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Understanding The Variability Of Circulation And Water Quality At Experimental Oyster Leases In The Mississippi Sound Using A High-Resolution Nested Modeling Approach, Shihab Hossain Saran Aug 2024

Understanding The Variability Of Circulation And Water Quality At Experimental Oyster Leases In The Mississippi Sound Using A High-Resolution Nested Modeling Approach, Shihab Hossain Saran

Master's Theses

Four 50-acre experimental oyster leases; two near Saint Louis Bay (StLB) and two near Pascagoula Bay (PB) were recommended to provide science-based guidance for oyster reef restoration efforts in response to continued limited productivity of oysters in the Mississippi Sound (MSS). Two-way nested simulations using ROMS within COAWST modeling framework have been run with improved forcings to analyze circulation, salinity and temperature variability within and around the lease areas under the extreme freshwater inflow from Bonnet Carré Spillway (BCS) openings and local rivers in 2019. High-resolution atmospheric forcing data is crucial because diurnal sea-land breeze affects salinity variability by increasing …


Investigation Of The Microbiome Of A Recirculating Aquaculture System (Ras) For Crassostrea Virginica Larvae, Isabelle Townsend Aug 2024

Investigation Of The Microbiome Of A Recirculating Aquaculture System (Ras) For Crassostrea Virginica Larvae, Isabelle Townsend

Master's Theses

Recirculating Aquaculture Systems (RAS) offer control over physicochemical and biological factors impacting aquaculture success. One understudied facet of RASs is the water microbiome. Oyster larval microbiomes are shaped by their aquatic microbiomes. Understanding the dynamics of and the factors shaping RAS microbiome may provide insights to how the microbiome can be a tool for optimizing larval production. This study’s goals were to investigate the microbiome stability of a RAS rearing oyster larvae across time and space, determine impacts of larval presence on the microbiome, and examine connections between larvae production outcomes and microbiome stability. Water samples were collected weekly from …


Projected Range Shift Of The Atlantic Surfclam, Spisula Solidissima, And The Ocean Quahog, Arctica Islandica, Under Climate-Induced Benthic Warming: Forecasting Fishery Influence In The Mid-Atlantic Bight Throughout The 21st Century, Molly Mae Spencer Aug 2024

Projected Range Shift Of The Atlantic Surfclam, Spisula Solidissima, And The Ocean Quahog, Arctica Islandica, Under Climate-Induced Benthic Warming: Forecasting Fishery Influence In The Mid-Atlantic Bight Throughout The 21st Century, Molly Mae Spencer

Master's Theses

The Atlantic surfclam, Spisula solidissima, and ocean quahog, Arctica islandica, are biomass dominant bivalve species on the eastern North American continental shelf, both supporting lucrative commercial fisheries in the Mid-Atlantic with a combined value of $53.6 million in ex-vessel revenue per year. Rapid climate change is expected to modify the geographic range of these bivalve populations across the Mid-Atlantic Bight (MAB), suggesting transformative consequences for the surfclam fishery. This study forecasted future distributions of the two species from years 2016 – 2095, based on projected bottom water temperatures and a temperature-dependent population dynamics model, to project subsequent fishery-based indicators …


Development Of A Flow Cytometry Method For The Identification And Enumeration Of Enterococcus Faecalis, Riza Magbitang Aug 2024

Development Of A Flow Cytometry Method For The Identification And Enumeration Of Enterococcus Faecalis, Riza Magbitang

Master's Theses

A multi-color flow cytometry method coupled with fluorescent staining was developed to detect and quantify E. faecalis concentrations in coastal waters as an alternative to the traditional membrane filtration method. The developed method was used to characterize E. faecalis during batch growth and yielded consistent results across the various physiological states of the cells. Additionally, the application of propidium iodide (i.e., a viability stain), afforded the method the ability to differentiate between cells with intact and compromised cell membranes, which raises the potential of quantifying cells that are in viable-but-non-culturable (VBNC) state. Initial field test using natural seawater samples spiked …


Sex-Dependent Differences In Vulnerability To Early Risk Factors For Posttraumatic Stress Disorder: Results From The Aurora Study, Stephanie Haering, Stacey L House, Et Al. Aug 2024

Sex-Dependent Differences In Vulnerability To Early Risk Factors For Posttraumatic Stress Disorder: Results From The Aurora Study, Stephanie Haering, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with …


The Role Of The Cerebellum In Learning To Predict Reward: Evidence From Cerebellar Ataxia, Jonathan Nicholas, Christian Amlang, Chi-Ying R Lin, Leila Montaser-Kouhsari, Natasha Desai, Ming-Kai Pan, Sheng-Han Kuo, Daphna Shohamy Aug 2024

The Role Of The Cerebellum In Learning To Predict Reward: Evidence From Cerebellar Ataxia, Jonathan Nicholas, Christian Amlang, Chi-Ying R Lin, Leila Montaser-Kouhsari, Natasha Desai, Ming-Kai Pan, Sheng-Han Kuo, Daphna Shohamy

Faculty, Staff and Students Publications

Recent findings in animals have challenged the traditional view of the cerebellum solely as the site of motor control, suggesting that the cerebellum may also be important for learning to predict reward from trial-and-error feedback. Yet, evidence for the role of the cerebellum in reward learning in humans is lacking. Moreover, open questions remain about which specific aspects of reward learning the cerebellum may contribute to. Here we address this gap through an investigation of multiple forms of reward learning in individuals with cerebellum dysfunction, represented by cerebellar ataxia cases. Nineteen participants with cerebellar ataxia and 57 age- and sex-matched …


Bigh3 Mediates Apoptosis And Gap Junction Failure In Osteocytes During Renal Cell Carcinoma Bone Metastasis Progression, Tianhong Pan, Fengshuo Liu, Xiaoxin Hao, Shubo Wang, Murtaza Wasi, Jian H Song, Valerae O Lewis, Patrick P Lin, Bryan Moon, Justin E Bird, Theocharis Panaretakis, Sue-Hwa Lin, Danielle Wu, Mary C Farach-Carson, Liyun Wang, Ningyan Zhang, Zhiqiang An, Xiang H-F Zhang, Robert L Satcher Aug 2024

Bigh3 Mediates Apoptosis And Gap Junction Failure In Osteocytes During Renal Cell Carcinoma Bone Metastasis Progression, Tianhong Pan, Fengshuo Liu, Xiaoxin Hao, Shubo Wang, Murtaza Wasi, Jian H Song, Valerae O Lewis, Patrick P Lin, Bryan Moon, Justin E Bird, Theocharis Panaretakis, Sue-Hwa Lin, Danielle Wu, Mary C Farach-Carson, Liyun Wang, Ningyan Zhang, Zhiqiang An, Xiang H-F Zhang, Robert L Satcher

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens …


Fence Talk Scoresheet 2024, Mikayla Cerney Aug 2024

Fence Talk Scoresheet 2024, Mikayla Cerney

UNH Cooperative Extension

No abstract provided.


Carroll County 4-H Fair Exhibit Information, Mikayla Cerney Aug 2024

Carroll County 4-H Fair Exhibit Information, Mikayla Cerney

UNH Cooperative Extension

No abstract provided.


Avian Influenza Statement August 2024, Mikayla Cerney Aug 2024

Avian Influenza Statement August 2024, Mikayla Cerney

UNH Cooperative Extension

No abstract provided.


Human Platelet Lysate Enhances In Vivo Activity Of Car-Vδ2 T Cells By Reducing Cellular Senescence And Apoptosis, Feiyan Mo, Chiou-Tsun Tsai, Rong Zheng, Chonghui Cheng, Helen E Heslop, Malcolm K Brenner, Maksim Mamonkin, Norihiro Watanabe Aug 2024

Human Platelet Lysate Enhances In Vivo Activity Of Car-Vδ2 T Cells By Reducing Cellular Senescence And Apoptosis, Feiyan Mo, Chiou-Tsun Tsai, Rong Zheng, Chonghui Cheng, Helen E Heslop, Malcolm K Brenner, Maksim Mamonkin, Norihiro Watanabe

Faculty, Staff and Students Publications

BACKGROUND AIMS: Vγ9Vδ2 T cells are an attractive cell platform for the off-the-shelf cancer immunotherapy as the result of their lack of alloreactivity and inherent multi-pronged cytotoxicity, which could be further amplified with chimeric antigen receptors (CARs). In this study, we sought to enhance the in vivo longevity of CAR-Vδ2 T cells by modulating ex vivo manufacturing conditions and selecting an optimal CAR costimulatory domain.

METHODS: Specifically, we compared the anti-tumor activity of Vδ2 T cells expressing anti-CD19 CARs with costimulatory endodomains derived from CD28, 4-1BB or CD27 and generated in either standard fetal bovine serum (FBS)- or human platelet …


Cognitive Behavioral Therapy Factors Related To Outcomes In Depression Among Youth With Hiv, Betsy D Kennard, Larry K Brown, Kristin Baltrusaitis, Miriam Chernoff, Graham J Emslie, Jessica Jones, Sarah Buisson, Jaime Deville, Megan Wilkins, Amber Bunch, Chivon Mcmullen Jackson, Christy Beneri, David E Shapiro Aug 2024

Cognitive Behavioral Therapy Factors Related To Outcomes In Depression Among Youth With Hiv, Betsy D Kennard, Larry K Brown, Kristin Baltrusaitis, Miriam Chernoff, Graham J Emslie, Jessica Jones, Sarah Buisson, Jaime Deville, Megan Wilkins, Amber Bunch, Chivon Mcmullen Jackson, Christy Beneri, David E Shapiro

Faculty, Staff and Students Publications

PURPOSE: This is a secondary analysis of a multi-site, cluster (site) randomized trial of the efficacy of a combined Health and Wellness Cognitive Behavior Therapy (H&W CBT) and medication management approach for depression in youth with HIV (YWH) compared to standard care. In this study, we explored the association between H&W CBT factors and depression outcomes after 24 weeks of treatment to discover treatment elements associated with symptom reduction.

METHODS: Participants (12-24 years of age) were YWH in the United States (US) diagnosed with moderate to severe depression [Quick Inventory of Depressive Symptomatology (QIDS), Clinician-Rated score ≥ 11]. Thirteen US …


A Group 3 Medulloblastoma Stem Cell Program Is Maintained By Otx2-Mediated Alternative Splicing, Olivier Saulnier, Jamie Zagozewski, Lisa Liang, Liam D Hendrikse, Paul Layug, Victor Gordon, Kimberly A Aldinger, Parthiv Haldipur, Stephanie Borlase, Ludivine Coudière-Morrison, Ting Cai, Emma Martell, Naomi M Gonzales, Gareth Palidwor, Christopher J Porter, Stéphane Richard, Tanveer Sharif, Kathleen J Millen, Brad W Doble, Michael D Taylor, Tamra E Werbowetski-Ogilvie Aug 2024

A Group 3 Medulloblastoma Stem Cell Program Is Maintained By Otx2-Mediated Alternative Splicing, Olivier Saulnier, Jamie Zagozewski, Lisa Liang, Liam D Hendrikse, Paul Layug, Victor Gordon, Kimberly A Aldinger, Parthiv Haldipur, Stephanie Borlase, Ludivine Coudière-Morrison, Ting Cai, Emma Martell, Naomi M Gonzales, Gareth Palidwor, Christopher J Porter, Stéphane Richard, Tanveer Sharif, Kathleen J Millen, Brad W Doble, Michael D Taylor, Tamra E Werbowetski-Ogilvie

Faculty, Staff and Students Publications

OTX2 is a transcription factor and known driver in medulloblastoma (MB), where it is amplified in a subset of tumours and overexpressed in most cases of group 3 and group 4 MB. Here we demonstrate a noncanonical role for OTX2 in group 3 MB alternative splicing. OTX2 associates with the large assembly of splicing regulators complex through protein-protein interactions and regulates a stem cell splicing program. OTX2 can directly or indirectly bind RNA and this may be partially independent of its DNA regulatory functions. OTX2 controls a pro-tumorigenic splicing program that is mirrored in human cerebellar rhombic lip origins. Among …


Fine-Tuning Ampk In Physiology And Disease Using Point-Mutant Mouse Models, Naghmana Ashraf, Jeanine L Van Nostrand Aug 2024

Fine-Tuning Ampk In Physiology And Disease Using Point-Mutant Mouse Models, Naghmana Ashraf, Jeanine L Van Nostrand

Faculty, Staff and Students Publications

AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that monitors the cellular energy status to adapt it to the fluctuating nutritional and environmental conditions in an organism. AMPK plays an integral part in a wide array of physiological processes, such as cell growth, autophagy and mitochondrial function, and is implicated in diverse diseases, including cancer, metabolic disorders, cardiovascular diseases and neurodegenerative diseases. AMPK orchestrates many different physiological outcomes by phosphorylating a broad range of downstream substrates. However, the importance of AMPK-mediated regulation of these substrates in vivo remains an ongoing area of investigation to better understand its precise …


Detection Of Soil-Transmitted Helminths And Schistosoma Spp By Nucleic Acid Amplification Test: Results Of The First 5 Years Of The Only International External Quality Assessment Scheme, Annemiek H J Schutte, Rob Koelewijn, Sitara S R Ajjampur, Bruno Levecke, James S Mccarthy, Rojelio Mejia, Steven A Williams, Jaco J Verweij, Lisette Van Lieshout, Jaap J Van Hellemond Aug 2024

Detection Of Soil-Transmitted Helminths And Schistosoma Spp By Nucleic Acid Amplification Test: Results Of The First 5 Years Of The Only International External Quality Assessment Scheme, Annemiek H J Schutte, Rob Koelewijn, Sitara S R Ajjampur, Bruno Levecke, James S Mccarthy, Rojelio Mejia, Steven A Williams, Jaco J Verweij, Lisette Van Lieshout, Jaap J Van Hellemond

Faculty, Staff and Students Publications

BACKGROUND: Infections with soil-transmitted helminths (STH) and schistosomiasis (SCH) result in a significant global health burden, particularly in rural communities in low and middle-income countries. While microscopy remains the primary diagnostic method for STH and SCH in resource-limited settings, nucleic acid amplification tests (NAATs) are gaining prominence as tools for evaluation of public health control programs in endemic countries, and individual diagnosis in high-income countries. Despite the high sensitivity and specificity of NAATs, previous research has highlighted inter-laboratory variations, both in technical and clinical performance, justifying the need for continuous proficiency testing.

METHODOLOGY: Results from 5 rounds over a 5-year …


Deletion Of Mipep In Adipocytes Protects Against Obesity And Insulin Resistance By Boosting Muscle Metabolism, Alexis Diaz-Vegas, Kristen C Cooke, Harry B Cutler, Belinda Yau, Stewart W C Masson, Dylan Harney, Oliver K Fuller, Meg Potter, Søren Madsen, Niamh R Craw, Yiju Zhang, Cesar L Moreno, Melkam A Kebede, G Gregory Neely, Jacqueline Stöckli, James G Burchfield, David E James Aug 2024

Deletion Of Mipep In Adipocytes Protects Against Obesity And Insulin Resistance By Boosting Muscle Metabolism, Alexis Diaz-Vegas, Kristen C Cooke, Harry B Cutler, Belinda Yau, Stewart W C Masson, Dylan Harney, Oliver K Fuller, Meg Potter, Søren Madsen, Niamh R Craw, Yiju Zhang, Cesar L Moreno, Melkam A Kebede, G Gregory Neely, Jacqueline Stöckli, James G Burchfield, David E James

Faculty, Staff and Students Publications

Mitochondria facilitate thousands of biochemical reactions, covering a broad spectrum of anabolic and catabolic processes. Here we demonstrate that the adipocyte mitochondrial proteome is markedly altered across multiple models of insulin resistance and reveal a consistent decrease in the level of the mitochondrial processing peptidase miPEP.

OBJECTIVE: To determine the role of miPEP in insulin resistance.

METHODS: To experimentally test this observation, we generated adipocyte-specific miPEP knockout mice to interrogate its role in the aetiology of insulin resistance.

RESULTS: We observed a strong phenotype characterised by enhanced insulin sensitivity and reduced adiposity, despite normal food intake and physical activity. Strikingly, …


Development Of A Novel Drug Delivery Platform To Treat Hiv-Associated Neurocognitive Disorder, Lina Zhou Aug 2024

Development Of A Novel Drug Delivery Platform To Treat Hiv-Associated Neurocognitive Disorder, Lina Zhou

Alternative Theses and Dissertations (AETDs)

Despite the significant reduction in HIV prevalence and improvement in life expectancy achieved through the availability of widespread antiretroviral therapy (ART), there remains no definitive cure for HIV. Further, HIV infects the brain as early as eight days after initial peripheral infection leading to neuroHIV and subsequently neuronal damage and cognitive impairment. HIV can enter the brain through several mechanisms, including the migration of infected immune cells (Trojan Horse Mechanism), direct infection of endothelial cells, and cytokine-mediated disruption of the blood-brain barrier (BBB). Consequently, HIV-associated neurocognitive disorder (HAND) remains a significant challenge in the ART era, with an estimated prevalence …


Amoxicillin And Penicillin G Dosing In Pediatric Community-Acquired Pneumococcal Pneumonia In The Era Of Conjugate Pneumococcal Vaccines, Dustin Huynh, Norint Tung, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Allison Nguyen, Tyler H Do, Amartya Setty, Jennifer Le Aug 2024

Amoxicillin And Penicillin G Dosing In Pediatric Community-Acquired Pneumococcal Pneumonia In The Era Of Conjugate Pneumococcal Vaccines, Dustin Huynh, Norint Tung, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Allison Nguyen, Tyler H Do, Amartya Setty, Jennifer Le

Faculty, Staff and Students Publications

Background: Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data.

Methods: Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12 h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages …


Something Seems Fishy: Hepatic Abscess Due To Foreign Body Ingestion In A Pediatric Patient, James Rhodes, Amanda Macias, Emma Cooke, Joel Jacob, Ashley Devoll, Chelsea Young, Bradford Nguyen Aug 2024

Something Seems Fishy: Hepatic Abscess Due To Foreign Body Ingestion In A Pediatric Patient, James Rhodes, Amanda Macias, Emma Cooke, Joel Jacob, Ashley Devoll, Chelsea Young, Bradford Nguyen

Faculty, Staff and Students Publications

Pediatric hepatic abscesses are uncommon in children. They are usually preceded by intra-abdominal infections or caused by acute or chronic biliary disease. Cases of hepatic abscesses secondary to foreign body ingestion are even rarer but are most reported in countries such as China, where ingestion of fish and chicken bones is common. We report a rare case of an adolescent patient who developed a hepatic abscess after ingestion of a fishbone foreign body. He presented to the emergency department with emesis, abdominal pain, and subjective fevers of unknown etiology. Initial imaging of the abdomen was pertinent for a heterogeneous hepatic …


Histone Serotonylation Regulates Ependymoma Tumorigenesis, Hsiao-Chi Chen, Peihao He, Malcolm Mcdonald, Michael R Williamson, Srinidhi Varadharajan, Brittney Lozzi, Junsung Woo, Dong-Joo Choi, Debosmita Sardar, Emmet Huang-Hobbs, Hua Sun, Siri M Ippagunta, Antrix Jain, Ganesh Rao, Thomas E Merchant, David W Ellison, Jeffrey L Noebels, Kelsey C Bertrand, Stephen C Mack, Benjamin Deneen Aug 2024

Histone Serotonylation Regulates Ependymoma Tumorigenesis, Hsiao-Chi Chen, Peihao He, Malcolm Mcdonald, Michael R Williamson, Srinidhi Varadharajan, Brittney Lozzi, Junsung Woo, Dong-Joo Choi, Debosmita Sardar, Emmet Huang-Hobbs, Hua Sun, Siri M Ippagunta, Antrix Jain, Ganesh Rao, Thomas E Merchant, David W Ellison, Jeffrey L Noebels, Kelsey C Bertrand, Stephen C Mack, Benjamin Deneen

Faculty, Staff and Students Publications

Bidirectional communication between tumors and neurons has emerged as a key facet of the tumor microenvironment that drives malignancy1,2. Another hallmark feature of cancer is epigenomic dysregulation, where alterations in gene expression influences cell states and interactions with the tumor microenvironment3. Ependymoma (EPN) is a pediatric brain tumor that relies on epigenomic remodeling to engender malignancy4,5; how these epigenetic mechanisms intersect with extrinsic neuronal signaling during EPN tumor progression is unknown. Here we show that activity of serotonergic neurons regulates EPN tumorigenesis, while serotonin itself also serves as an activating …


Modern Perspectives On Hypertrophic Cardiomyopathy-No One Size Fits All, Brett Doliner, Hadeel Gaddar, Ramsey Kalil, Alexander Postalian Aug 2024

Modern Perspectives On Hypertrophic Cardiomyopathy-No One Size Fits All, Brett Doliner, Hadeel Gaddar, Ramsey Kalil, Alexander Postalian

The Texas Heart Institute Journal

Despite substantial advances in the management of hypertrophic cardiomyopathy, advanced heart failure remains a major cause of morbidity in this patient population. This narrative review presents the case of a patient with hypertrophic obstructive cardiomyopathy who underwent alcohol septal ablation to frame a discussion of modern therapies for hypertrophic cardiomyopathy. The current treatment landscape includes medications, both old and new, and surgical and procedural interventions to relieve mechanical obstruction. Several promising new modalities for relieving obstruction are in the nascent stages of development.


Systematic Transcriptome Profiling Of Hpsc-Derived Osteoblasts Unveils Corin’S Mastery In Governing Osteogenesis Through Cebpd Modulation, Dandan Zhu, Mo-Fan Huang, An Xu, Xueqin Gao, Yu-Wen Huang, Trinh T T Phan, Linchao Lu, Ting-Yen Chi, Yulin Dai, Lon Kai Pang, Julian A Gingold, Jian Tu, Zijun Huo, Danielle A Bazer, Rachel Shoemaker, Jun Wang, Catherine G Ambrose, Jingnan Shen, Jun Kameoka, Zhongming Zhao, Lisa L Wang, Yang Zhang, Ruiying Zhao, Dung-Fang Lee Aug 2024

Systematic Transcriptome Profiling Of Hpsc-Derived Osteoblasts Unveils Corin’S Mastery In Governing Osteogenesis Through Cebpd Modulation, Dandan Zhu, Mo-Fan Huang, An Xu, Xueqin Gao, Yu-Wen Huang, Trinh T T Phan, Linchao Lu, Ting-Yen Chi, Yulin Dai, Lon Kai Pang, Julian A Gingold, Jian Tu, Zijun Huo, Danielle A Bazer, Rachel Shoemaker, Jun Wang, Catherine G Ambrose, Jingnan Shen, Jun Kameoka, Zhongming Zhao, Lisa L Wang, Yang Zhang, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Student Publications

The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and intrinsic transcriptional machinery. While rodent osteoblastic differentiation has been extensively studied, research on human osteogenesis has been limited by cell sources and existing models. Here, we systematically dissect human pluripotent stem cell-derived osteoblasts to identify functional membrane proteins and their downstream transcriptional networks involved in human osteogenesis. Our results reveal an enrichment of type II transmembrane serine protease CORIN in humans but not rodent osteoblasts. Functional analyses demonstrated that CORIN depletion significantly impairs osteogenesis. Genome-wide chromatin …


Lymph Node Targeting Of Cyclosporine Ameliorates Ocular Manifestations In A Mouse Model Of Systemic Lupus Erythematosus (Sle) Via Pd-L1, Raghu Ganugula, Kabirat T Babalola, Ingrid M Heyns, Meenakshi Arora, Sandeep K Agarwal, Chandra Mohan, M N V Ravi Kumar Aug 2024

Lymph Node Targeting Of Cyclosporine Ameliorates Ocular Manifestations In A Mouse Model Of Systemic Lupus Erythematosus (Sle) Via Pd-L1, Raghu Ganugula, Kabirat T Babalola, Ingrid M Heyns, Meenakshi Arora, Sandeep K Agarwal, Chandra Mohan, M N V Ravi Kumar

Faculty, Staff and Students Publications

One-third of systemic lupus erythematosus (SLE) patients experience various degrees of ocular manifestations, with immunosuppressants recommended as a treatment option. Targeted immune suppression via oral administration is challenging due to the harsh gastrointestinal tract environment combined with complex physiological barriers. Here, we report the efficacy of orally administered cyclosporine (CsA)-laden polymer nanoparticles decorated with the ligand - Gambogic Acid (P2Ns-GA-CsA) in sustained lymph node delivery. This is the first report demonstrating the CD71 specificity of P2Ns-GA-CsA in the CD71 knockout mouse model and the influence of spacer length in achieving target tissue bioavailability in a lupus mouse model. P2Ns-GA-CsA effectively …


Governing With Public Engagement: An Anticipatory Approach To Human Genome Editing, Dorit Barlevy, Eric Juengst, Jeffrey Kahn, Jonathan Moreno, Lauren Lambert, Alta Charo, Hervé Chneiweiss, Mahmud Farooque, David H Guston, Insoo Hyun, Paul S Knoepfler, Cynthia Selin, Rebecca Wilbanks, Manar Zaghlula, Christopher Thomas Scott Aug 2024

Governing With Public Engagement: An Anticipatory Approach To Human Genome Editing, Dorit Barlevy, Eric Juengst, Jeffrey Kahn, Jonathan Moreno, Lauren Lambert, Alta Charo, Hervé Chneiweiss, Mahmud Farooque, David H Guston, Insoo Hyun, Paul S Knoepfler, Cynthia Selin, Rebecca Wilbanks, Manar Zaghlula, Christopher Thomas Scott

Center for Medical Ethics and Health Policy Staff Publications

In response to calls for public engagement on human genome editing (HGE), which intensified after the 2018 He Jiankui scandal that resulted in the implantation of genetically modified embryos, we detail an anticipatory approach to the governance of HGE. By soliciting multidisciplinary experts’ input on the drivers and uncertainties of HGE development, we developed a set of plausible future scenarios to ascertain publics values—specifically, their hopes and concerns regarding the novel technology and its applications. In turn, we gathered a subset of multidisciplinary experts to propose governance recommendations for HGE that incorporate identified publics’ values. These recommendations include: (1) continued …


Generating Clinical-Grade Gene-Disease Validity Classifications Through The Clingen Data Platforms, Matt W Wright, Courtney L Thaxton, Tristan Nelson, Marina T Distefano, Juliann M Savatt, Matthew H Brush, Gloria Cheung, Mark E Mandell, Bryan Wulf, T J Ward, Scott Goehringer, Terry O'Neill, Phil Weller, Christine G Preston, Ingrid M Keseler, Jennifer L Goldstein, Natasha T Strande, Jennifer Mcglaughon, Danielle R Azzariti, Ineke Cordova, Hannah Dziadzio, Lawrence Babb, Kevin Riehle, Aleksandar Milosavljevic, Christa Lese Martin, Heidi L Rehm, Sharon E Plon, Jonathan S Berg, Erin R Riggs, Teri E Klein Aug 2024

Generating Clinical-Grade Gene-Disease Validity Classifications Through The Clingen Data Platforms, Matt W Wright, Courtney L Thaxton, Tristan Nelson, Marina T Distefano, Juliann M Savatt, Matthew H Brush, Gloria Cheung, Mark E Mandell, Bryan Wulf, T J Ward, Scott Goehringer, Terry O'Neill, Phil Weller, Christine G Preston, Ingrid M Keseler, Jennifer L Goldstein, Natasha T Strande, Jennifer Mcglaughon, Danielle R Azzariti, Ineke Cordova, Hannah Dziadzio, Lawrence Babb, Kevin Riehle, Aleksandar Milosavljevic, Christa Lese Martin, Heidi L Rehm, Sharon E Plon, Jonathan S Berg, Erin R Riggs, Teri E Klein

Center for Medical Ethics and Health Policy Staff Publications

Clinical genetic laboratories must have access to clinically validated biomedical data for precision medicine. A lack of accessibility, normalized structure, and consistency in evaluation complicates interpretation of disease causality, resulting in confusion in assessing the clinical validity of genes and genetic variants for diagnosis. A key goal of the Clinical Genome Resource (ClinGen) is to fill the knowledge gap concerning the strength of evidence supporting the role of a gene in a monogenic disease, which is achieved through a process known as Gene-Disease Validity curation. Here we review the work of ClinGen in developing a curation infrastructure that supports the …


Preeclampsia In The Context Of Covid-19: Mechanisms, Pathophysiology, And Clinical Outcomes, Guilherme M Nobrega, Brittany R Jones, Indira U Mysorekar, Maria Laura Costa Aug 2024

Preeclampsia In The Context Of Covid-19: Mechanisms, Pathophysiology, And Clinical Outcomes, Guilherme M Nobrega, Brittany R Jones, Indira U Mysorekar, Maria Laura Costa

Center on Aging Staff Publications

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with …


Treatments And The Perspectives Of Developing A Vaccine For Chagas Disease, Priscila Silva Grijó Farani, Kathryn Marie Jones, Cristina Poveda Aug 2024

Treatments And The Perspectives Of Developing A Vaccine For Chagas Disease, Priscila Silva Grijó Farani, Kathryn Marie Jones, Cristina Poveda

Faculty, Staff and Students Publications

Chagas disease (CD) treatment and vaccine development are critical due to the significant health burden caused by the disease, especially in Latin America. Current treatments include benznidazole and nifurtimox, which are most effective in the acute phase of the disease but less so in the chronic phase, often with significant side effects. Here, using the available literature, we summarize the progress in vaccine development and new treatments that promise to reduce CD incidence and improve the quality of life for those at risk, particularly in endemic regions. New treatment options, such as posaconazole and fexinidazole, are being explored to improve …


Augustus Waller's Foresight Realized: Sarm1 In Peripheral Neuropathies, Stefanie Geisler Aug 2024

Augustus Waller's Foresight Realized: Sarm1 In Peripheral Neuropathies, Stefanie Geisler

2020-Current year OA Pubs

Peripheral neuropathy is a common neurodegenerative condition characterized by numbness, tingling, pain, and weakness that frequently starts in the distal limbs. Arising from multiple etiologies, many peripheral neuropathies exhibit a slowly progressive course due to axon degeneration for which no effective treatments exist. During the past decade, numerous crucial insights into mechanisms of axon degeneration in peripheral neuropathies emerged from experiments involving nerve-cutting procedures, revealing the central role of the SARM1 axon degeneration pathway in both. Here I review commonalities and differences in the role of SARM1 after nerve cut and in several acquired and inherited peripheral neuropathies. This new …


A Response To “The Danger Of Ideology”, Amie Thurber, Ericka Kimball Aug 2024

A Response To “The Danger Of Ideology”, Amie Thurber, Ericka Kimball

School of Social Work Faculty Publications and Presentations

On January 9, 2024, Social Work journal published in advance access a commentary by Farber and Fram titled “The Danger of Ideology: Social Work, Israel, and Anti-Semitism” (Farber & Fram, 2024). Writing following the October 7 Hamas attack on Israel, the authors lay out their central thesis in the opening paragraph: “We watch in horror and stand in support of Israel. As social work educators and scholars, we must also speak about the complicity of our profession in nurturing anti-Semitism and the ideology that undergirds Hamas and other terrorist organizations” (p. 1). This is a serious claim, and one that …


Efficacy And Tolerability Of Levetiracetam In People With And Without Intellectual Disabilities: A Naturalistic Case Control Study, Jon Allard, Adrian Sellers, William Henley, Brendan Mclean, Mary Parrett, Sanjeev Rajakulendran, Lance Watkins, Melissa Maguire, Shan Ellawela, Phil Tittensor, Juliet Bransgrove, Arjune Sen, Rajiv Mohanraj, Many Bagary, Sunil Ram, Nathan Vernon, Sandy Baldwin, Jagdish Gill, Rohit Shankar Aug 2024

Efficacy And Tolerability Of Levetiracetam In People With And Without Intellectual Disabilities: A Naturalistic Case Control Study, Jon Allard, Adrian Sellers, William Henley, Brendan Mclean, Mary Parrett, Sanjeev Rajakulendran, Lance Watkins, Melissa Maguire, Shan Ellawela, Phil Tittensor, Juliet Bransgrove, Arjune Sen, Rajiv Mohanraj, Many Bagary, Sunil Ram, Nathan Vernon, Sandy Baldwin, Jagdish Gill, Rohit Shankar

Peninsula Medical School

IntroductionPeople with Intellectual Disabilities (PwID) are twenty times more likely than general population to have epilepsy. Guidance for prescribing antiseizure medication (ASM) to PwID is driven by trials excluding them. Levetiracetam (LEV) is a first-line ASM in the UK. Concerns exist regarding LEV's behavioural and psychological adverse effects, particularly in PwID. There is no high-quality evidence comparing effectiveness and adverse effects in PwID to those without, prescribed LEV.MethodsPooled casenote data for patients prescribed LEV (2000–2020) at 18 UK NHS Trusts were analysed. Demographics, starting and maximum dose, adverse effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and …