conformation Of The Dimeric Hiv-1 Genomic Rna 5'Utr, Robert J. Blakemore, Cleo Burnett, Canessa Swanson, Siarhei Kharytonchyk, Alice Telesnitsky, James B. Munro 2021 Tufts University

Stability And Conformation Of The Dimeric Hiv-1 Genomic Rna 5'Utr, Robert J. Blakemore, Cleo Burnett, Canessa Swanson, Siarhei Kharytonchyk, Alice Telesnitsky, James B. Munro

Open Access Publications by UMass Chan Authors

During HIV-1 assembly, the viral Gag polyprotein specifically selects the dimeric RNA genome for packaging into new virions. The 5' untranslated region (5'UTR) of the dimeric genome may adopt a conformation that is optimal for recognition by Gag. Further conformational rearrangement of the 5'UTR, promoted by the nucleocapsid (NC) domain of Gag, is predicted during virus maturation. Two 5'UTR dimer conformations, the kissing dimer (KD) and the extended dimer (ED), have been identified in vitro, which differ in the extent of intermolecular basepairing. Whether 5'UTRs from different HIV-1 strains with distinct sequences have access to the ...


Do Fragile X Syndrome And Other Intellectual Disorders Converge At Aberrant Pre-Mrna Splicing, Sneha Shah, Joel D. Richter 2021 University of Massachusetts Medical School

Do Fragile X Syndrome And Other Intellectual Disorders Converge At Aberrant Pre-Mrna Splicing, Sneha Shah, Joel D. Richter

Open Access Publications by UMass Chan Authors

Fragile X Syndrome is a neuro-developmental disorder caused by the silencing of the FMR1 gene, resulting in the loss of its protein product, FMRP. FMRP binds mRNA and represses general translation in the brain. Transcriptome analysis of the Fmr1-deficient mouse hippocampus reveals widespread dysregulation of alternative splicing of pre-mRNAs. Many of these aberrant splicing changes coincide with those found in post-mortem brain tissue from individuals with autism spectrum disorders (ASDs) as well as in mouse models of intellectual disability such as PTEN hamartoma syndrome (PHTS) and Rett Syndrome (RTT). These splicing changes could result from chromatin modifications (e.g., in ...


C. Elegans Lin-28 Controls Temporal Cell Fate Progression By Regulating Lin-46 Expression Via The 5' Utr Of Lin-46 Mrna, Orkan Ilbay, Charles J. Nelson, Victor R. Ambros 2021 University of Massachusetts Medical School

C. Elegans Lin-28 Controls Temporal Cell Fate Progression By Regulating Lin-46 Expression Via The 5' Utr Of Lin-46 Mrna, Orkan Ilbay, Charles J. Nelson, Victor R. Ambros

Open Access Publications by UMass Chan Authors

Lin28/LIN-28 is a conserved RNA-binding protein that promotes proliferation and pluripotency and can be oncogenic in mammals. Mammalian Lin28 and C. elegans LIN-28 have been shown to inhibit biogenesis of the conserved cellular differentiation-promoting microRNA let-7 by directly binding to unprocessed let-7 transcripts. Lin28/LIN-28 also bind and regulate many mRNAs in diverse cell types. However, the determinants and consequences of LIN-28-mRNA interactions are not well understood. Here, we report that C. elegans LIN-28 represses the expression of LIN-46, a downstream protein in the heterochronic pathway. We find that lin-28 and sequences within the lin-46 5' UTR are required ...


A Budding Yeast Model For Human Disease Mutations In The Exosc2 Cap Subunit Of The Rna Exosome Complex, Maria C. Sterrett, Liz Enyenihi, Sara W. Leung, Laurie Hess, Sarah E. Strassler, Daniela Farchi, Richard S. Lee, Elise S. Withers, Isaac Kremsky, Richard E. Baker, Munira A. Basrai, Ambro van Hoof, Milo B. Fasken, Anita H. Corbett 2021 Emory University

A Budding Yeast Model For Human Disease Mutations In The Exosc2 Cap Subunit Of The Rna Exosome Complex, Maria C. Sterrett, Liz Enyenihi, Sara W. Leung, Laurie Hess, Sarah E. Strassler, Daniela Farchi, Richard S. Lee, Elise S. Withers, Isaac Kremsky, Richard E. Baker, Munira A. Basrai, Ambro Van Hoof, Milo B. Fasken, Anita H. Corbett

Open Access Publications by UMass Chan Authors

RNA exosomopathies, a growing family of diseases, are linked to missense mutations in genes encoding structural subunits of the evolutionarily conserved, 10-subunit exoribonuclease complex, the RNA exosome. This complex consists of a three-subunit cap, a six-subunit, barrel-shaped core, and a catalytic base subunit. While a number of mutations in RNA exosome genes cause pontocerebellar hypoplasia, mutations in the cap subunit gene EXOSC2 cause an apparently distinct clinical presentation that has been defined as a novel syndrome SHRF (short stature, hearing loss, retinitis pigmentosa, and distinctive facies). We generated the first in vivo model of the SHRF pathogenic amino acid substitutions ...


Microinjection For Precision Genome Editing In Caenorhabditis Elegans, Krishna S. Ghanta, Takao Ishidate, Craig C. Mello 2021 University of Massachusetts Medical School

Microinjection For Precision Genome Editing In Caenorhabditis Elegans, Krishna S. Ghanta, Takao Ishidate, Craig C. Mello

Open Access Publications by UMass Chan Authors

In Caenorhabditis elegans, targeted genome editing techniques are now routinely used to generate germline edits. The remarkable ease of C. elegans germline editing is attributed to the syncytial nature of the pachytene ovary which is easily accessed by microinjection. This protocol describes the step-by-step details and troubleshooting tips for the entire CRISPR-Cas genome editing procedure, including gRNA design and microinjection of ribonucleoprotein complexes, followed by screening and genotyping in C. elegans, to help accessing this powerful genetic animal system. For complete details on the use and execution of this protocol, please refer to Ghanta and Mello (2020).


The Endogenous Mex-3 3 Utr Is Required For Germline Repression And Contributes To Optimal Fecundity In C. Elegans, Menna Albarqi, Sean P. Ryder 2021 University of Massachusetts Medical School

The Endogenous Mex-3 3 Utr Is Required For Germline Repression And Contributes To Optimal Fecundity In C. Elegans, Menna Albarqi, Sean P. Ryder

Open Access Publications by UMass Chan Authors

RNA regulation is essential to successful reproduction. Messenger RNAs delivered from parent to progeny govern early embryonic development. RNA-binding proteins (RBPs) are the key effectors of this process, regulating the translation and stability of parental transcripts to control cell fate specification events prior to zygotic gene activation. The KH-domain RBP MEX-3 is conserved from nematode to human. It was first discovered in Caenorhabditis elegans, where it is essential for anterior cell fate and embryo viability. Here, we show that loss of the endogenous mex-3 3 UTR disrupts its germline expression pattern. An allelic series of 3 UTR deletion variants identify ...


Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky 2021 Bronx Community College

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This ...


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