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Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Regulation Of Cerebral Blood Flow Boosts Precise Brain Targeting Of Vinpocetine-Derived Ionizable-Lipidoid Nanoparticles, Xufei Bian, Ling Yang, Dingxi Jiang, Adam J Grippin, Yifan Ma, Shuang Wu, Linchong Wu, Xiaoyou Wang, Zhongjie Tang, Kaicheng Tang, Weidong Pan, Shiyan Dong, Betty Y S Kim, Wen Jiang, Zhaogang Yang, Chong Li

Faculty, Staff and Student Publications

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid …

Phenome-Wide Identification Of Therapeutic Genetic Targets, Leveraging Knowledge Graphs, Graph Neural Networks, And Uk Biobank Data, Lawrence Middleton, Ioannis Melas, Chirag Vasavda, Arwa Raies, Benedek Rozemberczki, Ryan S Dhindsa, Justin S Dhindsa, Blake Weido, Quanli Wang, Andrew R Harper, Gavin Edwards, Slavé Petrovski, Dimitrios Vitsios

Faculty, Staff and Students Publications

The ongoing expansion of human genomic datasets propels therapeutic target identification; however, extracting gene-disease associations from gene annotations remains challenging. Here, we introduce Mantis-ML 2.0, a framework integrating AstraZeneca's Biological Insights Knowledge Graph and numerous tabular datasets, to assess gene-disease probabilities throughout the phenome. We use graph neural networks, capturing the graph's holistic structure, and train them on hundreds of balanced datasets via a robust semi-supervised learning framework to provide gene-disease probabilities across the human exome. Mantis-ML 2.0 incorporates natural language processing to automate disease-relevant feature selection for thousands of diseases. The enhanced models demonstrate a 6.9% average classification power …

The Inflammatory Response Of Patients With Major Burns And Traumatic Injuries, Sophia Trinh, J. Robinson, J. Dennis, C. Fontenot, O. Warren, Jeffrey Hobden, Jonathan Schoen, Herbert Phelan, Jeffrey Carter, Alison A. Smith

Surgery Research Symposium

No abstract provided.

Mitochondria Regulate Proliferation In Adult Cardiac Myocytes, Gregory B Waypa, Kimberly A Smith, Paul T Mungai, Vincent J Dudley, Kathryn A Helmin, Benjamin D Singer, Clara Bien Peek, Joseph Bass, Lauren Nelson, Sanjiv J Shah, Gaston Ofman, J Andrew Wasserstrom, William A Muller, Alexander V Misharin, G R Scott Budinger, Hiam Abdala-Valencia, Navdeep S Chandel, Danijela Dokic, Elizabeth Bartom, Shuang Zhang, Yuki Tatekoshi, Amir Mahmoodzadeh, Hossein Ardehali, Edward B Thorp, Paul T Schumacker

Faculty, Staff and Student Publications

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice. As RISP protein decreased, heart mitochondrial function declined, and glucose utilization increased. Simultaneously, the hearts underwent hyperplastic remodeling during which cardiomyocyte number doubled without cellular hypertrophy. Cellular energy supply was preserved, AMPK activation was absent, and mTOR activation was evident. In ischemic hearts with RISP deletion, new cardiomyocytes …

Topical Platelet-Rich Plasma As A Possible Treatment For Olfactory Dysfunction-A Randomized Controlled Trial, Alexander Duffy, Bita Naimi, Emily Garvey, Stephanie Hunter, Ayan Kumar, Chase Kahn, Douglas Farquhar, Glen D'Souza, Nancy Rawson, Pamela Dalton, Elina Toskala, Mindy Rabinowitz, Marc Rosen, Gurston G. Nyquist, David Rosen

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: Olfactory dysfunction (OD) affects many survivors of COVID-19. Prior studies have investigated the use of platelet-rich plasma (PRP) injections for OD. We describe the first randomized controlled trial investigating topical PRP for OD treatment and contribute to existing literature illustrating PRP as an emerging therapeutic.

METHODS: This is a single-blinded, randomized controlled trial conducted from July 2022 to December 2023. Adult patients with OD ≥6 months secondary to COVID-19 with Brief Smell Identification Test (BSIT) scores of ≤8/12 or SCENTinel odor intensity of ≤40/100 were included. Patients were randomized to three, monthly PRP or placebo-impregnated Surgifoam treatments into bilateral …

Pyogenic Tenosynovitis Of Tibialis Anterior Tendon After Cat Bite, Daniel Blascak, David Sosnoski, Aaron Seidman

Posters

Pyogenic tenosynovitis is a bacterial infection of the synovial sheath that surrounds a tendon.

Commonly occurs within flexor tendons of the hand; theoretically can occur within any sheathed tendon.

Delayed diagnosis may lead to spread of infection to surrounding tissues and tendon rupture.

Tibialis anterior tendon is encased in a synovial sheath that runs from above the superior extensor retinaculum to the talonavicular joint.

Only five cases of pyogenic tenosynovitis of the tibialis anterior tendon have been reported in the literature.

None of the reported cases were due to animal bite injury.

Sexual Function After Gender Affirming Surgery, Alicia R. Castellanos, Rachel Pope

Faculty Scholarship

Purpose of Review: Sexual function and satisfaction in the transgender community is a nascent field with a paucity of data due to the fast paced nature of improving upon surgical technique and variety of patient experiences. The authors aim to review the current literature for areas of success as well as areas of improvement in order to better the sexual health of the transgender community. Recent Findings: Gender dysphoria is a feeling of distress experienced by those whose gender assigned at birth is not in line with their gender identity. While social transition to the desired gender can suffice for …

Modulation Of The Blood-Brain Barrier By Sigma-1r Activation, Eugen Brailoiu, Jeffrey L Barr, Hailey N Wittorf, Saadet Inan, Ellen M Unterwald, Gabriela Cristina Brailoiu

Faculty, Staff and Student Publications

Sigma non-opioid intracellular receptor 1 (Sigma-1R) is an intracellular chaperone protein residing on the endoplasmic reticulum at the mitochondrial-associated membrane (MAM) region. Sigma-1R is abundant in the brain and is involved in several physiological processes as well as in various disease states. The role of Sigma-1R at the blood-brain barrier (BBB) is incompletely characterized. In this study, the effect of Sigma-1R activation was investigated in vitro on rat brain microvascular endothelial cells (RBMVEC), an important component of the blood-brain barrier (BBB), and in vivo on BBB permeability in rats. The Sigma-1R agonist PRE-084 produced a dose-dependent increase in mitochondrial calcium, …

Downregulation Of Mirlet7 Mirna Family Promotes Tc17 Differentiation And Emphysema Via De-Repression Of Rorγt, Phillip A Erice, Xinyan Huang, Matthew J Seasock, Matthew J Robertson, Hui-Ying Tung, Melissa A Perez-Negron, Shivani L Lotlikar, David B Corry, Farrah Kheradmand, Antony Rodriguez

Faculty, Staff and Students Publications

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with …

A Rat-Based Preclinical Platform Facilitating Transcatheter Hepatic Arterial Infusion In Immunodeficient Rats With Liver Xenografts Of Patient-Derived Pancreatic Ductal Adenocarcinoma, Masanori Ozaki, Ken Kageyama, Kenjiro Kimura, Shinpei Eguchi, Akira Yamamoto, Ryota Tanaka, Takehito Nota, Hiroki Yonezawa, Hideyuki Nishiofuku, Yuki Sakai, Naoki Tani, Atsushi Jogo, Mizue Terai, Takami Sato, Takeaki Ishizawa, Yukio Miki

Department of Medical Oncology Faculty Papers

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens …

Perinuclear Damage From Nuclear Envelope Deterioration Elicits Stress Responses That Contribute To Lmna Cardiomyopathy, Kunal Sikder, Elizabeth Phillips, Zhijiu Zhong, Nadan Wang, Jasmine Saunders, David Mothy, Andrew Kossenkov, Timothy Schneider, Zuzana Nichtova, György Csordás, Kenneth B. Margulies, Jason C. Choi

Center for Translational Medicine Faculty Papers

Mutations in the LMNA gene encoding lamins A/C cause an array of tissue-selective diseases, with the heart being the most commonly affected organ. Despite progress in understanding the perturbations emanating from LMNA mutations, an integrative understanding of the pathogenesis underlying cardiac dysfunction remains elusive. Using a novel conditional deletion model capable of translatome profiling, we observed that cardiomyocyte-specific Lmna deletion in adult mice led to rapid cardiomyopathy with pathological remodeling. Before cardiac dysfunction, Lmna-deleted cardiomyocytes displayed nuclear abnormalities, Golgi dilation/fragmentation, and CREB3-mediated stress activation. Translatome profiling identified MED25 activation, a transcriptional cofactor that regulates Golgi stress. Autophagy is disrupted …

Optimization Of The Antifungal Properties Of The Bacterial Peptide Entv By Variant Analysis, Shantanu Guha, Shane A Cristy, Giuseppe Buda De Cesare, Melissa R Cruz, Michael C Lorenz, Danielle A Garsin

Faculty, Staff and Student Publications

Fungal resistance to commonly used medicines is a growing public health threat, and there is a dire need to develop new classes of antifungals. We previously described a peptide produced by Enterococcus faecalis, EntV, that restricts Candida albicans to a benign form rather than having direct fungicidal activity. Moreover, we showed that one 12-amino acid (aa) alpha helix of this peptide retained full activity, with partial activity down to the 10aa alpha helix. Using these peptides as a starting point, the current investigation sought to identify the critical features necessary for antifungal activity and to screen for new variants …

Clearing The Light Path: Proteoglycans And Their Important Roles In The Lens And Cornea, Mary Ann Stepp, A. Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Some of the earliest studies of glycans were performed on mammalian corneas and lenses with many of the key concepts we currently recognize as being fundamental to our understanding of basic cell biology arising from these studies. Proteoglycans and their GAG side chains are essential components of the ECM of the lens capsule. They also are present in the anterior corneal epithelial basement membrane and the posterior (Decemet's) basement membrane, and they organize collagen fiber diameters and spacing in the corneal stroma to maintain stromal clarity. Studies using genetically engineered mice and characterization of spontaneously arising mutations in genes controlling …

Anxiety Overview And How To Help Your Child, Maggie Mckay, Meghan Kanya

Parent-ish Podcast

Meghan Kanya, PhD, discusses an overview of anxiety, including causes, signs your child may be struggling, and how you as a parent can help.

Click here to stream the podcast episode.

Protein Oxidation In Aging And Alzheimer’S Disease Brain, Rukhsana Sultana, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer’s disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate …

Single Extracellular Vesicle Imaging And Computational Analysis Identifies Inherent Architectural Heterogeneity, Kshipra S Kapoor, Seoyun Kong, Hikaru Sugimoto, Wenhua Guo, Vivek Boominathan, Yi-Lin Chen, Sibani Lisa Biswal, Tanguy Terlier, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Evaluating the heterogeneity of extracellular vesicles (EVs) is crucial for unraveling their complex actions and biodistribution. Here, we identify consistent architectural heterogeneity of EVs using cryogenic transmission electron microscopy (cryo-TEM), which has an inherent ability to image biological samples without harsh labeling methods while preserving their native conformation. Imaging EVs isolated using different methodologies from distinct sources, such as cancer cells, normal cells, immortalized cells, and body fluids, we identify a structural atlas of their dominantly consistent shapes. We identify EV architectural attributes by utilizing a segmentation neural network model. In total, 7,576 individual EVs were imaged and quantified by …

Histone Demethylase Kdm5 Regulates Cardiomyocyte Maturation By Promoting Fatty Acid Oxidation, Oxidative Phosphorylation, And Myofibrillar Organization, Manisha Deogharia, Leslye Venegas-Zamora, Akanksha Agrawal, Miusi Shi, Abhinav K Jain, Kevin J Mchugh, Francisco Altamirano, Ali J Marian, Priyatansh Gurha

Faculty, Staff and Student Publications

Aims: Human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a platform to identify and characterize factors that regulate the maturation of CMs. The transition from an immature foetal to an adult CM state entails coordinated regulation of the expression of genes involved in myofibril formation and oxidative phosphorylation (OXPHOS) among others. Lysine demethylase 5 (KDM5) specifically demethylates H3K4me1/2/3 and has emerged as potential regulators of expression of genes involved in cardiac development and mitochondrial function. The purpose of this study is to determine the role of KDM5 in iPSC-CM maturation.

Methods and results: KDM5A, B, and C proteins were mainly expressed …

Effects Of Improved Amino Acid Balance Diet On Lysine Mammary Utilization, Whole Body Protein Turnover And Muscle Protein Breakdown On Lactating Sows, Sai Zhang, Juan C Marini, Vengai Mavangira, Andrew Claude, Julie Moore, Mahmoud A Mohammad, Nathalie L Trottier

Children’s Nutrition Research Center Staff Publications

Background: The study objective was to test the hypothesis that low crude protein (CP) diet with crystalline amino acids (CAA) supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein breakdown. Eighteen lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets (10.80 MJ/kg net energy): control (CON; 19.24% CP) and reduced CP with "optimal" AA profile (OPT; 14.00% CP). Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1, 14, 18, and 21 of lactation. Between d 14 and 18, a …

Identification Of Potent Pan-Ephrin Receptor Kinase Inhibitors Using Dna-Encoded Chemistry Technology, Chandrashekhar Madasu, Zian Liao, Sydney E Parks, Kiran L Sharma, Kurt M Bohren, Qiuji Ye, Feng Li, Murugesan Palaniappan, Zhi Tan, Fei Yuan, Chad J Creighton, Suni Tang, Ramya P Masand, Xiaoming Guan, Damian W Young, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

EPH receptors (EPHs) are highly sought-after drug targets owing to their essential roles in maintaining appropriate cellular functions in both physiological and disease conditions. However, limited potency and specificity pose significant obstacles to the development of small-molecule inhibitors for EPHs. Here, using high-throughput DNA-encoded chemical library screenings, we developed potent and selective inhibitors of the EPH receptor kinase family. Our results also emphasize the therapeutic potential of our EPH inhibitors in cancer and endometriosis, a global health concern that causes chronic pain and often leads to infertility in women. This study showcases the robust pipeline of using DNA-encoded chemistry technology …

Progress Toward A Vaccine For Extraintestinal Pathogenic Coli (Expec) Ii: Efficacy Of A Toxin-Autotransporter Dual Antigen Approach, Yikun Xing, Justin R Clark, James D Chang, Jacob J Zulk, Dylan M Chirman, Felipe-Andres Piedra, Ellen E Vaughan, Haroldo J Hernandez Santos, Kathryn A Patras, Anthony W Maresso

Faculty, Staff and Students Publications

Extraintestinal pathogenic Escherichia coli (ExPEC) is a leading cause of worldwide morbidity and mortality, the top cause of antimicrobial-resistant (AMR) infections, and the most frequent cause of life-threatening sepsis and urinary tract infections (UTI) in adults. The development of an effective and universal vaccine is complicated by this pathogen’s pan-genome, its ability to mix and match virulence factors and AMR genes via horizontal gene transfer, an inability to decipher commensal from pathogens, and its intimate association and co-evolution with mammals. Using a pan virulome analysis of >20,000 sequenced E. coli strains, we identified the secreted cytolysin α-hemolysin (HlyA) as a …

Data Normalization For Addressing The Challenges In The Analysis Of Single-Cell Transcriptomic Datasets, Raquel Cuevas-Diaz Duran, Haichao Wei, Jiaqian Wu

Faculty, Staff and Student Publications

BACKGROUND: Normalization is a critical step in the analysis of single-cell RNA-sequencing (scRNA-seq) datasets. Its main goal is to make gene counts comparable within and between cells. To do so, normalization methods must account for technical and biological variability. Numerous normalization methods have been developed addressing different sources of dispersion and making specific assumptions about the count data.

MAIN BODY: The selection of a normalization method has a direct impact on downstream analysis, for example differential gene expression and cluster identification. Thus, the objective of this review is to guide the reader in making an informed decision on the most …

Hormonal Basis Of Brain Fog In Cancer Treatment, Yuan Pan, Jian Hu

Faculty, Staff and Student Publications

The cognitive side effects of cancer treatment are common, but no targeted therapy exists yet to treat or prevent such neurological sequelae. We explore the role of hormones as mediators between cancer therapy and cognitive impairment, discussing potential future directions.

Contraception And Menstrual Management In Transmasculine And Gender-Diverse Individuals, Adrian Chiem, Maria Cristina Marcos, Beth I. Schwartz

Department of Obstetrics and Gynecology Faculty Papers

Purpose of Review This review outlines the current evidence on the contraceptive and menstrual management methods that are used for transmasculine or gender-diverse (TGD) individuals, as well as the gaps in the literature for this population.

Recent Findings Contraception and menstrual management continue to be an understudied area in the care of TGD individuals, with much of existing research extrapolated from cisgender populations. Emerging studies have looked at contraceptive and menstrual management choices and outcomes in adolescents and highlight the 52 mg LNG-IUD as an option that is efficacious for both indications, as well as high-dose progestin-only pills for menstrual …

Ras G-Domains Allosterically Contribute To The Recognition Of Lipid Headgroups And Acyl Chains, Neha Arora, Huanwen Mu, Hong Liang, Wenting Zhao, Yong Zhou

Faculty, Staff and Student Publications

Mutant RAS are major contributors to cancer and signal primarily from nanoclusters on the plasma membrane (PM). Their C-terminal membrane anchors are main features of membrane association. However, the same RAS isoform bound to different guanine nucleotides spatially segregate. Different RAS nanoclusters all enrich a phospholipid, phosphatidylserine (PS). These findings suggest more complex membrane interactions. Our electron microscopy-spatial analysis shows that wild-types, G12V mutants, and membrane anchors of isoforms HRAS, KRAS4A, and KRAS4B prefer distinct PS species. Mechanistically, reorientation of KRAS4B G-domain exposes distinct residues, such as Arg 135 in orientation state 1 (OS1) and Arg 73/Arg 102 in OS2, …

Metaplastic Regeneration In The Mouse Stomach Requires A Reactive Oxygen Species Pathway, Zhi-Feng Miao, Jing-Xu Sun, Xuan-Zhang Huang, Shi Bai, Min-Jiao Pang, Jia-Yi Li, Han-Yu Chen, Qi-Yue Tong, Shi-Yu Ye, Xin-Yu Wang, Xiao-Hai Hu, Jing-Ying Li, Jin-Wei Zou, Wen Xu, Jun-Hao Yang, Xi Lu, Jason C Mills, Zhen-Ning Wang

Faculty, Staff and Students Publications

In pyloric metaplasia, mature gastric chief cells reprogram via an evolutionarily conserved process termed paligenosis to re-enter the cell cycle and become spasmolytic polypeptide-expressing metaplasia (SPEM) cells. Here, we use single-cell RNA sequencing (scRNA-seq) following injury to the murine stomach to analyze mechanisms governing paligenosis at high resolution. Injury causes induced reactive oxygen species (ROS) with coordinated changes in mitochondrial activity and cellular metabolism, requiring the transcriptional mitochondrial regulator Ppargc1a (Pgc1α) and ROS regulator Nf2el2 (Nrf2). Loss of the ROS and mitochondrial control in Ppargc1a-/- mice causes the death of paligenotic cells through ferroptosis. Blocking the cystine transporter SLC7A11(xCT), which …

Bronchopulmonary Dysplasia: Pathophysiology And The Effects Of The Microbiome, Anjali Jacob

Senior Honors Theses

Bronchopulmonary dysplasia (BPD) is a chronic neonatal lung disease that occurs in over 50% of premature infants. BPD is characterized by damage to the alveoli and bronchioles and improper vasculature formation. It is primarily caused by overexposure to oxygen through mechanical ventilation, but there are other risk factors that make infants more susceptible to BPD. Microbial composition impacts risk for developing BPD, and research is ongoing about the effects of the microbiome on BPD pathogenesis; this information is also valuable for preventative treatment. This paper reviews the normal function of the lungs, pathogenesis of BPD and how it affects normal …

Healthier Together: A Holistic Office Protocol Addressing The Chronic Nature Of Children And Adolescents With Adhd, Kimberly Olmos

Evidence-Based Practice Project Reports

Attention Deficit Hyperactivity Disorder (ADHD) is a highly prevalent, chronic condition with symptoms that include inattention, hyperactivity, and impulsivity. ADHD affects six million children in the United States (Tran et al., 2021). The purpose of this evidence-based practice project was to implement a holistic office protocol that addressed the chronicity and future health outcomes of children and adolescents, ages 2-17 years with ADHD through stimulant or non-stimulant medication prescriptions, behavioral therapy referrals, and education surrounding diet, and exercise. A comprehensive, systematic literature search yielded 16 articles to determine best practice when treating children and adolescents with ADHD in primary or …

Impact Of Nutritional Status And Placental Malaria Infection On Pregnancy Outcome In A Population Of Nigerian Maternal-Infant Dyads, Shirley F. Delair

Theses & Dissertations

Nigeria is the most populous country in Africa and accounts for one-quarter of the newborn mortality on the continent. Most newborn deaths are from prematurity (33%), infections (33%), and intrapartum complications (31%). Using an adapted analytical framework for the study of child survival in developing countries, this dissertation aimed to look at the pregnancy outcome of a population of Nigerian women and their offspring by looking at proximate determinants of health from nutritional status and environmental conditions. In Chapter 1, we characterized the micronutrients of the mother-infant dyads, looking specifically at concentrations of vitamin D and its metabolites. In Chapter …

Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou

Theses & Dissertations

Produced by steady state erythropoiesis, erythrocytes serve as vital regulators of metabolism and life by delivering oxygen to all the cells and tissues. Under acute anemia, steady state erythropoiesis is not sufficient to produce enough erythrocytes, leading to distinct mechanisms needed to regenerate large numbers of mature erythrocytes rapidly. Erythroid regeneration occurs in four stages: activation, expansion and differentiation, resolution, and post-resolution, according to the dynamics of erythrocyte numbers and progenitor activity. Erythroid regeneration throughout this timeline requires some critical extracellular cues, but the intrinsic molecular mechanisms needed to accelerate and decelerate the activity of erythroid progenitors in anemia and …