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Individual Risk Factors Associated With Cesarean Section Surgical Site Infections Among African American Women In California, Paula St Hill

Walden Dissertations and Doctoral Studies

No abstract provided.

System And Method Of Dynamic Light Source Control, Dennis Karl Killinger

USF Patents

A system and method of adjusting a field of view in an imaging system includes transmitting light across a transmission optical path and defining a field of view encompassing both uniform and spatially tenuous target objects within the transmitted light. A sensor within a return optical path of reflected light from at least a portion of one of the target objects allows a data processing computer to compile an image from a series of data outputs from the sensor. The image is analyzed to determine a region of interest within the image and by dynamically adjusting the light source, the …

Hsp90 Activator Aha1 Drives Production Of Pathological Tau Aggregates, Chad Dickey, Lindsey Shelton, Brian Blagg, John Koren, Laura Jenelle Blair

USF Patents

Disclosed herein are compounds and methods for inhibiting Aha1 for the treatment of tauopathies and neurodegenerative diseases. The Aha1 inhibitor may reduce the interaction between Aha1 and Hsp90. The Aha1 inhibitor may reduce aggregation of tau protein. The Aha1 inhibitor may include a compound selected from KU-177, KU-174, and KU-308.

A Longitudinal Investigation Of The Relationships Between Experiences With Sexual Harassment, Self-Objectification, And Self-Concept Clarity Among Women, Roxanne N. Felig

USF Tampa Graduate Theses and Dissertations

This longitudinal research investigates the nuanced relationship between sexual harassment and self-concept development among both men and women over a six-week period, presenting a unified model that integrates theories of self-objectification and self-concept clarity. Across three waves of data collection (N= 370, N=315, N=279, respectively), I find evidence that women experience higher rates of sexual harassment, greater self-objectification, and lower self-concept clarity than men. Across time, I find that experiencing sexual harassment predicts heightened self-objectification, which further predicts a disrupted sense of self among both men and women. Critically, this work investigates the reciprocal nature of self-objectification and self-concept clarity, …

Individual Risk Factors Associated With Cesarean Section Surgical Site Infections Among African American Women In California, Paula St Hill

Frank Dilley Award for Outstanding Doctoral Study

Healthcare-associated infections (HAIs) are a significant public health issue. More than 600,000 patients in the United States develop HAIs every year. Surgical site infections (SSIs) are a very common HAI and can develop when a woman has a Cesarean section (C-section). The complications from the development of an SSI can be severe. SSIs and C-section rates are high among African American women. The purpose of this quantitative study, utilizing secondary data provided by the California Health and Human Services Open Data Portal, was to determine if age at the time of delivery, smoking status of tobacco and non-tobacco products during …

Outcomes Of Hepatic Artery-Based Therapies And Systemic Multiagent Chemotherapy In Unresectable Colorectal Liver Metastases: A Systematic Review And Meta-Analysis, Henry Stitzel, Victoria Wu, David Bajor, Sakti Chakrabarti, Madison Conces, Lauren Henke, Melissa Lumish, Amit Mahipal, Amr Mohamed, Jordan M. Winter, Jeffrey M. Hardacre, John B. Ammori, Jennifer E. Selfridge, Lee M. Ocuin

Faculty Scholarship

Background: Treatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these treatment options has not been performed. Objective: A systematic review and meta-analysis was performed to calculate pooled outcomes of hepatic artery infusion with systemic chemotherapy (HAI-S), transarterial chemoembolization with systemic chemotherapy (TACE-S), transarterial radioembolization with systemic chemotherapy (TARE-S), doublet (FOLFOX, FOLFIRI), and triplet chemotherapy (FOLFOXIRI). Methods: Outcomes included overall survival (OS), progression-free survival (PFS), rate of conversion to resection (CTR), and response rate (RR). Results: A total of 32, 7, 9, and 14 publications were included in the HAI-S, …

Dorycnium Vuralii (Fabaceae), A New Species From Türkiye, Bilal Şahi̇n, Seher Karaman, Mevlüde Alev Ateş, Zeki Aytaç

Turkish Journal of Botany

The present study describes a new species Dorycnium vuralii (Fabaceae) from Çankırı, Türkiye. The new species is compared morphologically to the taxa of sect. Bonjeanea and sect. Dorycnium along with pollen micromorphology, leaflet, and seed micromorphology. The geographical distribution of Dorycnium vuralii is mapped. The phylogenetic relationships between the new species and other closely related species in the genus are inferred based on DNA data from both cpDNA and nrDNA (rbcL1&ITS). Although phylogenetic implications are different in the two DNA barcoding regions, D. vuralii is shown to be a new species in both molecular data. The new species is assessed …

Single-Cell Analysis Of Age-Related Changes In Leukocytes Of Diabetic Mouse Hindpaws, James M Nichols, Hoang Vu Pham, Eric F Lee, Rajasekaran Mahalingam, Andrew J Shepherd

Faculty, Staff and Student Publications

Complications associated with Type 1 and Type 2 diabetes, such as diabetic peripheral neuropathy and diabetic foot ulcers, are a growing health-care concern. In addition, this concern increases as diabetic patients age due to their increased susceptibility to complications. To address this growing problem, it is important to understand fluctuations in physiology which lead to pathological changes associated with the metabolic disturbances of diabetes. Our study explores dysregulation of immune cell populations in the hindpaws of healthy and diabetic mice at 12 and 21 weeks of age using single-cell RNA sequencing to provide insight into immune disruptions occurring in the …

The Outcomes Measured And Reported In Observational Studies Of Incidental And Untreated Intracranial Meningioma: A Systematic Review, Michael Mcdermott

All Publications

Background: The clinical management of patients with incidental intracranial meningioma varies markedly and is often based on clinician choice and observational data. Heterogeneous outcome measurement has likely hampered knowledge progress by preventing comparative analysis of similar cohorts of patients. This systematic review aimed to summarize the outcomes measured and reported in observational studies.

Methods: A systematic literature search was performed to identify published full texts describing active monitoring of adult cohorts with incidental and untreated intracranial meningioma (PubMed, EMBASE, MEDLINE, and CINAHL via EBSCO, completed January 24, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method …

A Machine Learning Approach To Predict Mortality Due To Immune-Mediated Thrombotic Thrombocytopenic Purpura, Camila Masias

All Publications

Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been externally validated in the United States. Recent advances in machine learning technology can help analyze large numbers of variables with complex interactions for the development of prediction models.

Objectives: To validate the French TMA Reference Score in the United States Thrombotic Microangiopathy (USTMA) iTTP database and subsequently develop a novel mortality prediction tool, the USTMA TTP Mortality Index.

Methods: We analyzed variables available at the time of initial presentation, including demographics, …

Two Dot1 Enzymes Cooperatively Mediate Efficient Ubiquitin-Independent Histone H3 Lysine 76 Tri-Methylation In Kinetoplastids, Victoria Frisbie, Hideharu Hashimoto, Yixuan Xie, Francisca De Luna Vitorino, Josue Baeza, Tam Nguyen, Zhangerjiao Yuan, Janna Kiselar, Benjamin Garcia, Erik Debler

Department of Biochemistry and Molecular Biology Faculty Papers

In higher eukaryotes, a single DOT1 histone H3 lysine 79 (H3K79) methyltransferase processively produces H3K79me2/me3 through histone H2B mono-ubiquitin interaction, while the kinetoplastid Trypanosoma brucei di-methyltransferase DOT1A and tri-methyltransferase DOT1B efficiently methylate the homologous H3K76 without H2B mono-ubiquitination. Based on structural and biochemical analyses of DOT1A, we identify key residues in the methyltransferase motifs VI and X for efficient ubiquitin-independent H3K76 methylation in kinetoplastids. Substitution of a basic to an acidic residue within motif VI (Gx₆K) is essential to stabilize the DOT1A enzyme-substrate complex, while substitution of the motif X sequence VYGE by CAKS renders a rigid active-site …

No Such Thing As Nappy, Alan Roosevelt Atkins

Theses and Dissertations

This supportive statement examines how my upbringings influenced my cultural and societal perspectives and how I strive to challenge perceptions of race, history, and culture through my artwork. I include representations of people from various diasporas in drawings, prints, and animations to speak to the global reach of colorism and Eurocentrism. Influenced by the DIY nature of punk art and the urgency of protest art, I utilize materials such as Sharpies, fabric markers, collage, and cardboard. Use of cardboard suggests commercial exchange and the physical movement of goods from one place to another, as well as modern throw-away culture. Parallels …

Polyamine-Mediated Ferroptosis Amplification Acts As A Targetable Vulnerability In Cancer, Guoshu Bi, Jiaqi Liang, Yunyi Bian, Guangyao Shan, Yiwei Huang, Tao Lu, Huan Zhang, Xing Jin, Zhencong Chen, Mengnan Zhao, Hong Fan, Qun Wang, Boyi Gan, Cheng Zhan

Faculty, Staff and Student Publications

Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload of lipid peroxides, in cancer therapy is impeded by our limited understanding of the intersection of tumour’s metabolic feature and ferroptosis vulnerability. In the present study, arginine is identified as a ferroptotic promoter using a metabolites library. This effect is mainly achieved through arginine’s conversion to polyamines, which exerts their potent ferroptosis-promoting property in an H2O2-dependent manner. Notably, the expression of ornithine decarboxylase 1 (ODC1), the critical enzyme catalysing polyamine synthesis, is significantly activated by the ferroptosis signal——iron overload——through WNT/MYC signalling, as well as the subsequent …

Intensive Blood Pressure Lowering In Individuals With Low Diastolic Blood Pressure And Elevated Troponin Levels In Sprint, Cady Smith, Jarett D Berry, Rebecca Scherzer, James A De Lemos, Vijay Nambi, Christie M Ballantyne, Richard L Kravitz, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Simon B Ascher

Faculty, Staff and Students Publications

Background: Among individuals with hypertension and low diastolic blood pressure (DBP), the optimal BP target remains controversial due to concerns that BP lowering may reduce coronary perfusion. We determined the impact of intensive BP control among individuals with elevated systolic BP who have low DBP and elevated hs-cTnT (high-sensitivity cardiac troponin T) levels.

Methods and results: A total of 8828 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were stratified by baseline DBP. Those with low DBP (< 70 mm Hg) were further stratified by elevated hs-cTnT (≥14 ng/L) at baseline. The effects of intensive versus standard BP lowering on a cardiovascular disease composite end point, all-cause death, and 1-year change in hs-cTnT were determined. The combination of low DBP/high hs-cTnT was independently associated with a higher risk for cardiovascular disease and all-cause death, as well as greater 1-year increases in hs-cTnT, compared with DBP ≥70 mm Hg. However, randomization to intensive versus standard BP lowering led to similar reductions in cardiovascular disease risk among individuals with low DBP/high hs-cTnT (hazard ratio [HR], 0.82 [95% CI, 0.57-1.19]), low DBP/low hs-cTnT (HR, 0.48 [95% CI, 0.29-0.79]), and DBP ≥70 mm Hg (HR, 0.73 [95% CI, 0.60-0.89]; P for interaction=0.20). Intensive BP lowering also led to a reduction in all-cause death that was similar across groups (P for …

Synthetic Pet From Ct Improves Diagnosis And Prognosis For Lung Cancer: Proof Of Concept, Morteza Salehjahromi, Tatiana V Karpinets, Sheeba J Sujit, Mohamed Qayati, Pingjun Chen, Muhammad Aminu, Maliazurina B Saad, Rukhmini Bandyopadhyay, Lingzhi Hong, Ajay Sheshadri, Julie Lin, Mara B Antonoff, Boris Sepesi, Edwin J Ostrin, Iakovos Toumazis, Peng Huang, Chao Cheng, Tina Cascone, Natalie I Vokes, Carmen Behrens, Jeffrey H Siewerdsen, John D Hazle, Joe Y Chang, Jianhua Zhang, Yang Lu, Myrna C B Godoy, Caroline Chung, David Jaffray, Ignacio Wistuba, J Jack Lee, Ara A Vaporciyan, Don L Gibbons, Gregory Gladish, John V Heymach, Carol C Wu, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

[18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are indispensable components in modern medicine. Although PET can provide additional diagnostic value, it is costly and not universally accessible, particularly in low-income countries. To bridge this gap, we have developed a conditional generative adversarial network pipeline that can produce FDG-PET from diagnostic CT scans based on multi-center multi-modal lung cancer datasets (n = 1,478). Synthetic PET images are validated across imaging, biological, and clinical aspects. Radiologists confirm comparable imaging quality and tumor contrast between synthetic and actual PET scans. Radiogenomics analysis further proves that the dysregulated cancer hallmark pathways of …

Durvalumab And Tremelimumab Before Surgery In Patients With Hormone Receptor Positive, Her2-Negative Stage Ii-Iii Breast Cancer, Haven R Garber, Sreyashi Basu, Sonali Jindal, Zhong He, Khoi Chu, Akshara Singareeka Raghavendra, Clinton Yam, Lumarie Santiago, Beatriz E Adrada, Padmanee Sharma, Elizabeth A Mittendorf, Jennifer K Litton

Faculty, Staff and Student Publications

A clinical trial was conducted to assess the feasibility of enrolling patients with Stage II or III hormone receptor positive (HR+)/HER2-negative breast cancer to pre-operative dual PD-L1/CTLA-4 checkpoint inhibition administered prior to neoadjuvant chemotherapy (NACT). Eight eligible patients were treated with upfront durvalumab and tremelimumab for two cycles. Patients then received NACT prior to breast surgery. Seven patients had baseline and interval breast ultrasounds after combination immunotherapy and the responses were mixed: 3/7 patients experienced a ≥30% decrease in tumor volume, 3/7 a ≥30% increase, and 1 patient had stable disease. At the time of breast surgery, 1/8 patients had …

Three-Dimensional Optothermal Manipulation Of Light-Absorbing Particles In Phase-Change Gel Media, Pavana Siddhartha Kollipara, Zilong Wu, Kan Yao, Dongdong Lin, Zhengyu Ju, Xiaotian Zhang, Taizhi Jiang, Hongru Ding, Jie Fang, Jingang Li, Brian A Korgel, Joan M Redwing, Guihua Yu, Yuebing Zheng

Faculty, Staff and Student Publications

Rational manipulation and assembly of discrete colloidal particles into architected superstructures have enabled several applications in materials science and nanotechnology. Optical manipulation techniques, typically operated in fluid media, facilitate the precise arrangement of colloidal particles into superstructures by using focused laser beams. However, as the optical energy is turned off, the inherent Brownian motion of the particles in fluid media impedes the retention and reconfiguration of such superstructures. Overcoming this fundamental limitation, we present on-demand, three-dimensional (3D) optical manipulation of colloidal particles in a phase-change solid medium made of surfactant bilayers. Unlike liquid crystal media, the lack of fluid flow …

Visual Outcome And Ocular Complications In Patients With Lacrimal Gland Carcinoma After Eye-Sparing Surgery And Adjuvant Radiation Therapy, Zhenyang Zhao, Steven Jay Frank, Jing Ning, Jiawei Zhao, Xinyang Jiang, Xin A Wang, Amy C Schefler, Ehab Hanna, Amy Moreno, Brandon Gunn, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Background: We report visual outcomes and ocular complications in patients with lacrimal gland carcinoma who had eye-sparing surgery followed by radiotherapy.

Methods: This review included consecutive patients with lacrimal gland carcinoma who underwent eye-sparing surgery and adjuvant radiotherapy or concurrent chemoradiation therapy between 2007 and 2018. Clinical data, including details of ophthalmological examinations and radiation treatment were reviewed.

Results: The study included 23 patients, 15 males and 8 females, with median age 51 years. Twenty patients (87%) received intensity-modulated proton therapy; 3 (13%) received intensity-modulated radiotherapy. Nineteen patients (83%) received concurrent chemotherapy. After a median follow-up time of 37 months …

The Illegal Exploitation Of Threatened Manta And Devil Rays In The Chagos Archipelago, One Of The World’S Largest No-Take Mpas, Joanna Harris, Guy M.W. Stevens

School of Biological and Marine Sciences

Illegal fishing is a concern within marine protected areas (MPA) worldwide, particularly for threatened species such as manta and devil rays (mobulids). However, due to the lack of taxonomic knowledge of enforcement personnel, illegal fishing catch records relating to mobulids can be limited. Here, an examination of illegal catch photographs from local enforcement authorities of the Chagos Archipelago’s vast no-take MPA revealed approximately 79 individual mobulids from just seven vessels, equating to an estimated 20 tonnes. This is likely a vast underestimation due to the limited detection of illegal fishing activity and species-specific reporting. If catches of this magnitude are …

Examining The Utility Of The Early Childhood Development Index (Ecdi) Among Children In The Nigeria Context, Ngozi V. Enelamah, Smitha Rao, Margaret Lombe, Mansoo Yu, Chrisann Newransky, Chrisann Newransky, Melissa L. Villodas, Andrew Foell, Von Nebbitt

Faculty Publications

An estimated 6 million children under the age of five in Nigeria (out of nearly 31 million) risk not reaching their full developmental potential. The dearth of context-relevant measures poses a challenge to the planning and implementation of effective interventions. This study assesses the utility of the Early Childhood Development Index (ECDI) in Nigeria. We used the Multiple Indicator Cluster Surveys to track progress among 3- to 4-year-old children (n = 11,073); 3-year-old, 51%; female, 49%. Using random calibration samples, the results from psychometric tests indicate that while over half of the children were on track in their development based …

Germline Structural Variation Globally Impacts The Cancer Transcriptome Including Disease-Relevant Genes, Fengju Chen, Yiqun Zhang, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Germline variation and somatic alterations contribute to the molecular profile of cancers. We combine RNA with whole genome sequencing across 1,218 cancer patients to determine the extent germline structural variants (SVs) impact expression of nearby genes. For hundreds of genes, recurrent and common germline SV breakpoints within 100 kb associate with increased or decreased expression in tumors spanning various tissues of origin. A significant fraction of germline SV expression associations involves duplication of intergenic enhancers or 3' UTR disruption. Genes altered by both somatic and germline SVs include ATRX and CEBPA. Genes essential in cancer cell lines include BARD1 and …

Controlled Release Of Radioactive Water From The Fukushima Daiichi Nuclear Power Plant: Should We Be Concerned?, Maria F. Ferreira, Andrew Turner, Awadhesh N. Jha

School of Biological and Marine Sciences

Following the Fukushima Daiichi nuclear disaster in 2011, the decision to release more than 1 million tons of radioactive water into the ocean by the Japanese government, with approval from the IAEA, has divided public and scientific opinion. The discharge began on August 24, 2023, with the premise that, after removal of long-lived radionuclides (i.e., 137Cs and 90Sr), tritium (3H), the primary remaining radionuclide as tritiated water (HTO), will be sufficiently and safely diluted over a 30-year period. (1) Concerns, however, relate to (a) the safety of seafood and its consumers and (b) potential long-term consequences on human and environmental …

A Partial Drp1 Knockout Improves Autophagy Flux Independent Of Mitochondrial Function, Rebecca Z. Fan, Carolina Sportelli, Yanhao Lai, Said S. Salehe, Jennifer R. Pinnell, Harry J. Brown, Jason R. Richardson, Shouqing Luo, Kim Tieu

Peninsula Medical School

Background: Dynamin-related protein 1 (Drp1) plays a critical role in mitochondrial dynamics. Partial inhibition of this protein is protective in experimental models of neurological disorders such as Parkinson’s disease and Alzheimer’s disease. The protective mechanism has been attributed primarily to improved mitochondrial function. However, the observations that Drp1 inhibition reduces protein aggregation in such neurological disorders suggest the involvement of autophagy. To investigate this potential novel protective mechanism of Drp1 inhibition, a model with impaired autophagy without mitochondrial involvement is needed. Methods: We characterized the effects of manganese (Mn), which causes parkinsonian-like symptoms in humans, on autophagy and mitochondria by …

Cover And Contents

Turkish Journal of Botany

No abstract provided.

Identification Of Carrying Alien Dna Fragments In Solanum Melongena X Solanum Incanum Interspecific Progeny By Using Cosii Marker, Görkem Sülü, İlknur Polat, Hati̇ce Fi̇li̇z Boyaci, Ahmet Naci̇ Onus

Turkish Journal of Botany

Cultivated eggplant (Solanum melongena L.) is produced in many countries with temperate and tropical climates and has great economic importance. In recent years, resistance to biotic and abiotic stress conditions in addition to increasing yield and quality has gained importance in plant breeding including eggplant breeding. Therefore, the wild relative S. incanum is an important parent in breeding studies as it provides resistance to some important biotic and abiotic stresses for eggplant. It is possible to obtain a fully fertile hybrid between the two species, as well as to establish F2 lines. However, it is a mystery whether there is …

Isolation And Assessment Of Halophilic Rhizobacteria Plant Growth-Promoting Traits For Alleviating Salt Stress In Wheat, Alev Sezen, Ömer Faruk Algur, Ferruh Aşçi, Arzu Ünal

Turkish Journal of Botany

In this study, 22 halophilic bacteria were isolated from plants collected together with rhizosphere soil from habitats with high salt content in and around Erzurum. Various plant growth-promoting (PGP) properties of these isolates (nitrogen fixing, phosphate solubilizing, ACC deaminase, and IAA and siderephore production) were determined. Bacteria positive for PGP properties and various combinations with these bacteria were subjected to pot experiments in saline medium (greenhouse conditions) and their effects on growth parameters (root and stem length, fresh and dry weight, protein, and chlorophyll and carotenoid content) of wheat plants were determined. As a result of the research, the isolates …

A New Permineralized Corypha-Type Coryphoid Palm Stem From K-Pg Of India: Anatomy, Systematics, Saprophytic Fungi, And Paleoecology, Ashif Ali, Kaustav Roy, Biswajit Mukherjee, Subir Bera, Mahasin Khan

Turkish Journal of Botany

Palms are known to be an important and diverse angiosperm component in the Deccan Intertrappean beds of Central India. However, the report of fossilized palm stems inhibiting saprophytic fungal remains is empty in the field of paleobotany. Here, we document for the first time the occurrence of fungal remains in a petrified palm stem collected from the latest Maastrichtian (Late Cretaceous)-earliest Danian (early Paleocene) sediments of the Deccan Intertrappean beds of Madhya Pradesh, Central India. The anatomical features of the fossil stem are characterized by the presence of Corypha-type general stem pattern (progressive decrease of fibrous parts of fibrovascular bundles, …

Coastal Discharge Extremes And Their Environmental Impact On The Sea Of Marmara, Nüvi̇t Berkay Başdurak

Turkish Journal of Earth Sciences

Increases in evaporation driven by global warming change the hydrological cycle by fueling extreme precipitation and exacerbating the frequency and intensity of extreme floods. Combined with the increase in terrestrial waste and pollutants, the changing climate exposes coastal zones to natural hazards. The Sea of Marmara, as an inland sea with a dense coastal population, is more vulnerable to such changes and subject to eutrophication and extreme environmental events (e.g., mucilage). Therefore, quantification of daily and along-coast variation of river discharge and evaluation of its annual trend of extremes are crucial. The daily discharges from the coastal watersheds Biga, Gönen, …

Network Of Epistatic Interactions In An Enzyme Active Site Revealed By Large-Scale Deep Mutational Scanning, Allison Judge, Banumathi Sankaran, Liya Hu, Murugesan Palaniappan, André Birgy, B V Venkataram Prasad, Timothy Palzkill

Faculty, Staff and Students Publications

Cooperative interactions between amino acids are critical for protein function. A genetic reflection of cooperativity is epistasis, which is when a change in the amino acid at one position changes the sequence requirements at another position. To assess epistasis within an enzyme active site, we utilized CTX-M β-lactamase as a model system. CTX-M hydrolyzes β-lactam antibiotics to provide antibiotic resistance, allowing a simple functional selection for rapid sorting of modified enzymes. We created all pairwise mutations across 17 active site positions in the β-lactamase enzyme and quantitated the function of variants against two β-lactam antibiotics using next-generation sequencing. Context-dependent sequence …

Two Dot1 Enzymes Cooperatively Mediate Efficient Ubiquitin-Independent Histone H3 Lysine 76 Tri-Methylation In Kinetoplastids, Victoria S Frisbie, Hideharu Hashimoto, Yixuan Xie, Francisca N De Luna Vitorino, Josue Baeza, Tam Nguyen, Zhangerjiao Yuan, Janna Kiselar, Benjamin A Garcia, Erik W Debler

2020-Current year OA Pubs

In higher eukaryotes, a single DOT1 histone H3 lysine 79 (H3K79) methyltransferase processively produces H3K79me2/me3 through histone H2B mono-ubiquitin interaction, while the kinetoplastid Trypanosoma brucei di-methyltransferase DOT1A and tri-methyltransferase DOT1B efficiently methylate the homologous H3K76 without H2B mono-ubiquitination. Based on structural and biochemical analyses of DOT1A, we identify key residues in the methyltransferase motifs VI and X for efficient ubiquitin-independent H3K76 methylation in kinetoplastids. Substitution of a basic to an acidic residue within motif VI (Gx