Digital Commons Network^™

Alternative Splicing Mediates The Compensatory Upregulation Of Mbnl2 Upon Mbnl1 Loss-Of-Function, Larissa Nitschke, Rong-Chi Hu, Andrew N Miller, Lathan Lucas, Thomas A Cooper

Faculty, Staff and Students Publications

Loss of gene function can be compensated by paralogs with redundant functions. An example of such compensation are the paralogs of the Muscleblind-Like (MBNL) family of RNA-binding proteins that are sequestered and lose their function in Myotonic Dystrophy Type 1 (DM1). Loss of MBNL1 increases the levels of its paralog MBNL2 in tissues where Mbnl2 expression is low, allowing MBNL2 to functionally compensate for MBNL1 loss. Here, we show that loss of MBNL1 increases the inclusion of Mbnl2 exon 6 and exon 9. We find that inclusion of Mbnl2 exon 6 increases the translocation of MBNL2 to the nucleus, while …

Combined Molnupiravir-Nirmatrelvir Treatment Improves The Inhibitory Effect On Sars-Cov-2 In Macaques, Kyle Rosenke, Matt C. Lewis, F Feldmann, Eric Bohrnsen, Benjamin Schwarz, Atsushi Okumura, W. Forrest Bohler, Julie Callison, Carl Shaia, Catharine M. Bosio, Jamie Lovaglio, Greg Saturday, Michael A. Jarvis, H Feldmann

School of Biomedical Sciences

The periodic emergence of SARS-CoV-2 variants of concern (VOCs) with unpredictable clinical severity and ability to escape preexisting immunity emphasizes the continued need for antiviral interventions. Two small molecule inhibitors, molnupiravir (MK-4482), a nucleoside analog, and nirmatrelvir (PF-07321332), a 3C-like protease inhibitor, have recently been approved as monotherapy for use in high-risk patients with COVID-19. As preclinical data are only available for rodent and ferret models, here we assessed the efficacy of MK-4482 and PF-07321332 alone and in combination against infection with the SARS-CoV-2 Delta VOC in the rhesus macaque COVID-19 model. Macaques were infected with the SARS-CoV-2 Delta variant …

Whole Genomes Of Deep-Sea Sponge-Associated Bacteria Exhibit High Novel Natural Product Potential, Poppy J. Hesketh-Best, Grant G. January, Matthew J. Koch, Philip J. Warburton, Kerry L. Howell, Mathew Upton

School of Biomedical Sciences

Abstract Global antimicrobial resistance is a health crisis that can change the face of modern medicine. Exploring diverse natural habitats for bacterially-derived novel antimicrobial compounds has historically been a successful strategy. The deep-sea presents an exciting opportunity for the cultivation of taxonomically novel organisms and exploring potentially chemically novel spaces. In this study, the draft genomes of 12 bacteria previously isolated from the deep-sea sponges Phenomena carpenteri and Hertwigia sp. are investigated for the diversity of specialized secondary metabolites. In addition, early data support the production of antibacterial inhibitory substances produced from a number of these strains, including activity against …

Skeletal Dysplasia-Causing Trpv4 Mutations Suppress The Hypertrophic Differentiation Of Human Ipsc-Derived Chondrocytes, Amanda R Dicks, Grigory I Maksaev, Zainab Harissa, Alireza Savadipour, Ruhang Tang, Nancy Steward, Wolfgang Liedtke, Colin G Nichols, Chia-Lung Wu, Farshid Guilak

2020-Current year OA Pubs

Mutations in the TRPV4 ion channel can lead to a range of skeletal dysplasias. However, the mechanisms by which TRPV4 mutations lead to distinct disease severity remain unknown. Here, we use CRISPR-Cas9-edited human-induced pluripotent stem cells (hiPSCs) harboring either the mild V620I or lethal T89I mutations to elucidate the differential effects on channel function and chondrogenic differentiation. We found that hiPSC-derived chondrocytes with the V620I mutation exhibited increased basal currents through TRPV4. However, both mutations showed more rapid calcium signaling with a reduced overall magnitude in response to TRPV4 agonist GSK1016790A compared to wildtype (WT). There were no differences in …

Setd2 Regulates Chromatin Accessibility And Transcription To Suppress Lung Tumorigenesis, Yuchen Xie, Merve Sahin, Toru Wakamatsu, Akane Inoue-Yamauchi, Wanming Zhao, Song Han, Amrita M. Nargund, Shaoyuan Yang, Yang Lyu, James J. Hsieh, Christina S. Leslie, Emily H. Cheng

2020-Current year OA Pubs

SETD2, a H3K36 trimethyltransferase, is the most frequently mutated epigenetic modifier in lung adenocarcinoma, with a mutation frequency of approximately 9%. However, how SETD2 loss of function promotes tumorigenesis remains unclear. Using conditional Setd2-KO mice, we demonstrated that Setd2 deficiency accelerated the initiation of KrasG12D-driven lung tumorigenesis, increased tumor burden, and significantly reduced mouse survival. An integrated chromatin accessibility and transcriptome analysis revealed a potentially novel tumor suppressor model of SETD2 in which SETD2 loss activates intronic enhancers to drive oncogenic transcriptional output, including the KRAS transcriptional signature and PRC2-repressed targets, through regulation of chromatin accessibility and histone chaperone recruitment. …

A Scanning-To-Incision Switch In Tfiih-Xpg Induced By Dna Damage Licenses Nucleotide Excision Repair, Amer Bralić, Muhammad Tehseen, Mohamed A Sobhy, Chi-Lin Tsai, Lubna Alhudhali, Gang Yi, Jina Yu, Chunli Yan, Ivaylo Ivanov, Susan E Tsutakawa, John A Tainer, Samir M Hamdan

Faculty, Staff and Student Publications

Nucleotide excision repair (NER) is critical for removing bulky DNA base lesions and avoiding diseases. NER couples lesion recognition by XPC to strand separation by XPB and XPD ATPases, followed by lesion excision by XPF and XPG nucleases. Here, we describe key regulatory mechanisms and roles of XPG for and beyond its cleavage activity. Strikingly, by combing single-molecule imaging and bulk cleavage assays, we found that XPG binding to the 7-subunit TFIIH core (coreTFIIH) stimulates coreTFIIH-dependent double-strand (ds)DNA unwinding 10-fold, and XPG-dependent DNA cleavage by up to 700-fold. Simultaneous monitoring of rates for coreTFIIH single-stranded (ss)DNA translocation and dsDNA unwinding …

Hyperprogression Of Cutaneous T Cell Lymphoma After Anti-Pd-1 Treatment, Yumei Gao, Simeng Hu, Ruoyan Li, Shanzhao Jin, Fengjie Liu, Xiangjun Liu, Yingyi Li, Yicen Yan, Weiping Liu, Jifang Gong, Shuxia Yang, Ping Tu, Lin Shen, Fan Bai, Yang Wang

Faculty, Staff and Student Publications

BACKGROUND

Immune checkpoint blockade is an emerging treatment for T cell non-Hodgkin’s lymphoma (T-NHL), but some patients with T-NHL have experienced hyperprogression with undetermined mechanisms upon anti–PD-1 therapy.

METHODS

Single-cell RNA-Seq, whole-genome sequencing, whole-exome sequencing, and functional assays were performed on primary malignant T cells from a patient with advanced cutaneous T cell lymphoma who experienced hyperprogression upon anti–PD-1 treatment.

RESULTS

The patient was enrolled in a clinical trial of anti–PD-1 therapy and experienced disease hyperprogression. Single-cell RNA-Seq revealed that PD-1 blockade elicited a remarkable activation and proliferation of the CD4+ malignant T cells, which showed functional PD-1 expression and …

Investigating The Molecular Mechanisms Of Spore Killing By Neurospora’S Meiotic Drive Elements, Nicholas Rhoades

Theses and Dissertations

Meiosis is a fundamental and highly conserved biological program that is required for sexual reproduction in eukaryotes. During meiosis, duplicated chromosomes synapse with their homologous partner and undergo a physical exchange of genetic material through recombination. The meiotic products resulting from this program contain novel combinations of alleles that are inherited by individuals in the succeeding generation. The random assortment of alleles during meiotic recombination allows for the chance that any such allelic combination may provide an increase (or decrease) in fitness for an individual. Alleles, or combinations of alleles, that are beneficial to the organism may be retained within …

Uncovering The Complex Genetic Architecture Of Human Plasma Lipidome Using Machine Learning Methods, Miikael Lehtimäki, Binisha H Mishra, Coral Del-Val, Leo-Pekka Lyytikäinen, Mika Kähönen, C Robert Cloninger, Olli T Raitakari, Reijo Laaksonen, Igor Zwir, Terho Lehtimäki, Pashupati P Mishra

2020-Current year OA Pubs

Genetic architecture of plasma lipidome provides insights into regulation of lipid metabolism and related diseases. We applied an unsupervised machine learning method, PGMRA, to discover phenotype-genotype many-to-many relations between genotype and plasma lipidome (phenotype) in order to identify the genetic architecture of plasma lipidome profiled from 1,426 Finnish individuals aged 30-45 years. PGMRA involves biclustering genotype and lipidome data independently followed by their inter-domain integration based on hypergeometric tests of the number of shared individuals. Pathway enrichment analysis was performed on the SNP sets to identify their associated biological processes. We identified 93 statistically significant (hypergeometric p-value < 0.01) lipidome-genotype relations. Genotype biclusters in these 93 relations contained 5977 SNPs across 3164 genes. Twenty nine of the 93 relations contained genotype biclusters with more than 50% unique SNPs and participants, thus representing most distinct subgroups. We identified 30 significantly enriched biological processes among the SNPs involved in 21 of these 29 most distinct genotype-lipidome subgroups through which the identified genetic variants can influence and regulate plasma lipid related metabolism and profiles. This study identified 29 distinct genotype-lipidome subgroups in the studied Finnish population that may have distinct disease trajectories and therefore could be useful in precision medicine research.

Uncovering The Complex Genetic Architecture Of Human Plasma Lipidome Using Machine Learning Methods, Miikael Lehtimäki, Binisha H. Mishra, Coral Del-Val, Leo-Pekka Lyytikäinen, Mika Kähönen, C. Robert Cloninger, Olli T. Raitakari, Reijo Laaksonen, Igor Zwir, Terho Lehtimäki, Pashupati P. Mishra

School of Medicine Publications

Genetic architecture of plasma lipidome provides insights into regulation of lipid metabolism and related diseases. We applied an unsupervised machine learning method, PGMRA, to discover phenotype-genotype many-to-many relations between genotype and plasma lipidome (phenotype) in order to identify the genetic architecture of plasma lipidome profiled from 1,426 Finnish individuals aged 30–45 years. PGMRA involves biclustering genotype and lipidome data independently followed by their inter-domain integration based on hypergeometric tests of the number of shared individuals. Pathway enrichment analysis was performed on the SNP sets to identify their associated biological processes. We identified 93 statistically significant (hypergeometric p-value < 0.01) lipidome-genotype relations. Genotype biclusters in these 93 relations contained 5977 SNPs across 3164 genes. Twenty nine of the 93 relations contained genotype biclusters with more than 50% unique SNPs and participants, thus representing most distinct subgroups. We identified 30 significantly enriched biological processes among the SNPs involved in 21 of these 29 most distinct genotype-lipidome subgroups through which the identified genetic variants can influence and regulate plasma lipid related metabolism and profiles. This study identified 29 distinct genotype-lipidome subgroups in the studied Finnish population that may have distinct disease trajectories and therefore could be useful in precision medicine research.

Tfeb-Mediated Lysosomal Exocytosis Alleviates High-Fat Diet-Induced Lipotoxicity In The Kidney, Jun Nakamura, Takeshi Yamamoto, Yoshitsugu Takabatake, Tomoko Namba-Hamano, Satoshi Minami, Atsushi Takahashi, Jun Matsuda, Shinsuke Sakai, Hiroaki Yonishi, Shihomi Maeda, Sho Matsui, Isao Matsui, Takayuki Hamano, Masatomo Takahashi, Maiko Goto, Yoshihiro Izumi, Takeshi Bamba, Miwa Sasai, Masahiro Yamamoto, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Shuhei Nakamura, Tamotsu Yoshimori, Andrea Ballabio, Yoshitaka Isaka

Duncan NRI Faculty and Staff Publications

Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in obesity-related kidney disease, in both humans and experimental animal models. However, the regulatory factors involved in countering renal lipotoxicity are largely unknown. Here, we found that palmitic acid strongly promoted dephosphorylation and nuclear translocation of transcription factor EB (TFEB) by inhibiting the mechanistic target of rapamycin kinase complex 1 pathway in a Rag GTPase-dependent manner, though these effects gradually diminished after extended treatment. We then investigated the role of TFEB in the pathogenesis of obesity-related kidney …

The Objective Penal Protection Of The Terrestrial Environment In Light Of The Provisions Of The Kuwaiti Environmental Protection Law, Its Amendments And Implementing Regulations, Bader Ahmed Al-Rajhi Dr.

UAEU Law Journal

terrestrial environment and the statement of what environmental pollution is, the terrestrial environment means soil, which is the earth, that important element of the environment, it is where human settle, and has his residence and shelter, it is the source of his food, just as it is the settle of animals and their source of food.

However, this terrestrial environment has been exposed to environmental pollution, namely all human and natural activities that contribute to the presence of any pollutants or agents in the environment in quantities or characteristics for a period of time that may lead directly or indirectly …

Investigating Respiratory Simplification Caused By Prenatal Rage Upregulation, Paul Reynolds

Annual Research Symposium

No abstract provided.

Potential Role For Rage In The Development Of Secondhand Smoke-Induced Chronic Sinusitis, Paul Reynolds

Annual Research Symposium

No abstract provided.

Rage Inhibition Reduces Timp And Decreases Cell Invasion In Cigarette Smoke Extract (Cse) Treated Oral Squamous Carcinoma Cells, Paul Reynolds

Annual Research Symposium

No abstract provided.

Inflammatory Cytokine Elaboration Following Secondhand Smoke Exposure Is Mediated In Part By Rage Signaling, Paul Reynolds

Annual Research Symposium

No abstract provided.

Rage Availability Lessens The Degree Of Dysfunctional Mitochondrial Bioenergetics Following Chronic Secondhand Smoke Exposure, Paul Reynolds

Annual Research Symposium

No abstract provided.

Gestational Dependent Responses To Second Hand Smoke (Shs) In Mouse Pregnancies, Paul Reynolds

Annual Research Symposium

No abstract provided.

Teen Appeal, Memphis, 06.05, 2003

Documents

Issue 6.5 of the "Teen Appeal" published by the University of Memphis Journalism Department and Commercial Appeal, Memphis, Tennessee, on January 28, 2003.

Hay Mechanization And New Equipment, Noah Pendry

Kentucky Alfalfa and Stored Forage Conference

Review of the latest developments in hay mechanization equipment.

Potential Yield Of Cocksfoot (Dactylis Glomerata) Monocultures In Response To Irrigation And Nitrogen, A. Mills, D. J. Moot, R. L. Lucas, P. D. Jamieson, B. A. Mckenzie

IGC Proceedings (1977-2023)

Cocksfoot is a widely sown grass in temperate pastures. However, while potential yield of cocksfoot can exceed 28 t DM/ha per year, it is often restricted by water, temperature and nitrogen (N). Of these, Peri et al. (2002) showed that N was severely limiting in all seasons. The aim of this study was to confirm the potential yield of cocksfoot and quantify the extent of yield reductions due to environmental constraints.

Diverse Forage Mixtures Effect On Herbage Yield, Sward Composition, And Dairy Cattle Performance, M. A. Sanderson, K. Soder, N. Brzezinski, S. Goslee, H. Skinner, M. Wachendorf, F. Taube, L. Muller

IGC Proceedings (1977-2023)

Managing complex mixtures of plants to take advantage of spatial and temporal variability in land and climate may be one ecological approach to increase productivity of pastures. We tested the hypothesis that complex mixtures of forage species would yield more herbage and reduce weed competition compared with a simple grass-legume mixture in grazed pastures.

Hygienic Value And Mycotoxins Level Of Grass Silage In Bales For Horses, A. Potkański, J. Grajewski, K. Raczkowska-Werwińska, B. Miklaszewska, A. Gubała, M. Selwet, M. Szumacher-Strabel

IGC Proceedings (1977-2023)

Mycotoxins are secondary metabolites of moulds which have adverse effects on humans, animals, and crops and result in illnesses and economic losses. The toxins may occur in storage under conditions favourable for the growth of the toxin-producing fungus or fungi. The highest forage concentration of toxins was found in horizontal storage methods such as bunker silos and feed piles, which were left open to oxygen. In any fermentation storage system, temperature and the presence of moisture is sufficient for toxin production. In a plastic covered storage system, oxygen penetration is slowed but not eliminated. The longer silage is stored, the …

Participatory Approach To Common Use Grazing Management In Dry Area Developing Countries, J. Tiedeman, A. Larbi, F. Ghassali, N. Battikha

IGC Proceedings (1977-2023)

Key points

1. Range restoration technology is available but useless when not followed by management.

2. Institutional mechanisms for grazing management are needed for communal range.

3. Community participatory approaches help pastoralists better manage rangeland grazing.

Campus Assembly Minutes 02/21/2023 & 02/23/2023, Campus Assembly

Campus Assembly

No abstract provided.

Population Dynamics And Harvest Management Of Eastern Mallards, Anthony J. Roberts, Jeffrey A. Hostetler, Joshua C. Stiller, Patrick K. Devers, William A. Link

United States Fish and Wildlife Service: Publications

Managing sustainable harvest of wildlife populations requires regular collection of demographic data and robust estimates of demographic parameters. Estimates can then be used to develop a harvest strategy to guide decision‐making. Mallards (Anas platyrhynchos) are an important species in the Atlantic Flyway for many users and they exhibited exponential growth in the eastern United States between the 1970s and 1990s. Since then, estimates of mallard abundance have declined 16%, prompting the Atlantic Flyway Council and United States Fish and Wildlife Service to implement more restrictive hunting regulations and develop a new harvest strategy predicated on an updated population …

Population Dynamics And Harvest Management Of Eastern Mallards, Anthony J. Roberts, Jeffrey A. Hostetler, Joshua C. Stiller, Patrick K. Devers, William A. Link

United States Fish and Wildlife Service: Publications

Managing sustainable harvest of wildlife populations requires regular collection of demographic data and robust estimates of demographic parameters. Estimates can then be used to develop a harvest strategy to guide decision‐making. Mallards (Anas platyrhynchos) are an important species in the Atlantic Flyway for many users and they exhibited exponential growth in the eastern United States between the 1970s and 1990s. Since then, estimates of mallard abundance have declined 16%, prompting the Atlantic Flyway Council and United States Fish and Wildlife Service to implement more restrictive hunting regulations and develop a new harvest strategy predicated on an updated population …

Spartan Daily, February 21, 2023, San Jose State University, School Of Journalism And Mass Communications

Spartan Daily, 2023

Volume 160, Issue 11

Space Environment Effects On The Electron Yields Of Ldef Thermal Control Coatings, Trace Taylor, Matthew Robertson, Heather Allen, Jr Dennison, Michael Guy, Emily Willis

Journal Articles

Space-environment-induced degradation of white thermal control coatings from the Long Duration Exposure Facility (LDEF) was investigated. Much of the exterior of the LDEF was painted with a white thermal control coating, Aeroglaze A276; and most of the interior was coated with a black thermal control coating, Aeroglaze Z306. Outgassing from these coatings and other LDEF materials interacted with the white surface when exposed to sunlight after volatile materials condensed on the LDEF surfaces. Surface morphology was characterized by optical and scanning electron microscopies. Fourier-transform infrared spectroscopy and energy-dispersive x-ray spectroscopy were used to identify the chemical compounds and elements present …

Impacting African American Student Achievement In The Middle School Stem Classroom By Teaching Mathematics Through Arts Integration And Design Thinking, Robert Lippert, Tjuannia R. Seals

Dissertations

Middle school is a transitional period in which many students experience content-specific teachers, travel between classrooms, and explore extracurricular activity options for the first time. Historically, African American middle school students have not fared well in Science, Technology, Engineering, and Mathematics (STEM) on standardized assessments, performing significantly below their Caucasian counterparts in mathematics and science. From the beginning of their academic careers, a lack of access to quality teachers, excessive use of direct instruction strategies, and a lack of resources in their school communities, contribute to their overall apathy towards the subject matter and factor into their underperformance. As a …