Digital Commons Network^™

Delineation Of New Mechanisms Of Dna Damage Responses And Repair, Yanqiu Li

Theses & Dissertations

Upon DNA damage,cells promptly activate the cellular DNA damage response (DDR), a surveillance mechanism that leads to DNA repair, cell cycle arrest, and apoptosis. DDR deficiencies cause genomic instability, and are tightly associated with cancer predisposition, immunodeficiency, neurological diseases, and aging. On the other hand, radiation and many chemotherapeutics eliminate cancer cells by inducing DNA damage. Therefore, understanding the DDR and its involvement in cancer is a crucial step toward improving anti-cancer therapeutics. The overarching goal of this project is to delineate how cells respond to, and repair, DNA damage, thus to develop new strategies to overcome cancer resistance.Microtubule associated …

Cultural Practices, Knowledge, And Beliefs Of Newborn Care And Health-Seeking In Rural Zambia, Julie M. Buser

Dissertations

Decreasing newborn morbidity and mortality remains a serious global health challenge. For this reason, interventions like maternity waiting homes (MWHs) and the Saving Mothers, Giving Life (SMGL) initiative may improve maternal-newborn newborn health and delivery outcomes. The overarching goal of this dissertation was to explore and describe the cultural practices, knowledge, and beliefs of essential newborn care and health-seeking in the context of MWHs and the SMGL initiative in rural Zambia. Guided by the Ecological Systems Theory, this goal was met through three studies with the following aims: (1) Describe knowledge and beliefs of newborn care and illness from the …

Research Snapshot: Protecting Smelt, Tim Briggs

UNH Today Archive

No abstract provided.

Dynamics Of Protein-Dna Interactions Characterized By Atomic Force Microscopy, Yaqing Wang

Theses & Dissertations

This thesis describes the nanoscale studies of protein-DNA interactions with different complexities using atomic force microscopy (AFM). One of the systems deals with DNA replication rescue. To maintain the genetic integrity, replication machinery needs to minimize the error rate, repair the damages, and restart the stalled replication caused by the attacks from the environment and inside the cell. The stalled replication rescue is orchestrated by a series of proteins, for example, the DNA helicases PriA and RecG and the ssDNA binding protein (SSB).

We demonstrated that SSB stimulates the restart process in two aspects. First, SSB facilitates the binding of …

Utilizing Proteolysis-Targeting Chimeras To Target The Transcriptional Cyclin-Dependent Kinases 9 And 12, Hannah King

Theses & Dissertations

Cyclin-dependent kinases (CDKs) are a family of serine-threonine kinases involved in various cellular functions, such as regulating the cell cycle and gene transcription. CDK9, a transcriptional CDK, regulates highly expressed enhancer-associated oncogenic transcription factors, including the oncogene Myc. CDK9 is responsible for the transcription and stabilization of Myc; consequently, it was a validated target for pancreatic cancer treatment.

As such, we developed a panel of aminopyrazole based proteolysis targeting chimera where we identified PROTAC 2 as a selective degrader of CDK9 (DC₅₀ = 158 ± 6 nM). PROTAC 2 was capable of cereblon mediated proteasomal degradation of CDK9 while …

Fgfr4 Glycosylation And Processing In Cholangiocarcinoma Promote Cancer Signaling, Andrew J. Phillips

Theses & Dissertations

Cholangiocarcinoma is a cancer of cholangiocytes, or epithelial cells lining the biliary tract. It is associated with a poor prognosis and additional therapeutic treatments are needed to help patients affected by this disease. Fibroblast growth factor receptor 4 (FGFR4) is receptor tyrosine kinase that is involved in various physiologic and pathologic processes. TCGA analysis of thirty different tumor types showed the highest FGFR4 mRNA levels in cholangiocarcinoma. At the protein level, FGFR4 was observed in the majority of cholangiocarcinomas screened and, higher levels were associated with a poorer prognosis. FGFR4 is an N-linked glycosylated receptor tyrosine kinase that we show …

Molecular Pathogenesis Of A Novel Subgroup Of Peripheral T-Cell Lymphomas, Jiayu Yu

Theses & Dissertations

Peripheral T-cell Lymphoma (PTCL) consists of numerous distinct disease entities. With the current diagnostic criteria over a third of the cases cannot be further classified and are called "not otherwise specified" (PTCL-NOS). Using gene expression profiling (GEP) of tumors, we identified two novels PTCL-NOS molecular subgroups either characterized by high expression of GATA3 (33%), which is associated with Th2 cell differentiation, or high expression of TBX21 (49%) which regulates Th1 cell maturation. Therefore, stratifying patients for diagnosis and identifying the underlying genetic basis to improve clinical therapy becomes critical to prognosis.

First, we performed DNA copy number analysis by using …

Superoxide And Pulmonary Hypertension, Tammy Wichman

Theses & Dissertations

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disease, which is progressive and fatal despite advances in therapy. Animal models have shown that oxidative stress may be pathogenic in PAH. We hypothesize that oxidative stress, as measured by increased levels of a specific reactive oxygen species, superoxide (O₂^•-), mayplay a role in PAH in humans. Using a novel application of electron paramagnetic resonance (EPR) spectroscopy, we initially evaluated whether levels of O₂^•- from whole blood collected from the pulmonary artery collected during right heart catheterization (RHC) would correlate with O₂^•- levels in peripheral …

Mechanism Of The Superoxide Dismutase Mimic Mntnbuoe-2-Pyp5+ And Its Nanoformulation On Blood Pressure Regulation, Sarah L. Schlichte

Theses & Dissertations

It is well-established that reactive oxygen species (ROS), particularly superoxide (O₂^·-), produced in the vasculature and brain contribute to the pathogenesis of hypertension. We, and others, have previously reported that in vivo scavenging of O₂^·- via overexpression of superoxide dismutase (SOD) protein or SOD mimics decreases blood pressure in hypertensive animals. While few SOD mimics have transitioned to clinical trials, MnTnBuOE-2-PyP⁵⁺ (BuOE), a manganese porphyrin SOD mimic, is currently in clinical trials for normal tissue protection in cancer patients exposed to radiation therapy. Furthermore, our collaborators developed a nanoformulated BuOE (nanoBuOE) in which BuOE …

Development Of Macromolecular Prodrug Of Sinomenine For The Treatment Of Rheumatoid Arthritis, Roshni Mukundan

Theses & Dissertations

Inflammation is a natural response of the body to infections or any potential threat to the body. But, sometimes the immune system attacks its own body causing persistent inflammation leading to inflammatory diseases. One of the common chronic inflammatory diseases is rheumatoid arthritis (RA) which causes inflammation of the synovial membrane. The current treatments for RA are effective in controlling the symptoms but they come with severe side effects and economic burden. Further, the management of pain is still a problem with these drugs. Sinomenine is a natural alkaloid obtained from the Chinese medicinal plant Sinomenium acutum that has been …

Fibroblast Growth Factor Receptor 4 And R4-Icd Increased Proliferation, Cell Survival And Metastasis In Cholangiocarcinoma, Yamnah Hafeji

Theses & Dissertations

Fibroblast growth factor receptor 4 (FGFR4) is over-expressed in many cancers, including cholangiocarcinoma (CCA). FGFR4 is activated by fibroblast growth factor ligand 19 (FGF19) and plays a critical role in CCA progression. An intracellular cleaved product of FGFR4, referred as R4-ICD (FGFR4 intracellular domain) is also overexpressed in CCA. However, the specific role of R4-ICD in CCA is unknown. In this study, we hypothesized that FGFR4 and R4-ICD play a role in cell proliferation, cell survival and metastasis in CCA. To test this, FGFR4 and R4-ICD were cloned into a cholangiocarcinoma cell line (HuCCT-1) that does not endogenously express FGFR4. …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Pancreatic Cancer: Novel Therapy, Research Tools, And Educational Outreach, Ayrianne J. Crawford

Theses & Dissertations

Since the 1980’s, legislatures have invested immense effort into strategies to capitalize on the United States’ global lead in basic and translational research. This is largely motivated by the discrepancy the US faces in converting its world leading research discoveries and innovations into commercial products, relative to other countries. This truncated productivity leaves the US out of substantial GDP growth and reduces public access to new innovations. Proponents of government and university owned patents reason that enhanced public private partnerships narrow the gap between the technology transfer of basic research discoveries and accessible commercial products.

With these concepts of technology …

Stress Response Of Stone Martens And Red Foxes In Two Different Live Traps, Friederike Gethöffer, Wolfgang Baumgärtner, Marion Schmicke, Nicole Kemper, Charlotte Lempp, Nicole Jungwirth, Joseph G. Schnitzler, Ursula Siebert

Human–Wildlife Interactions

Trapping of terrestrial animals is an important tool for harvest, pest control and research worldwide. To catch animals alive, animal welfare has to be ensured, which is reflected in different agreements on trading and trapping of animals between sovereign nations (Council Regulation [EEC] No 3254/91). The red fox (Vulpes vulpes) and stone marten (Martes foina) represent important predatory animals. Their influence on protected species as well as their increasing appearance in urban areas demand responsible handling. In our study, we evaluated 2 trap systems used for trapping red foxes and stone martens in accordance with criteria stipulated in the Agreement …

Mid-South Glbt News Press, Volume 1, Number 3

Other publications

Patricia Pair, President/ Publisher. Anita Moyt, General Manager/ Managing Editor. Jim Easter, columnist. John Crossen, cartoonist. Rex Wockner, columnist.

Special thanks to Rhodes College and the Paul Barret Jr. Library for providing initial scanning of this collection.

The Lavender Pages

Other publications

The Official Memphis Pride Inc. Guide. The theme, 2001: Our Pride Odyssey.

Special thanks to Rhodes College and the Paul Barret Jr. Library for providing initial scanning of this collection.

Cardio-Renal Syndrome Type 2: The Role Of Cardiac Spinal Afferent Reflex, Zhiqiu Xia

Theses & Dissertations

Cardio-renal syndrome type 2 (CRS type 2) is defined as a chronic cardiovascular disease, usually chronic heart failure (CHF), resulting in chronic kidney disease. We hypothesized that the cardiac spinal afferent reflex (CSAR), a cardiogenic sympatho-excitatory reflex mediated by cardiac spinal afferents plays a critical role in the development of CRS type 2. We examined the effects of acute activation and chronic ablation of the CSAR on renal blood flow (RBF), renal vascular resistance (RVR), central venous pressure (CVP), renal function and renal histology in sham and myocardial infarction (MI)-induced CHF rats. RNA sequencing analysis (RNA-Seq) and validation by real-time …

Implementing Ecosystem-Based Management, Brian Gray, Jennifer Harder, Karrigan Bork

Duke Environmental Law & Policy Forum

Most freshwater ecosystems in the United States are in a state of collapse. Existing management efforts take a piecemeal approach, addressing individual stressors, managing the systems for individual benefits, and protecting individual species. These disjointed efforts are doomed to fail. Both the legal literature and the scientific literature are rich with articles extolling the advantages of ecosystem-based management; that is, simultaneous management of water, land, and organisms to achieve a desired ecosystem condition benefiting both native biodiversity and human well-being. This approach has succeeded in other aquatic systems, particularly marine ecosystems, but the ecosystem-based management approach has struggled for adoption …

Note: Modernizing Conservationism: Renewable Energy's Species-Preserving Effect And The Endangered Species Act, Chase Hamilton

Duke Environmental Law & Policy Forum

Environmental policymakers face a dilemma, for the construction and operation of renewable energy facilities mitigates ecologically destructive climate change in the long term but often adversely affects species in the short term. This paper provides empirical, legal, and normative resources for analyzing what I call "species clash." In most cases, renewable energy is much more helpful than harmful when it comes to preventing species extinctions, but the Endangered Species Act paradoxically poses a barrier to such species-preserving projects. Framing the benefits of renewable energy in terms of species conservation may not only help secure speedy and cost-efficient compliance with the …

Daily Energy Expenditure Through The Human Life Course, Herman Pontzer, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G Camps, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marjije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Teresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia Loechl, Amy H Luke, Jennifer Rood, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

Total daily energy expenditure (“total expenditure”, MJ/d) reflects daily energy needs and is a critical variable in human health and physiology, yet it is unclear how daily expenditure changes over the life course. Here, we analyze a large, globally diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 yr. We show that total expenditure is strongly related to fat free mass in a power-law manner and identify four distinct metabolic life stages. Fat free mass-adjusted daily expenditure accelerates rapidly in neonates (0-1yr) to ~46% above adult values at …

Machine Learning As A Tool For Wildlife Management And Research: The Case Of Wild Pig-Related Content On Twitter, Lauren M. Jaebker, Hailey E. Mclean, Stephanie A. Shwiff, Keith M. Carlisle, Tara L. Teel, Alan D. Bright, Aaron M. Anderson

Human–Wildlife Interactions

Wild pigs (Sus scrofa) are a non-native, invasive species that cause considerable damage and transmit a variety of diseases to livestock, people, and wildlife. We explored Twitter, the most popular social media micro-blogging platform, to demonstrate how social media data can be leveraged to investigate social identity and sentiment toward wild pigs. In doing so, we employed a sophisticated machine learning approach to investigate: (1) the overall sentiment associated with the dataset, (2) online identities via user profile descriptions, and (3) the extent to which sentiment varied by online identity. Results indicated that the largest groups of online …

Navigating Methodological Concerns At The Data Collection Stage: Lessons From A Qualitative Indian-Irish Adoption Study, Sahana Mitra Dr., Valerie O'Brien Dr.

The Qualitative Report

This paper was written to describe the experiences of the researchers in designing cross-cultural research on the culturally sensitive topic of adoptive parenthood, a field in which there is a dearth of literature. Taking the experience and examples from an Indian-Irish study on domestic adoptive parenthood, the paper details the steps as to how the researchers used their own relationship with adoption, and the different cultural contexts to which they belonged, as a starting point in designing and implementing this research. The discussion utilizes a conceptual framework involving insider-outsider positioning, reflexivity and five philosophical assumptions (ontology, epistemology, methodology, axiology, and …

The Staphylococcus Aureus Lrgab Operon Encodes A Holin-Like Protein Involved In Pyruvate Transport, Jennifer L. Endres

Theses & Dissertations

The Staphylococcus aureus cidABC and lrgAB operons encode a well-conserved family of proteins involved in programmed cell death (PCD) during biofilm development. Based on the structural similarities that CidA and LrgA share with bacteriophage holins, we have hypothesized that these proteins function by forming pores within the cytoplasmic membrane. To test this, we utilized a “lysis cassette” system that demonstrated the abilities of the cidA and lrgA genes to support bacteriophage endolysin-induced cell lysis. In addition, the CidA and LrgA proteins were shown to localize to the surface of membrane vesicles and cause leakage of small molecules, providing direct evidence …

Affirming Strength-Based Practices In Disability And Inclusion: A Shared Autoethnographic Study Of The Experiences Of A Teacher, Alina Kewanian, Edwin Creely, Jane Southcott

The Qualitative Report

In this autoethnographic article we focus on the issues of “disability” and “inclusive education” and the challenges of being positive and affirming in this area of research and practice. As a teacher, I (Alina) continue to encounter regularly the dominant deficit view of “disability,” in spite of the extensive body of literature that advocates for the rights of people with disabilities as well as the benefits of inclusive education best built on strength-based thinking. The autoethnographic methodology allowed me to explore my experiences as an educator and reflect on specific events, presented through four vignettes that capture how my beliefs …

Respons Fisiologis Dan Agronomis Bibit Kopi Pada Kerapatan Naungan Yang Berbeda, Mochamad Arief Soleh, Tommy Ario Sirait, Mira Ariyanti, Santi Rosniawaty

Jurnal Kultivasi

Tanaman kopi seringkali dibudidayakan di areal hutan, dimana terdapat tanaman tahunan seperti pepohonan yang terus tumbuh sehingga menurunkan intensitas cahaya yang jatuh ke tanaman kopi. Hal ini menjadi masalah bagi pertumbuhan dan perkembangan tanaman kopi yang dinaungi pohon tersebut. Penelitian ini bertujuan untuk menguji fisiologis dan agronomis dua kultivar kopi dalam intensitas naungan yang berbeda untuk mendapatkan informasi kultivar kopi yang terbaik. Percobaan dilaksanakan dari bulan Maret hingga Juni 2020 di Kebun Percobaan Ciparanje, Fakultas Pertanian, Universitas Padjadjaran, Jatinangor, Sumedang, Jawa Barat. Percobaan menggunakan Rancangan Petak Terbagi (Split plot) dengan dua faktor dan diulang sebanyak tiga kali. Taraf dari main …

Antibacterial Activity Of Red Yeast Rice Extract Against Propionibacterium Acnes Atcc 11827 And Methicilin-Resistant Staphylococcus Aureus Atcc Baa-1683, Tiana Milanda, Ade Zuhrotun, Ulya Nabila, Vesara A. Gathera, Arif S.W Kusuma

Pharmacology and Clinical Pharmacy Research

Propionibacterium acnes ATCC 11827 and Methicillin-Resistant Staphylococcus aureus ATCC BAA-1683 are bacteria that cause skin infections, namely acne vulgaris and skin and soft tissue infection/SSTI. The increase in the number of resistant bacterial strains, such as MRSA, requires the search for alternative antibiotics, including using natural ingredients. Red yeast rice is a product of rice fermentation by Monascus purpureus, which is known to have antibacterial, antifungal, antitumor, antioxidant, anti-inflammatory, anti-cholesterol and immunomodulator. This study aims to determine the antibacterial activity of several red yeast rice extracts against these bacteria that cause skin infections. The research was carried out through the …

An Optimized O9-1/Hydrogel System For Studying Mechanical Signals In Neural Crest Cells, Tram P Le, Xiaolei Zhao, Shannon Erhardt, Jianhua Gu, Huie Wang, Tina O Findley, Jun Wang

Faculty, Staff and Student Publications

Neural crest cells (NCCs) are vertebrate embryonic multipotent cells that can migrate and differentiate into a wide array of cell types that give rise to various organs and tissues. Tissue stiffness produces mechanical force, a physical cue that plays a critical role in NCC differentiation; however, the mechanism remains unclear. The method described here provides detailed information for the optimized generation of polyacrylamide hydrogels of varying stiffness, the accurate measurement of such stiffness, and the evaluation of the impact of mechanical signals in O9-1 cells, a NCC line that mimics in vivo NCCs.

Hydrogel stiffness was measured using atomic force …

Examination Of Methylation Status And Occupancy Of Dna Methylation Modifying Proteins On Regulatory Regions Of The Dax-1 Gene, Caroline P. Riedstra

Master's Theses

Epigenetic modifications influence gene expression and thereby play a pivotal role in development and disease. Misregulation and mutations in the DAX-1 gene, or Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1, have been implicated in Adrenal Hypoplasia Congenita (AHC) and Dosage Sensitive Sex Reversal (DSS). The orphan nuclear hormone receptor DAX-1 is expressed predominantly in tissues such as the testes, ovaries, breast, adrenal cortex, and lung. Critically, DAX-1 may serve as an indicator of aberrant growth in these tissues. Here we hypothesize that DAX-1 is epigenetically regulated, specifically in cancer cells, thereby reducing its …

Assessment And Deployment Of Genetic Tools For North American River Otters (Lontra Canadensis), Kelsey Lawton

Theses

North American River Otters (Lontra canadensis) once thrived in large numbers in most wetlands of North America. However, due to human pressures such as trapping, habitat loss and pollution, these carnivorous mammals have decreased in numbers significantly in the last 100+ years, becoming extirpated in many traditionally inhabited areas. The use of genetic data from molecular techniques (PCR, DNA sequencing) can guide the identification and management of populations used for relocations to better maintain genetic diversity in both wild and captive otter populations and help inform the Association of Zoos and Aquariums (AZA) breeding programs. Management organizations are concerned with …

Oil Bodies Sizes Variation Analyses Of Rapeseed In Two Locations As A Novel Trait For Genetic Engineering, Rita Andini, Muhammad Ikhsan Sulaiman, Murna Muzaifa, Yulia Dewi Fazlina, Christian Moellers

Jurnal Kultivasi

Tanaman raps (Brassica napus L.) adalah tanaman penghasil minyak utama di negara dengan iklim dingin seperti di Jerman. Minyak raps (Brassica napus L.) digunakan untuk bahan pangan, biodiesel, dan sebagai pakan ternak. Kandungan minyaknya bisa mencapai 33 – 48%. Tanaman minyak seperti kedelai (Glycine max), raps (Brassica napus L.), bunga matahari (Helianthus annuus) pada umumnya menyimpan kandungan minyaknya dalam suatu organela penyimpanan dikenal dengan ‘oil body’ yang mempunyai diameter antara 0,6 hingga 2,0 µm, tergantung dari spesies tanaman. Peningkatan kandungan minyak merupakan salah satu target pemuliaan di banyak tanaman minyak, termasuk di raps. Tulisan ini menceritakan tentang isolasi ‘oil body’ …