Cell and Developmental Biology Commons^™

Environmental Transmission Of Toxoplasma Gondii: Oocysts In Water, Soil And Food, Karen Shapiro, Lillian Bahia-Oliveira, Brent Dixon, Aurélien Dumètre, Luz A. De Wit, Elizabeth Vanwormer, Isabelle Villena

School of Veterinary and Biomedical Sciences: Faculty Publications

Toxoplasma gondii is a zoonotic protozoan parasite that can cause morbidity and mortality in humans, domestic animals, and terrestrial and aquatic wildlife. The environmentally robust oocyst stage of T. gondii is fundamentally critical to the parasite's success, both in terms of its worldwide distribution as well as the extensive range of infected intermediate hosts. Despite the limited definitive host species (domestic and wild felids), infections have been reported on every continent, and in terrestrial as well as aquatic environments. The remarkable resistance of the oocyst wall enables dissemination of T. gondii through watersheds and ecosystems, and long-term persistence in diverse …

The Drosophila Neuroblasts: A Model System For Human Ribosomopathies, Sonu Shrestha Baral

LSU Doctoral Dissertations

This dissertation describes the use of Drosophila neuroblasts (NBs) to model human ribosomopathies; the overall goal is to understand why specific stem cell and progenitor cell populations are the primary targets in nucleolar stress as seen in the ribosomopathies. Chapter 1 provides an overview of relevant literature. Chapter 2 describes nucleolar stress in Drosophila neuroblasts as a model for human ribosomopathies. For this, we induce nucleolar stress by using the UAS-GAL4 system to express RNAi that depletes Nopp140 transcripts, and we also employ homozygous, CRISPR-Cas9-generated Nopp140 gene disruptions with a systemic null phenotype (Nopp140-/-). Embryonic lethality was observed …

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards …

Induction Of Ampk Activation By N,N'-Diarylurea Fnd-4b Decreases Growth And Increases Apoptosis In Triple Negative And Estrogen-Receptor Positive Breast Cancers, Jeremy Johnson, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers

Markey Cancer Center Faculty Publications

Purpose

Triple negative breast cancer (TNBC) is the most lethal and aggressive subtype of breast cancer. AMP-activated protein kinase (AMPK) is a major energy regulator that suppresses tumor growth, and 1-(3-chloro-4-((trifluoromethyl)thio)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea (FND-4b) is a novel AMPK activator that inhibits growth and induces apoptosis in colon cancer. The purpose of this project was to test the effects of FND-4b on AMPK activation, proliferation, and apoptosis in breast cancer with a particular emphasis on TNBC.

Materials and methods

(i) Estrogen-receptor positive breast cancer (ER+BC; MCF-7, and T-47D), TNBC (MDA-MB-231 and HCC-1806), and breast cancer stem cells were treated with FND-4b for 24h. …

Does Family Communication Matter? Exploring Knowledge Of Breast Cancer Genetics In Cancer Families, Deborah Himes, Sarah H. Davis, Jane Lassetter Phd, Rn, Neil E. Peterson, Margaret F. Clayton, Wendy C. Birmingham, Anita Y. Kinney

Faculty Publications

Purpose: Knowledge of breast cancer genetics is critical for those at increased hereditary risk who must make decisions about breast cancer screening options. This descriptive study explored theory-based relationships among cognitive and emotional variables related to knowledge of breast cancer genetics in cancer families. Methods: Participants included first-degree relatives of women with breast cancer who had received genetic counseling and testing. Study participants themselves did not have breast cancer and had not received genetic counseling or testing. Data were collected by telephone interviews and surveys. Variables analyzed included numeracy, health literacy, cancer-related distress, age, education, and the reported amount of …

Integrated Molecular Characterization Of Lung Adenocarcinoma With Implications For Immunotherapy, Nicholas T. Gimbrone

USF Tampa Graduate Theses and Dissertations

This dissertation covers a variety of the genetic and molecular abnormalities of lung adenocarcinoma with an emphasis on STK11 loss and its implications on immunotherapy response. Given that lung cancer is the leading cancer killer, novel therapies are in great demand. In particular, immunotherapy has shown some of the most promise in the last decade but remains limited due to nearly 80% of patients not significantly responding. This dissertation aims to molecularly characterize lung adenocarcinoma while attempting to explain the reason why patients with STK11 loss do not respond to immunotherapy.

In the first chapter we discuss the relationship between …

Computational Modelling Of Peptides Containing Non-Standard Amino Acids, David W. Kastner

Undergraduate Honors Theses

Peptides represent a class of abundant and potent pharmaceutic compounds. Despite their appeal, the design, synthesis, and engineering of biologically relevant peptides remain a challenge. Chapter 1 introduces the various computational methods that will be used. Chapter 2 focuses on the incorporation of a special class of amino acids called bulky dehydroamino acids into the turn of β-hairpins to proteolytically stabilize peptides. Our results suggest that dehydroamino acids confer proteolytic stability by favoring a more folded state. Chapter 3 describes the structural calculations of a rare anticancer peptide called Yaku’amide using a combined molecular mechanics/quantum mechanics hybrid method. The …

Moderating Effect Of Cortical Thickness On Bold Signal Variability Age-Related Changes, Daiana R. Pur, Roy Eagleson, Anik De Ribaupierre, Nathalie Mella, Sandrine De Ribaupierre

Anatomy and Cell Biology Publications

The time course of neuroanatomical structural and functional measures across the lifespan is commonly reported in association with aging. Blood oxygen-level dependent signal variability, estimated using the standard deviation of the signal, or "BOLDSD", is an emerging metric of variability in neural processing, and has been shown to be positively correlated with cognitive flexibility. Generally, BOLDSD is reported to decrease with aging, and is thought to reflect age-related cognitive decline. Additionally, it is well established that normative aging is associated with structural changes in brain regions, and that these predict functional decline in various cognitive domains. Nevertheless, the interaction between …

Tryptophan Confers Resistance To Sds-Associated Cell Membrane Stress In Saccharomyces Cerevisiae, Lea Schroeder, Amy E. Ikui

Publications and Research

Sodium dodecyl sulfate is a detergent that disrupts cell membranes, activates cell wall integrity signaling and restricts cell growth in Saccharomyces cerevisiae. However, the underlying mechanism of how sodium dodecyl sulfate inhibits cell growth is not fully understood. Previously, we have shown that deletion of the MCK1 gene leads to sensitivity to sodium dodecyl sulfate; thus, we implemented a suppressor gene screening revealing that the overexpression of TAT2 tryptophan permease rescues cell growth in sodium dodecyl sulfatetreated Δmck1 cells. Therefore, we questioned the involvement of tryptophan in the response to sodium dodecyl sulfate treatment. In this work, we show that …

H727 Cells Are Inherently Resistant To The Proteasome Inhibitor Carfilzomib, Yet Require Proteasome Activity For Cell Survival And Growth, Min Jae Lee, Zachary Miller, Ji Eun Park, Deepak Bhattarai, Wooin Lee, Kyung Bo Kim

Pharmaceutical Sciences Faculty Publications

The second-in-class proteasome inhibitor (PI) carfilzomib (Kyprolis, Cfz) has contributed to a substantial advancement in multiple myeloma treatment by improving patient survival and quality of life. A considerable portion of patients however display intrinsic resistance to Cfz. Our mechanistic understanding of intrinsic Cfz resistance is limited due to a lack of suitable cell-based models. We report that H727 human bronchial carcinoid cells are inherently resistant to Cfz, yet susceptible to other PIs and inhibitors targeting upstream components of the ubiquitin-proteasome system (UPS). These results indicate that H727 cells remain dependent on the UPS for cell survival and growth despite harboring …

Cryo-Em Structure Of The Human Ferritin–Transferrin Receptor 1 Complex, Linda Celeste Montemiglio, Claudia Testi, Pierpaolo Ceci, Elisabetta Falvo, Martina Pitea, Carmelinda Savino, Alessandro Arcovito, Giovanna Peruzzi, Paola Baiocco, Filippo Mancia, Alberto Boffi, Amédée Des Georges, Beatrice Vallone

Publications and Research

Human transferrin receptor 1 (CD71) guarantees iron supply by endocytosis upon binding of iron-loaded transferrin and ferritin. Arenaviruses and the malaria parasite exploit CD71 for cell invasion and epitopes on CD71 for interaction with transferrin and pathogenic hosts were identified. Here, we provide the molecular basis of the CD71 ectodomain-human ferritin interaction by determining the 3.9 Å resolution single-particle cryo-electron microscopy structure of their complex and by validating our structural findings in a cellular context. The contact surfaces between the heavy-chain ferritin and CD71 largely overlap with arenaviruses and Plasmodium vivax binding regions in the apical part of the receptor …

Kinetic Analysis And Epitope Mapping Of Monoclonal Antibodies To Salmonella Typhimurium Flagellin Using A Surface Plasmon Resonance Biosensor, Devendra Bhandari, Fur-Chi Chen, Shreya Hamal, Roger C. Bridgman

Human Sciences Faculty Research

Salmonella Typhimurium is one of the leading causes of foodborne diseases worldwide. Biosensors and immunoassays utilizing monoclonal antibodies are widely used for the detection and subtyping of S. Typhimurium. However, due to insufficient information on the nature of binding with S. Typhimurium flagellin, the selection of appropriate antibodies for assay development is a cumbersome task. Hence, we aimed to compare the binding kinetics of a panel of monoclonal antibodies and their relative binding sites to flagellin antigen using a surface plasmon resonance biosensor. Initially, the flagellin was captured on the sensor surface through an immobilized anti-flagellin antibody. The interactions of …

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential …

A Human Papillomavirus-Independent Cervical Cancer Animal Model Reveals Unconventional Mechanisms Of Cervical Carcinogenesis, Chunbo He, Xiangmin Lv, Cong Huang, Peter C. Angeletti, Guohua Hua, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bowen Ma, Xingcheng Chen, Paul F. Lambert, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 to …

Deciphering The Consequences Of Yolk Testosterone Metabolism In Birds, Nicole A. Campbell

Theses and Dissertations

Maternal steroids transferred to eggs can elicit permanent effects on various aspects of offspring phenotype. Although, testosterone was thought to be a key mediator of maternal effects in birds, we now know that vertebrate embryos actively regulate their exposure to maternal testosterone through steroid metabolism, suggesting testosterone metabolites may elicit the observed phenotypic effects. To address the role steroid metabolism plays in mediating yolk testosterone effects, we used European starling (Sturnus vulgaris) eggs to characterize the timing of testosterone metabolism and determine whether etiocholanolone, a prominent testosterone metabolite in avian embryos, is capable of influencing early embryonic development. Tritiated testosterone …

Diversity Of Resistance Mechanisms In Carbapenem-Resistant Enterobacteriaceae At A Health Care System In Northern California, From 2013 To 2016, Fiona Senchyna, Rajiv L. Gaur, Johanna Sandlund, Cynthia Truong, Guillaume Tremintin, Dietmar Kültz, Carlos A. Gomez, Fiona B. Tamburini, Tessa Andermann, Ami Bhatt, Isabella A. Tickler, Nancy Watz, Indre Budvytiene, Gongyi Shi, Fred C. Tenover, Niaz Banaei

Biology Faculty Publications

The mechanism of resistance in carbapenem-resistant Enterobacteriaceae (CRE) has therapeutic implications. We comprehensively characterized emerging mechanisms of resistance in CRE between 2013 and 2016 at a health system in Northern California. A total of 38.7% (24/62) of CRE isolates were carbapenemase gene-positive, comprising 25.0% (6/24) blaOXA-48 like, 20.8% (5/24) bla_KPC, 20.8% (5/24) bla_NDM, 20.8% (5/24) bla_SME, 8.3% (2/24) bla_IMP, and 4.2% (1/24) bla_VIM. Between carbapenemases and porin loss, the resistance mechanism was identified in 95.2% (59/62) of CRE isolates. Isolates expressing bla_KPC were 100% susceptible to ceftazidime–avibactam, meropenem–vaborbactam, …

Exploring Nutraceuticals To Enhance Scientific Literacy Aligning With Vision And Change, Nathaniel Buteyn, Ye In Oh, Jonathan Knott, Paige Bokach

University Faculty Publications and Creative Works

An introductory cell biology laboratory course was redesigned using two inquiry-based modules to align with the goals of scientific inquiry as described in Vision and Change. To evaluate the lab’s efficacy, we used a broad range of materials, including pretests and posttests, online surveys, focus group interviews, and course evaluations. Although our students produced significant learning gains on technical laboratory skills, methods, and data analyses, during the first two years their affective dispositions toward the experience were more negative. By evaluating our class data in light of insights from the scholarship of teaching and learning, we were able to provide …

Investigating The Role Of Free Radicals In Huntington's Disease Using Drosophila Melanogaster, Jennifer Libov

Honors Program: Senior Projects (Public)

During normal cell metabolism, reactive oxygen species (ROS) are produced as a byproduct of oxidative phosphorylation. ROS are utilized in the cell as a signaling molecule and can be maintained at healthy levels by cellular antioxidants. However, when the cell experiences oxidative stress due to environmental or genetic conditions, levels of ROS can exceed healthy levels and inhibit necessary life functions by damaging biomolecules and cellular structures. This loss of function can lead to physiological decline and neurodegeneration, such as in diseases like Alzheimer’s, amyotrophic lateral sclerosis (ALS), and, potentially, Huntington’s disease. The following experiments use the model genetic organism …

Ablation Of Both Cx40 And Panx1 Results In Similar Cardiovascular Phenotypes Exhibited In Cx40 Knockout Mice, Nicole M. Novielli-Kuntz, Meghan L. Jelen, Kevin Barr, Leon J. Delalio, Qingping Feng, Brant E. Isakson, Robert Gros, Dale Laird

Anatomy and Cell Biology Publications

Connexins (Cxs) and pannexins (Panxs) are highly regulated large-pore channel-forming proteins that participate in cellular communication via small molecular exchange with the extracellular microenvironment, or in the case of connexins, directly between cells. Given the putative functional overlap between single membrane-spanning connexin hemichannels and Panx channels, and cardiovascular system prevalence, we generated the first Cx40(-/-)Panx1(-/-) mouse with the anticipation that this genetic modification would lead to a severe cardiovascular phenotype. Mice null for both Cx40 and Panx1 produced litter sizes and adult growth progression similar to wild-type (WT), Cx40(-/-) and Panx1(-/-) mice. Akin to Cx40(-/-) mice, Cx40(-/-) Panx1(-/-) mice exhibited …

Serum Amyloid A Binds To Gibrin(Ogen), Promoting Fibrin Amyloid Formation, Martin J. Page, Greig J. A. Thomson, J. Massimo Nunes, Anna-Mart Engelbrecht, Theo A. Nell, Willem J. S. De Villiers, Maria C. De Beer, Lize Engelbrecht, Douglas B. Kell, Etheresia Pretorius

Physiology Faculty Publications

Complex associations exist between inflammation and thrombosis, with the inflammatory state tending to promote coagulation. Fibrinogen, an acute phase protein, has been shown to interact with the amyloidogenic ß-amyloid protein of Alzheimer’s disease. However, little is known about the association between fibrinogen and serum amyloid A (SAA), a highly fibrillogenic protein that is one of the most dramatically changing acute phase reactants in the circulation. To study the role of SAA in coagulation and thrombosis, in vitro experiments were performed where purified human SAA, in concentrations resembling a modest acute phase response, was added to platelet-poor plasma (PPP) and whole …

Small Peptide Ligands For Targeting Egfr In Triple Negative Breast Cancer Cells, Hanieh Hossein-Nejad-Ariani, Emad Althagafi, Kamaljit Kaur

Pharmacy Faculty Articles and Research

The efficacy of chemotherapy for cancer treatment can be increased by targeted drug delivery to the cancer cells. This is particularly important for triple negative breast cancer (TNBC) for which chemotherapy is a major form of treatment. Here we designed and screened a library of 30 peptides starting with a previously reported epidermal growth factor receptor (EGFR) targeting peptide GE11 (YHWYGYTPQNVI). A direct peptide array-whole cell binding assay, where the peptides are conjugated to a cellulose membrane, was used to identify four peptides with enhanced binding to TNBC cells. Next, the four peptides were synthesized as FITC-labelled soluble peptides to …

Autophagic Flux Modulation By Wnt/Β-Catenin Pathway Inhibition In Hepatocellular Carcinoma, Lilia Turcios, Heather E. Chacon, Catherine Garcia, Pedro Eman, Virgilius Cornea, Jieyun Jiang, Brett T. Spear, Chunming Liu, David S. Watt, Francesc Marti, Roberto Gedaly

Surgery Faculty Publications

Autophagy targets cellular components for lysosomal-dependent degradation in which the products of degradation may be recycled for protein synthesis and utilized for energy production. Autophagy also plays a critical role in cell homeostasis and the regulation of many physiological and pathological processes and prompts this investigation of new agents to effect abnormal autophagy in hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is a synthetic inhibitor of the Wnt/β-catenin pathway that exhibits anti-proliferative and anti-angiogenic effects on different types of cancer cells. The combination of FH535 with sorafenib promotes a synergistic inhibition of HCC and liver cancer stem cell proliferation, …

Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism And Lipid Droplet Formation, Brandon C. Farmer, Jude Kluemper, Lance A. Johnson

Physiology Faculty Publications

Lipid droplets (LDs) serve as energy rich reservoirs and have been associated with apolipoprotein E (APOE) and neurodegeneration. The E4 allele of APOE (E4) is the strongest genetic risk factor for the development of late onset Alzheimer’s disease (AD). Since both E4 carriers and individuals with AD exhibit a state of cerebral lipid dyshomeostasis, we hypothesized that APOE may play a role in regulating LD metabolism. We found that astrocytes expressing E4 accumulate significantly more and smaller LDs compared to E3 astrocytes. Accordingly, expression of perilipin-2, an essential LD protein component, was higher in E4 astrocytes. We then …

Circular Rna Circhipk3 Promotes The Proliferation And Differentiation Of Chicken Myoblast Cells By Sponging Mir-30a-3p, Biao Chen, Jiao Yu, Lijin Guo, Mary Shannon Byers, Zhijun Wang, Xiaolan Chen, Haiping Xu, Qinghua Nie

Biology Student Research

Circular RNAs and microRNAs widely exist in various species and play crucial roles in multiple biological processes. It is essential to study their roles in myogenesis. In our previous sequencing data, both miR-30a-3p and circular HIPK3 (circHIPK3) RNA, which are produced by the third exon of the HIPK3 gene, were differentially expressed among chicken skeletal muscles at 11 embryo age (E11), 16 embryo age (E16), and 1-day post-hatch (P1). Here, we investigated their potential roles in myogenesis. Proliferation experiment showed that miR-30a-3p could inhibit the proliferation of myoblast. Through dual-luciferase assay and Myosin heavy chain (MYHC) immunofluorescence, we found that …

A Cross-Species Analysis Reveals A General Role For Piezo2 In Mechanosensory Specialization Of Trigeminal Ganglia From Tactile Specialist Birds, Eve R. Schneider, Evan O. Anderson, Viktor V. Feketa, Marco Mastrotto, Yury A. Nikolaev, Elena O. Gracheva, Sviatoslav N. Bagriantsev

Biology Faculty Publications

A major challenge in biology is to link cellular and molecular variations with behavioral phenotypes. Here, we studied somatosensory neurons from a panel of bird species from the family Anatidae, known for their tactile-based foraging behavior. We found that tactile specialists exhibit a proportional expansion of neuronal mechanoreceptors in trigeminal ganglia. The expansion of mechanoreceptors occurs via neurons with intermediately and slowly inactivating mechanocurrent. Such neurons contain the mechanically gated Piezo2 ion channel whose expression positively correlates with the expression of factors responsible for the development and function of mechanoreceptors. Conversely, Piezo2 expression negatively correlates with expression of molecules mediating …

Efficacy Of Taurine Against Aluminum Maltolate-Induced Apoptosis In Sh-Sy5y Cells Via Reduction Of Oxidative Stress, Endoplasmic Reticulum Stress, And Mitochondrial Dysfunction, Bi-Yu Liu, Yuh-Ju Lee, Hsian-Chin Jen, Deng-Fwu Hwang

Journal of Marine Science and Technology–Taiwan

Aluminum (Al) is one of the most abundant elements on the earth’s crust and is used in various industrial applications. However, Al is known to be associated with various neurodegenerative diseases. Taurine is a free amino acid presents at high concentrations in the brain and is crucial for neuron development. Here, the protective effects of taurine against Al-induced neurotoxicity were investigated. Al, at a concentration of 600 M, induced apoptosis of and cell cycle arrest in human neuroblastoma SH-SY5Y cells. Additionally, Al induced a 55% increase in the levels of reactive oxygen species and inhibited mitochondrial membrane potential up to …

Clinical Features, Survival And Prognostic Factors Of Glycogen-Rich Clear Cell Carcinoma (Grcc) Of The Breast In The U.S. Population, Zhengqiu Zhou, Connor J. Kinslow, Hanina Hibshoosh, Hua Guo, Simon K. Cheng, Chunyan He, Matthew S. Gentry, Ramon C. Sun

Molecular and Cellular Biochemistry Faculty Publications

The World Health Organization (WHO) defines glycogen-rich clear cell carcinoma (GRCC) of the breast as a carcinoma with glycogen accumulation in more than 90% of its tumor cells. Due to the rarity of this disease, its reported survival and clinical associations have been inconsistent due to reliance on case reports and limited case series. As a result, the prognostic implication of this cancer subtype remains unclear. Using the U.S. Surveillance, Epidemiology, and End Results (SEER) program database, we compared the incidence, demographics and prognostic factors of 155 cases of GRCC of the breast to 1,251,584 cases of other (non-GRCC) breast …

Advances In Geometric Techniques For Analyzing Blebbing In Chemotaxing Dictyostelium Cells, Zully Santiago, John Loustau, David Meretzky, Devarshi Rawal, Derrick Brazill

Publications and Research

We present a technical platform that allows us to monitor and measure cortex and membrane dynamics during bleb-based chemotaxis. Using D. discoideum cells expressing LifeAct-GFP and crawling under agarose containing RITC-dextran, we were able to simultaneously visualize the actin cortex and the cell membrane throughout bleb formation. Using these images, we then applied edge detect to generate points on the cell boundary with coordinates in a coordinate plane. Then we fitted these points to a curve with known x and y coordinate functions. The result was to parameterize the cell outline. With the parameterization, we demonstrate how to compute data …

Predicting Alzheimer’S Disease Progression Using Multi-Modal Deep Learning Approach, Garam Lee, Kwangsik Nho, Byungkon Kang, Kyung-Ah Sohn, Dokyoon Kim, Alzheimer's Disease Neuroimaging Initiative

Anatomy and Cell Biology Publications

Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer’s Disease Neuroimaging …

Yap1-Lats2 Feedback Loop Dictates Senescent Or Malignant Cell Fate To Maintain Tissue Homeostasis, Chunbo He, Xiangmin Lv, Cong Huang, Guohua Hua, Bowen Ma, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Jin Zhou, Zhengfeng Wang, Bo R. Rueda, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

Dysfunction of the homeostasis-maintaining systems in specific cell types or tissues renders the organism susceptible to a range of diseases, including cancers. One of the emerging mechanisms for maintaining tissue homeostasis is cellular senescence. Here, we report that the Hippo pathway plays a critical role in controlling the fate of ovarian cells. Hyperactivation of Yes-associated protein 1 (YAP1), the major effector of the Hippo pathway, induces senescence in cultured primary human ovarian surface epithelial cells (hOSEs). Large tumor suppressor 2 (LATS2), the primary upstream negative regulator of YAP1, is elevated in both YAP1-induced and natural replicative-triggered senescence. Deletion of LATS2 …