Life Sciences Commons^™

Treatment Of Older Adults With Flt3-Mutated Aml: Emerging Paradigms And The Role Of Frontline Flt3 Inhibitors, Nicholas J Short, Daniel Nguyen, Farhad Ravandi

Faculty, Staff and Student Publications

FLT3 is the most frequently mutated gene in acute myeloid leukemia (AML), with FLT3 internal tandem duplication (ITD) mutations being associated with a more aggressive clinical course. While two large, randomized clinical trials have shown a survival benefit with the frontline use of an oral FLT3 inhibitor (midostaurin or quizartinib) in patients with FLT3-mutated AML, the role of FLT3 inhibitors in older adults with newly diagnosed FLT3-mutated AML remains unclear. A definitive improvement in survival has not been observed in intensively treated patients over 60 years of age receiving frontline FLT3 inhibitors. Furthermore, many patients with FLT3-mutated AML are unsuitable …

Krasg12d Inhibition Reprograms The Tumor Microenvironment Of Early And Advanced Pancreatic Cancer To Promote Fas-Mediated Killing By Cd8+ T Cells, Krishnan K Mahadevan, Kathleen M Mcandrews, Valerie S Lebleu, Sujuan Yang, Hengyu Lyu, Amari M Sockwell, Sami J Morse, Barbara A Moreno Diaz, Michael P Kim, Ningping Feng, Anastasia M Lopez, Paola A Guerrero, Francesca Paradiso, Hikaru Sugimoto, Kent A Arian, Haoqiang Ying, Yasaman Barekatain, Lakshmi Kavitha Sthanam, Patience J Kelly, Anirban Maitra, Timothy P Heffernan, Raghu Kalluri

Faculty, Staff and Student Publications

The KRASG12D mutation is present in nearly half of pancreatic adenocarcinomas (PDAC). We investigated the effects of inhibiting the KRASG12D mutant protein with MRTX1133, a non-covalent small molecule inhibitor of KRASG12D, on early and advanced PDAC and its influence on the tumor microenvironment. Employing 16 different models of KRASG12D-driven PDAC, we demonstrate that MRTX1133 reverses early PDAC growth, increases intratumoral CD8+ effector T cells, decreases myeloid infiltration, and reprograms cancer associated fibroblasts. MRTX1133 leads to regression of both established PanINs and advanced PDAC. Regression of advanced PDAC requires CD8+ T cells and immune checkpoint blockade (ICB) synergizes with MRTX1133 …

Global Proteomic Identifies Multiple Cancer-Related Signaling Pathways Altered By A Gut Pathobiont Associated With Colorectal Cancer, Ewa Pasquereau-Kotula, Giulia Nigro, Florent Dingli, Damarys Loew, Patrick Poullet, Scott Kopetz, Lucie Peduto, Catherine Robbe-Masselot, Philippe Sansonetti, Patrick Trieu-Cuot, Shaynoor Dramsi

Faculty, Staff and Student Publications

In this work, we investigated the oncogenic role of Streptococcus gallolyticus subsp. gallolyticus (SGG), a gut bacterium associated with colorectal cancer (CRC). We showed that SGG UCN34 accelerates colon tumor development in a chemically induced CRC murine model. Full proteome and phosphoproteome analysis of murine colons chronically colonized by SGG UCN34 revealed that 164 proteins and 725 phosphorylation sites were differentially regulated. Ingenuity Pathway Analysis (IPA) indicates a pro-tumoral shift specifically induced by SGG UCN34, as ~ 90% of proteins and phosphoproteins identified were associated with digestive cancer. Comprehensive analysis of the altered phosphoproteins using ROMA software revealed up-regulation of …

Elimination Of Oncogenic Kras In Genetic Mouse Models Eradicates Pancreatic Cancer By Inducing Fas-Dependent Apoptosis By Cd8+ T Cells, Krishnan K Mahadevan, Valerie S Lebleu, Elena V Ramirez, Yang Chen, Bingrui Li, Mihai Gagea, Lakshmi Kavitha Sthanam, Desiree Tampe, Michael Zeisberg, Haoqiang Ying, Abhinav K Jain, Ronald A Depinho, Anirban Maitra, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Oncogenic KRASG12D (KRAS∗) is critical for the initiation and maintenance of pancreatic ductal adenocarcinoma (PDAC) and is a known repressor of tumor immunity. Conditional elimination of KRAS∗ in genetic mouse models of PDAC leads to the reactivation of FAS, CD8+ T cell-mediated apoptosis, and complete eradication of tumors. KRAS∗ elimination recruits activated CD4+ and CD8+ T cells and promotes the activation of antigen-presenting cells. Mechanistically, KRAS∗-mediated immune evasion involves the epigenetic regulation of Fas death receptor in cancer cells, via methylation of its promoter region. Furthermore, analysis of human RNA sequencing identifies that high KRAS expression in PDAC tumors shows …

Integrative Multi-Omic Cancer Profiling Reveals Dna Methylation Patterns Associated With Therapeutic Vulnerability And Cell-Of-Origin, Wen-Wei Liang, Rita Jui-Hsien Lu, Reyka G Jayasinghe, Steven M Foltz, Eduard Porta-Pardo, Michael C Wendl, Iga Kolodziejczak, Yizhe Song, Akshay Govindan, Elizabeth G Demicco, Xiang Li, Yize Li, Sunantha Sethuraman, Samuel H Payne, David Fenyö, Henry Rodriguez, Maciej Wiznerowicz, Hui Shen, D R Mani, Karin D Rodland, Alexander J Lazar, Ana I Robles, Li Ding, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Student Publications

DNA methylation plays a critical role in establishing and maintaining cellular identity. However, it is frequently dysregulated during tumor development and is closely intertwined with other genetic alterations. Here, we leveraged multi-omic profiling of 687 tumors and matched non-involved adjacent tissues from the kidney, brain, pancreas, lung, head and neck, and endometrium to identify aberrant methylation associated with RNA and protein abundance changes and build a Pan-Cancer catalog. We uncovered lineage-specific epigenetic drivers including hypomethylated FGFR2 in endometrial cancer. We showed that hypermethylated STAT5A is associated with pervasive regulon downregulation and immune cell depletion, suggesting that epigenetic regulation of STAT5A …

Multiple Structural And Functional Annotations Based In-Silico Characterization Of Q9brx8 Protein, Eiman Zahid, Muhammad Farhan Sarwar

Karbala International Journal of Modern Science

Numerous proteins found in humans are poorly understood because there is a dearth of experimental evidence. Hypothetical proteins (HPs) or uncharacterized proteins are the terms used to describe these proteins. In this work, one of these proteins, Q9BRX8, is investigated using in-silico or bioinformatics tools to reveal its significant properties. In this regard, NCBI for the sequence retrieval, ProtParam tool for analysis of physiochemical properties, SOPMA for secondary structure prediction, SWISS-Model for homology modelling, STRING for protein-protein interaction and HDOCK for protein-protein docking analysis among other tools, were incorporated. The physiochemical characteristics indicated that Q9BRX8, which has an instability score …

Development Of An Antibiotic Resistance Breaker To Combat Staphylococcus Aureus Pathogenesis Skin Infections Ssis A Multidisciplinary, Gopalakrishnan T Mr

Theses and Dissertations

Problem Statement: Staphylococcus aureus is a highly adaptable and tenacious pathogen known to cause a wide range of infections. The survival characteristics of the pathogen in different host niches are due to their ability to produce various pathogenic determinants. Although there lies the first line of treatment regimens with antibiotics, the pathogen defends at various levels to cause the waves of resistance - a silent pandemic “AMR”.

Notable strategies are through the protective layer, biofilm that enables the inter-/intra species communication (Quorum Sensing; QS) and emerges as a battleground to withstand host-immune response and antibiotic pressure. In parallel, several research …

Sprouting Alters Metabolite And Peptide Contents In The Gastrointestinal Digest Of Soybean And Enhances In-Vitro Anti-Inflammatory Activity, Emerson Nolasco, Inga Krassovskaya, Kelvin Hong, Kali Hansen, Sophie Alvarez, Toshihiro Obata, Kaustav Majumder

Department of Nutrition and Health Sciences: Faculty Publications

Sprouting of soybeans can enhance the release of health-beneficial bioactive compounds, especially peptides, and metabolites, while gastrointestinal (GI) digestion alters their biotransformation and bioaccessibility. The present study aimed to evaluate the effect of soybean sprouting and GI digestion in modulating its anti-inflammatory activity. Soybeans were soaked in water overnight (Day 0) and sprouted for two and four days, subjected to simulated GI digestion, and human intestinal epithelial cells (Caco-2) were pretreated (2 h) with soybean sprout digest (SSD: 1000 μg/mL) before inflammation induction with IL-1β. Pre-treatment with Day 4 SSD specifically reduced the secretion of cytokine IL-8 by 19.5%. Sprouting …

Stereotactic Ablative Radiotherapy With Or Without Immunotherapy For Early-Stage Or Isolated Lung Parenchymal Recurrent Node-Negative Non-Small-Cell Lung Cancer: An Open-Label, Randomised, Phase 2 Trial, Joe Y Chang, Steven H Lin, Wenli Dong, Zhongxing Liao, Saumil J Gandhi, Jianjun Zhang, Yasir Y Elamin, Frank V Fossella, George Blumenschein, Tina Cascone, Xiuning Le, Jenny V Pozadzides, Anne Tsao, Vivek Verma, James W Welsh, Aileen B Chen, Mehmet Altan, Reza J Mehran, Ara A Vaporciyan, Stephen G Swisher, Peter A Balter, Junya Fujimoto, Ignacio I Wistuba, Lei Feng, J Jack Lee, John V Heymach

Faculty, Staff and Student Publications

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small-cell lung cancer (NSCLC), but regional or distant relapses, or both, are common. Immunotherapy reduces recurrence and improves survival in people with stage III NSCLC after chemoradiotherapy, but its utility in stage I and II cases is unclear. We therefore conducted a randomised phase 2 trial of SABR alone compared with SABR with immunotherapy (I-SABR) for people with early-stage NSCLC.

METHODS: We did an open-label, randomised, phase 2 trial comparing SABR to I-SABR, conducted at three different hospitals in TX, USA. People aged 18 years or older …

Helping Families Adapt To Individual Circumstances: The Case Of Stay-At-Home Fathers, Kade Cope

Family Perspectives

No abstract provided.

The Interactive Role Of Shared Reading And Child Participation In Cognitive Development, Joanne Anderson

Family Perspectives

No abstract provided.

What We Say Matters! How Parents Affect Their Child's Emotional Knowledge, Savanna Nielson

Family Perspectives

No abstract provided.

The Importance Of Teaching Kids How To Be Hopeful, Cambria Siddoway

Family Perspectives

No abstract provided.

Starved For Conversation: The Lost Art Of Human Connection, Emily Scott

Family Perspectives

No abstract provided.

Don't Forget About Their Siblings: Mental Health In Siblings Of Autism, Kylie W. Martin

Family Perspectives

No abstract provided.

Childhood Screen Time And Child Development, Angela Webb

Family Perspectives

No abstract provided.

Oxytocin And Attachment Development, Sage Delamare

Family Perspectives

No abstract provided.

Raising Praise: A Parent's Role In Influencing Adolescent Self-Esteem Through Different Forms Of Praise, Karlee Mcrae

Family Perspectives

No abstract provided.

How To Better Support Your Loved Ones With Ocd, Sarah Jacobs

Family Perspectives

No abstract provided.

Marital Satisfaction Among Interracial And Intercultural Couples, Brynly Rich

Family Perspectives

No abstract provided.

For The Strength Of Parents, Macall Smith

Family Perspectives

No abstract provided.

Adhd In Women: Psychological, Academic, And Social Effects, Sienna Kelson

Family Perspectives

Attention-deficit/hyperactivity disorder (ADHD) is a neurological disorder that involves a persistent pattern of inattention and/or hyperactivity-impulsivity which interferes with functioning or development. ADHD is commonly diagnosed in childhood and can persist into adulthood (Kok et al., 2020; Fraticelli et al., 2022). It is estimated that ADHD affects 5-7% of school-age children with a male-to-female ratio of approximately 3:1 (Kok et al., 2016). For a long time, ADHD was assumed to be primarily a male disorder, but researchers are increasingly finding that the number of males and females with ADHD is likely close to equal (Nussbaum, 2012). There is increasing evidence …

Bridging The Cultural Gap, Trish Ramos

Journal of Multicultural Affairs

Multicultural education is about teaching people about each other without bias. Banks, C. (2016) states “Teachers need to understand their students’ community and home life (pg. 278).” As teachers it is our duty to ensure that every student that enters our classroom leaves with a sense of worth and knowing that each of them matter regardless of ethnicity, religion, gender or cultural.

Directions Of Attack And Their Effectiveness Of Male Judo Medalists At The Olympic Competitions., Amar Ait Ali Yahia

Baltic Journal of Health and Physical Activity

Introduction: To perform a technical action, the elite judo athlete examines the direction of attack relative to the opponent's body position. This study aimed to analyze and compare the most frequent and effective attack directions carried out by male Olympic medalists. Materials and Methods: A sample of 112 male medalists performed 3,664 attacks in four Olympic tournaments (2004–2016). ANOVA (one factor) determined inter and intra-Olympic comparisons, followed by the post hoc Bonferroni test (p< 0.05). Eta squared η2 and Cohen's d calculated the effect size, respectively. Results: Olympic medalists oriented their attacks principally in right forward (30.5±11.3%), left forward (29.9±10.5%), left backward (18.8±8.1%), and right backward (15.8±6.1%). The effectiveness of right forward (25.7±13.1%) and left forward (26.2±12.5%) dominates left backward (20.5±10.1%) and right backward (15.5±9.7%), respectively. In terms of frequencies and effectiveness, the contribution of secondary directions is negligible. Conclusions: Attacking in eight orientations made the defense vulnerable. Beside the uncertainty and unpredictability, they created more points of imbalance to overcome defensive issues.

An Improved Digestion And Analysis Procedure For Silicon In Plant Tissue, Noah James Langenfeld, Bruce Bugbee

Plants, Soils, and Climate Faculty Publications

Silicon (Si) in plant tissues reduces abiotic and biotic stress, but it is incorporated as silica (SiO₂), which is difficult to solubilize for analysis. We modified an oven-induced tissue-digestion and analysis method to improve Si solubilization and validated its accuracy by quantifying the mass-balance recovery of Si from the hydroponic solution and plant tissues of cucumber (Cucumis sativus). Leaf, stem, and root tissues were dried, finely-ground, and digested in 12.5 molar sodium hydroxide at 95°C for 4 hours. Solutions were then acidified with 6 molar hydrochloric acid to achieve a pH below 2 for measurement of …

Diminazene Aceturate-Induced Cytotoxicity Is Associated With The Deregulation Of Cell Cycle Signaling And Downregulation Of Oncogenes Furin, C-Myc, And Foxm1 In Human Cervical Carcinoma Hela Cells, Rajendra Gharbaran

Publications and Research

Diminazene aceturate (DIZE) is an FDA‐listed small molecule known for thetreatment of African sleeping sickness. In vivo studies showed that DIZE may bebeneficial for a range of human ailments. However, there is very limited informationon the effects of DIZE on human cancer cells. The current study aimed to investigatethe cytotoxic responses of DIZE, using the human carcinoma Hela cell line. WST‐1cell proliferation assay showed that DIZE inhibited the viability of Hela cells in adose‐dependent manner and the observed response was associated with thedownregulation of Ki67 and PCNA cell proliferation markers. DIZE‐treated cellsstained with acridine orange‐ethidium and JC‐10 dye revealed cell …

Reproductively Viable Population Of American Black Bears (Ursus Americanus) In Lowland Chihuahuan Desert Habitat Of Trans-Pecos Texas, Franklin D. Yancey Ii, Stephen Kasper

Western North American Naturalist

During a 6.5-year camera-trap study in Big Bend Ranch State Park (situated in the Trans-Pecos region of West Texas), we documented a persistent breeding population of American black bears (Ursus americanus) in the Solitario region of the park. The habitat in the Solitario, which is an isolated, eroded remnant of volcanic activity, is low-elevation Chihuahuan Desert scrub but includes significant and complex localized topography and prolonged water sources in the form of tinajas. From January 2016 to May 2022, camera traps captured 367,301 photographs. Of these, 868 contained one or more black bears, resulting in 1010 black bear …

Western Australian Regional Development Trust Annual Report 2022-23, West Australian Regional Development Trust

Western Australian Regional Development Trust Annual Reports

The Trust is an independent statutory advisory body to the Minister, established under the Royalties for Regions Act 2009 (Act).

The functions of the Trust are to provide advice and make recommendations to the Minister:

• for the purposes of sections 5(2) and 9(1) of the Act; and
• on any other matter relating to the operation of the Fund that is referred to it by the Minister.

In addition to its monitoring and advisory role, the Trust also works to engage and enhance relationships with key regional stakeholders and influencers to promote greater collaboration and innovation in the delivery of regional …

Development Of Bioactive Peptidomimetics, Lei Wang

USF Tampa Graduate Theses and Dissertations

In the past two decades, a lot of different peptidomimetics, such as β-peptides, oligoureas, azapeptides, peptoids, aromatic oligoamides, and others, have been developed. These peptidomimetics with distinctive scaffolds have shown potential in protein surface recognition and mimicry, PPI regulation, catalysis, etc. Moreover, these bioactive peptidomimetics demonstrate much better bioavailability and biostability than the bioactive peptides. To expand the application of peptidomimetics, our group have developed a new sequence-specific peptidomimetics- γ-AApeptide, which is derived from chiral γ-PNA. It shows excellent advantages including highly resistant to various proteolytical degradations and has the potential to increase chemodiversity. γ-AApeptide also exhibits remarkable biomedical applications, …

Color Stability, Physical Properties And Antifungal Effects Of Zro2 Additions To Experimental Maxillofacial Silicones: Comparisons With Tio2, Mazen Alkahtany, Mark W. Beatty, Fahd Alsalleeh, Thomas M. Petro, Bobby Simetich, You Zhou, Dennis Feely, Grigoris Polyzois

School of Veterinary and Biomedical Sciences: Faculty Publications

(1) Background: Color changes, physical degradation, and fungal infections are challenges to the longevity of maxillofacial polydimethylsiloxane (PDMS) elastomers. This study aimed to evaluate color changes, physical properties, and antifungal properties of PDMS loaded with ZrO₂ and TiO₂ submicron- and nano-sized particles. (2) Methods: A 1% weight of 40 nm or 200 nm diameter ZrO₂ or TiO₂ nanoparticles was mixed into PDMS with 2% functional intrinsic yellow pigment and polymerized. Control materials contained 13% weight 200 nm silica. Samples were exposed to 3000 h of UVB radiation (200 μW/cm²) or darkness. Color parameters L*a*b* …