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Emergence Of Transferable Daptomycin Resistance In Gram-Positive Bacteria, Tessa Marciniak, Lukas Kirchner, Silver A. Wolf, Birgit Walther, Thorsten Bischler, Justin Nyasinga, R Gunturu, Torsten Semmler, Tom Gräfenhan, Andrew Whitelaw Apr 2025

Emergence Of Transferable Daptomycin Resistance In Gram-Positive Bacteria, Tessa Marciniak, Lukas Kirchner, Silver A. Wolf, Birgit Walther, Thorsten Bischler, Justin Nyasinga, R Gunturu, Torsten Semmler, Tom Gräfenhan, Andrew Whitelaw

Pathology, East Africa

Daptomycin (DAP) is a last-resort antibiotic to treat infections by multiresistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. DAP resistance and clinical treatment failure has been associated with adaptive chromosomal mutations, but so far not with transmissible resistance traits. Here we report for the first time an acquired DAP-R determinant (named drc) that we detected in a livestock-associated Mammaliicoccus sciuri isolate. drc consists of a two-gene operon (drcAB) that is controlled by an adjacent two-component system (drcRS). The DrcAB proteins, which mediate DAP inactivation, are similar to BceAB-like antimicrobial peptide transporters of Gram-positives, but are distinct from …


Title: An Analysis Of Hmbs Variants Associated With Acute Intermittent Porphyria, Elaine Vanterpool, Jason Kahari Apr 2025

Title: An Analysis Of Hmbs Variants Associated With Acute Intermittent Porphyria, Elaine Vanterpool, Jason Kahari

Student Posters

HMBS, also known as hydroxymethylbilane synthase, is a gene that is responsible for providing instructions for making the enzyme named hydroxymethylbilane synthase. This enzyme is involved in the creation of a molecule called heme. Heme plays an important part in all of the body’s vital organs. It is important to all organs however, it is most prevalent in the blood, bone marrow, and liver. Heme is essential in making iron-containing proteins called hemeproteins. To produce heme, an eight-step process must occur that requires 8 different enzymes. “Hydroxymethylbilane synthase is responsible for the third step in this process, which combines four …


Lysyl Hydroxylase 2 Glucosylates Collagen Vi To Drive Lung Cancer Progression, Shike Wang, Houfu Guo, Reo Fukushima, Masahiko Terajima, Min Liu, Guan-Yu Xiao, Lenka Koudelková, Chao Wu, Xin Liu, Jiang Yu, Emma Burris, Jun Xu, Alvise Schiavinato, William K Russell, Mitsuo Yamauchi, Xiaochao Tan, Jonathan M Kurie Apr 2025

Lysyl Hydroxylase 2 Glucosylates Collagen Vi To Drive Lung Cancer Progression, Shike Wang, Houfu Guo, Reo Fukushima, Masahiko Terajima, Min Liu, Guan-Yu Xiao, Lenka Koudelková, Chao Wu, Xin Liu, Jiang Yu, Emma Burris, Jun Xu, Alvise Schiavinato, William K Russell, Mitsuo Yamauchi, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

Lysyl hydroxylase 2 (LH2) is highly expressed in multiple tumor types and accelerates disease progression by hydroxylating lysine residues on fibrillar collagen telopeptides to generate stable collagen cross links in tumor stroma. Here, we show that a galactosylhydroxylysyl glucosyltransferase (GGT) domain on LH2-modified type-VI collagen (Col6) to promote lung adenocarcinoma (LUAD) growth and metastasis. In tumors generated by LUAD cells lacking LH2 GGT domain activity, stroma was less stiff, and stable types of collagen cross links were reduced. Mass spectrometric analysis of total and glycosylated peptides in parental and GGT-inactive tumor samples identified Col6 chain α3 (Col6a3), a component of …


Role Of Peripheral Amyloid-Β Aggregates In Alzheimer's Disease: Mechanistic, Diagnostic, And Therapeutic Implications, Nazaret Gamez, Rodrigo Morales Apr 2025

Role Of Peripheral Amyloid-Β Aggregates In Alzheimer's Disease: Mechanistic, Diagnostic, And Therapeutic Implications, Nazaret Gamez, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.


In Vivo Antibody Labeling Route And Fluorophore Dictate Labeling Efficiency, Sensitivity, And Longevity, Natalie B Hagan, Charles Inaku, Nikesh Kunder, Tayleur White, Thierry Iraguha, Anna Meyer, Kristen E Pauken, Jason M Schenkel Apr 2025

In Vivo Antibody Labeling Route And Fluorophore Dictate Labeling Efficiency, Sensitivity, And Longevity, Natalie B Hagan, Charles Inaku, Nikesh Kunder, Tayleur White, Thierry Iraguha, Anna Meyer, Kristen E Pauken, Jason M Schenkel

Faculty, Staff and Student Publications

Leukocytes migrate through the blood and extravasate into organs to surveil the host for infection or cancer. Recently, we demonstrated that intravenous (IV) anti-CD45.2 antibody labeling allowed for precise tracking of leukocyte migration. However, the narrow labeling window can make this approach challenging for tracking rare migration events. Here, we show that altering antibody administration route and fluorophore can significantly extend the antibody active labeling time. We found that while both IV and intraperitoneal (IP) anti-CD45.2 antibody labeled circulating leukocytes after injection, they had different kinetic properties that impacted labeling time and intensity. Quantification of circulating antibody revealed that while …


Il13rα2-Targeting Antibodies For Immuno-Pet In Solid Malignancies, Leah Gajecki, Irina V Lebedeva, Yu-Rou Liao, Daisy Ambriz, Lukas M Carter, Melina Kumpf, Samantha Lovibond, Justin S Hachey, Maya S Graham, Michael Postow, Jason S Lewis, David P Andrew, Manuel Baca, Heiko Schöder, Steven M Larson, Darren R Veach, Simone Krebs Apr 2025

Il13rα2-Targeting Antibodies For Immuno-Pet In Solid Malignancies, Leah Gajecki, Irina V Lebedeva, Yu-Rou Liao, Daisy Ambriz, Lukas M Carter, Melina Kumpf, Samantha Lovibond, Justin S Hachey, Maya S Graham, Michael Postow, Jason S Lewis, David P Andrew, Manuel Baca, Heiko Schöder, Steven M Larson, Darren R Veach, Simone Krebs

Faculty, Staff and Student Publications

Interleukin-13 receptor α-2 (IL13Rα2) is a cell surface receptor frequently expressed in solid malignancies, such as glioblastoma and melanoma, with limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor delineation. In this study, we report the development of 5 novel IL13Rα2-targeted human monoclonal antibodies (mAbs) KLG-1-5; in subsequent in vitro and in vivo studies after radiolabeling with 89Zr, we evaluate their performance to identify a lead candidate.

Methods: Five novel human anti-IL13Rα2 mAbs KLG-1-5 were developed and in vitro binding properties and target specificity assessed. In vivo 89Zr-immuno-PET using KLG-1-5 was conducted in a …


Age-Associated Proteins Explain The Role Of Medial Temporal Lobe Networks In Alzheimer’S Disease, Adam Turnbull, Yejin Kim, Kai Zhang, Xiaoqian Jiang, Zihuai He, Victor W Henderson, F Vankee Lin Apr 2025

Age-Associated Proteins Explain The Role Of Medial Temporal Lobe Networks In Alzheimer’S Disease, Adam Turnbull, Yejin Kim, Kai Zhang, Xiaoqian Jiang, Zihuai He, Victor W Henderson, F Vankee Lin

Faculty, Staff and Student Publications

The structural connectivity (SC) of the medial temporal lobe and its associated cortical anterior temporal and posterior medial networks (MTL-AT-PM) is linked to pathologies and memory decline in Alzheimer's disease (AD). However, neuroimaging analyses cannot tell us how SC changes occur in AD at the molecular level and do not provide a means of intervening to slow/prevent pathology-related changes in MTL-AT-PM SC. The current study aimed to understand how and where AD-related changes occur within MTL-AT-PM using proteomics. We used a 4-step approach in 101 older adults from a local sample, aiming to understand how proteins and SC in combination …


Defining A 'Cells To Society' Research Framework For Appendiceal Tumours, Andreana N Holowatyj, Michael J Overman, Konstantinos I Votanopoulos, Andrew M Lowy, Patrick Wagner, Mary K Washington, Cathy Eng, Wai Chin Foo, Richard M Goldberg, Mojgan Hosseini, Kamran Idrees, Douglas B Johnson, Ardaman Shergill, Erin Ward, Nicholas C Zachos, Deborah Shelton Apr 2025

Defining A 'Cells To Society' Research Framework For Appendiceal Tumours, Andreana N Holowatyj, Michael J Overman, Konstantinos I Votanopoulos, Andrew M Lowy, Patrick Wagner, Mary K Washington, Cathy Eng, Wai Chin Foo, Richard M Goldberg, Mojgan Hosseini, Kamran Idrees, Douglas B Johnson, Ardaman Shergill, Erin Ward, Nicholas C Zachos, Deborah Shelton

Faculty, Staff and Student Publications

Tumours of the appendix — a vestigial digestive organ attached to the colon — are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity — wherein the potential misclassification of appendiceal tumours as …


Insulin-Like Growth Factor 2 As A Driving Force For Exponential Expansion And Differentiation Of The Neonatal Thymus, Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Anusha Vasudev, Ken S Lau, Qi Liu, Ellen R Richie, Laura P Hale, Nancy R Manley Apr 2025

Insulin-Like Growth Factor 2 As A Driving Force For Exponential Expansion And Differentiation Of The Neonatal Thymus, Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Anusha Vasudev, Ken S Lau, Qi Liu, Ellen R Richie, Laura P Hale, Nancy R Manley

Faculty, Staff and Student Publications

Like all organs, the thymus grows in size and function rapidly during development, but this growth comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated that IGF2 activity promotes a cortical thymic epithelial cell-specific proliferation …


Characterization Of A Time-Resolved, Real-Time Scintillation Dosimetry System For Ultra-High Dose-Rate Radiation Therapy Applications, Alexander Baikalov, Daline Tho, Kevin Liu, Stefan Bartzsch, Sam Beddar, Emil Schüler Apr 2025

Characterization Of A Time-Resolved, Real-Time Scintillation Dosimetry System For Ultra-High Dose-Rate Radiation Therapy Applications, Alexander Baikalov, Daline Tho, Kevin Liu, Stefan Bartzsch, Sam Beddar, Emil Schüler

Faculty, Staff and Student Publications

Purpose: Scintillation dosimetry has promising qualities for ultra-high-dose-rate (UHDR) radiation therapy (RT), but no system has shown compatibility with mean dose rates (DR¯) above 100 Gy/s and doses per pulse (Dp) exceeding 1.5 Gy typical of UHDR (FLASH)-RT. The aim of this study was to characterize a novel scintillation dosimetry system with the potential of accommodating UHDRs.

Methods and materials: We undertook a thorough dosimetric characterization of the system on an UHDR electron beamline. The system's response as a function of dose, DR¯, Dp, and the pulse dose-rate (DRp) was investigated, as was the system's dose sensitivity (signal per unit …


Examining The Mechanism Of Spore Sacs Undergoing Sk-3-Based Spore Killing After Deletion Of Neurospora Crassa Dna Intervals I382 And I400, Makenna Klann Apr 2025

Examining The Mechanism Of Spore Sacs Undergoing Sk-3-Based Spore Killing After Deletion Of Neurospora Crassa Dna Intervals I382 And I400, Makenna Klann

Senior Theses – Biological Sciences

Neurospora crassa is a well-known model organism for studying eukaryotic genetics, particularly non-Mendelian inheritance mechanisms such as meiotic drive. In N. crassa, meiotic drive can be observed in fungal spore killing, where Spore killer-3 (Sk-3) is a selfish genetic element transmitted to offspring through spore killing. Sk-3 is thought to contain two principal components: a killer (poison) gene and a resistance (antidote) gene. While the resistance gene (rsk) has been identified, the killer gene remains unknown. Building on previous research that identified a 1.3 kb DNA interval (i350) essential for Sk-3-based spore killing, I …


Small-Molecule Mitotic Inhibitors As Anticancer Agents: Discovery, Classification, Mechanisms Of Action, And Clinical Trials, Yazmin Salinas, Subhash Chauhan, Debasish Bandyopadhyay Apr 2025

Small-Molecule Mitotic Inhibitors As Anticancer Agents: Discovery, Classification, Mechanisms Of Action, And Clinical Trials, Yazmin Salinas, Subhash Chauhan, Debasish Bandyopadhyay

School of Medicine Publications

Despite decades of research, cancer continues to be a disease of great concern to millions of people around the world. It has been responsible for a total of 609,820 deaths in the U.S. alone in 2023. Over the years, many drugs have been developed to remove or reduce the disease’s impact, all with varying mechanisms of action and side effects. One class of these drugs is small-molecule mitotic inhibitors. These drugs inhibit cancer cell mitosis or self-replication, impeding cell proliferation and eventually leading to cell death. In this paper, small-molecule mitotic inhibitors are discussed and classified through their discovery, underlying …


Warm-Ischemia And Cold Storage Induced Modulation Of Ferroptosis Observed In Human Hearts Donated After Circulatory Death And Brain Death, Shiyi Li, Katherine V Nordick, Abdussalam E Elsenousi, Rishav Bhattacharya, Randall P Kirby, Adel M Hassan, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal Apr 2025

Warm-Ischemia And Cold Storage Induced Modulation Of Ferroptosis Observed In Human Hearts Donated After Circulatory Death And Brain Death, Shiyi Li, Katherine V Nordick, Abdussalam E Elsenousi, Rishav Bhattacharya, Randall P Kirby, Adel M Hassan, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

We investigated ferroptosis, a type of programmed cell death mechanism, in human hearts donated after brain death (DBD) and those donated after circulatory death (DCD), focusing on warm ischemia time (WIT) and cold storage. A total of 24 hearts were procured, with six from the DBD group and 18 from the DCD group. The DCD group was divided into three subgroups, each containing six hearts, based on different WITs of 20, 40, and 60 min. All procured hearts were placed in cold storage for up to 6 h. Left ventricular biopsies were performed at 0, 2, 4, and 6 h. …


Culex Quinquefasciatus Mosquitoes In Abu Dhabi Emirate: Assessing Deltamethrin Insecticide Resistance And Associated Microbial Communities, Amgdsayed Ismat Ali Apr 2025

Culex Quinquefasciatus Mosquitoes In Abu Dhabi Emirate: Assessing Deltamethrin Insecticide Resistance And Associated Microbial Communities, Amgdsayed Ismat Ali

Theses

Culex quinquefasciatus is a major vector of West Nile virus, lymphatic filariasis, and arboviruses, which represent public health risk. Widespread application of pyrethroid insecticides has increased resistance in mosquito populations threatening the effectiveness of control strategies. This study aims to (1) assess deltamethrin resistance in Culex quinquefasciatus populations across the Abu Dhabi Emirate, (2) characterize the microbial communities associated with these mosquitoes.

Mosquitoes from sites around the Abu Dhabi Emirate were collected and genomic DNA extracted for molecular analysis. PCR and allele-specific primers were used to detect knockdown resistance (kdr) mutations in the sodium channel gene, classifying mosquitoes as susceptible …


Know Where You Go: Infestation Dynamics And Potential Distribution Of Two Bed Bug Species (Hemiptera: Cimicidae) In Africa, Dennis M. Mbuta, Bonoukpoè M. Sokame, Fathiya M. Khamis, Komivi S. Akutse Apr 2025

Know Where You Go: Infestation Dynamics And Potential Distribution Of Two Bed Bug Species (Hemiptera: Cimicidae) In Africa, Dennis M. Mbuta, Bonoukpoè M. Sokame, Fathiya M. Khamis, Komivi S. Akutse

All Peer-Reviewed Publications

Bed bugs (Hemiptera: Cimicidae) are blood-feeding insects closely linked with humans and animals, causing discomfort, and posing potential threats as disease vectors. This study focuses on Cimex lectularius (common bed bug) and Cimex hemipterus (tropical bed bug), the two key species identified in Africa. Cimex lectularius infests human habitats, while C. hemipterus, more common in Africa, infests diverse habitats, including bat colonies. In our study, we investigated the infestation dynamics and distribution of bed bugs in Africa, when considering climate, habitat, and host availability using system dynamics and ecological niche modelling techniques. System dynamics modelling analyses in Kenya revealed varied …


The Cellular Trafficking And Targeting Of Angiotensin-Converting-Enzyme-2 (Ace2) And Neutral-Amino-Acid-Transporter (B0at1) Variants: Implications For The Pathogenesis Of Associated Diseases And Therapy, Nesreen Fayyad Alkhofash Apr 2025

The Cellular Trafficking And Targeting Of Angiotensin-Converting-Enzyme-2 (Ace2) And Neutral-Amino-Acid-Transporter (B0at1) Variants: Implications For The Pathogenesis Of Associated Diseases And Therapy, Nesreen Fayyad Alkhofash

Dissertations

Angiotensin-converting enzyme 2 (ACE2) and the neutral amino acid transporter B0AT1, encoded by SLC6A19, are membrane proteins with pivotal roles in human physiology. ACE2 is involved in regulating blood pressure and serves as the cellular entry receptor for SARS-CoV-2, while B0AT1 facilitates amino acid absorption in the intestine. The interplay between ACE2 and B0AT1, particularly their physical interaction and co-expression in the intestine, underscores their relevance in both normal physiology and disease. Dysregulation of these proteins has been implicated in conditions such as hypertension, and Hartnup disease and they have been usurped by SARS-CoV-2 to cause COVID-19. Despite their …


Exploring Date Pomace As A Functional Ingredient In Bread: Nutritional And Functional Properties, Alaa Almoumen Apr 2025

Exploring Date Pomace As A Functional Ingredient In Bread: Nutritional And Functional Properties, Alaa Almoumen

Dissertations

This study investigated the incorporation of desugared date fruit pomace into wheat bread rolls and evaluated its effects on dough handling, bread quality, staling behavior, sensory acceptability, and nutritional composition. The research was conducted in three experimental phases: (i) development and characterization of a high-fiber dietary ingredient (HFDI) from date pomace, including its physicochemical and functional properties; (ii) bread fortification and quality assessment, where wheat flour was partially replaced with 0–20% HFDI to evaluate its effects on dough rheology, bread texture, color, moisture retention, shelf life, and consumer acceptance; and (iii) nutritional and physiological evaluation of the fortified breads, including …


From Microplastic Impact To Biodegradation Solutions: Investigating Microplastic Pollution, Microbial Responses, And Efficacy Of Synthetic Microbial Consortia In Plastic Degradation, Rener Sahot De Jesus Apr 2025

From Microplastic Impact To Biodegradation Solutions: Investigating Microplastic Pollution, Microbial Responses, And Efficacy Of Synthetic Microbial Consortia In Plastic Degradation, Rener Sahot De Jesus

Dissertations

Plastics, including microplastics, pose significant environmental threats due to their widespread presence and harmful ecological effects. This dissertation present three distinct, yet interconnected studies. First, a study on microplastic contamination in urban recreational parks was conducted in Al Ain, United Arab Emirates. Results showed that low-density microplastics were present in 87% of soil samples, with spectroscopic analysis identifying synthetic polymers such as polyethylene and polypropylene. Additionally, these microplastics were found to negatively affect soil pH and moisture levels, emphasizing the need for enhanced monitoring and management strategies. Second, the effects of ground microplastics on Photobacterium leiognathi strains, a marine luminous …


Anthropogenic Influences On Parasitoid Wasps’ Biocontrol Of Invasive Insect Pest Species In Africa, Fathiya M. Khamis, Inusa J. Ajene Apr 2025

Anthropogenic Influences On Parasitoid Wasps’ Biocontrol Of Invasive Insect Pest Species In Africa, Fathiya M. Khamis, Inusa J. Ajene

All Peer-Reviewed Publications

Sustainable agriculture is crucial to ensuring food and nutritional security and improving livelihoods of millions across Africa. However, agricultural production is constrained by native and invasive pests. Indiscriminate insecticide use is often the first line of action to manage these pests, harming human and animal health, and impacting biodiversity. Thus, shifting to more ecologically sustainable alternatives is key to biodiversity conservation and sustainable agriculture. Biological control is a core component of integrated pest management strategies, and natural enemies, like parasitoid wasps, are considered one of the most environmentally sustainable means of managing pests. However, the Anthropocene plays a significant role …


4-Ethylacetophenone From Potato Plants Repels Phthorimaea Operculella And Inhibits Oviposition: A Sustainable Management Strategy, Xinyu Ma, Junjie Yan, Guangyuan Su, Fathiya M. Khamis, Athanase Hategekiman, Yulin Gao Apr 2025

4-Ethylacetophenone From Potato Plants Repels Phthorimaea Operculella And Inhibits Oviposition: A Sustainable Management Strategy, Xinyu Ma, Junjie Yan, Guangyuan Su, Fathiya M. Khamis, Athanase Hategekiman, Yulin Gao

All Peer-Reviewed Publications

The potato tuber moth, Phthorimaea operculella (Zeller), is an important pest of potato crops capable of boring into and consuming the potato tubers. Although chemical insecticides are employed to control P. operculella populations, their efficacy is frequently limited, raising environmental concerns. Host plant volatiles are important allelochemicals that can be exploited for the management of pests. In our previous studies, we identified five volatile organic compounds (3-ethylacetophenone, 4-ethylacetophenone, geranylacetone, ethylbenzene, and 4-hydroxy-4-methyl-2-pentanone) as allelochemicals potentially influencing the oviposition behavior of P. operculella. Using electroantennography (EAG) and behavioral assays, we found that 4-ethylacetophenone significantly repelled P. operculella at all tested concentrations …


Nanosilica Supplementation In Tomato Increases Oviposition On Stems And Caterpillar Mortality In The Tomato Pinworm, Kokou R. Fiaboe, Fathiya M. Khamis, Xavier Cheseto, Abdullahi A. Yusuf, Baldwyn Torto Apr 2025

Nanosilica Supplementation In Tomato Increases Oviposition On Stems And Caterpillar Mortality In The Tomato Pinworm, Kokou R. Fiaboe, Fathiya M. Khamis, Xavier Cheseto, Abdullahi A. Yusuf, Baldwyn Torto

All Peer-Reviewed Publications

Silicon-induced responses play a key role in plant defense against herbivory, though the underlying mechanisms remain underexplored. In this study, we examined how mesoporous silica nanoparticles (MSNs) affect tomato (Solanum lycopersicum) defense against an invasive and highly destructive lepidopteran herbivore, the tomato pinworm (TPW), Phthorimaea absoluta. In tomato plants supplemented with MSN, prior exposure to TPW oviposition shifted subsequent egg-laying from a preference for leaves to an even distribution between stems and leaves. This shift was not observed in nonsilicon-supplemented plants. Prolonged oviposition triggered pigmentation in the basal cells of type I glandular trichomes on the stems of silicon-supplemented plants. …


Meat, The Future: The Role Of Regulators In The Lab-Grown Revolution, Joseph B. Davault, Michael S. Sinha Apr 2025

Meat, The Future: The Role Of Regulators In The Lab-Grown Revolution, Joseph B. Davault, Michael S. Sinha

All Faculty Scholarship

The United States is one of the largest consumers of meat globally. The production of meat contributes substantially to climate change due to the levels of greenhouse gasses emitted and the amount of land, water, feed, and other natural resources required to raise animals used for meat. Traditional meat production is another major source for the emergence of zoonotic diseases and antimicrobial-resistant pathogens. Nevertheless, Americans consume more meat now than at any time in the nation’s history.

Advocates for policy change aimed at addressing the risks associated with meat production have typically focused on reducing meat consumption, alternatives to meat, …


Development Of A Noninvasive Genotyping-In-Thousands (Gtseq) Panel For Long-Term Conservation Of Western Great Lakes Gray Wolves (Canis Lupus), Samuel D. Hervey, Bridgett M. Vonholdt, Mark C. Romanski, Tyler J. Wheeldon, Brent R. Patterson, Kristin Brzeski Apr 2025

Development Of A Noninvasive Genotyping-In-Thousands (Gtseq) Panel For Long-Term Conservation Of Western Great Lakes Gray Wolves (Canis Lupus), Samuel D. Hervey, Bridgett M. Vonholdt, Mark C. Romanski, Tyler J. Wheeldon, Brent R. Patterson, Kristin Brzeski

Michigan Tech Publications

The application of noninvasive genetic methods toward the field of conservation has increased our understanding of many wildlife populations that are difficult to sample, allowing for better management. In molecular ecology, the use of noninvasive sampling became widely feasible with the advent of microsatellites, a highly polymorphic, short-length marker that could be genotyped from low-quality DNA sources. Despite decades of use, many microsatellite panels continue to suffer from high genotyping error rates, allelic dropout, and limited reproducibility across laboratories. To address these issues, single nucleotide polymorphisms (SNPs) offer advantages such as lower genotyping error rates, avoidance of allelic dropout due …


Il-12-Producing Cytokine Factories Induce Precursor Exhausted T Cells And Elimination Of Primary And Metastatic Tumors, Amanda Nash, Jonathon Debonis, Danna Murungi, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh Apr 2025

Il-12-Producing Cytokine Factories Induce Precursor Exhausted T Cells And Elimination Of Primary And Metastatic Tumors, Amanda Nash, Jonathon Debonis, Danna Murungi, Bertha Castillo, Boram Kim, Fangheng Hu, Courtney Chambers, Annie Nguyen, Andrea Hernandez, Zeshi Wang, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Ningbo Zheng, Weiyi Peng, Oleg A Igoshin, Jose Oberholzer, H Courtney Hodges, Nathan Reticker-Flynn, Omid Veiseh

Faculty, Staff and Students Publications

Background: Curative responses to immunotherapy require the generation of robust systemic immunity with limited toxicity. Recruitment of T cell populations such as precursor exhausted T cells (Tpex) from lymphoid tissues to tumors is a hallmark of effective treatment. However, the ability to efficiently induce this recruitment is lacking in current immunotherapy approaches. Furthermore, systemic administration of immunotherapies frequently results in dose-limiting toxicities, yielding an inadequate therapeutic window for eliciting durable responses.

Methods: In this investigation, we evaluated the safety and antitumor efficacy of locally administered interleukin 12 (IL-12) using a clinically translatable cytokine delivery platform (NCT05538624) to identify …


Suppression Of Hypothalamic Oestrogenic Signal Sustains Hyperprolactinemia And Metabolic Adaptation In Lactating Mice, Meng Yu, Bing Feng, Jonathan C Bean, Qianru Zhao, Yongjie Yang, Hailan Liu, Yongxiang Li, Benjamin P Eappen, Hesong Liu, Longlong Tu, Kristine M Conde, Mengjie Wang, Xi Chen, Na Yin, Darah Ave Threat, Nathan Xu, Junying Han, Peiyu Gao, Yi Zhu, Darryl L Hadsell, Yang He, Pingwen Xu, Yanlin He, Chunmei Wang Apr 2025

Suppression Of Hypothalamic Oestrogenic Signal Sustains Hyperprolactinemia And Metabolic Adaptation In Lactating Mice, Meng Yu, Bing Feng, Jonathan C Bean, Qianru Zhao, Yongjie Yang, Hailan Liu, Yongxiang Li, Benjamin P Eappen, Hesong Liu, Longlong Tu, Kristine M Conde, Mengjie Wang, Xi Chen, Na Yin, Darah Ave Threat, Nathan Xu, Junying Han, Peiyu Gao, Yi Zhu, Darryl L Hadsell, Yang He, Pingwen Xu, Yanlin He, Chunmei Wang

Faculty, Staff and Students Publications

17β-oestradiol (E2) inhibits overeating and promotes brown adipose tissue (BAT) thermogenesis, whereas prolactin (PRL) does the opposite. During lactation, the simultaneous decline in E2 and surge in PRL contribute to maternal metabolic adaptations, including hyperphagia and suppressed BAT thermogenesis. However, the underlying neuroendocrine mechanisms remain unclear. Here, we find that oestrogen receptor alpha (ERα)-expressing neurons in the medial basal hypothalamus (MBH), specifically the arcuate nucleus of the hypothalamus and the ventrolateral subdivision of the ventromedial hypothalamus (vlVMH), are suppressed during lactation. Deletion of ERα from MBH neurons in virgin female mice induces metabolic phenotypes characteristic of lactation, including hyperprolactinemia, hyperphagia …


Preparation And Evaluation Of Mesoporous Celecoxib For Improved Antiarthritic Activity In Rodents, Reena I. Fernandaes, Sayani Bhattacharyya Mar 2025

Preparation And Evaluation Of Mesoporous Celecoxib For Improved Antiarthritic Activity In Rodents, Reena I. Fernandaes, Sayani Bhattacharyya

The Thai Journal of Pharmaceutical Sciences

Background: Celecoxib, a model anti-inflammatory drug, used in the management of arthritis exhibits limited oral bioavailability and slow onset of action due to its poor solubility. Objective: The present study explores a mesoporous drug delivery of celecoxib to investigate the efficacy of its antiarthritic activity in animal models, and develops a low-oral dose therapy. Materials and Methods: The solvent evaporation method was employed for the preparation of mesoporous delivery of celecoxib, using Syloid®, and Neusilin®, at a molar ratio of silica/ drug 1:2.5. The formulations were characterized for drug loading, in vitro drug release, and material …


Enhancing Topical Drug Delivery Of Apremilast Through Niosomal Gel Formulation: Ex Vivo Skin Permeation And In Vivo Evaluation For Psoriasis, Megha Shyam Matlapudi, Anka Rao Areti, Yukti Jaiswal, Veeresh Bantal, Raghavender Medishetti Mar 2025

Enhancing Topical Drug Delivery Of Apremilast Through Niosomal Gel Formulation: Ex Vivo Skin Permeation And In Vivo Evaluation For Psoriasis, Megha Shyam Matlapudi, Anka Rao Areti, Yukti Jaiswal, Veeresh Bantal, Raghavender Medishetti

The Thai Journal of Pharmaceutical Sciences

Background: Psoriasis is a dynamic and chronic disease characterized by inflammatory changes and an increased rate of keratinocyte proliferation leading to the formation of erythematous scleroderma plaques with a silvery sheen. The existing therapies come with shortcomings in terms of effectiveness and leave behind a trail of side effects. Hence, there is a need of alternative therapeutic measures. Objectives: This study aimed to assess the therapeutic potential of Apremilast Niosomal Gel (APR Nio Gel) in treating psoriasis, comparing its effectiveness with conventional gel (APR Gel) and oral suspension (APR Oral) formulations. Materials and Methods: Apremilast niosomes were prepared by thin …


The Intensity Of 10-Minute Classroom Physical Activity Breaks In Elementary School Children, Jeffery J. Honas, Amanda N. Szabo-Reed, Joe Sherman, Anna Rice, Robert Montgomery, Ken Murfay, Richard A. Washburn, Joseph E. Donnelly Mar 2025

The Intensity Of 10-Minute Classroom Physical Activity Breaks In Elementary School Children, Jeffery J. Honas, Amanda N. Szabo-Reed, Joe Sherman, Anna Rice, Robert Montgomery, Ken Murfay, Richard A. Washburn, Joseph E. Donnelly

International Journal of Physical Activity and Health

This study examined the intensity of different physical activity (PA) breaks for elementary school children in a simulated classroom setting. Researchers compared the energy expenditure (Kcals/min, METs) of PA breaks developed for the Physical Activity Across the Curriculum (PAAC-3) program, delivered via video or in-person, to commercially available GoNoodle© videos. 71 children (age 9.0 ± 1.1 yrs., 47 males, 24 females, 18% minority) participated in 10-minute PA breaks. The intensity of activity breaks was assessed using a COSMED® K5 portable indirect calorimeter (weight ~ 1 kg) (COSMED®, Rome, Italy) and and portable accelerometer (ActiGraph GT3X+; ActiGraph LLC, Pensacola, FL) …


Uterine Pgrmc2 Deficiency Attenuates Endometrial Hyperplasia And Cancer And Prolongs Lifespan In A Pten Loss-Of-Function-Induced Cancer Model, Nicole C Kelp, Cindy A Pru, Sandeep Paudel, John P Lydon, J Julie Kim, John J Peluso, James K Pru Mar 2025

Uterine Pgrmc2 Deficiency Attenuates Endometrial Hyperplasia And Cancer And Prolongs Lifespan In A Pten Loss-Of-Function-Induced Cancer Model, Nicole C Kelp, Cindy A Pru, Sandeep Paudel, John P Lydon, J Julie Kim, John J Peluso, James K Pru

Faculty, Staff and Students Publications

The expression of members of the progesterone receptor membrane component (PGRMC) family, particularly PGRMC1, is elevated in diverse types of cancers, particularly those of the female reproductive system. While xenograft tumor studies using human transformed cell lines in immunocompromised mice have suggested that PGRMC1 enhances tumor growth and chemoresistance, the exact role of members of the PGRMC family in cancer development in vivo remains unclear. In this study, we examined the effect of deleting Pgrmc2 on the development of endometrial hyperplasia and cancer using a murine phosphatase and tensin homologue (Pten) conditional loss-of-function model. We previously established that …


The Prillwitz Mammoth: Taxonomy, Sex, Age, & Delayed Skeletal Maturation Of A Geologically Young Mammoth, Anna Rybachek Mar 2025

The Prillwitz Mammoth: Taxonomy, Sex, Age, & Delayed Skeletal Maturation Of A Geologically Young Mammoth, Anna Rybachek

Honors Theses

The Prillwitz mammoth, a nearly complete mammoth skeleton found in Southwest Michigan in 1962, is one of the geologically youngest mammoths from North America (AMS C-14 date: 11,300 ± 100 BP). Bones are well preserved; some long bones show post-mortem flaking, scratches, or grooves of unknown origin. All long-bone epiphyses remain unfused except the distal humerus, suggesting it was < 28 years old at death. In contrast, the skull and mandible preserve M3s and m3s, respectively, that are in mid-wear, indicating an Asian Elephant Year dental age of ~45-50 years. Long bone size and inferred shoulder height are consistent with the size of a large woolly mammoth (Mammuthus primigenius) or small to mid-sized Columbian mammoth (Mammuthus columbi), but dental evidence is most consistent with M. columbi.

Pelvic dimensions suggest it is a male. The ≥ 17-year mismatch between age inferred from tooth progression and wear (~45 Asian Elephant Years) and age inferred from epiphyseal fusion (< ~28 Asian EY if male) may indicate either substantially accelerated dental progression or delayed skeletal maturation for this mammoth; we deem the latter more likely. Based on modern analogs, delayed maturation could have been due to severe malnutrition, hormonal imbalance, illness, or genetic factors. Given the geologically young age of the Prillwitz mammoth (likely near the time of mammoth extinction), we speculate that delayed skeletal maturation may have been attributed to environmental stressors near the end of the Pleistocene. Further work is warranted on very late mammoths.