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2024

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Neuroimmune Interactions In The Development And Chronification Of Migraine Headache, Jintao Zhang, Roli Simoes, Tingting Guo, Yu-Qing Cao Oct 2024

Neuroimmune Interactions In The Development And Chronification Of Migraine Headache, Jintao Zhang, Roli Simoes, Tingting Guo, Yu-Qing Cao

2020-Current year OA Pubs

Migraine is highly prevalent and debilitating. The persistent headaches in this condition are thought to arise from the activation and sensitization of the trigeminovascular pathway. Both clinical and animal model studies have suggested that neuroimmune interactions contribute to the pathophysiology of migraine headache. In this review, we first summarize the findings from human studies implicating the dysregulation of the immune system in migraine, including genetic analyses, measurement of circulatory factors, and neuroimaging data. We next discuss recent advances from rodent studies aimed at elucidating the neuroimmune interactions that manifest at various levels of the trigeminovascular pathway and lead to the …


Theistic Illiberal Constitutionalism: A Review Of Adrian Vermeule’S Common Good Constitutionalism, Kyron J. Huigens Oct 2024

Theistic Illiberal Constitutionalism: A Review Of Adrian Vermeule’S Common Good Constitutionalism, Kyron J. Huigens

Articles

Adrian Vermeule’s Common Good Constitutionalism drew a remarkable amount of attention from constitutional law scholars when it was published in 2020. About eighteen months later, Vermeule published a piece complaining that the critics had missed the point, that they had ignored the natural law jurisprudence that grounds the work. He was correct. This Review addresses Vermeule’s natural law jurisprudence, emphasizing the fact that it is a religious natural law jurisprudence. His arguments are in the tradition of ScholasticismAristotelian logic incorporated into Christian theology by St. Thomas Aquinas. Scholasticism is a remarkably weak foundation for constitutional jurisprudence. It is a vast …


An Approach To Multi-Attribute Decision-Making Based On Single-Valued Neutrosophic Hesitant Fuzzy Aczel-Alsina Aggregation Operator, Raiha Imran, Kifayat Ullah, Zeeshan Ali, Maria Akram Oct 2024

An Approach To Multi-Attribute Decision-Making Based On Single-Valued Neutrosophic Hesitant Fuzzy Aczel-Alsina Aggregation Operator, Raiha Imran, Kifayat Ullah, Zeeshan Ali, Maria Akram

Neutrosophic Systems with Applications

A single-valued Neutrosophic hesitant fuzzy set (SVNHFS) is a combination of a single-valued neutrosophic set (SVNS) and hesitant fuzzy set (HFS) that has been developed to address insufficient, unreliable, and vague environments in which each element has several possible options determined by the truthiness, indeterminacy and falsity value. By considering this, in this paper, we have proposed the Aczel-Alsina aggregation operator (AAAO) for SVNHFS, which is more flexible t-norm and t-conorm than the other and due to the flexible nature of parameters to solve Multi-Attribute decision making (MADM) problems. Further, the score function, accuracy function, and certainty function of SVNHFS …


Evaluation Of Renewable Energy Sources For A Sustainable Future: A Multi-Criteria Decision-Making Approach, Mai Mohamed, Asmaa Elsayed Oct 2024

Evaluation Of Renewable Energy Sources For A Sustainable Future: A Multi-Criteria Decision-Making Approach, Mai Mohamed, Asmaa Elsayed

Neutrosophic Systems with Applications

The urgent global challenges of climate change, energy security, and environmental degradation highlight the need for sustainable energy solutions. Renewable energy sources (RES) present a viable pathway towards sustainability by mitigating greenhouse gas emissions, reducing reliance on fossil fuels, and fostering economic resilience. Purpose: The purpose of this paper is to propose an advanced Multi-Criteria Decision-Making (MCDM) approach to evaluate various RES by integrating environmental, economic, technological, social acceptance, and resource availability criteria, to identify the most suitable RES for sustainable energy solutions. Methodology: The study employs a hybrid method combining Type-2 Neutrosophic Numbers (T2NN) with LOPCOW (Logarithmic Percentage Change …


Selected Aspects Of The Organization Of Tourism And Recreation In Natural Areas With Different Status Of Legal Protection, Marcin Pasek, Dominik Borek Oct 2024

Selected Aspects Of The Organization Of Tourism And Recreation In Natural Areas With Different Status Of Legal Protection, Marcin Pasek, Dominik Borek

internetowy Kwartalnik Antymonopolowy i Regulacyjny (internet Quarterly on Antitrust and Regulation)

An important place in the strategy of promoting health of modern societies, especially in the post-pandemic world, is played by orienting recommendations on how to spend free time towards tourism and recreation in the natural environment. The utilitarian nature of this type of activity is associated with the need to respect legal provisions, relating to the use of statutory forms of nature conservation, as well as non-statutory protection areas. The aim of the study is to characterize the tourist-recreational use in both of the abovementioned types of ecological habitats, and to indicate the similarities and differences in the conditions of …


Cardiomyocyte Adaptation To Exercise: K+ Channels, Contractility And Ischemic Injury, Robert H. Fitts, Xinrui Wang, Wai-Meng Kwok, Amadou K.S. Camara Oct 2024

Cardiomyocyte Adaptation To Exercise: K+ Channels, Contractility And Ischemic Injury, Robert H. Fitts, Xinrui Wang, Wai-Meng Kwok, Amadou K.S. Camara

Biological Sciences Faculty Research and Publications

Cardiovascular disease is a leading cause of morbidity and mortality, and exercise-training (TRN) is known to reduce risk factors and protect the heart from ischemia and reperfusion injury. Though the cardioprotective effects of exercise are well-documented, underlying mechanisms are not well understood. This review highlights recent findings and focuses on cardiac factors with emphasis on K+ channel control of the action potential duration (APD), β-adrenergic and adenosine regulation of cardiomyocyte function, and mitochondrial Ca2+ regulation. TRN-induced prolongation and shortening of the APD at low and high activation rates, respectively, is discussed in the context of a reduced response …


Piezo Ion Channels: Force Sensors Of The Interoceptive Nervous System, Yasmeen M F Hamed, Britya Ghosh, Kara L Marshall Oct 2024

Piezo Ion Channels: Force Sensors Of The Interoceptive Nervous System, Yasmeen M F Hamed, Britya Ghosh, Kara L Marshall

Duncan NRI Faculty and Staff Publications

Many organs are designed to move: the heart pumps each second, the gastrointestinal tract squeezes and churns to digest food, and we contract and relax skeletal muscles to move our bodies. Sensory neurons of the peripheral nervous system detect signals from bodily tissues, including the forces generated by these movements, to control physiology. The processing of these internal signals is called interoception, but this is a broad term that includes a wide variety of both chemical and mechanical sensory processes. Mechanical senses are understudied, but rapid progress has been made in the last decade, thanks in part to the discovery …


The International Legal Framework Of Oceanic Shipping Of Carbon Dioxide For Permanent Storage, Carolina Arlota, Michael B. Gerrard Oct 2024

The International Legal Framework Of Oceanic Shipping Of Carbon Dioxide For Permanent Storage, Carolina Arlota, Michael B. Gerrard

Faculty Scholarship

The Intergovernmental Panel on Climate Change defines carbon dioxide capture and storage (CCS) as “a process in which a relatively pure stream of carbon dioxide (CO2) from industrial and energy-related sources is separated (captured), conditioned, compressed, and transported to a storage location for long-term isolation from the atmosphere.” Therefore, CCS encompasses a series of steps, at minimum: capturing carbon dioxide, its transportation to a storage site, and its injection into the subsurface for permanent storage. As such, CCS does not refer to any single activity or technology. This Article focuses on the transportation aspect of CCS and, more precisely, …


Green Utopias: A Possible Green Ground For Performing Arts Training, Renee Newman, Alexa Taylor, Luke Cowling, Jason Garbenis, Tom Heath, Fleur Kingsland, Vahri Mckenzie, Jeremy Neideck, Richard Reddrop, Simon Stewart Oct 2024

Green Utopias: A Possible Green Ground For Performing Arts Training, Renee Newman, Alexa Taylor, Luke Cowling, Jason Garbenis, Tom Heath, Fleur Kingsland, Vahri Mckenzie, Jeremy Neideck, Richard Reddrop, Simon Stewart

Research outputs 2022 to 2026

No abstract provided.


Navigating Ethical Challenges In Online Wildlife Trade Research, Thais Q. Morcatty, Shan Su, Penthai Siriwat, Astrid Alex Andersson, Sadek Atoussi, Kim Feddema, Sergio Henriques, Jordi Janssen, Anushri Karve, Jennifer Pytka, Ruth M. Thompson, Vincent Nijman, Joss Wright, David L. Roberts Oct 2024

Navigating Ethical Challenges In Online Wildlife Trade Research, Thais Q. Morcatty, Shan Su, Penthai Siriwat, Astrid Alex Andersson, Sadek Atoussi, Kim Feddema, Sergio Henriques, Jordi Janssen, Anushri Karve, Jennifer Pytka, Ruth M. Thompson, Vincent Nijman, Joss Wright, David L. Roberts

Research outputs 2022 to 2026

The surge in internet accessibility has transformed wildlife trade by facilitating the acquisition of wildlife through online platforms. This scenario presents unique ethical challenges for researchers, as traditional ethical frameworks for in-person research cannot be readily applied to the online realm. Currently, there is a lack of clearly defined guidelines for appropriate ethical procedures when conducting online wildlife trade (OWT) research. In response to this, we consulted the scientific literature on ethical considerations in online research and examined existing guidelines established by professional societies and ethical boards. Based on these documents, we present a set of recommendations that can inform …


Htlv-1 Infected T Cells Cause Bone Loss Via Small Extracellular Vesicles, Nitin Kumar Pokhrel, Haniya Habib, Shamreethaa Seeniraj, Ancy Joseph, Daniel Rauch, Linda Cox, Robert Sprung, Petra Erdmann Gilmore, Qiang Zhang, Robert Reid Townsend, Lee Ratner, Katherine N Weilbaecher, Deborah J Veis, Et Al. Oct 2024

Htlv-1 Infected T Cells Cause Bone Loss Via Small Extracellular Vesicles, Nitin Kumar Pokhrel, Haniya Habib, Shamreethaa Seeniraj, Ancy Joseph, Daniel Rauch, Linda Cox, Robert Sprung, Petra Erdmann Gilmore, Qiang Zhang, Robert Reid Townsend, Lee Ratner, Katherine N Weilbaecher, Deborah J Veis, Et Al.

2020-Current year OA Pubs

Adult T cell leukaemia (ATL), caused by infection with human T- lymphotropic virus type 1 (HTLV-1), is often complicated by hypercalcemia and osteolytic lesions. Therefore, we studied the communication between patient-derived ATL cells (ATL-PDX) and HTLV-1 immortalized CD4+ T cell lines (HTLV/T) with osteoclasts and their effects on bone mass in mice. Intratibial inoculation of some HTLV/T leads to a profound local decrease in bone mass similar to marrow-replacing ATL-PDX, despite the fact that few HTLV/T cells persisted in the bone. To study the direct effect of HTLV/T and ATL-PDX on osteoclasts, supernatants were added to murine and human osteoclast …


Microfracture For Medium Size To Large Knee Chondral Defects Has Limited Long-Term Efficacy: A Systematic Review, Varun Gopinatth, Garrett R Jackson, Daniel C Touhey, Jorge Chahla, Matthew V Smith, Matthew J Matava, Robert H Brophy, Derrick M Knapik Oct 2024

Microfracture For Medium Size To Large Knee Chondral Defects Has Limited Long-Term Efficacy: A Systematic Review, Varun Gopinatth, Garrett R Jackson, Daniel C Touhey, Jorge Chahla, Matthew V Smith, Matthew J Matava, Robert H Brophy, Derrick M Knapik

2020-Current year OA Pubs

PURPOSE: To evaluate clinical and radiographic outcomes, return to sport, failure rate, operations and complications in patients undergoing microfracture of the knee, including the femoral condyle, tibial plateau, patella and trochlea, at a mean 10-year or greater follow-up.

METHODS: A literature search was performed by querying SCOPUS, PubMed, Medline and the Cochrane Central Register for Controlled Trials from database inception through May 2023 according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Inclusion criteria were level I-IV human studies reporting on outcomes, reoperations and complications following microfracture of the knee at a mean 10-year or greater …


Leptospirosis In The Platypus (Ornithorhynchus Anatinus) In Australia: Who Is Infecting Whom?, Richard J. Whittington, Thomas R. Grant, Jarrad Mckercher, Monica Suann, Keith Hart, Kathrine A. Handasyde, James Macgregor, Mark E. Westman, Joanne H. Connolly Oct 2024

Leptospirosis In The Platypus (Ornithorhynchus Anatinus) In Australia: Who Is Infecting Whom?, Richard J. Whittington, Thomas R. Grant, Jarrad Mckercher, Monica Suann, Keith Hart, Kathrine A. Handasyde, James Macgregor, Mark E. Westman, Joanne H. Connolly

Research outputs 2022 to 2026

The platypus (Ornithorhynchus anatinus) is an amphibious, egg-laying mammal of high conservation value that is found only in Australia. The zoonotic bacterium Leptospira interrogans serovar Hardjo was discovered in platypuses in prior studies, but little is known about its epidemiology. Samples in the Platypus Serum Bank were tested in 2023 and the results were combined with historical records. Antibodies against L. interrogans serovar Hardjo were found in 50% of 464 serum samples from 411 platypuses collected from 14 river basins in southeastern Australia between 1981 and 2012; prevalence remained high over three decades in the Shoalhaven River population. Seroprevalence increased …


Acute Changes In Liver Function Tests During Initiation Of Ketogenic Diet, Akshat Katyayan, Anuranjita Nayak, Gloria Diaz-Medina, Maureen Handoko, James John Riviello Oct 2024

Acute Changes In Liver Function Tests During Initiation Of Ketogenic Diet, Akshat Katyayan, Anuranjita Nayak, Gloria Diaz-Medina, Maureen Handoko, James John Riviello

Faculty, Staff and Students Publications

BACKGROUND: Ketogenic diet is an effective therapy for patients with medically refractory epilepsy. It is generally well tolerated, with the most common side effects being gastrointestinal. Hepatic toxicity has been described as an uncommon side effect of ketogenic diet, usually with long-term use. However, there are limited data to implicate ketogenic diet in acute liver toxicity.

METHODS AND RESULTS: We analyzed all patients who underwent elective inpatient ketogenic diet initiation at our institution from June 2019 to June 2022. Of the 25 patients reviewed, we found 6 patients who showed acute, asymptomatic changes in liver function tests during initiation, in …


Distinct Landscape And Clinical Implications Of Therapy-Related Clonal Hematopoiesis, Koichi Takahashi, Daisuke Nakada, Margaret Goodell Oct 2024

Distinct Landscape And Clinical Implications Of Therapy-Related Clonal Hematopoiesis, Koichi Takahashi, Daisuke Nakada, Margaret Goodell

Faculty, Staff and Student Publications

Therapy-related clonal hematopoiesis (t-CH) is defined as clonal hematopoiesis detected in individuals previously treated with chemotherapy and/or radiation therapy. With the increased use of genetic analysis in oncological care, the detection of t-CH among cancer patients is becoming increasingly common. t-CH arises through the selective bottleneck imposed by chemotherapies and potentially through direct mutagenesis from chemotherapies, resulting in a distinct mutational landscape enriched with mutations in DNA damage-response pathway genes such as TP53, PPM1D, and CHEK2. Emerging evidence sheds light on the mechanisms of t-CH development and potential strategies to mitigate its emergence. Due to its unique characteristics that predominantly …


Dna Methylation-Derived Immune Cell Proportions And Cancer Risk In Black Participants, Christopher S Semancik, Naisi Zhao, Devin C Koestler, Eric Boerwinkle, Jan Bressler, Rachel J Buchsbaum, Karl T Kelsey, Elizabeth A Platz, Dominique S Michaud Oct 2024

Dna Methylation-Derived Immune Cell Proportions And Cancer Risk In Black Participants, Christopher S Semancik, Naisi Zhao, Devin C Koestler, Eric Boerwinkle, Jan Bressler, Rachel J Buchsbaum, Karl T Kelsey, Elizabeth A Platz, Dominique S Michaud

Faculty, Staff and Student Publications

Prior cohort studies assessing cancer risk based on immune cell subtype profiles have predominantly focused on White populations. This limitation obscures vital insights into how cancer risk varies across race. Immune cell subtype proportions were estimated using deconvolution based on leukocyte DNA methylation markers from blood samples collected at baseline on participants without cancer in the Atherosclerosis Risk in Communities Study. During a mean of 17.5 years of follow-up, 668 incident cancers were diagnosed in 2,467 Black participants. Cox proportional hazards regression was used to examine immune cell subtype proportions and overall cancer incidence and site-specific incidence (lung, breast, and …


Tau Is Required For Glial Lipid Droplet Formation And Resistance To Neuronal Oxidative Stress, Lindsey D Goodman, Isha Ralhan, Xin Li, Shenzhao Lu, Matthew J Moulton, Ye-Jin Park, Pinghan Zhao, Oguz Kanca, Ziyaneh S Ghaderpour Taleghani, Julie Jacquemyn, Joshua M Shulman, Kanae Ando, Kai Sun, Maria S Ioannou, Hugo J Bellen Oct 2024

Tau Is Required For Glial Lipid Droplet Formation And Resistance To Neuronal Oxidative Stress, Lindsey D Goodman, Isha Ralhan, Xin Li, Shenzhao Lu, Matthew J Moulton, Ye-Jin Park, Pinghan Zhao, Oguz Kanca, Ziyaneh S Ghaderpour Taleghani, Julie Jacquemyn, Joshua M Shulman, Kanae Ando, Kai Sun, Maria S Ioannou, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism. We found that overexpressing Tau in glia disrupts LDs in flies and rat neuron-astrocyte co-cultures, sensitizing the glia to toxic, neuronal LPOs. Using a new fly tau loss-of-function allele and RNA-mediated interference, we found that endogenous Tau is required for glial LD formation and protection against neuronal LPOs. Similarly, …


Oligodendroglial Fatty Acid Metabolism As A Central Nervous System Energy Reserve, Ebrahim Asadollahi, Andrea Trevisiol, Aiman S Saab, Zoe J Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E Dale Abel, Andrea Ballabio, Brian Popko, Celia M Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave Oct 2024

Oligodendroglial Fatty Acid Metabolism As A Central Nervous System Energy Reserve, Ebrahim Asadollahi, Andrea Trevisiol, Aiman S Saab, Zoe J Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E Dale Abel, Andrea Ballabio, Brian Popko, Celia M Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave

Duncan NRI Faculty and Staff Publications

Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial …


Does Glial Lipid Dysregulation Alter Sleep In Alzheimer’S And Parkinson’S Disease?, Lindsey D Goodman, Matthew J Moulton, Guang Lin, Hugo J Bellen Oct 2024

Does Glial Lipid Dysregulation Alter Sleep In Alzheimer’S And Parkinson’S Disease?, Lindsey D Goodman, Matthew J Moulton, Guang Lin, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

In this opinion article, we discuss potential connections between sleep disturbances observed in Alzheimer's disease (AD) and Parkinson's disease (PD) and the dysregulation of lipids in the brain. Research using Drosophila has highlighted the role of glial-mediated lipid metabolism in sleep and diurnal rhythms. Relevant to AD, the formation of lipid droplets in glia, which occurs in response to elevated neuronal reactive oxygen species (ROS), is required for sleep. In disease models, this process is disrupted, arguing a connection to sleep dysregulation. Relevant to PD, the degradation of neuronally synthesized glucosylceramides by glia requires glucocerebrosidase (GBA, a PD-associated risk factor) …


Mouse Corneal Immune Cell Heterogeneity Revealed By Single-Cell Rna Sequencing, Ebru Yaman, Nicole Heyer, Cintia S De Paiva, Mary Ann Stepp, Stephen C Pflugfelder, Jehan Alam Oct 2024

Mouse Corneal Immune Cell Heterogeneity Revealed By Single-Cell Rna Sequencing, Ebru Yaman, Nicole Heyer, Cintia S De Paiva, Mary Ann Stepp, Stephen C Pflugfelder, Jehan Alam

Faculty, Staff and Students Publications

PURPOSE: This study aimed to define the heterogeneity, spatial localization, and functional roles of immune cells in the mouse cornea using single-cell RNA sequencing (scRNA-seq) and immunofluorescent staining.

METHODS: Enriched mouse corneal immune cells (C57BL/6 strain, age 16-20 weeks) underwent single-cell RNA sequencing library preparation, sequencing, and analysis with Seurat, Monocle 3, and CellChat packages in R. Pathway analysis used Qiagen Ingenuity Pathway Analysis software. Immunostaining confirmed cell distribution.

RESULTS: We identified 14 distinct immune cell clusters (56% myeloid and 44% lymphoid). Myeloid populations included resident macrophages, conventional dendritic cells (cDC2s), Langerhans cells, neutrophils, monocytes, and mast cells. Additionally, lymphocyte …


Perineuronal Nets’ Role In Metabolism, Nan Zhang, Beite Song, Peng Bai, Li Du, Lulu Chen, Yong Xu, Tianshu Zeng Oct 2024

Perineuronal Nets’ Role In Metabolism, Nan Zhang, Beite Song, Peng Bai, Li Du, Lulu Chen, Yong Xu, Tianshu Zeng

Faculty, Staff and Students Publications

Perineuronal nets (PNNs), specialized extracellular matrix (ECM) structures that envelop neurons, have recently been recognized as key players in the regulation of metabolism. This review explores the growing body of knowledge concerning PNNs and their role in metabolic control, drawing insights from recent research and relevant studies. The pivotal role of PNNs in the context of energy balance and whole body blood glucose is examined. This review also highlights novel findings, including the effects of astroglia, microglia, sex and gonadal hormones, nutritional regulation, circadian rhythms, and age on PNNs dynamics. These findings illuminate the complex and multifaceted role of PNNs …


Nh 4-H Youth Enrollment Paper Form, Unh Cooperative Extension Oct 2024

Nh 4-H Youth Enrollment Paper Form, Unh Cooperative Extension

UNH Cooperative Extension

No abstract provided.


Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Beom-Jun Kim, Aparna Mitra, Craig T Vollert, Jonathan T Lei, Diana Fandino, Meenakshi Anurag, Matthew V Holt, Xuxu Gou, Jacob B Pilcher, Matthew P Goetz, Donald W Northfelt, Susan G Hilsenbeck, C Gary Marshall, Marc L Hyer, Robert Papp, Shou-Yun Yin, Carmine De Angelis, Rachel Schiff, Suzanne A W Fuqua, Cynthia X Ma, Charles E Foulds, Matthew J Ellis Oct 2024

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Beom-Jun Kim, Aparna Mitra, Craig T Vollert, Jonathan T Lei, Diana Fandino, Meenakshi Anurag, Matthew V Holt, Xuxu Gou, Jacob B Pilcher, Matthew P Goetz, Donald W Northfelt, Susan G Hilsenbeck, C Gary Marshall, Marc L Hyer, Robert Papp, Shou-Yun Yin, Carmine De Angelis, Rachel Schiff, Suzanne A W Fuqua, Cynthia X Ma, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …


Behavioral Screening Reveals A Conserved Residue In Y-Box Rna-Binding Protein Required For Associative Learning And Memory In C Elegans, Ashley N Hayden, Katie L Brandel, Edward W Pietryk, Paul R Merlau, Priyadharshini Vijayakumar, Emily J Leptich, Elizabeth S Gaytan, Meredith I Williams, Connie W Ni, Hsiao-Tuan Chao, Jill A Rosenfeld, Rachel N Arey Oct 2024

Behavioral Screening Reveals A Conserved Residue In Y-Box Rna-Binding Protein Required For Associative Learning And Memory In C Elegans, Ashley N Hayden, Katie L Brandel, Edward W Pietryk, Paul R Merlau, Priyadharshini Vijayakumar, Emily J Leptich, Elizabeth S Gaytan, Meredith I Williams, Connie W Ni, Hsiao-Tuan Chao, Jill A Rosenfeld, Rachel N Arey

Faculty, Staff and Students Publications

RNA-binding proteins (RBPs) regulate translation and plasticity which are required for memory. RBP dysfunction has been linked to a range of neurological disorders where cognitive impairments are a key symptom. However, of the 2,000 RBPs in the human genome, many are uncharacterized with regards to neurological phenotypes. To address this, we used the model organism C. elegans to assess the role of 20 conserved RBPs in memory. We identified eight previously uncharacterized memory regulators, three of which are in the C. elegans Y-Box (CEY) RBP family. Of these, we determined that cey-1 is the closest ortholog to the mammalian Y-Box …


Disruption Of Neural Periodicity Predicts Clinical Response After Deep Brain Stimulation For Obsessive-Compulsive Disorder, Nicole R Provenza, Sandesh Reddy, Anthony K Allam, Sameer V Rajesh, Nabeel Diab, Gabriel Reyes, Rose M Caston, Kalman A Katlowitz, Ajay D Gandhi, Raphael A Bechtold, Huy Q Dang, Ricardo A Najera, Nisha Giridharan, Katherine E Kabotyanski, Faiza Momin, Mohammed Hasen, Garrett P Banks, Brian J Mickey, Brent M Kious, Ben Shofty, Benjamin Y Hayden, Jeffrey A Herron, Eric A Storch, Ankit B Patel, Wayne K Goodman, Sameer A Sheth Oct 2024

Disruption Of Neural Periodicity Predicts Clinical Response After Deep Brain Stimulation For Obsessive-Compulsive Disorder, Nicole R Provenza, Sandesh Reddy, Anthony K Allam, Sameer V Rajesh, Nabeel Diab, Gabriel Reyes, Rose M Caston, Kalman A Katlowitz, Ajay D Gandhi, Raphael A Bechtold, Huy Q Dang, Ricardo A Najera, Nisha Giridharan, Katherine E Kabotyanski, Faiza Momin, Mohammed Hasen, Garrett P Banks, Brian J Mickey, Brent M Kious, Ben Shofty, Benjamin Y Hayden, Jeffrey A Herron, Eric A Storch, Ankit B Patel, Wayne K Goodman, Sameer A Sheth

Faculty, Staff and Students Publications

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high …


Dna Vaccines Against Gprc5d Synergize With Pd-1 Blockade To Treat Multiple Myeloma, Praveen Neeli, Perry Ayn Mayson A Maza, Dafei Chai, Dan Zhao, Xen Ping Hoi, Keith Syson Chan, Ken H Young, Yong Li Oct 2024

Dna Vaccines Against Gprc5d Synergize With Pd-1 Blockade To Treat Multiple Myeloma, Praveen Neeli, Perry Ayn Mayson A Maza, Dafei Chai, Dan Zhao, Xen Ping Hoi, Keith Syson Chan, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Multiple myeloma (MM), a hematological malignancy of the bone marrow, remains largely incurable. The orphan G protein-coupled receptor, GPRC5D, which is uniquely expressed in plasma cells and highly expressed in MM, is a compelling candidate for immunotherapy. In this study, we investigated the efficacy of a combination of DNA vaccine encoding mouse GPRC5D and PD-1 blockade in preventing and treating MM using the 5TGM1 murine model of MM. The mouse vaccine alone was effective in preventing myeloma growth but required PD-1 antibodies to inhibit established MM tumors. We next evaluated the prophylactic and therapeutic efficacy of a nanoplasmid vector encoding …


A Mouse Model For Conditional Expression Of Activated Β-Catenin In Epidermal Keratinocytes, Vineet K Maurya, Yan Ying, John P Lydon Oct 2024

A Mouse Model For Conditional Expression Of Activated Β-Catenin In Epidermal Keratinocytes, Vineet K Maurya, Yan Ying, John P Lydon

Faculty, Staff and Students Publications

We report the generation and characterization of the K5: CAT bigenic mouse in which the constitutively activated form of β-catenin (ΔN89 β-catenin) is conditionally expressed in cytokeratin-5 (K5) positive epidermal keratinocytes. Following short-term doxycycline intake during the telogen resting phase, the adult K5: CAT bigenic develops enlarged pilosebaceous units that expand deep into the dermis, an expansion usually observed during the anagen growth phase. Prolonged doxycycline treatment results in significant thickening and folding of the K5: CAT epidermis. During this persistent induction period, there is clear evidence of increased keratinocyte proliferation, particularly in the epidermal basal cell layer and the …


Biological Evaluation Of Anti-Cancer Activities Of Novel Small-Molecule Tubulin Polymerization Inhibitors In Prostate And Pancreatic Cancer, Rui Wang Oct 2024

Biological Evaluation Of Anti-Cancer Activities Of Novel Small-Molecule Tubulin Polymerization Inhibitors In Prostate And Pancreatic Cancer, Rui Wang

Alternative Theses and Dissertations (AETDs)

Colchicine binding site inhibitors (CBSIs) are an emerging class of microtubule-targeting agents (MTAs) with promising potential for cancer therapy. Traditional MTAs like paclitaxel, docetaxel, and Cabazitaxel, are three FDA-approved taxanes for treating various cancers. Acquired chemoresistance and toxicities caused by chemotherapy are some of the main barriers that limit their clinical outcomes. More effective novel agents and therapeutic strategies are needed to overcome these challenges. Tremendous efforts have been made in discovering novel CBSIs and evaluating many cancer types, reporting their promising potential to treat both primary, resistant, and metastatic cancers including breast cancer, ovarian cancer, lung cancer, and melanoma. …


Aging Skeletal Muscle: Influence Of Obesity And Role Of The Exercise Responsive Nuclear Receptor Nor-1, Hector G. Paez Oct 2024

Aging Skeletal Muscle: Influence Of Obesity And Role Of The Exercise Responsive Nuclear Receptor Nor-1, Hector G. Paez

Alternative Theses and Dissertations (AETDs)

Skeletal muscle mass and function are critical components of overall health and quality of life. Advanced age is associated with skeletal muscle disease characterized by a loss of muscle mass, function, and quality. Indeed, low muscle mass and function is associated with poor disease outcomes and greater mortality, greater incidence of falls, and a high fiscal and societal cost. Aging contributes to a decline in skeletal muscle health through several intrinsic and extrinsic mechanisms including impaired nutrient sensing, mitochondrial dysfunction, inflammation, physical inactivity, and proteostatic imbalance. Obesity, an increasingly prominent public health concern, is becoming more common in the elderly …


What Would Happen In The United States If There Were No Cow Milk-Based Preterm Infant Nutritional Products: Historical Perspective And Evaluation Of Nutrient-Related Challenges, Steven A Abrams, Robert J Shulman Oct 2024

What Would Happen In The United States If There Were No Cow Milk-Based Preterm Infant Nutritional Products: Historical Perspective And Evaluation Of Nutrient-Related Challenges, Steven A Abrams, Robert J Shulman

Faculty, Staff and Students Publications

Recent litigation has led to a situation where preterm cow milk-based infant nutritional products (PCMBPs) may soon have limited or no availability in the United States. Given their limited availability, similar products based only on human milk are unlikely to meet the needs of most preterm infants requiring such products, especially those born >1500 g or very preterm infants born at < 1500 g after they reach 34-35 wk postmenstrual age. Alternative nutritional strategies, used before the introduction of specialized preterm products, would require modular nutrient additions to a formula designed for full-term infants and donor or maternal milk. The addition of modular products would require careful calibration to provide needed macro and micronutrients which would expose infants to risks of contamination, poor growth, and limited bioavailability of some of these modulars. Substantial risks of metabolic derangements, and ultimately, poor outcomes would occur. In the long-term greater availability and support for the use of human milk-based products is needed. However, policymakers cannot assume that PCMBPs will not be critically needed and should identify strategies for their continued marketplace availability.