Digital Commons Network^™

The Role Of Anti-Viral Immune Response On The Therapeutic Efficacy Of Oncolytic Virotherapy For High-Grade Gliomas, Dong Ho Shin Phd

Dissertations and Theses (Open Access)

Currently, there is no effective treatment for high-grade gliomas that are resistant to conventional treatments and immune checkpoint blockade therapies. Oncolytic viruses offer a new treatment modality by selectively replicating in cancer cells and inducing anti-tumor immunity. Among these viruses, the oncolytic adenovirus Delta-24-RGD has shown safety and efficacy in clinical trials for high-grade gliomas. Strategies to improve the efficacy of oncolytic virotherapy have aimed to heighten the immunogenicity of oncolytic viruses, either by incorporating immune-stimulating transgenes or by combining treatments with immune checkpoint blockades. However, such strategies may inadvertently trigger heightened immune responses to viral antigens, which may not …

Loss Of Ptdss1 In Tumor Cells Improves Anti-Pd-1 Therapy, Jielin Liu

Dissertations and Theses (Open Access)

PTDSS1 (Phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of PTDSS1 in tumor cells increased expression of IFNγ-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1. Loss of PTDSS1 in tumor cells also led to increased expression of MHC-I, which was associated with increased expression of cytolytic function related genes in CD8⁺ T cells and increased frequency of an iNOS⁺ myeloid subset. A gene signature derived from the iNOS⁺ myeloid …

Exploring The Role Of Il-1Β/Il-1r In The Pathogenesis Of K-Ras Mutant Lung Cancer, Avantika Krishna

Dissertations and Theses (Open Access)

As the leading cause of cancer-related deaths worldwide, the development of targeted therapeutics to treat lung cancer remains crucial. Non-small cell lung cancer (NSCLC), the most common histological subtype predominantly comprises lung adenocarcinoma with driver mutations in the K-ras oncogene (KM-LUAD). KM-LUAD progression partly occurs through activation of the NF-κB pathway initiating an inflammatory response and creating a pro-tumor microenvironment. Notably, the pro-inflammatory cytokine IL-1β a potent activator and product of the NF-κB pathway is elevated in the lungs and sera of KM-LUAD patients. We have shown that IL-1β blockade promotes an anti-tumor immune phenotype in a mouse model of …

Rna Knockdown Of The Immune Checkpoint Vista Promotes Tumor Regression, Brittany Morrow, Brittany A. Morrow

Dissertations and Theses (Open Access)

Blockade of negative immune regulators for example CTLA-4, and PD-1/PD-L1 has proven to be a clinically effective strategy to enhance tumor specific immune responses. Recently discovered novel immunoglobulin superfamily ligand V-domain Ig suppressor of T-cell Activation (VISTA) is a new target for immunotherapy. VISTA expression is specifically upregulated on tumor infiltrating myeloid cells such as dendritic cells (DCs), tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs). In addition, VISTA expression is increased on tumor-infiltrating regulatory T cells (Tregs) compared to those in the periphery. VISTA has been shown to suppress effector T cells through multiple mechanisms, primarily by …

Importance Of Specific Nk Cell Subsets For Antitumor Immunity In Hpv+ Cancers, Madison O'Hara

Dissertations and Theses (Open Access)

High-risk type human papillomaviruses (HPV) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing worldwide. Survival rates for patients with locally advanced disease are poor and variable after standard of care (SOC) treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential for improving clinical outcome. The natural killer (NK) cells are a critical component for antitumor innate effector immunity. Among the multitude of activation and inhibitory receptors on immune cells, HLA-DR is recognized as an important activation marker …

Regulation Of Cd4 T Cell Functions By Ncrna-Mediated Signaling Pathways During Chronic Viral Infections, Lam Nguyen

Electronic Theses and Dissertations

CD4 T cell homeostasis and competency are critical for the effectiveness of antiviral immunity. However, CD4 T cells derived from people living with HIV (PLWH) and individuals with chronic HCV infection often exhibit an inflammaging phenotype, evidenced by persistent inflammation, immune activation, exhaustion, senescence, and cellular apoptosis. Despite intensive investigations, the molecular mechanisms underlying CD4 T cell dysfunction in antiretroviral therapy (ART)-controlled PLWH and HCV-infected patients remain poorly understood. By investigating the roles of non-coding (nc)RNA transcripts in regulating the functions of CD4 T cells derived from PLWH and HCV-infected patients, we demonstrated that long non-coding (lnc)RNA - growth arrest-specific …

Defining The Phylogenetics And Resistome Of The Major Clostridioides Difficile Ribotypes Circulating In Australia, Keeley O’Grady, Stacey Hong, Papanin Putsathit, Narelle George, Christine Hemphill, Peter G. Huntington, Tony M. Korman, Despina Kotsanas, Monica Lahra, Rodney Mcdougall, Andrew Mcglinchey, Avram Levy, Casey V. Moore, Graeme Nimmo, Louise Prendergast, Jennifer Robson, David J. Speers, Lynette Waring, Michael C. Wehrhahn, Gerhard F. Weldhagen, Richard M. Wilson, Thomas V. Riley, Daniel R. Knight

Research outputs 2022 to 2026

Clostridioides difficile infection (CDI) remains a significant public health threat globally. New interventions to treat CDI rely on an understanding of the evolution and epidemiology of circulating strains. Here we provide longitudinal genomic data on strain diversity, transmission dynamics and antimicrobial resistance (AMR) of C. difficile ribotypes (RTs) 014/020 (n=169), 002 (n=77) and 056 (n=36), the three most prominent C. difficile strains causing CDI in Australia. Genome scrutiny showed that AMR was uncommon in these lineages, with resistance-conferring alleles present in only 15/169 RT014/020 strains (8.9 %), 1/36 RT056 strains (2.78 %) and none of 77 RT002 strains. Notably, ~90 …

Selective Transfection Of A Transferrin Receptor-Expressing Cell Line With Dna-Lipid Nanoparticles And Synthesis Of Parasite-Derived Glycans As Biomarkers For Leishmaniasis, Irodiel Vinales Lozano

Open Access Theses & Dissertations

Despite notable progress in lipid nanoparticle (LNP)-mediated gene delivery, achieving selective transfection of specific cell types, such as cancer cells, remains a significant hurdle, hindering the advancement of innovative gene therapies. In this study, we engineered an LNP formulation encapsulating plasmid DNA (pDNA) encoding the monomeric Green Lantern (mGL) fluorescent reporter protein. The DT7 peptide ligand targeting human transferrin receptor 1 (hTfR1) was also conjugated to the LNP surface for targeted delivery to hTfR1-expressing cells. Optimization of LNP composition yielded favorable particle diameter, ζ-potential, yield, and pDNA encapsulation efficiency. Evaluation of transfection selectivity using a panel of two engineered cell …

Synthesis Of Neoglycoproteins As Potential Biomarkers For Chagas Disease And Cutaneous Leishmaniasis Caused By Leishmania (Viannia) Braziliensis, Eileni Rodriguez Gil

Open Access Theses & Dissertations

Protozoan parasites are responsible for causing numerous diseases in humans and mammals worldwide. Among them are Chagas disease (CD), caused by the parasite Trypanosoma cruzi (T. cruzi), and tegumentary leishmaniasis (TL), caused by the parasite Leishmania (Viannia). Both diseases coexist in many regions of Latin America, and current hurdles to differentially diagnose them and determine chemotherapy success need to be overcome. CD can be diagnosed by traditional serological tests and polymerase chain reaction (PCR), but disadvantages of these methods are that they may produce false negatives because the antigens used in commercial CD kits are not conserved across all T.cruzi …

Evaluation Of The Effect Of A Commercial Lippia Origanoides Essential Oil Extract On Salmonella Serovar Enteritidis As A Natural Alternative To Antibiotics In The Poultry Industry, Abdiel Atencio

Graduate Theses and Dissertations

The purpose of the present research was to evaluate the bactericidal activity of a microencapsulated Lippia origanoides essential oils (LOEOs) against Salmonella Enteritidis (SE) in an in vitro crop assay and in a prophylactic broiler chicken model using three low doses of the product: 75 ppm, 150 ppm and 300 ppm. Two trials of each assay were conducted. Day-of-hatch male Cobb-Vantress broiler chickens were randomly allotted to one of four groups: 1) positive control group; 2) 75 ppm LOEOs group; 3) 150 ppm LOEOs group; 4) 300 LOEOs group. Chicks were fed and watered ad libitum in heated brooder batteries …

Utilization Of The NuTrack System To Objectively Evaluate Changes In Active And Passive Behaviors Of Group-Housed Nursery Pigs Exposed To An Endotoxin Challenge, Aaron Holliday

Department of Animal Science: Dissertations, Theses, and Student Research

This study aimed to evaluate the changes in activity of group-housed, newly weaned pigs challenged with lipopolysaccharide (LPS). At weaning, pigs (n = 192, 5.73 ± 1.8 kg) were stratified by sex, litter, and body weight (BW) and randomly assigned to one of three treatments (16 pigs/pen, 4 pens/treatment): 1) Saline-injected (SAL), 2) 50% challenged [50%-LPS) – only half of the pigs in a pen (8 pigs) were challenged with LPS and 3) 100% challenged (100%-LPS) – all pigs in a pen were challenged with LPS. Pigs in the SAL and 32 in the 50%-LPS treatment received a 3.0 …

Adding Parasite Resistance To A Hair Sheep Breeding Objective, Robert M. Forbes

Department of Animal Science: Dissertations, Theses, and Student Research

The United States Hair Sheep Index was designed to increase total weight of lamb weaned per ewe lambing (TW) using estimated breeding values (EBV) for direct (DWWT) and maternal (MWWT) weaning weight, and number of lambs born (NLB) and weaned (NLW), as selection criteria. Producers are interested in adding post-weaning fecal egg count EBV (PFEC), an indicator of parasite resistance, to the index to achieve genetic change in both TW and PFEC.

First, the effects of adding PFEC alongside TW to the breeding objective of indexes that used either phenotypes or EBV as selection criteria were studied. Since MWWT …

Hierarchal Single-Cell Lineage Tracing Reveals Differential Fate Commitment Of Cd8 T-Cell Clones In Response To Acute Infection., Leena Abdullah

Dartmouth College Ph.D Dissertations

Generating balanced populations of CD8 effector and memory T cells is necessary for immediate and durable immunity to infections and cancer. Yet, a definitive understanding of CD8 differentiation remains unclear. Here we used CARLIN, a processive lineage recording mouse model with single-cell RNA-seq and TCR-seq to track endogenous antigen-specific CD8 T cells during acute viral infection.

Transcriptional profiling of antigen-specific T cells at the peak of the effector response to Vesicular stomatitis virus uncovered a diverse repertoire of expanded antigen-specific T-cell clones represented by seven transcriptional states. TCR enrichment analysis identified TCR clones with differential memory- or effector-fate biases during …

Immune-Monitoring Of Myelodysplastic Neoplasms: Recommendations From The I4mds Consortium, Cristina A Tentori, Lin P Zhao, Benedetta Tinterri, Kathryn E Strange, Katharina Zoldan, Konstantinos Dimopoulos, Xingmin Feng, Elena Riva, Benjamin Lim, Yannick Simoni, Vidhya Murthy, Madeline J Hayes, Antonella Poloni, Eric Padron, Bruno A Cardoso, Michael Cross, Susann Winter, Aida Santaolalla, Bhavisha A Patel, Emma M Groarke, Daniel H Wiseman, Katy Jones, Lauren Jamieson, Charles Manogaran, Naval Daver, Laura Gallur, Wendy Ingram, P Brent Ferrell, Katja Sockel, Nicolas Dulphy, Nicolas Chapuis, Anne S Kubasch, Astrid M Olsnes, Austin Kulasekararaj, Hugues De Lavellade, Wolfgang Kern, Mieke Van Hemelrijck, Dominique Bonnet, Theresia M Westers, Sylvie Freeman, Uta Oelschlaegel, David Valcarcel, Marco G Raddi, Kirsten Grønbæk, Michaela Fontenay, Sanam Loghavi, Valeria Santini, Antonio M Almeida, Jonathan M Irish, David A Sallman, Neal S Young, Arjan A Van De Loosdrecht, Lionel Adès, Matteo G Della Porta, Catherine Cargo, Uwe Platzbecker, Shahram Kordasti, I4mds Consortium

Faculty, Staff and Student Publications

Advancements in comprehending myelodysplastic neoplasms (MDS) have unfolded significantly in recent years, elucidating a myriad of cellular and molecular underpinnings integral to disease progression. While molecular inclusions into prognostic models have substantively advanced risk stratification, recent revelations have emphasized the pivotal role of immune dysregulation within the bone marrow milieu during MDS evolution. Nonetheless, immunotherapy for MDS has not experienced breakthroughs seen in other malignancies, partly attributable to the absence of an immune classification that could stratify patients toward optimally targeted immunotherapeutic approaches. A pivotal obstacle to establishing "immune classes" among MDS patients is the absence of validated accepted immune …

Benefit Of Axicabtagene Ciloleucel Versus Chemoimmunotherapy In Older Patients And/Or Patients With Poor Ecog Performance Status With Relapsed Or Refractory Large B-Cell Lymphoma After 2 Or More Lines Of Prior Therapy, Matthew A Lunning, Hai-Lin Wang, Zhen-Huan Hu, Frederick L Locke, Tanya Siddiqi, Caron A Jacobson, Sairah Ahmed, David B Miklos, Yi Lin, Brian T Hill, Armin Ghobadi, Sattva S Neelapu, Jason Westin, Chrisopher Dieyi, Polly Field, Harry Miao, Shilpa A Shahani, Anik Patel, Clare Spooner, Christine Fu, David Muramoto, Hairong Xu, Marcelo C Pasquini

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients …

High-Grade Pleomorphic Sarcomas Treated With Immune Checkpoint Blockade: The Md Anderson Cancer Center Experience, Lewis F Nasr, Marianne Zoghbi, Rossana Lazcano, Michael Nakazawa, Andrew J Bishop, Ahsan Farooqi, Devarati Mitra, Beverly Ashleigh Guadagnolo, Robert Benjamin, Shreyaskumar Patel, Vinod Ravi, Dejka M Araujo, Andrew Livingston, Maria A Zarzour, Anthony P Conley, Ravin Ratan, Neeta Somaiah, Alexander J Lazar, Christina Roland, Emily Z Keung, Elise F Nassif Haddad

Faculty, Staff and Student Publications

BACKGROUND: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available.

PURPOSE: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution.

METHODS: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in …

The Constitutively Active Form Of A Key Cholesterol Synthesis Enzyme Is Lipid Droplet-Localized And Upregulated In Endometrial Cancer Tissues, Hudson W Coates, Tina B Nguyen, Ximing Du, Ellen M Olzomer, Rhonda Farrell, Frances L Byrne, Hongyuan Yang, Andrew J Brown

Faculty, Staff and Student Publications

Cholesterol is essential for both normal cell viability and cancer cell proliferation. Aberrant activity of squalene monooxygenase (SM, also known as squalene epoxidase), the rate-limiting enzyme of the committed cholesterol synthesis pathway, is accordingly implicated in a growing list of cancers. We previously reported that hypoxia triggers the truncation of SM to a constitutively active form, thus preserving sterol synthesis during oxygen shortfalls. Here, we show SM truncation is upregulated and correlates with the magnitude of hypoxia in endometrial cancer tissues, supporting the in vivo relevance of our earlier work. To further investigate the pathophysiological consequences of SM truncation, we …

Effect Of Source Of Trace Minerals On Nutrient Digestibility And Rumen Fermentation Of Dairy Cows, Cesar Velasquez Rios

All Theses

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Characterization Of Ato Family Transporters In The Fungal Pathogen Cryptococcus Neoformans, Will Betsill

All Theses

Fungal pathogens are a significant threat to public health as they are becoming increasingly common and more resistant to treatment. Cryptococcus neoformans contributes greatly to this threat annually by causing an estimated 278,000 cases of cryptococcal meningitis resulting in approximately 181,000 deaths globally according to the CDC. C. neoformans is ubiquitous across most of the globe and can be found in such places as in trees or soil. Exposure to this fungus is especially dangerous to individuals who are immunocompromised or immunosuppressed. In these cases, inhalation of spores can lead to infection in the lungs. Once in the lungs, C. …

Neoadjuvant Chemoimmunotherapy For Nsclc: A Systematic Review And Meta-Analysis, Mark Sorin, Connor Prosty, Louis Ghaleb, Kathy Nie, Khaled Katergi, Muhammad H Shahzad, Laurie-Rose Dubé, Aline Atallah, Anikka Swaby, Matthew Dankner, Trafford Crump, Logan A Walsh, Pierre O Fiset, Boris Sepesi, Patrick M Forde, Tina Cascone, Mariano Provencio, Jonathan D Spicer

Faculty, Staff and Student Publications

IMPORTANCE: To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%.

OBJECTIVE: To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials.

DATA SOURCES: MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of …

Spatiotemporal Dynamics Of Disease: Social And Environmental Drivers Of Movement, Connectivity, And Disease Transmission In Bighorn Sheep, Lauren E. Ricci

All Graduate Theses and Dissertations, Fall 2023 to Present

Movement is a fundamental component of animal ecology. Animals move in order to access resources and avoid risk. Movement decisions aggregated across time determine how individuals use space, contact dynamics between individuals within a population, and connectivity across a species range. These patterns that emerge from movement decisions have downstream implications for many ecological processes and a mechanistic understanding of movement can help answer broader questions about ecology.

Disease dynamics are intrinsically tied to movement. Understanding the mechanisms that drive movement can elucidate how disease will spread and impact host populations. In this vein, I employed a suite of movement …

Spatial Ecology Of Mule Deer Migrations From Grand Teton National Park And The Teton Range, Justin K. Schwabedissen

All Graduate Theses and Dissertations, Fall 2023 to Present

The Greater Yellowstone Ecosystem hosts several of the longest, fully intact ungulate migrations remaining in the continental United States. However, expanding development and an increasing human footprint continue to truncate migratory routes. While the endpoints are often a seasonal range on protected lands, these migration corridors frequently cross other jurisdictional boundaries, including large tracts of private or multiple-use lands, with varying levels of protection. Thus, it is critical resource managers understand the dynamics of migratory movements to define population-level corridors and prioritize appropriate conservation strategies. Mule deer in Wyoming have been documented traveling long distances between summer and winter ranges; …

Immunotherapy Withdrawal By Step-Down To Mesalamine In Pediatric Patients With Ulcerative Colitis, Reka Szigeti, Richard Kellermayer

Faculty, Staff and Students Publications

OBJECTIVE: Parents and pediatric patients with ulcerative colitis (UC) who progressed to systemic immunotherapy are concerned about lifelong risks from such treatments. There is limited knowledge about withdrawal of such agents and step-down (SD) to enteral 5-aminosalicylic acid (mesalamine) before transitioning to adult care.

METHODS: We studied nine pediatric cases with moderate to severe UC who after a median of 2.18 years of clinical remission on systemic immunotherapy stepped down to oral mesalamine treatment.

RESULTS: Average follow-up time from SD was 3.49 years. Five patients (55.5%) had sustained remission (without any flare noted) after SD during follow-up. Sustained clinical remission …

Effects Of Silymarin On S. Aureus Atcc25923 Biofilm And Its Virulence Factors, Wang Jiakang, Tang Haoguo, Chen Jing, Si Qihe, Shen Ruxiao

Food and Machinery

Objective: In this study, the effects of silymarin on the biofilm S. aureus ATCC25923 and its virulence factors were investigated. Methods: The inhibition and clearance of silymarin on S. aureus ATCC25923 biofilm formation were detected by crystal violet staining, the effects of silymarin on its biofilm metabolism were investigated by MTT staining, and the effects of silymarin on its coagulase expression and hemolytic activity were investigated by freeze-dried plasma and aseptic defibrinated sheep blood. In parallel, the effects of different concentrations of silymarin on its biofilm and Fourier transform were observed under an optical microscope. Results: The results showed that …

The Differences In Maternal Clean And Healthy Living Behavior In The Incidence Of Stunting In Yogyakarta, Shafa Ramadhita, Anindhita Syahbi Syagata, Nor Eka Noviani

Indonesian Journal of Public Health Nutrition (IJPHN)

An indirect cause of stunting is maternal behavior. Moreover, good nutritional knowledge relates to good nutritional behaviors. Maternal clean and Healthy Living Behavior (PHBS) in daily life can reduce the risk of infectious diseases and be role models for children in implementing their future health behavior. The study aims to investigate the differences in PHBS of mothers in the incidence of stunting ages 24-59 months in the Minggir Primary Health Center working area. The cross-sectional approach of this research was conducted from March to April 2023. The subjects of this study were 69 respondents selected by cluster random sampling. The …

Factors Associated With Wasting In Toddlers Aged 6 – 59 Months At Cimpaeun Village, Depok City, West Java, Indonesia In 2023, Early Vici Azmia, Triyanti Triyanti

Indonesian Journal of Public Health Nutrition (IJPHN)

The prevalence of wasting under five in Indonesia in 2022 is 7.7%; according to WHO, this wasting problem is a serious public health problem. Wasting is a nutritional problem in toddlers that has an impact on morbidity and mortality. The research objective was to determine the factors associated with wasting in toddlers aged 6–59 months in Cimpaeun Village in 2023. The dependent variable is wasting, and the independent variables are birth weight, history of fever, diarrhea, acute respiratory infection, energy intake, carbohydrate intake, protein intake, fat intake, mother’s age, pregnancy, mother’s education level, mother’s nutritional knowledge, and family income. This …

Loss Of Tumor Suppressor Tmem127 Drives Ret-Mediated Transformation Through Disrupted Membrane Dynamics, Timothy J Walker, Eduardo Reyes-Alvarez, Brandy D Hyndman, Michael G Sugiyama, Larissa C B Oliveira, Aisha N Rekab, Mathieu J F Crupi, Rebecca Cabral-Dias, Qianjin Guo, Patricia L M Dahia, Douglas S Richardson, Costin N Antonescu, Lois M Mulligan

Faculty, Staff and Student Publications

Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTKs) are important regulators of signaling in normal cells that can frequently be disrupted in cancer. The adrenal tumor pheochromocytoma (PCC) can be caused by activating mutations of the rearranged during transfection (RET) receptor tyrosine kinase, or inactivation of TMEM127, a transmembrane tumor suppressor implicated in trafficking of endosomal cargos. However, the role of aberrant receptor trafficking in PCC is not well understood. Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and …

Modeling The Transmission Dynamics Of Tuberculosis In Humans, Farida Kisinda, Joshua A. Mwasunda, Mbwiga S. Aloni

Tanzania Journal of Science

Tuberculosis (TB) is a major threat to human health particularly in most of developing countries. In this article, we formulate and analyze a deterministic model for the transmission dynamics of pulmonary and extra-pulmonary tuberculosis. The next generation method is employed to find the basic reproduction number which helps to determine whether TB clears or persists in the human population. Global stability of model equilibria is done through Lyapunov functions whereas the normalized forward sensitivity index method is adopted to determine parameters that drive tuberculosis. Analysis shows that both TB free and endemic equilibria exist. The TB free equilibrium is globally …

Modelling The Combined Use Of Long-Lasting Insecticidal Nets And Insecticides Zooprophylaxis Against The Resilience Of Anopheles Arabiensis For Effective Malaria Control, Watson Levens

Tanzania Journal of Science

Malaria is a significant public health concern, especially in tropical regions. It remains endemic in many areas where malaria mosquitoes are prevalent. This study investigates the viability of insecticide zooprophylaxis (IZ) in conjunction with Long Lasting Insecticidal Nets (LLINs) as a strategic approach to combat malaria transmission, particularly in regions dominated by zoophagic vectors. Through the presentation and analysis of a mathematical model that integrates IZ and LLINs for the control of Anopheles arabiensis (An. arabiensis), the research underscores IZ's role in reducing zoophagic vector populations and enhancing malaria control efforts. Notably, the study reveals that achieving comprehensive coverage of …

Quorum-Sensing Agr System Of Staphylococcus Aureus Primes Gene Expression For Protection From Lethal Oxidative Stress, Magdalena Podkowik, Andrew I Perault, Gregory Putzel, Andrew Pountain, Jisun Kim, Ashley L Dumont, Erin E Zwack, Robert J Ulrich, Theodora K Karagounis, Chunyi Zhou, Andreas F Haag, Julia Shenderovich, Gregory A Wasserman, Junbeom Kwon, John Chen, Anthony R Richardson, Jeffrey N Weiser, Carla R Nowosad, Desmond S Lun, Dane Parker, Alejandro Pironti, Xilin Zhao, Karl Drlica, Itai Yanai, Victor J Torres, Bo Shopsin

Faculty, Staff and Student Publications

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic …