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Role Of The Crosstalk B:Neoplastic T Follicular Helper Cells In The Pathobiology Of Nodal T Follicular Helper Cell Lymphomas, Tania P Sainz, Vishal Sahu, Javier A Gomez, Nicholas J Dcunha, Akshay V Basi, Claudia Kettlun, Iman Sarami, Jared K Burks, Deepa Sampath, Francisco Vega Nov 2024

Role Of The Crosstalk B:Neoplastic T Follicular Helper Cells In The Pathobiology Of Nodal T Follicular Helper Cell Lymphomas, Tania P Sainz, Vishal Sahu, Javier A Gomez, Nicholas J Dcunha, Akshay V Basi, Claudia Kettlun, Iman Sarami, Jared K Burks, Deepa Sampath, Francisco Vega

Faculty, Staff and Student Publications

Angioimmunoblastic T-cell lymphoma (AITL), the most common form of peripheral T-cell lymphoma, originates from follicular helper T (Tfh) cells and is notably resistant to current treatments. The disease progression and maintenance, at least in early stages, are driven by a complex interplay between neoplastic Tfh and clusters of B-cells within the tumor microenvironment, mirroring the functional crosstalk observed inside germinal centers. This interaction is further complicated by recurrent mutations, such as TET2 and DNMT3A, which are present in both Tfh cells and B-cells. These findings suggest that the symbiotic relationship between these 2 cell types could represent a therapeutic vulnerability. …


Genome-Wide Study Of Gene-By-Sex Interactions Identifies Risks For Cleft Palate, Kelsey Robinson, Randy Parrish, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, Lord J J Gowans, Jacqueline T Hecht, Lina Moreno Uribe, Jeffrey C Murray, Gary M Shaw, Seth M Weinberg, Harrison Brand, Mary L Marazita, David J Cutler, Michael P Epstein, Jingjing Yang, Elizabeth J Leslie Nov 2024

Genome-Wide Study Of Gene-By-Sex Interactions Identifies Risks For Cleft Palate, Kelsey Robinson, Randy Parrish, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, Lord J J Gowans, Jacqueline T Hecht, Lina Moreno Uribe, Jeffrey C Murray, Gary M Shaw, Seth M Weinberg, Harrison Brand, Mary L Marazita, David J Cutler, Michael P Epstein, Jingjing Yang, Elizabeth J Leslie

Faculty, Staff and Student Publications

Structural birth defects affect 3–4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific risks for CL/P, but these risks have yet to be evaluated in CP. CL/P is more common in males and CP is more frequently observed in females, so we hypothesized there would also be sex-specific differences for CP. Using a trio-based cohort, we performed sex-stratified …


Allosteric Competition And Inhibition In Ampa Receptors, W Dylan Hale, Alejandra Montaño Romero, Cuauhtemoc U Gonzalez, Vasanthi Jayaraman, Albert Y Lau, Richard L Huganir, Edward C Twomey Nov 2024

Allosteric Competition And Inhibition In Ampa Receptors, W Dylan Hale, Alejandra Montaño Romero, Cuauhtemoc U Gonzalez, Vasanthi Jayaraman, Albert Y Lau, Richard L Huganir, Edward C Twomey

Faculty, Staff and Student Publications

Excitatory neurotransmission is principally mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-subtype ionotropic glutamate receptors (AMPARs). Negative allosteric modulators are therapeutic candidates that inhibit AMPAR activation and can compete with positive modulators to control AMPAR function through unresolved mechanisms. Here we show that allosteric inhibition pushes AMPARs into a distinct state that prevents both activation and positive allosteric modulation. We used cryo-electron microscopy to capture AMPARs bound to glutamate, while a negative allosteric modulator, GYKI-52466, and positive allosteric modulator, cyclothiazide, compete for control of the AMPARs. GYKI-52466 binds in the ion channel collar and inhibits AMPARs by decoupling the ligand-binding domains from the …


Ctla4 Blockade Abrogates Keap1/Stk11-Related Resistance To Pd-(L)1 Inhibitors, Ferdinandos Skoulidis, Haniel A Araujo, Minh Truong Do, Yu Qian, Xin Sun, Ana Galan Cobo, John T Le, Meagan Montesion, Rachael Palmer, Nadine Jahchan, Joseph M Juan, Chengyin Min, Yi Yu, Xuewen Pan, Kathryn C Arbour, Natalie Vokes, Stephanie T Schmidt, David Molkentine, Dwight H Owen, Regan Memmott, Pradnya D Patil, Melina E Marmarelis, Mark M Awad, Joseph C Murray, Jessica A Hellyer, Justin F Gainor, Anastasios Dimou, Christine M Bestvina, Catherine A Shu, Jonathan W Riess, Collin M Blakely, Chad V Pecot, Laura Mezquita, Fabrizio Tabbó, Matthias Scheffler, Subba Digumarthy, Meghan J Mooradian, Adrian G Sacher, Sally C M Lau, Andreas N Saltos, Julia Rotow, Rocio Perez Johnson, Corinne Liu, Tyler Stewart, Sarah B Goldberg, Jonathan Killam, Zenta Walther, Kurt Schalper, Kurtis D Davies, Mark G Woodcock, Valsamo Anagnostou, Kristen A Marrone, Patrick M Forde, Biagio Ricciuti, Deepti Venkatraman, Eliezer M Van Allen, Amy L Cummings, Jonathan W Goldman, Hiram Shaish, Melanie Kier, Sharyn Katz, Charu Aggarwal, Ying Ni, Joseph T Azok, Jeremy Segal, Lauren Ritterhouse, Joel W Neal, Ludovic Lacroix, Yasir Y Elamin, Marcelo V Negrao, Xiuning Le, Vincent K Lam, Whitney E Lewis, Haley N Kemp, Brett Carter, Jack A Roth, Stephen Swisher, Richard Lee, Teng Zhou, Alissa Poteete, Yifan Kong, Tomohiro Takehara, Alvaro Guimaraes Paula, Edwin R Parra Cuentas, Carmen Behrens, Ignacio I Wistuba, Jianjun Zhang, George R Blumenschein, Carl Gay, Lauren A Byers, Don L Gibbons, Anne Tsao, J Jack Lee, Trever G Bivona, D Ross Camidge, Jhannelle E Gray, Natasha B Leighl, Benjamin Levy, Julie R Brahmer, Marina C Garassino, David R Gandara, Edward B Garon, Naiyer A Rizvi, Giorgio Vittorio Scagliotti, Jürgen Wolf, David Planchard, Benjamin Besse, Roy S Herbst, Heather A Wakelee, Nathan A Pennell, Alice T Shaw, Pasi A Jänne, David P Carbone, Matthew D Hellmann, Charles M Rudin, Lee Albacker, Helen Mann, Zhou Zhu, Zhongwu Lai, Ross Stewart, Solange Peters, Melissa L Johnson, Kwok K Wong, Alan Huang, Monte M Winslow, Michael J Rosen, Ian P Winters, Vassiliki A Papadimitrakopoulou, Tina Cascone, Philip Jewsbury, John V Heymach Nov 2024

Ctla4 Blockade Abrogates Keap1/Stk11-Related Resistance To Pd-(L)1 Inhibitors, Ferdinandos Skoulidis, Haniel A Araujo, Minh Truong Do, Yu Qian, Xin Sun, Ana Galan Cobo, John T Le, Meagan Montesion, Rachael Palmer, Nadine Jahchan, Joseph M Juan, Chengyin Min, Yi Yu, Xuewen Pan, Kathryn C Arbour, Natalie Vokes, Stephanie T Schmidt, David Molkentine, Dwight H Owen, Regan Memmott, Pradnya D Patil, Melina E Marmarelis, Mark M Awad, Joseph C Murray, Jessica A Hellyer, Justin F Gainor, Anastasios Dimou, Christine M Bestvina, Catherine A Shu, Jonathan W Riess, Collin M Blakely, Chad V Pecot, Laura Mezquita, Fabrizio Tabbó, Matthias Scheffler, Subba Digumarthy, Meghan J Mooradian, Adrian G Sacher, Sally C M Lau, Andreas N Saltos, Julia Rotow, Rocio Perez Johnson, Corinne Liu, Tyler Stewart, Sarah B Goldberg, Jonathan Killam, Zenta Walther, Kurt Schalper, Kurtis D Davies, Mark G Woodcock, Valsamo Anagnostou, Kristen A Marrone, Patrick M Forde, Biagio Ricciuti, Deepti Venkatraman, Eliezer M Van Allen, Amy L Cummings, Jonathan W Goldman, Hiram Shaish, Melanie Kier, Sharyn Katz, Charu Aggarwal, Ying Ni, Joseph T Azok, Jeremy Segal, Lauren Ritterhouse, Joel W Neal, Ludovic Lacroix, Yasir Y Elamin, Marcelo V Negrao, Xiuning Le, Vincent K Lam, Whitney E Lewis, Haley N Kemp, Brett Carter, Jack A Roth, Stephen Swisher, Richard Lee, Teng Zhou, Alissa Poteete, Yifan Kong, Tomohiro Takehara, Alvaro Guimaraes Paula, Edwin R Parra Cuentas, Carmen Behrens, Ignacio I Wistuba, Jianjun Zhang, George R Blumenschein, Carl Gay, Lauren A Byers, Don L Gibbons, Anne Tsao, J Jack Lee, Trever G Bivona, D Ross Camidge, Jhannelle E Gray, Natasha B Leighl, Benjamin Levy, Julie R Brahmer, Marina C Garassino, David R Gandara, Edward B Garon, Naiyer A Rizvi, Giorgio Vittorio Scagliotti, Jürgen Wolf, David Planchard, Benjamin Besse, Roy S Herbst, Heather A Wakelee, Nathan A Pennell, Alice T Shaw, Pasi A Jänne, David P Carbone, Matthew D Hellmann, Charles M Rudin, Lee Albacker, Helen Mann, Zhou Zhu, Zhongwu Lai, Ross Stewart, Solange Peters, Melissa L Johnson, Kwok K Wong, Alan Huang, Monte M Winslow, Michael J Rosen, Ian P Winters, Vassiliki A Papadimitrakopoulou, Tina Cascone, Philip Jewsbury, John V Heymach

Faculty, Staff and Student Publications

For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) with CTLA4 inhibitors and PD-1 or PD-L1 inhibitors (hereafter, PD-(L)1 inhibitors) is associated with higher rates of anti-tumour activity and immune-related toxicities, when compared with treatment with PD-(L)1 inhibitors alone. However, there are currently no validated biomarkers to identify which patients will benefit from dual ICB1,2. Here we show that patients with NSCLC who have mutations in the STK11 and/or KEAP1 tumour suppressor genes derived clinical benefit from dual ICB with the PD-L1 inhibitor durvalumab and the CTLA4 inhibitor tremelimumab, but not from durvalumab alone, when added …


Mechanisms Of Response And Tolerance To Active Ras Inhibition In Kras-Mutant Non-Small Cell Lung Cancer, Haniel A Araujo, Ximo Pechuan-Jorge, Teng Zhou, Minh Truong Do, Xin Hu, Frank R Rojas Alvarez, Maria E Salvatierra, Heladio P Ibarguen, Richard Lee, Rashi Raghulan, Harshit Shah, Mariela A Moreno Ayala, Kevin Chen, Nataliya Tovbis Shifrin, Shuhong Wu, Luisa M Solis Soto, Marcelo V Negrao, Don L Gibbons, David S Hong, Jack A Roth, John V Heymach, Jianjun Zhang, Jingjing Jiang, Mallika Singh, Jacqueline A M Smith, Elsa Quintana, Ferdinandos Skoulidis Nov 2024

Mechanisms Of Response And Tolerance To Active Ras Inhibition In Kras-Mutant Non-Small Cell Lung Cancer, Haniel A Araujo, Ximo Pechuan-Jorge, Teng Zhou, Minh Truong Do, Xin Hu, Frank R Rojas Alvarez, Maria E Salvatierra, Heladio P Ibarguen, Richard Lee, Rashi Raghulan, Harshit Shah, Mariela A Moreno Ayala, Kevin Chen, Nataliya Tovbis Shifrin, Shuhong Wu, Luisa M Solis Soto, Marcelo V Negrao, Don L Gibbons, David S Hong, Jack A Roth, John V Heymach, Jianjun Zhang, Jingjing Jiang, Mallika Singh, Jacqueline A M Smith, Elsa Quintana, Ferdinandos Skoulidis

Faculty, Staff and Student Publications

Resistance to inactive state-selective RASG12C inhibitors frequently entails accumulation of RASGTP, rendering effective inhibition of active RAS potentially desirable. Here, we evaluated the antitumor activity of the RAS(ON) multiselective tricomplex inhibitor RMC-7977 and dissected mechanisms of response and tolerance in KRASG12C-mutant non-small cell lung cancer (NSCLC). Broad-spectrum reversible RASGTP inhibition with or without concurrent covalent targeting of active RASG12C yielded superior and differentiated antitumor activity across diverse comutational KRASG12C-mutant NSCLC mouse models of primary or acquired RASG12C(ON) or RASG12C(OFF) inhibitor resistance. Interrogation of time-resolved single-cell transcriptional responses established an in vivo atlas of multimodal acute and chronic RAS pathway inhibition …


Fractionated Photoimmunotherapy Stimulates An Anti-Tumour Immune Response: An Integrated Mathematical And In Vitro Study, Mohammad U Zahid, Matthew Waguespack, Rebecca C Harman, Eric M Kercher, Shubhankar Nath, Tayyaba Hasan, Imran Rizvi, Bryan Q Spring, Heiko Enderling Nov 2024

Fractionated Photoimmunotherapy Stimulates An Anti-Tumour Immune Response: An Integrated Mathematical And In Vitro Study, Mohammad U Zahid, Matthew Waguespack, Rebecca C Harman, Eric M Kercher, Shubhankar Nath, Tayyaba Hasan, Imran Rizvi, Bryan Q Spring, Heiko Enderling

Faculty, Staff and Student Publications

Background: Advanced epithelial ovarian cancer (EOC) has high recurrence rates due to disseminated initial disease presentation. Cytotoxic phototherapies, such as photodynamic therapy (PDT) and photoimmunotherapy (PIT, cell-targeted PDT), have the potential to treat disseminated malignancies due to safe intraperitoneal delivery.

Methods: We use in vitro measurements of EOC tumour cell and T cell responses to chemotherapy, PDT, and epidermal growth factor receptor targeted PIT as inputs to a mathematical model of non-linear tumour and immune effector cell interaction. The model outputs were used to calculate how photoimmunotherapy could be utilised for tumour control.

Results: In vitro measurements of PIT dose …


Apoptotic Extracellular Vesicles Carrying Mif Regulate Macrophage Recruitment And Compensatory Proliferation In Neighboring Epithelial Stem Cells During Tissue Maintenance, Safia A Essien, Ivanshi Ahuja, George T Eisenhoffer Nov 2024

Apoptotic Extracellular Vesicles Carrying Mif Regulate Macrophage Recruitment And Compensatory Proliferation In Neighboring Epithelial Stem Cells During Tissue Maintenance, Safia A Essien, Ivanshi Ahuja, George T Eisenhoffer

Faculty, Staff and Student Publications

Apoptotic cells can signal to neighboring cells to stimulate proliferation and compensate for cell loss to maintain tissue homeostasis. While apoptotic cell-derived extracellular vesicles (AEVs) can transmit instructional cues to mediate communication with neighboring cells, the molecular mechanisms that induce cell division are not well understood. Here, we show that macrophage migration inhibitory factor (Mif)-containing AEVs regulate compensatory proliferation via ERK signaling in epithelial stem cells of larval zebrafish. Time-lapse imaging showed efferocytosis of AEVs from dying epithelial stem cells by healthy neighboring stem cells. Proteomic and ultrastructure analysis of purified AEVs identified Mif localization on the AEV surface. Pharmacological …


Enriched G4 Forming Repeats In The Human Genome Are Associated With Robust Well-Coordinated Transcription And Reduced Cancer Transcriptome Variation, Ruth B De-Paula, Albino Bacolla, Aleem Syed, John A Tainer Nov 2024

Enriched G4 Forming Repeats In The Human Genome Are Associated With Robust Well-Coordinated Transcription And Reduced Cancer Transcriptome Variation, Ruth B De-Paula, Albino Bacolla, Aleem Syed, John A Tainer

Faculty, Staff and Student Publications

Non-B DNA G-quadruplex (G4) structures with guanine (G) runs of 2 to 4 repeats can trigger opposing experimental transcriptional impacts. Here, we used bioinformatic algorithms to comprehensively assess correlations of steady-state RNA transcript levels with all putative G4 sequence (pG4) locations genome-wide in three mammalian genomes and in normal and tumor human tissues. The human pG4-containing gene set displays higher expression levels than the set without pG4, supporting and extending some prior observations. pG4 enrichment at transcription start sites (TSSs) in human, but not chimpanzee and mouse genomes, suggests possible positive selection pressure for pG4 at human TSS, potentially driving …


Mature Microrna-Binding Protein Qki Suppresses Extracellular Microrna Let-7b Release, Kyung-Won Min, Kyoung-Min Choi, Hyejin Mun, Seungbeom Ko, Ji Won Lee, Cari A Sagum, Mark T Bedford, Young-Kook Kim, Joe R Delaney, Jung-Hyun Cho, Ted M Dawson, Valina L Dawson, Waleed Twal, Dong-Chan Kim, Clarisse H Panganiban, Hainan Lang, Xin Zhou, Seula Shin, Jian Hu, Tilman Heise, Sang-Ho Kwon, Dongsan Kim, Young Hwa Kim, Sung-Ung Kang, Kyungmin Kim, Sydney Lewis, Ahmet Eroglu, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Junyang Jung, Je-Hyun Yoon Nov 2024

Mature Microrna-Binding Protein Qki Suppresses Extracellular Microrna Let-7b Release, Kyung-Won Min, Kyoung-Min Choi, Hyejin Mun, Seungbeom Ko, Ji Won Lee, Cari A Sagum, Mark T Bedford, Young-Kook Kim, Joe R Delaney, Jung-Hyun Cho, Ted M Dawson, Valina L Dawson, Waleed Twal, Dong-Chan Kim, Clarisse H Panganiban, Hainan Lang, Xin Zhou, Seula Shin, Jian Hu, Tilman Heise, Sang-Ho Kwon, Dongsan Kim, Young Hwa Kim, Sung-Ung Kang, Kyungmin Kim, Sydney Lewis, Ahmet Eroglu, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Junyang Jung, Je-Hyun Yoon

Faculty, Staff and Student Publications

Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNAs (miRNAs) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNAs, the roles of other miRNA-binding proteins (miRBPs) remain unclear in the regulation of miRNA loading, dissociation from RISCs and extracellular release. In this study, we performed protein arrays to profile miRBPs and identify 118 RBPs that directly bind to miRNAs. Among those proteins, the RBP quaking (QKI) inhibits extracellular release of the mature microRNA let-7b by controlling the loading of let-7b into extracellular …


Mechanisms Of Resistance To Oncogenic Kras Inhibition In Pancreatic Cancer, Julien Dilly, Megan T Hoffman, Laleh Abbassi, Ziyue Li, Francesca Paradiso, Brendan D Parent, Connor J Hennessey, Alexander C Jordan, Micaela Morgado, Shatavisha Dasgupta, Giselle A Uribe, Annan Yang, Kevin S Kapner, Felix P Hambitzer, Li Qiang, Hanrong Feng, Jacob Geisberg, Junning Wang, Kyle E Evans, Hengyu Lyu, Aislyn Schalck, Ningping Feng, Anastasia M Lopez, Christopher A Bristow, Michael P Kim, Kimal I Rajapakshe, Vahid Bahrambeigi, Jennifer A Roth, Kavita Garg, Paola A Guerrero, Ben Z Stanger, Simona Cristea, Scott W Lowe, Timour Baslan, Eliezer M Van Allen, Joseph D Mancias, Emily Chan, Abraham Anderson, Yuliya V Katlinskaya, Alex K Shalek, David S Hong, Shubham Pant, Jill Hallin, Kenna Anderes, Peter Olson, Timothy P Heffernan, Seema Chugh, James G Christensen, Anirban Maitra, Brian M Wolpin, Srivatsan Raghavan, Jonathan A Nowak, Peter S Winter, Stephanie K Dougan, Andrew J Aguirre Nov 2024

Mechanisms Of Resistance To Oncogenic Kras Inhibition In Pancreatic Cancer, Julien Dilly, Megan T Hoffman, Laleh Abbassi, Ziyue Li, Francesca Paradiso, Brendan D Parent, Connor J Hennessey, Alexander C Jordan, Micaela Morgado, Shatavisha Dasgupta, Giselle A Uribe, Annan Yang, Kevin S Kapner, Felix P Hambitzer, Li Qiang, Hanrong Feng, Jacob Geisberg, Junning Wang, Kyle E Evans, Hengyu Lyu, Aislyn Schalck, Ningping Feng, Anastasia M Lopez, Christopher A Bristow, Michael P Kim, Kimal I Rajapakshe, Vahid Bahrambeigi, Jennifer A Roth, Kavita Garg, Paola A Guerrero, Ben Z Stanger, Simona Cristea, Scott W Lowe, Timour Baslan, Eliezer M Van Allen, Joseph D Mancias, Emily Chan, Abraham Anderson, Yuliya V Katlinskaya, Alex K Shalek, David S Hong, Shubham Pant, Jill Hallin, Kenna Anderes, Peter Olson, Timothy P Heffernan, Seema Chugh, James G Christensen, Anirban Maitra, Brian M Wolpin, Srivatsan Raghavan, Jonathan A Nowak, Peter S Winter, Stephanie K Dougan, Andrew J Aguirre

Faculty, Staff and Student Publications

KRAS inhibitors demonstrate clinical efficacy in pancreatic ductal adenocarcinoma (PDAC); however, resistance is common. Among patients with KRASG12C-mutant PDAC treated with adagrasib or sotorasib, mutations in PIK3CA and KRAS, and amplifications of KRASG12C, MYC, MET, EGFR, and CDK6 emerged at acquired resistance. In PDAC cell lines and organoid models treated with the KRASG12D inhibitor MRTX1133, epithelial-to-mesenchymal transition and PI3K-AKT-mTOR signaling associate with resistance to therapy. MRTX1133 treatment of the KrasLSL-G12D/+; Trp53LSL-R172H/+; p48-Cre (KPC) mouse model yielded deep tumor regressions, but drug resistance ultimately emerged, accompanied by amplifications of Kras, Yap1, Myc, Cdk6, and Abcb1a/b, and co-evolution of drug-resistant transcriptional programs. …


State Of The Fisheries: Status Reports Of The Fisheries And Aquatic Resources Of Western Australia 2023/24, Stephen J. Newman, Jenny Moore, Daniel J. Gaughan Nov 2024

State Of The Fisheries: Status Reports Of The Fisheries And Aquatic Resources Of Western Australia 2023/24, Stephen J. Newman, Jenny Moore, Daniel J. Gaughan

Status Reports of the Fisheries and Aquatic Resources

This edition of the “State of the fisheries” continues the tradition of annually reporting on the status of exploited fish and their habitats in Western Australia. Critically, the reports provide overviews of the science outcomes that underpin management of fishing across the state.

Scientifically assessing the status of fish resources and potential impacts on ecosystems is inherently challenging; I acknowledge and thank the dedicated fisheries science teams and various support staff for again producing outstanding, robust scientific results that are summarised herein. I similarly acknowledge (i) the fisheries management team who use the science outcomes in policy development and to …


Therapeutic Targeting Of Hypoxia Inducible Factor In Acute Respiratory Distress Syndrome, Thu T Tran, Holger K Eltzschig, Xiaoyi Yuan Nov 2024

Therapeutic Targeting Of Hypoxia Inducible Factor In Acute Respiratory Distress Syndrome, Thu T Tran, Holger K Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

Acute respiratory distress syndrome (ARDS) is characterized by bilateral chest infiltration and acute hypoxic respiratory failure. ARDS carries significant morbidity and mortality despite advancements in medical management, calling for the development of novel therapeutic targets. Hypoxia-inducible factor (HIF) is a heterodimeric protein involved in various essential pathways, including metabolic reprogramming, immune modulation, angiogenesis and cell cycle regulation. HIF is routinely degraded in homeostasis conditions via the prolyl hydroxylase domain/von Hippel-Lindau protein pathway. However, HIF is stabilized in ARDS via various mechanisms (oxygen-dependent and independent) as an endogenous protective pathway and plays multifaceted roles in different cell populations. This review focuses …


Bacillus Licheniformis Suppresses Clostridium Perfringens Infection Via Modulating Inflammatory Response, Antioxidant Status, Inflammasome Activation And Microbial Homeostasis In Broilers, Xiao Xiao, Songke Qin, Tiantian Cui, Jinsong Liu, Yanping Wu, Yifan Zhong, Caimei Yang Nov 2024

Bacillus Licheniformis Suppresses Clostridium Perfringens Infection Via Modulating Inflammatory Response, Antioxidant Status, Inflammasome Activation And Microbial Homeostasis In Broilers, Xiao Xiao, Songke Qin, Tiantian Cui, Jinsong Liu, Yanping Wu, Yifan Zhong, Caimei Yang

Faculty, Staff and Student Publications

Pathogenic bacteria infection, especially Clostridium perfringens (C. perfringens), markedly threatened the health of animals, and further caused huge economic loss. In this study, Bacillus licheniformis HJ0135 (BL) was used. Oxford cup bacteriostatic test and inhibitory rate test were conducted to evaluate the antibacterial ability of BL. Results showed the strongest inhibitory role of BL on C. perfringens (P < 0.05). Afterwards, 540 one-day-old yellow-feather broilers (32.7 ± 0.2 g) were randomly allocated into 3 groups, including CON group (basal diet), CP group (basal diet + 1 × 109 CFU C. perfringens in gavage), and BL + CP group (basal diet containing 7.5 × 106 CFU/g BL + 1 × 109 CFU C. perfringens in gavage). At d 70, broilers in the CP and BL + CP groups were treated with C. perfringens by continuously oral administration for 5 d. The experiment lasted for 75 d. The serum, immune organs, jejunal mucosa, and cecal contents were collected for analysis. In vivo experiment showed that BL supplementation markedly improved (P < 0.05) BW, ADG, thymus index, serum immunoglobins and antioxidases, reduced feed conversion ratio (FCR) and serum pro-inflammatory cytokines of C. perfringens-infected broilers. Furthermore, the increased jejunal injury and levels of pro-inflammatory cytokines, decreased gene expressions of tight junction proteins in the jejunal mucosa were significantly alleviated (P < 0.05) by BL. More importantly, the activation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome was inhibited (P < 0.05) by BL to further attenuate jejunal damage. Besides, BL supplementation markedly increased (P < 0.05) the cecal isobutyric acid and isovaleric acid. Microbial analysis showed that BL changed the composition and relative abundances of microbiota in the cecal contents (P < 0.05), especially the short chain fatty acids (SCFAs)-producing bacteria including Eubacterium_coprostanoligenes_group, Megamonas, Faecalibacterium, and Lactobacillus, which further protected against C. perfringens-induced jejunal inflammation in broilers. Our study laid a theoretical basis for the application of probiotics in lessening C. perfringens-related diseases in poultry farming.


Calcineurin Inhibition Enhances Caenorhabditis Elegans Lifespan By Defecation Defects-Mediated Calorie Restriction And Nuclear Hormone Signaling, Priyanka Das, Alejandro Aballay, Jogender Singh Nov 2024

Calcineurin Inhibition Enhances Caenorhabditis Elegans Lifespan By Defecation Defects-Mediated Calorie Restriction And Nuclear Hormone Signaling, Priyanka Das, Alejandro Aballay, Jogender Singh

Faculty, Staff and Student Publications

Calcineurin is a highly conserved calcium/calmodulin-dependent serine/threonine protein phosphatase with diverse functions. Inhibition of calcineurin is known to enhance the lifespan of Caenorhabditis elegans through multiple signaling pathways. Aiming to study the role of calcineurin in regulating innate immunity, we discover that calcineurin is required for the rhythmic defecation motor program (DMP) in C. elegans. Calcineurin inhibition leads to defects in the DMP, resulting in intestinal bloating, rapid colonization of the gut by bacteria, and increased susceptibility to bacterial infection. We demonstrate that intestinal bloating caused by calcineurin inhibition mimics the effects of calorie restriction, resulting in enhanced lifespan. …


Black Widow Spider Envenomation And Cardiovascular Complications, Parmjot Khakh, William Q Lavercombe, Juan M Farina, Meera Kapadia, Gabriel M Aisenberg, Adrian Baranchuk Nov 2024

Black Widow Spider Envenomation And Cardiovascular Complications, Parmjot Khakh, William Q Lavercombe, Juan M Farina, Meera Kapadia, Gabriel M Aisenberg, Adrian Baranchuk

Faculty, Staff and Student Publications

Envenomation (latrodectism) with black widow spider (BWS) venom can cause dysfunction in the cardiovascular system. The pathophysiology and consequences of cardiovascular effects have not been fully elucidated. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Of 364 initial results, 22 articles (20 case reports and two case series) were used with 25 patients in total. Seventeen (68%) patients had hypertension, and 16 (64%) had tachycardia. High troponin levels were found in 16 (64%) patients. Electrocardiographic changes consisted of nine (36%) patients with ST-T segment abnormalities and three (12%) patients with supraventricular tachyarrhythmias. Wall motion …


Localized Intratumoral Delivery Of Immunomodulators For Oral Cancer And Oral Potentially Malignant Disorders, Nourhan I Hussein, Andrea H Molina, Gemalene M Sunga, Moran Amit, Yu Leo Lei, Xiao Zhao, Jeffrey D Hartgerink, Andrew G Sikora, Simon Young Nov 2024

Localized Intratumoral Delivery Of Immunomodulators For Oral Cancer And Oral Potentially Malignant Disorders, Nourhan I Hussein, Andrea H Molina, Gemalene M Sunga, Moran Amit, Yu Leo Lei, Xiao Zhao, Jeffrey D Hartgerink, Andrew G Sikora, Simon Young

Faculty, Staff and Student Publications

Immunotherapy has developed into an important modality of modern cancer treatment. Unfortunately, checkpoint inhibitor immunotherapies are currently delivered systemically and require frequent administration, which can result in toxicity and severe, sometimes fatal, adverse events. Localized delivery of immunomodulators for oral cancer and oral potentially malignant disorders offers the promise of maximum therapeutic potential and reduced systemic adverse effects. This review will discuss the limitations of current standard-of-care systemic therapies and highlight research advances in localized, intratumoral delivery platforms for immunotherapy for oral cancer and oral potentially malignant disorders.


Uterine-Conserving Treatment Options For Atypical Endometrial Hyperplasia And Early Endometrial Cancer, Naomi N Adjei, Mikayla Borthwick Bowen, Roni Nitecki Wilke, Melinda S Yates, Shannon N Westin Nov 2024

Uterine-Conserving Treatment Options For Atypical Endometrial Hyperplasia And Early Endometrial Cancer, Naomi N Adjei, Mikayla Borthwick Bowen, Roni Nitecki Wilke, Melinda S Yates, Shannon N Westin

Faculty, Staff and Student Publications

Purpose of review: This review aims to synthesize available literature on uterine-conserving treatment options for atypical endometrial hyperplasia and grade 1 endometrial carcinoma while highlighting remaining unanswered questions.

Recent findings: The need for uterine-conserving treatment options for atypical endometrial hyperplasia and grade 1 endometrial carcinoma is growing with the increasing number of cases in younger patients or those who cannot undergo surgery. We reviewed the oncological and reproductive outcomes associated with endocrine therapies used for atypical endometrial hyperplasia and grade 1 endometrial carcinoma. The rising prevalence of delayed childbearing, obesity, and diabetes in reproductive-age individuals and of medical comorbidities associated …


Mouse Mammary Tumor Virus (Mmtv) Genomic Rna (Grna) Packaging: Selective Grna Encapsidation Is Facilitated By Long-Range Interactions (Lris) That Facilitate Specific Gag Binding, Suresha G. Prabhu Nov 2024

Mouse Mammary Tumor Virus (Mmtv) Genomic Rna (Grna) Packaging: Selective Grna Encapsidation Is Facilitated By Long-Range Interactions (Lris) That Facilitate Specific Gag Binding, Suresha G. Prabhu

Dissertations

Mouse mammary tumor virus (MMTV) is a betaretrovirus that induces breast cancer and sporadically, T-cell lymphomas in mice. MMTV serves as a pertinent model for elucidating the mechanism(s) of oncogenesis and the genetics associated with the development of mammary tumors. Being a rodent retrovirus, MMTV is phylogenetically distant from human and other primate retroviruses; thus, positioning it ideally as a potential vector of choice for human gene therapy. This may circumvent safety concerns such as recombination with other related endogenous human retroviruses. In addition, MMTV is distinct from most other retroviruses, but similar to lentiviruses, in that it has the …


Preparation And Characterization Of Nanocomposite Textile Filter For Separation Of The Oil/Water Mixture Using Pa-Pva Blends Reinforced With Carbon Nanoparticles, Rusul Mohamed Darweesh, Balqees Mohamed Al-Dabbag, Hanaa Jawad Kadhim Nov 2024

Preparation And Characterization Of Nanocomposite Textile Filter For Separation Of The Oil/Water Mixture Using Pa-Pva Blends Reinforced With Carbon Nanoparticles, Rusul Mohamed Darweesh, Balqees Mohamed Al-Dabbag, Hanaa Jawad Kadhim

Baghdad Science Journal

The electrospinning technique used to prepare a nano fibre filter under limited conditions involves (20 kV applied voltage, 15 cm gap distance, 1 ml/h: flow rate, and 0.4 mm needle diameter). Several tests for prepared materials were conducted including [scanning electron microscopy (SEM-EDX), Fourier Transform Infrared (FTIR), contact angle, and particle size analysis]. As well as, the characterization of the water/oil mixture was tested before the filtration process and after it. According to the SEM data, smooth and homogeneous nanofibers with an approximate diameter of 350 nm and open porosity morphology were produced using the electrospinning approach. The liquid particles …


Yeast Diversity In Honey Produced By Wild Honeybees At Different Elevations, Medhina Magdalena, Candra Rahmani Priyambada, Donny Widianto, Sri Wedhastri, Irfan Dwidya Prijambada Nov 2024

Yeast Diversity In Honey Produced By Wild Honeybees At Different Elevations, Medhina Magdalena, Candra Rahmani Priyambada, Donny Widianto, Sri Wedhastri, Irfan Dwidya Prijambada

Baghdad Science Journal

Yeasts inhabit diverse natural environments, including the honeycombs of wild honeybee colonies residing at different elevations. This study investigates yeast populations in honeycombs located at two sampling sites, Bligo and Sukomulyo, Central Java Province, Indonesia, situated in a montane region at elevations of 131.1 and 676 meters above sea level, respectively. Out of the 40 yeast isolates collected, 12 distinct fingerprints were identified, representing ten strains across four species. Debaryomyces hansenii emerged as the predominant species, accounting for seven of the total strains, and being found at both sampling sites. The remaining species included Priceomyces melissophilus, Cystobasidium minutum, and Meyerozyma …


A Proposed Image Scaling Technique By Using Bezier Curve, Rafal Ali Sameer Nov 2024

A Proposed Image Scaling Technique By Using Bezier Curve, Rafal Ali Sameer

Baghdad Science Journal

The process of resizing a digital image using geometrical transformation without changing the quality of image is known as image scaling or image resizing. Image processing such as digital image scaling has a wide range of applications on computer, mobile, and other digital devices. This paper proposes a digital image resizing (scaling) approach and explaining how the algorithms have been modified to meet accuracy and performance. Bezier curve have been used in previous works for processing in various fields while in this paper Bezier curve equations used to resize the digital image (scaling-up or scaling-down). The idea of using Bezier …


Utilization Of Localized Surface Plasmon Resonance Of Silver Nanoparticles For ‎The Spectrophotometric Estimation Of Amlodipine And Hydrochlorothiazide, Rasul Jameel Ali, Lazeeza Sattar Omer, Nagham Nadhim Habeeb, Asmaa Ghanim Dawood Nov 2024

Utilization Of Localized Surface Plasmon Resonance Of Silver Nanoparticles For ‎The Spectrophotometric Estimation Of Amlodipine And Hydrochlorothiazide, Rasul Jameel Ali, Lazeeza Sattar Omer, Nagham Nadhim Habeeb, Asmaa Ghanim Dawood

Baghdad Science Journal

A potent long-acting calcium channel blockers is amlodipine. Patient with high blood pressure can take it to treat high blood pressure, angina pectoris, and reduce the risk of stroke. Hydrochlorothiazide, a diuretic, is used to treat edema and hypertension. Additionally, it is used to treat certain types of diabetes, hyperglycemia and hypokalemia. These drugs are widely available in the market and are commonly used orally. Therefore, a rapid, accurate, and inexpensive method for the determination of amlodipine and hydrochlorothiazide was developed and validated. This method is based on the ability of these drugs to reduce Ag +1 to Ag 0 …


Effect Of Graphene And Fe3o4 On The Protection Efficiency Of Polyeugenol Conducted Coating For Stainless Steel 316l In Nacl Solution, Ayat Monther Alqudsi, Khulood Abid Saleh Nov 2024

Effect Of Graphene And Fe3o4 On The Protection Efficiency Of Polyeugenol Conducted Coating For Stainless Steel 316l In Nacl Solution, Ayat Monther Alqudsi, Khulood Abid Saleh

Baghdad Science Journal

Corrosion is the term for the surface disintegration of metals and alloys in a specific environment. Corrosion processes change a metal alloy's chemical properties as well as its mechanical behaviors. To stop rusting, a novel strategy based on an original material has been applied. By electrochemically synthesizing polyEugenol(PE)/nanocomposite (Grapgene,Fe3O4) on stainless steel 316L (SS316L), which serves as the working electrode, using the electropolymerization approach, conducting polymer-composites are material types that show promise for anticorrosion. The atomic force microscopy images (AFM) and Fourier transform-infrared spectroscopy analyses were used to evaluate the produced coated polymer. The results showed that, in comparison to …


Spectrophotometric Determination Of Some Adrenergic Drugs Using H2o2 And Dichlorophenolindophenol, Mohamed Y. Dhamra, Mohammed Salim Al-Enizzi, Reem A. Al-Luhaiby Nov 2024

Spectrophotometric Determination Of Some Adrenergic Drugs Using H2o2 And Dichlorophenolindophenol, Mohamed Y. Dhamra, Mohammed Salim Al-Enizzi, Reem A. Al-Luhaiby

Baghdad Science Journal

Based on the catalytic response between hydrogen peroxide and dichlorophenolindophenol, a spectrophotometric method was developed to estimate adrenaline hydrochloride (ADR), Salbutamol sulfate (sal), and dopamine hydrochloride (DOPA) in pharmaceutical preparations. A calculated value of the oxidizing agent (hydrogen peroxide) was added to the basic medium in the presence of dichlorophenolindophenol to form a blue color, which suffers from a bleaching process due to the oxidation process of the drugs mentioned above by the oxidizing agent at λmax 552 nm. The estimated amounts of adrenaline hydrochloride and Salbutamol sulfate were between 0.25 - 5 μg/ml and 0.5 - 5 μg/ml, respectively. …


Eeg Eye Blink Artifacts Removal With Wavelet Denoising And Bandpass Filtering, Ebtesam N. Alshemmary, Bushra K. Hilal, Azmi Sh. Abdulbaqi, Mohammed A. Ahmed, Zhentai Lu Nov 2024

Eeg Eye Blink Artifacts Removal With Wavelet Denoising And Bandpass Filtering, Ebtesam N. Alshemmary, Bushra K. Hilal, Azmi Sh. Abdulbaqi, Mohammed A. Ahmed, Zhentai Lu

Baghdad Science Journal

Many data sources can be analyzed using Wavelet Transforms (WT), a mathematical technique frequently used for extracting information from them. Although WT was effective at Blind Source Separation (BSS), it had some limitations, such as signal loss. The problem has been addressed with the introduction of a joint algorithm that combines WT with Frequency Domain Filtering (BPF). Wavelet Denoising Technique (WDT) and Band-Pass Filtering (BPF) are employed in this research to propose an innovative algorithm for combining advanced wavelet transform methods. Combining these two techniques helps reduce eye flutter in electroencephalograms (EEGs).FP1 signals produced by eye movement are filtered out …


Synthesis And Identification Of Triorganotin (Iv)-Tyrosine Complexes And Study Their Applications As Antioxidant By Dpph And Cuprac Methods., Rafid Ryyis Arraq, Angham G. Hadi Nov 2024

Synthesis And Identification Of Triorganotin (Iv)-Tyrosine Complexes And Study Their Applications As Antioxidant By Dpph And Cuprac Methods., Rafid Ryyis Arraq, Angham G. Hadi

Baghdad Science Journal

Abstract Through condensation reactions between tyrosine (ligand) and triorganotin (IV) chloride salts in the presence of sodium hydroxide, three triorganotin (IV)-tyrosine complexes were successfully synthesized. All the components were dissolved in methanol and refluxed for five hours. The produced complexes were characterized by elemental analysis (CHN), Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy (1H, 13C and 119Sn-NMR). Based on spectrum measurements, trigonal bipyramidal geometries for the complexes produced in yields of 85–97% were assigned. Using the DPPH and CUPRAC methods, this study examined the antioxidant activity of tri organotin (IV)-tyrosine complexes. Due to the metal moiety, organotin (IV) …


Deep Learning Based Models For Drug-Target Interactions, Ali K. Abdul Raheem, Ban N. Dhannoon Nov 2024

Deep Learning Based Models For Drug-Target Interactions, Ali K. Abdul Raheem, Ban N. Dhannoon

Baghdad Science Journal

The typical drug development approach is slow, costly, and fraught with failure - scientists examine millions of compounds, but only a few make it to preclinical or clinical testing. Machine learning (ML), a subset of AI, is a fast-expanding subject many pharmaceutical businesses increasingly utilize. Incorporating machine learning technologies into the drug development process can aid in automating repetitive data processing and analysis processes. ML techniques may be used at several stages of drug development, including drug property prediction, drug-target interaction (DTI) prediction, and De Novo drug design. DTIs are a critical component of the drug development process. When a …


Phytochemical Analysis Of The Ethanol Extract Of Binahong (Anredera Cordifolia (Ten.) Steenis) Leaves By Uv-Vis Spectroscopy, Rusdiana Rusdiana, Tri Widyawati, Dina Keumala Sari, Sry Suryani Widjaja Nov 2024

Phytochemical Analysis Of The Ethanol Extract Of Binahong (Anredera Cordifolia (Ten.) Steenis) Leaves By Uv-Vis Spectroscopy, Rusdiana Rusdiana, Tri Widyawati, Dina Keumala Sari, Sry Suryani Widjaja

Baghdad Science Journal

Binahong (Anredera cordifolia) leaves contain chemical compounds that can be used to promote anti-obesity. This study aimed to examine the phytochemical and anti-obesity properties of the ethanol extract of binahong leaves. The binahong extract was obtained by maceration of the leaves, followed by ethanol extraction. Phytochemical analysis was performed by UV-Vis spectroscopy to identify and determine the levels of flavonoids, phenolic compounds, alkaloids, and tannins in the extract, using quercetin as a standard for calibration. Absorbance was measured at a wavelength of 430 nm. The flavonoid, glycoside, tannin, saponin, and steroid/terpenoid contents were determined, but alkaloid compounds were not found. …


Estimation Of Copula Density Using The Wavelet Transform, Fatimah Hashim Falhi, Munaf Yousif Hmood Nov 2024

Estimation Of Copula Density Using The Wavelet Transform, Fatimah Hashim Falhi, Munaf Yousif Hmood

Baghdad Science Journal

This paper proposes a new method to estimate the copula density function using wavelet decomposition as a nonparametric method, to obtain more accurate results and address the issue of boundary effects that nonparametric estimation methods suffer from. The wavelet method is an automatic method for dealing with boundary effects because it does not take into Consideration whether the time series is stationary or nonstationary. To estimate the copula density function, simulation was used to generate data using five different copula functions, such as Gaussian, Frank, Tawn, Rotation Tawn, and Joe copulas. With five different sample sizes at three positive correlation …


Coupled Of Semi Analytic Approach Associated With Laplace Transform First Step For Solving Matrix Differential Equations Quadratic Form When The Time-Delay In Noise Term, Khalid Hammood Al-Jizani Nov 2024

Coupled Of Semi Analytic Approach Associated With Laplace Transform First Step For Solving Matrix Differential Equations Quadratic Form When The Time-Delay In Noise Term, Khalid Hammood Al-Jizani

Baghdad Science Journal

A novel technique and an efficient modification based on Adomian decomposition method and homotopy approach for finding accurately analytic solutions to non-linear (noise term) quadratic matrix retarded delay equations connected with the method of steps to make the problem more easily is discussed. These approaches more efficiently, effectively and accurately. Wholly integration for homotopy analysis method use in state the wholly integration for Adomian approach. Main advantage of this technique is to get more an accurate and efficient results with more extended of the convergence region of iterative approximate solutions obtained with bigger and whole time interval and to know …