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Long-Chain Polyunsaturated Lipids Associated With Responsiveness To Anti-Pd-1 Therapy Are Colocalized With Immune Infiltrates In The Tumor Microenvironment, Mary E King, Robert Yuan, Jeremy Chen, Komal Pradhan, Isabel Sariol, Shirley Li, Ashish Chakraborty, Oscar Ekpenyong, Jennifer H Yearley, Janica C Wong, Luis Zúñiga, Daniela Tomazela, Maribel Beaumont, Jin-Hwan Han, Livia S Eberlin Mar 2023

Long-Chain Polyunsaturated Lipids Associated With Responsiveness To Anti-Pd-1 Therapy Are Colocalized With Immune Infiltrates In The Tumor Microenvironment, Mary E King, Robert Yuan, Jeremy Chen, Komal Pradhan, Isabel Sariol, Shirley Li, Ashish Chakraborty, Oscar Ekpenyong, Jennifer H Yearley, Janica C Wong, Luis Zúñiga, Daniela Tomazela, Maribel Beaumont, Jin-Hwan Han, Livia S Eberlin

Faculty, Staff and Students Publications

The programmed cell death protein-1 (PD-1) is highly expressed on the surface of antigen-specific exhausted T cells and, upon interaction with its ligand PD-L1, can result in inhibition of the immune response. Anti-PD-1 treatment has been shown to extend survival and result in durable responses in several cancers, yet only a subset of patients benefit from this therapy. Despite the implication of metabolic alteration following cancer immunotherapy, mechanistic associations between antitumor responses and metabolic changes remain unclear. Here, we used desorption electrospray ionization mass spectrometry imaging to examine the lipid profiles of tumor tissue from three syngeneic murine models with …


Sinus Node Dysfunction: Current Understanding And Future Directions, Pavan Manoj, Jitae A Kim, Stephanie Kim, Tingting Li, Maham Sewani, Mihail G Chelu, Na Li Mar 2023

Sinus Node Dysfunction: Current Understanding And Future Directions, Pavan Manoj, Jitae A Kim, Stephanie Kim, Tingting Li, Maham Sewani, Mihail G Chelu, Na Li

Faculty, Staff and Students Publications

The sinoatrial node (SAN) is the primary pacemaker of the heart. Normal SAN function is crucial in maintaining proper cardiac rhythm and contraction. Sinus node dysfunction (SND) is due to abnormalities within the SAN, which can affect the heartbeat frequency, regularity, and the propagation of electrical pulses through the cardiac conduction system. As a result, SND often increases the risk of cardiac arrhythmias. SND is most commonly seen as a disease of the elderly given the role of degenerative fibrosis as well as other age-dependent changes in its pathogenesis. Despite the prevalence of SND, current treatment is limited to pacemaker …


New Mouse Models With Hypomorphic Sumf1 Variants Mimic Attenuated Forms Of Multiple Sulfatase Deficiency, Nicolina Cristina Sorrentino, Maximiliano Presa, Sergio Attanasio, Vincenzo Cacace, Martina Sofia, Aamir Zuberi, Jennifer Ryan, Somdatta Ray, Igor Petkovic, Karthikeyan Radhakrishnan, Lars Schlotawa, Andrea Ballabio, Cathleen Lutz, Nicola Brunetti-Pierri Mar 2023

New Mouse Models With Hypomorphic Sumf1 Variants Mimic Attenuated Forms Of Multiple Sulfatase Deficiency, Nicolina Cristina Sorrentino, Maximiliano Presa, Sergio Attanasio, Vincenzo Cacace, Martina Sofia, Aamir Zuberi, Jennifer Ryan, Somdatta Ray, Igor Petkovic, Karthikeyan Radhakrishnan, Lars Schlotawa, Andrea Ballabio, Cathleen Lutz, Nicola Brunetti-Pierri

Duncan NRI Faculty and Staff Publications

Multiple sulfatase deficiency (MSD) is an ultrarare lysosomal storage disorder due to deficiency of all known sulfatases. MSD is caused by mutations in the Sulfatase Modifying Factor 1 (SUMF1) gene encoding the enzyme responsible for the post-translational modification and activation of all sulfatases. Most MSD patients carry hypomorph SUMF1 variants resulting in variable degrees of residual sulfatase activities. In contrast, Sumf1 null mice with complete deficiency in all sulfatase enzyme activities, have very short lifespan with significant pre-wean lethality, owing to a challenging preclinical model. To overcome this limitation, we genetically engineered and characterized in mice two commonly …


Potential Mirna Biomarkers And Therapeutic Targets For Early Atherosclerotic Lesions, Genesio M. Karere, Jeremy P. Glenn, Ge Li, Ayati Konar, John L. Vandeberg, Laura A. Cox Mar 2023

Potential Mirna Biomarkers And Therapeutic Targets For Early Atherosclerotic Lesions, Genesio M. Karere, Jeremy P. Glenn, Ge Li, Ayati Konar, John L. Vandeberg, Laura A. Cox

School of Medicine Publications

Identification of potential therapeutic targets and biomarkers indicative of burden of early atherosclerosis that occur prior to advancement to life-threatening unstable plaques is the key to eradication of CAD prevalence and incidences. We challenged 16 baboons with a high cholesterol, high fat diet for 2 years and evaluated early-stage atherosclerotic lesions (fatty streaks, FS, and fibrous plaques, FP) in formalin-fixed common iliac arteries (CIA). We used small RNA sequencing to identify expressed miRNAs in CIA and in baseline blood samples of the same animals. We found 412 expressed miRNAs in CIA and 356 in blood samples. Eight miRNAs (miR-7975, -486-5p, …


Curative Effects Of Triphala Extract Against Swim Stress-Induced Gastric Ulcers Via Reduced Ulcer Index, Strengthened Gastric Mucosa And Improved Redox State In Rats, M Khushtar, H H. Siddiqui, R K. Dixit, Sahir Sultan Alvi Mar 2023

Curative Effects Of Triphala Extract Against Swim Stress-Induced Gastric Ulcers Via Reduced Ulcer Index, Strengthened Gastric Mucosa And Improved Redox State In Rats, M Khushtar, H H. Siddiqui, R K. Dixit, Sahir Sultan Alvi

School of Medicine Publications

Recently, the percentage of Peptic ulcer disease not linked to either Helicobacter pylori or non-steroidal anti-inflammatory drugs has increased and signifies the prominent role of psychophysiological stress in the establishment and advancements of gastric ulcers and other peptic ulcer diseases. The current study was intended not only to develop post-treatment swim stress-induced peptic ulcer disease rat model but also to analyze the curative effects of hydro-alcoholic extract of Triphala in swim stress-induced peptic ulcer disease model. A post-treatment swim stress-induced peptic ulcer disease rat model was developed followed by therapeutic intervention of hydro-alcoholic extract of Triphala. The gross evaluation of …


Botulinum Neurotoxin A4 Has A 1000-Fold Reduced Potency Due To Three Single Amino Acid Alterations In The Protein Receptor Binding Domain, William H. Tepp, Marite Bradshaw, Alexander P. Gardner, Rebecca L. Kaufman, Joseph T. Barbieri, Sabine Pellett Mar 2023

Botulinum Neurotoxin A4 Has A 1000-Fold Reduced Potency Due To Three Single Amino Acid Alterations In The Protein Receptor Binding Domain, William H. Tepp, Marite Bradshaw, Alexander P. Gardner, Rebecca L. Kaufman, Joseph T. Barbieri, Sabine Pellett

College of Nursing Faculty Research and Publications

Botulinum neurotoxin subtype A4 (BoNT/A4) is ~1000-fold less potent than BoNT/A1. This study addresses the basis for low BoNT/A4 potency. Utilizing BoNT/A1-A4 and BoNT/A4-A1 Light Chain-Heavy Chain (LC-HC) chimeras, HC-A4 was responsible for low BoNT/A4 potency. Earlier studies showed BoNT/A1-receptor binding domain (Hcc) bound a β-strand peptide (556–564) and glycan-N559 within Luminal Domain 4 (LD4) of SV2C, the BoNT/A protein receptor. Relative to BoNT/A1, the Hcc of BoNT/A4 possesses two amino acid variants (D1141 and N1142) within the β-peptide binding interface and one amino acid variant (R1292) located near the SV2C glycan-N559. …


Ectopic Lymphoid Structures In The Aged Lacrimal Glands, Jeremias G Galletti, Kaitlin K Scholand, Claudia M Trujillo-Vargas, Zhiyuan Yu, Olivier Mauduit, Vanessa Delcroix, Helen P Makarenkova, Cintia S De Paiva Mar 2023

Ectopic Lymphoid Structures In The Aged Lacrimal Glands, Jeremias G Galletti, Kaitlin K Scholand, Claudia M Trujillo-Vargas, Zhiyuan Yu, Olivier Mauduit, Vanessa Delcroix, Helen P Makarenkova, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6J had increased lacrimal gland (LG) lymphoid infiltrates that suggest ectopic lymphoid structures. However, these ectopic lymphoid structures have not been fully investigated. Using C57BL/6J mice of different ages, we analyzed the transcriptome of aged murine LGs and characterized the B and T cell populations. Age-related changes in the LG include increased differentially expressed genes associated with B and T cell activation, germinal center formation, and infiltration by marginal zone-like B cells. We also identified an age-related increase in B1


Longitudinal Evaluation Of Serum Micrornas As Biomarkers For Neuroblastoma Burden And Therapeutic P53 Reactivation, Alan Van Goethem, Jill Deleu, Nurten Yigit, Celine Everaert, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Fjoralba Zeka, Fleur Demuynck, Eveline Barbieri, Frank Speleman, Pieter Mestdagh, Jason Shohet, Jo Vandesompele, Tom Van Maerken Mar 2023

Longitudinal Evaluation Of Serum Micrornas As Biomarkers For Neuroblastoma Burden And Therapeutic P53 Reactivation, Alan Van Goethem, Jill Deleu, Nurten Yigit, Celine Everaert, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Fjoralba Zeka, Fleur Demuynck, Eveline Barbieri, Frank Speleman, Pieter Mestdagh, Jason Shohet, Jo Vandesompele, Tom Van Maerken

Faculty, Staff and Students Publications

Accurate assessment of treatment response and residual disease is indispensable for the evaluation of cancer treatment efficacy. However, performing tissue biopsies for longitudinal follow-up poses a major challenge in the management of solid tumours like neuroblastoma. In the present study, we evaluated whether circulating miRNAs are suitable to monitor neuroblastoma tumour burden and whether treatment-induced changes of miRNA abundance in the tumour are detectable in serum. We performed small RNA sequencing on longitudinally collected serum samples from mice carrying orthotopic neuroblastoma xenografts that were exposed to treatment with idasanutlin or temsirolimus. We identified 57 serum miRNAs to be differentially expressed …


A Randomized, Controlled Phase 1b Trial Of The Sm-Tsp-2 Vaccine For Intestinal Schistosomiasis In Healthy Brazilian Adults Living In An Endemic Area, David J Diemert, Rodrigo Correa-Oliveira, Carlo Geraldo Fraga, Frederico Talles, Marcella Rezende Silva, Shital M Patel, Shirley Galbiati, Jessie K Kennedy, Jordan S Lundeen, Maria Flavia Gazzinelli, Guangzhao Li, Lara Hoeweler, Gregory A Deye, Maria Elena Bottazzi, Peter J Hotez, Hana M El Sahly, Wendy A Keitel, Jeffrey Bethony, Robert L Atmar Mar 2023

A Randomized, Controlled Phase 1b Trial Of The Sm-Tsp-2 Vaccine For Intestinal Schistosomiasis In Healthy Brazilian Adults Living In An Endemic Area, David J Diemert, Rodrigo Correa-Oliveira, Carlo Geraldo Fraga, Frederico Talles, Marcella Rezende Silva, Shital M Patel, Shirley Galbiati, Jessie K Kennedy, Jordan S Lundeen, Maria Flavia Gazzinelli, Guangzhao Li, Lara Hoeweler, Gregory A Deye, Maria Elena Bottazzi, Peter J Hotez, Hana M El Sahly, Wendy A Keitel, Jeffrey Bethony, Robert L Atmar

Faculty, Staff and Students Publications

BACKGROUND: Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing S. mansoni transmission in Brazil, and preclinical studies in which vaccination with Sm-TSP-2 protected mice following infection challenge.

METHODS: A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing S. mansoni transmission. In each cohort of 20 participants, 16 were randomized to receive …


Tennessee Farm Bureau News - March 2023, Tennessee Farm Bureau Federation Mar 2023

Tennessee Farm Bureau News - March 2023, Tennessee Farm Bureau Federation

Tennessee Farm Bureau News

No abstract provided.


Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty Mar 2023

Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty

2020-Current year OA Pubs

In females, the hippocampus, a critical brain region for coordination of learning, memory, and behavior, displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gene


Prevalence Of Long-Term Physical Sequelae Among Patients Treated With Multi-Drug And Extensively Drug-Resistant Tuberculosis: A Systematic Review And Meta-Analysis, Ty Akalu, Aca Clements, Hf Wolde, Ka Alene Mar 2023

Prevalence Of Long-Term Physical Sequelae Among Patients Treated With Multi-Drug And Extensively Drug-Resistant Tuberculosis: A Systematic Review And Meta-Analysis, Ty Akalu, Aca Clements, Hf Wolde, Ka Alene

Peninsula Medical School

Background Physical sequelae related to multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are emerging and under-recognised global challenges. This systematic review and meta-analysis aimed to quantify the prevalence and the types of long-term physical sequelae associated with patients treated for MDR- and XDR-TB. Methods We systematically searched CINAHL (EBSCO), MEDLINE (via Ovid), Embase, Scopus, and Web of Science from inception through to July 1, 2022, and the last search was updated to January 23, 2023. We included studies reporting physical sequelae associated with all forms of drug-resistant TB, including rifampicin-resistant TB (RR-TB), MDR-TB, Pre-XDR-TB, and XDR-TB. The primary …


Epibionts Provide Their Basibionts With Associational Resistance To Predation But At A Cost, S Downes, L Firth, Am Knights Mar 2023

Epibionts Provide Their Basibionts With Associational Resistance To Predation But At A Cost, S Downes, L Firth, Am Knights

School of Biological and Marine Sciences

Epibiosis is increasingly considered a survival strategy in space-limited environments. However, epibionts can create a new interface between its host, environment and potential predators which may alter predator-prey relationships and biological functioning. Ex-situ experiments investigated the potential costs and benefits of epibiont barnacles on mortality and feeding rate of the mussel, Mytilus edulis, and its predator, the whelk Nucella lapillus. Mussels with living epibiont barnacles suffered no mortality from whelk predation, but when barnacles were absent, mortality was ~21% over 48 days. Further comparisons revealed the structural complexity of barnacles provided mussels with protection from whelk predation, while the presence …


Uav High-Resolution Imaging And Disease Surveys Combine To Quantify Climate-Related Decline In Seagrass Meadows, Lillian R. Aoki, Bo Yang, Olivia J. Graham, Carla Gomes, Brendan Rappazzo, Timothy L. Hawthorne, J. Emmett Duffy, Drew Harvell Mar 2023

Uav High-Resolution Imaging And Disease Surveys Combine To Quantify Climate-Related Decline In Seagrass Meadows, Lillian R. Aoki, Bo Yang, Olivia J. Graham, Carla Gomes, Brendan Rappazzo, Timothy L. Hawthorne, J. Emmett Duffy, Drew Harvell

Faculty Research, Scholarly, and Creative Activity

No abstract provided.


Can Biodiversity Of Preexisting And Created Salt Marshes Match Across Scales? An Assessment From Microbes To Predators, Friedrich W. Keppeler, James R. Junker, Margaret J. Shaw, Scott B. Alford, Annette S. Engel, Linda M. Hooper-Bùi, Olaf P. Jensen, Katelyn Lamb, Paola C. López-Duarte, Charles W. Martin, Ashley M. Mcdonald, Jill A. Olin, Audrey T. Paterson, Michael J. Polito, Nancy N. Rabalais, Brian J. Roberts, Ryann E. Rossi, Erick M. Swenson Mar 2023

Can Biodiversity Of Preexisting And Created Salt Marshes Match Across Scales? An Assessment From Microbes To Predators, Friedrich W. Keppeler, James R. Junker, Margaret J. Shaw, Scott B. Alford, Annette S. Engel, Linda M. Hooper-Bùi, Olaf P. Jensen, Katelyn Lamb, Paola C. López-Duarte, Charles W. Martin, Ashley M. Mcdonald, Jill A. Olin, Audrey T. Paterson, Michael J. Polito, Nancy N. Rabalais, Brian J. Roberts, Ryann E. Rossi, Erick M. Swenson

Michigan Tech Publications, Part 1

Coastal wetlands are rapidly disappearing worldwide due to a variety of processes, including climate change and flood control. The rate of loss in the Mississippi River Delta is among the highest in the world and billions of dollars have been allocated to build and restore coastal wetlands. A key question guiding assessment is whether created coastal salt marshes have similar biodiversity to preexisting, reference marshes. However, the numerous biodiversity metrics used to make these determinations are typically scale dependent and often conflicting. Here, we applied ecological theory to compare the diversity of different assemblages (surface and below-surface soil microbes, plants, …


Urologic Sequelae Following Phalloplasty: An Explanation Of Common Complications Following Transmale Gender Affirmation Surgery, Michelle Kittleman Mar 2023

Urologic Sequelae Following Phalloplasty: An Explanation Of Common Complications Following Transmale Gender Affirmation Surgery, Michelle Kittleman

Theses

Medical advancement and societal acceptance in recent years has paved the way for gender affirmation surgery to become a growing subspecialty, with more transgender individuals seeking permanent methods to treating gender dysphoria. In a 2016 report from the American Society of Plastic Surgeons (ASPS), there had been a 20% increase in female-to-male gender affirmation surgeries over the past year, totaling over 1,700 surgeries (Schardein, 2020). Those seeking genital gender affirmation surgery, also known as ‘bottom’ surgery (Puckett, 2018), often have goals pertaining to the ability to urinate upright, with secondary goals relating to sexual penetration functions. Gender reconstruction procedures, such …


Association Of Healthful Plant-Based Diet Adherence With Risk Of Mortality And Major Chronic Diseases Among Adults In The Uk, Alysha S. Thompson, Anna Tresserra-Rimbau, Nena Karavasiloglou, Amy Jennings, Marie Cantwell, Claire Hill, Aurora Perez-Cornago, Nicola P. Bondonno, Neil Murphy, Sabine Rohrmann, Aedín Cassidy, Tilman Kühn Mar 2023

Association Of Healthful Plant-Based Diet Adherence With Risk Of Mortality And Major Chronic Diseases Among Adults In The Uk, Alysha S. Thompson, Anna Tresserra-Rimbau, Nena Karavasiloglou, Amy Jennings, Marie Cantwell, Claire Hill, Aurora Perez-Cornago, Nicola P. Bondonno, Neil Murphy, Sabine Rohrmann, Aedín Cassidy, Tilman Kühn

Research outputs 2022 to 2026

Importance: Plant-based diets have gained popularity for both environmental and health reasons, but a comprehensive assessment of their quality in relation to risk of mortality and major chronic diseases is lacking. Objective: To examine whether healthful vs unhealthful plant-based dietary patterns are associated with mortality and major chronic diseases among UK adults. Design, Setting, and Participants: This prospective cohort study used data from adults in the UK Biobank, a large-scale population-based study. Participants were recruited between 2006 and 2010 and followed up using record linkage data until 2021; follow-up for different outcomes ranged between 10.6 and 12.2 years. Data analysis …


Tweak/Fn14 Signalling Regulates The Tissue Microenvironment In Chronic Pancreatitis, N. Dianah B. Abu Bakar, Rodrigo Carlessi, Jully Gogoi-Tiwari, Julia Köhn-Gaone, Vincent Williams, Marco Falasca, John K. Olynyk, Grant A. Ramm, Janina E. E. Tirnitz-Parker Mar 2023

Tweak/Fn14 Signalling Regulates The Tissue Microenvironment In Chronic Pancreatitis, N. Dianah B. Abu Bakar, Rodrigo Carlessi, Jully Gogoi-Tiwari, Julia Köhn-Gaone, Vincent Williams, Marco Falasca, John K. Olynyk, Grant A. Ramm, Janina E. E. Tirnitz-Parker

Research outputs 2022 to 2026

Chronic pancreatitis increases the risk of developing pancreatic cancer through the upregulation of pathways favouring proliferation, fibrosis, and sustained inflammation. We established in previous studies that the ligand tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) signals through its cognate receptor fibroblast growth factor-inducible 14 (Fn14) to regulate these underlying cellular processes in the chronic liver injury niche. However, the role of the TWEAK/Fn14 signalling pathway in pancreatic disease is entirely unknown. An analysis of publicly available datasets demonstrated that the TWEAK receptor Fn14 is upregulated in pancreatitis and pancreatic adenocarcinoma, with single cell RNA sequencing revealing pancreatic ductal …


Using Switchable Solvents For Enhanced Biodiesel Production, Eyad Abdel Rahman Sowan Mar 2023

Using Switchable Solvents For Enhanced Biodiesel Production, Eyad Abdel Rahman Sowan

Theses

This thesis presents a sustainable approach to biodiesel production using in-situ technology for direct conversion of microalgae-to-biodiesel. The proposed method operates on wet, untreated microalgae, thereby eliminating the cost/energy intensive drying and cell disruption steps. Owing to their favorable properties, the use of enzymes, specifically lipase, as a catalyst for the process was suggested over acid/base catalysts. However, the high cost of the enzyme necessitates its reuse at sustained activity for the process to be economically feasible. The use of non-toxic green solvents, such as switchable solvents, as an alternative to conventional organic solvents was a significant challenge for the …


Hiv Increases The Risk Of Cigarette Smoke-Induced Emphysema Through Mmp-9, Bashar S. Staitieh, Simran Malik, Sara C. Auld, Gregory W. Wigger, Xian Fan, Andrew T. Roth, Tanima Chatterjee, Itika Arora, S. Vamsee Raju, Sonya Heath, Saurabh Aggrawal Mar 2023

Hiv Increases The Risk Of Cigarette Smoke-Induced Emphysema Through Mmp-9, Bashar S. Staitieh, Simran Malik, Sara C. Auld, Gregory W. Wigger, Xian Fan, Andrew T. Roth, Tanima Chatterjee, Itika Arora, S. Vamsee Raju, Sonya Heath, Saurabh Aggrawal

2020-Current year OA Pubs

BACKGROUND: HIV is associated with an increased risk for emphysema. Matrix metalloproteinase 9 (MMP-9) is a lung tissue remodeling enzyme associated with emphysema. We previously found MMP-9 activity increases with increases in oxidative stress and that HIV increases alveolar oxidative stress. We hypothesized that HIV proteins would increase the risk of cigarette smoke-induced emphysema due to MMP-9.

METHODS: HIV-1 transgenic rats and wild-type littermates were exposed to cigarette smoke or sham for 8 weeks. Lung compliance and histology were assessed. Bronchoalveolar lavage (BAL), primary alveolar macrophages (AM), and serum samples were obtained. A rat alveolar macrophage cell line was exposed …


Relationships Between Farmer Psychological Profiles And Farm Business Performance Amongst Smallholder Beef And Poultry Farmers In South Africa, Renato A. Villano, Isaac Koomson, Nkhanedzeni B. Nengovhela, Livhuwani Mudau, Heather M. Burrow, Navjot Bhullar Mar 2023

Relationships Between Farmer Psychological Profiles And Farm Business Performance Amongst Smallholder Beef And Poultry Farmers In South Africa, Renato A. Villano, Isaac Koomson, Nkhanedzeni B. Nengovhela, Livhuwani Mudau, Heather M. Burrow, Navjot Bhullar

Research outputs 2022 to 2026

Beef cattle and poultry are critically important livestock for improving household food security and alleviating poverty amongst smallholder farmers in South Africa. In this paper, our goal is to examine the relationships between farmer psychological profiles and farm business performance of commercially oriented beef cattle and poultry smallholder farmers in South Africa. We employ a multipronged interdisciplinary approach to test the theory of planned behaviour and its relationship to farm business performance. First, a behavioural science-informed survey instrument was employed to collect data from randomly selected farmer participants in two major beef and poultry projects undertaken by the authors. Second, …


The Menin Inhibitor Revumenib In Kmt2a-Rearranged Or Npm1-Mutant Leukaemia, Ghayas C Issa, John Dipersio, Shalini Shenoy, Et Al. Mar 2023

The Menin Inhibitor Revumenib In Kmt2a-Rearranged Or Npm1-Mutant Leukaemia, Ghayas C Issa, John Dipersio, Shalini Shenoy, Et Al.

2020-Current year OA Pubs

Targeting critical epigenetic regulators reverses aberrant transcription in cancer, thereby restoring normal tissue function


Targeted Deletion Of Fgf9 In Tendon Disrupts Mineralization Of The Developing Enthesis, Elahe Ganji, Connor Leek, William Duncan, Debabrata Patra, David M Ornitz, Megan L Killian Mar 2023

Targeted Deletion Of Fgf9 In Tendon Disrupts Mineralization Of The Developing Enthesis, Elahe Ganji, Connor Leek, William Duncan, Debabrata Patra, David M Ornitz, Megan L Killian

2020-Current year OA Pubs

The enthesis is a transitional tissue between tendon and bone that matures postnatally. The development and maturation of the enthesis involve cellular processes likened to an arrested growth plate. In this study, we explored the role of fibroblast growth factor 9 (Fgf9), a known regulator of chondrogenesis and vascularization during bone development, on the structure and function of the postnatal enthesis. First, we confirmed spatial expression of Fgf9 in the tendon and enthesis using in situ hybridization. We then used Cre-lox recombinase to conditionally knockout Fgf9 in mouse tendon and enthesis (Scx-Cre) and characterized enthesis morphology as well as mechanical …


Aging And Obesity Prime The Methylome And Transcriptome Of Adipose Stem Cells For Disease And Dysfunction, Shaojun Xie, Sulbha Choudhari, Chia-Lung Wu, Karen Abramson, David Corcoran, Simon G Gregory, Jyothi Thimmapuram, Farshid Guilak, Dianne Little Mar 2023

Aging And Obesity Prime The Methylome And Transcriptome Of Adipose Stem Cells For Disease And Dysfunction, Shaojun Xie, Sulbha Choudhari, Chia-Lung Wu, Karen Abramson, David Corcoran, Simon G Gregory, Jyothi Thimmapuram, Farshid Guilak, Dianne Little

2020-Current year OA Pubs

The epigenome of stem cells occupies a critical interface between genes and environment, serving to regulate expression through modification by intrinsic and extrinsic factors. We hypothesized that aging and obesity, which represent major risk factors for a variety of diseases, synergistically modify the epigenome of adult adipose stem cells (ASCs). Using integrated RNA- and targeted bisulfite-sequencing in murine ASCs from lean and obese mice at 5- and 12-months of age, we identified global DNA hypomethylation with either aging or obesity, and a synergistic effect of aging combined with obesity. The transcriptome of ASCs in lean mice was relatively stable to …


Resolution Of Hepatic Fibrosis After Zfn-Mediated Gene Editing In The Piz Mouse Model Of Human Α1-Antitrypsin Deficiency, Yanfeng Li, Chandan Guha, Patrik Asp, Xia Wang, Tatyana L. Tchaikovskya, Kenneth Kim, Matthew Mendel, Gregory J. Cost, David H. Perlmutter, Namita Roy-Chowdhury, Ira J. Fox, Anthony Conway, Jayanta Roy-Chowdhury Mar 2023

Resolution Of Hepatic Fibrosis After Zfn-Mediated Gene Editing In The Piz Mouse Model Of Human Α1-Antitrypsin Deficiency, Yanfeng Li, Chandan Guha, Patrik Asp, Xia Wang, Tatyana L. Tchaikovskya, Kenneth Kim, Matthew Mendel, Gregory J. Cost, David H. Perlmutter, Namita Roy-Chowdhury, Ira J. Fox, Anthony Conway, Jayanta Roy-Chowdhury

2020-Current year OA Pubs

BACKGROUND: α1-antitrypsin deficiency is most commonly caused by a mutation in exon-7 of SERPINA1 (SA1-ATZ), resulting in hepatocellular accumulation of a misfolded variant (ATZ). Human SA1-ATZ-transgenic (PiZ) mice exhibit hepatocellular ATZ accumulation and liver fibrosis. We hypothesized that disrupting the SA1-ATZ transgene in PiZ mice by in vivo genome editing would confer a proliferative advantage to the genome-edited hepatocytes, enabling them to repopulate the liver.

METHODS: To create a targeted DNA break in exon-7 of the SA1-ATZ transgene, we generated 2 recombinant adeno-associated viruses (rAAV) expressing a zinc-finger nuclease pair (rAAV-ZFN), and another rAAV for gene correction by targeted insertion …


A New Mouse Model Of Elastin Haploinsufficiency Highlights The Importance Of Elastin To Vascular Development And Blood Pressure Regulation, Bridget M Brengle, Michelle Lin, Robyn A Roth, Kara D Jones, Jessica E Wagenseil, Robert P Mecham, Carmen M Halabi Mar 2023

A New Mouse Model Of Elastin Haploinsufficiency Highlights The Importance Of Elastin To Vascular Development And Blood Pressure Regulation, Bridget M Brengle, Michelle Lin, Robyn A Roth, Kara D Jones, Jessica E Wagenseil, Robert P Mecham, Carmen M Halabi

2020-Current year OA Pubs

Supravalvular aortic stenosis (SVAS) is an autosomal dominant disease resulting from elastin (ELN) haploinsufficiency. Individuals with SVAS typically develop a thickened arterial media with an increased number of elastic lamellae and smooth muscle cell (SMC) layers and stenosis superior to the aortic valve. A mouse model of SVAS (Eln


Tnk2/Ack1-Mediated Phosphorylation Of Atp5f1a (Atp Synthase F1 Subunit Alpha) Selectively Augments Survival Of Prostate Cancer While Engendering Mitochondrial Vulnerability, Surbhi Chouhan, Mithila Sawant, Cody Weimholt, Jingqin Luo, Robert W Sprung, Mailyn Terrado, David M Mueller, H Shelton Earp, Nupam P. Mahajan Mar 2023

Tnk2/Ack1-Mediated Phosphorylation Of Atp5f1a (Atp Synthase F1 Subunit Alpha) Selectively Augments Survival Of Prostate Cancer While Engendering Mitochondrial Vulnerability, Surbhi Chouhan, Mithila Sawant, Cody Weimholt, Jingqin Luo, Robert W Sprung, Mailyn Terrado, David M Mueller, H Shelton Earp, Nupam P. Mahajan

2020-Current year OA Pubs

The challenge of rapid macromolecular synthesis enforces the energy-hungry cancer cell mitochondria to switch their metabolic phenotypes, accomplished by activation of oncogenic tyrosine kinases. Precisely how kinase activity is directly exploited by cancer cell mitochondria to meet high-energy demand, remains to be deciphered. Here we show that a non-receptor tyrosine kinase, TNK2/ACK1 (tyrosine kinase non receptor 2), phosphorylated ATP5F1A (ATP synthase F1 subunit alpha) at Tyr243 and Tyr246 (Tyr200 and 203 in the mature protein, respectively) that not only increased the stability of complex V, but also increased mitochondrial energy output in cancer cells. Further, phospho-ATP5F1A (p-Y-ATP5F1A) prevented its binding …


Association Of Hospital Resource Utilization With Neurodevelopmental Outcomes In Neonates With Hypoxic-Ischemic Encephalopathy, Vilmaris Quinones Cardona, Rakesh Rao, Amy Distler, Et Al. Mar 2023

Association Of Hospital Resource Utilization With Neurodevelopmental Outcomes In Neonates With Hypoxic-Ischemic Encephalopathy, Vilmaris Quinones Cardona, Rakesh Rao, Amy Distler, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Intercenter variation exists in the management of hypoxic-ischemic encephalopathy (HIE). It is unclear whether increased resource utilization translates into improved neurodevelopmental outcomes.

OBJECTIVE: To determine if higher resource utilization during the first 4 days of age, quantified by hospital costs, is associated with survival without neurodevelopmental impairment (NDI) among infants with HIE.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort analysis of neonates with HIE who underwent therapeutic hypothermia (TH) at US children's hospitals participating in the Children's Hospitals Neonatal Database between 2010 and 2016. Data were analyzed from December 2021 to December 2022.

EXPOSURES: Infants who survived to 4 days …


Harmonization And Standardization Of Nucleus Pulposus Cell Extraction And Culture Methods, Shaghayegh Basatvat, Liufang Jing, Lori Setton, Xiaohong Tan, Et Al. Mar 2023

Harmonization And Standardization Of Nucleus Pulposus Cell Extraction And Culture Methods, Shaghayegh Basatvat, Liufang Jing, Lori Setton, Xiaohong Tan, Et Al.

2020-Current year OA Pubs

BACKGROUND: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources.

METHODS: The most commonly applied methods for NP cell extraction, expansion, and re-differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, …


Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities For Mucocutaneous Bleeding Disorders, Robert F Sidonio Jr, Jorge Di Paola, Et Al. Mar 2023

Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities For Mucocutaneous Bleeding Disorders, Robert F Sidonio Jr, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Excessive or abnormal mucocutaneous bleeding (MCB) may impact all aspects of the physical and psychosocial wellbeing of those who live with it (PWMCB). The evidence base for the optimal diagnosis and management of disorders such as inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD), Ehlers-Danlos syndromes (EDS), and von Willebrand disease (VWD) remains thin with enormous potential for targeted research.

RESEARCH DESIGN AND METHODS: National Hemophilia Foundation and American Thrombosis and Hemostasis Network initiated the development of a National Research Blueprint for Inherited Bleeding Disorders with extensive all-stakeholder consultations to identify the priorities of people with …