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2022

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Articles 31 - 60 of 444

Full-Text Articles in Cell and Developmental Biology

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson Dec 2022

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson

Electronic Theses and Dissertations

Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …


Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess Dec 2022

Exploring The Anticancer Mechanism Of Thienopyrazole Derivative Tpz-1 In Acute Myeloid Leukemia, Jessica Dyanne Hess

Open Access Theses & Dissertations

Anticancer drug discovery is a time and resource-consuming process for which exceedingly reliable and efficient modern approaches are needed. Phenotypic drug screenings can generate highly potent and innovative drug candidates; however, deconvolution of the drugâ??s target often presents significant barriers to drug development. To overcome this hurdle, we have originally combined in vitro and in silico analyses to uncover the molecular mechanism(s) driving the anticancer activity of the uniquely structured small molecule drug candidate, Tpz-1. Our study revealed that Tpz-1 is a multitargeted agent which induces the programmed death of HL-60 acute myeloid leukemia cells primarily through disruption of microtubule …


Effect Of Umbilical Cord Essential And Toxic Elements, Thyroid Levels, And Vitamin D On Childhood Development, Jesse Cottrell, Chelsea Nelson, Catherine Waldron, Mackenzie Bergeron, Abigail Samson, Monica Valentovic Dec 2022

Effect Of Umbilical Cord Essential And Toxic Elements, Thyroid Levels, And Vitamin D On Childhood Development, Jesse Cottrell, Chelsea Nelson, Catherine Waldron, Mackenzie Bergeron, Abigail Samson, Monica Valentovic

Biomedical Sciences

Introduction: The in-utero environment has dramatic effects on childhood development. We hypothesized prenatal levels of inorganic agents, thyroid levels, and Vitamin D effect childhood development.

Methods: Umbilical cord blood was collected from April 3, 2013 to January 30, 2014 and analyzed for 20 different elements, thyroid and Vitamin D. A retrospective review (n = 60) was performed of well-child examinations from birth to 5 years old (y.o.).

Results: There were associations with calcium and 4 month BMI (p = <0.01), 12 month language (p = 0.03); Magnesium and 6 month language (p = 0.04) and gross motor skills at 5 years old (y.o.) (p = 0.03); Copper and 12 month fine motor (p = 0.02); Zinc with fine motor (p = <0.01) and language (p = 0.03) at 2 y.o.; Manganese was associated with language development at 2 y.o. (p = 0.02); Molybdenum and fine motor at 12 months of age (p = 0.02); Selenium with gross motor (p = 0.04) and BMI (p = 0.02) at 5 y.o.; Lead with cognitive function at 4 months (p = 0.04) and 2 y.o. (p = 0.01); Mercury with gross motor at 4 months (p = 0.04) and language at 2 y.o. (p = 0.02). Platinum at 12 months of age (p = <.01) as well as multiple associations at 5 y.o. (p = <.01). Thyroid function tests for free T3 were associated with multiple cognitive and physical milestones. T3 Uptake was associated with 5 y.o. gross motor skills (p = 0.02). Total and Free T4 was associated with cognitive development (p = <.01) and fine motor development, respectively. Vitamin D was associated with a delay of fine motor development (p<0.01).

Conclusion: There were multiple associations between umbilical cord essential and toxic elements, thyroid levels, and Vitamin D on childhood development.


Light And Temperature Entrainment Of Two Circadian-Driven Behaviors In The Flesh Fly Sarcophaga Crassipalpis, Raven Ragsdale Dec 2022

Light And Temperature Entrainment Of Two Circadian-Driven Behaviors In The Flesh Fly Sarcophaga Crassipalpis, Raven Ragsdale

Electronic Theses and Dissertations

Circadian rhythms dictate the timing of both once-in-a-lifetime adult emergence (eclosion) and daily locomotor activity rhythms in the flesh fly S. crassipalpis. Light cycles are considered the primary environmental time cue (zeitgeber), but the life history of S. crassipalpis suggests that temperature cycles (thermocycles) may also play a key role. This work evaluates the efficacy of thermocycling as a zeitgeber in S. crassipalpis. We found that shifting both light and temperature cycles of sufficient amplitude affect the phasing of eclosion and locomotor activity, but result in different patterns. Additional experiments suggest greater thermocycle sensitivity during the late metamorphic …


The Adar-Mavs Pathway Is A Critical Mediator Of The Innate Immune System In Pancreatic Development And Cancer, Dhwani Rupani Dec 2022

The Adar-Mavs Pathway Is A Critical Mediator Of The Innate Immune System In Pancreatic Development And Cancer, Dhwani Rupani

Dissertations and Theses (Open Access)

Adenosine deaminase acting on RNA (ADAR) is an RNA-binding protein that deaminates adenosine (A) to inosine (I). A-to-I editing is an important post-transcriptional mechanism to prevent recognition of endogenous RNA by MDA5, a cytosolic RNA sensor. Activation of MDA5 by viral RNA can stimulate the innate immune system. Thus, ADAR-mediated RNA editing is crucial to distinguish “self” from “non-self”. ADAR has an important role in gene regulation as A-to-I editing alters RNA processing affecting both RNA and protein abundance. Given its importance in regulating innate immunity and transcript abundance, aberrations in Adar expression are implicated in developmental deformities and carcinogenesis. …


Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam Dec 2022

Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam

Dissertations and Theses (Open Access)

ANK2 mutations in patients are associated with numerous arrhythmias, cardiomyopathies, and other heart defects. In the heart, AnkB, the protein encoded by ANK2, clusters relevant ion channels and cell adhesion molecules in several important domains; however, its role at Mitochondria Associated ER/SR Membranes (MAMs) has yet to be investigated. MAMs are crucial to mitochondrial function and metabolism and are signaling hubs implicated in various cardiac pathologies. Among several functions, these sites mediate the direct transfer of calcium from the ER/SR to the mitochondria to modulate ATP synthesis. Given that mitochondrial function and energy production are paramount to cardiovascular heath, …


The Role Of Fatty Acid Metabolism In The Pathogenesis Of Trypanosoma Brucei, Nava Poudyal Dec 2022

The Role Of Fatty Acid Metabolism In The Pathogenesis Of Trypanosoma Brucei, Nava Poudyal

All Dissertations

Trypanosoma brucei is the protozoan parasite that causes African Sleeping Sickness in humans and nagana, a wasting disease in cattle. T. brucei completes its life cycle in two hosts, mammals and the tsetse fly insect vector. Due to the geographical restriction of the tsetse fly, the disease is endemic in sub-Saharan Africa. Both the insect and mammalian forms of the parasite need fatty acids to anchor their surface proteins. We worked on three projects on fatty acid metabolism and its role in immune evasion strategies of T. brucei. First, we assessed the role of T. brucei surface proteins in …


Differential Impacts Of Hhv-6a Versus Hhv-6b Infection In Differentiated Human Neural Stem Cells, Elham Bahramian Dec 2022

Differential Impacts Of Hhv-6a Versus Hhv-6b Infection In Differentiated Human Neural Stem Cells, Elham Bahramian

Graduate Theses and Dissertations

Within the family Herpesviridae, sub-family β-herpesvirinae, and genus Roseolovirus, there areonly three human herpesviruses that have been described: HHV-6A, HHV-6B, and HHV-7. Initially, HHV-6A and HHV-6B were considered as two variants of the same virus (i.e., HHV6). Despite high overall genetic sequence identity (~90%), HHV-6A and HHV-6B are now recognized as two distinct viruses. Sequence divergence (e.g., >30%) in key coding regions and significant differences in physiological and biochemical profiles (e.g., use of different receptors for viral entry) underscores the conclusion that HHV-6A and HHV-6B are distinct viruses of the β-herpesvirinae. Despite these viruses being implicated as causative agents in …


A Study On Interactions Between Metal-Organic Frameworks And Biological Materials, Josh Phipps Dec 2022

A Study On Interactions Between Metal-Organic Frameworks And Biological Materials, Josh Phipps

Graduate Theses and Dissertations

Metal-organic frameworks or MOFs are an extremely useful tool in many areas of applications. Their popularity in recent years has arisen from their high efficiency in catalytic chemical reactions. This is made possible due to their porous interior and the ability of the MOFs components to be functionalized. These same traits make MOFs excellent for use in protein encapsulation or immobilization and have the potential to become excellent drug carriers. Their development in this utilization has been limited dramatically compared to MOFs chemical applications. This is due in part to the nature of biological processes taking longer to study, but …


Seeing The Big Picture: System Architecture Trends In Endoscopy And Led-Based Hyperspectral Subsystem Intergration, Craig M. Browning Dec 2022

Seeing The Big Picture: System Architecture Trends In Endoscopy And Led-Based Hyperspectral Subsystem Intergration, Craig M. Browning

Graduate Theses and Dissertations (2019 - present)

Early-stage colorectal lesions remain difficult to detect. Early development of neoplasia tends to be small (less than 10 mm) and flat and difficult to distinguish from surrounding mucosa. Additionally, optical diagnosis of neoplasia as benign or malignant is problematic. Low rates of detection of these lesions allow for continued growth in the colorectum and increased risk of cancer formation. Therefore, it is crucial to detect neoplasia and other non-neoplastic lesions to determine risk and guide future treatment. Technology for detection needs to enhance contrast of subtle tissue differences in the colorectum and track multiple biomarkers simultaneously. This work implements one …


Hypothesis Testing And Parameter Estimation In Mixture Cure Models For Cancer Survival Data, Mohammod Mahmudur Rahman Dec 2022

Hypothesis Testing And Parameter Estimation In Mixture Cure Models For Cancer Survival Data, Mohammod Mahmudur Rahman

Graduate Theses and Dissertations

In oncology clinical trials, when a treatment is administered to the patient population, a certain subset of patients may respond to the treatment while the other does not. The positive responders with long-term survival are considered “statistically cured” and can be referred to as cured patients or long-term survivors. When a proportion of patients achieve long-term survival, the hazard functions of two arms (control vs. treatment) are no longer proportional. As a result, the traditional log-rank test, which is the most popular test to evaluate the effectiveness of a treatment in clinical trials, tends to lose its power. In this …


Npgreat: Assembly Of The Human Subtelomere Regions With The Use Of Ultralong Nanopore Reads And Linked Reads, Eleni Adam, Desh Ranjan, Harold Riethman Dec 2022

Npgreat: Assembly Of The Human Subtelomere Regions With The Use Of Ultralong Nanopore Reads And Linked Reads, Eleni Adam, Desh Ranjan, Harold Riethman

Computer Science Faculty Publications

Background: Human subtelomeric DNA regulates the length and stability of adjacent telomeres that are critical for cellular function, and contains many gene/pseudogene families. Large evolutionarily recent segmental duplications and associated structural variation in human subtelomeres has made complete sequencing and assembly of these regions difficult to impossible for many loci, complicating or precluding a wide range of genetic analyses to investigate their function.

Results: We present a hybrid assembly method, NanoPore Guided REgional Assembly Tool (NPGREAT), which combines Linked-Read data with mapped ultralong nanopore reads spanning subtelomeric segmental duplications to potentially overcome these difficulties. Linked-Read sets of DNA sequences identified …


The Role Of Akirin/Nurd Interactions During Heart Development, Mia Jones Nov 2022

The Role Of Akirin/Nurd Interactions During Heart Development, Mia Jones

Symposium of Student Scholars

Congenital heart defects are often identified during pregnancy or infancy and are the most common birth defect presented in humans, affecting blood circulation resultant from small holes in a blood chamber to deformity-inducing missing structures. Recent advancements in medicine have allowed those affected to live healthier, longer lives. Gene combinations and chromosomal changes play pivotal roles in congenital heart defects, but the specific genes involved remain unknown. The Nowak Lab has discovered several novel regulatory proteins that are critical for embryonic heart development and is studying them for a potential link to congenital heart defects.

During embryogenesis, the heart of …


A Common Mechanism Links Epstein‐Barr Virus Infections And Autoimmune Diseases, Luwen Zhang Nov 2022

A Common Mechanism Links Epstein‐Barr Virus Infections And Autoimmune Diseases, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Epstein‐Barr virus (EBV) infection is associated with a variety of the autoimmune diseases. There is apparently no unified model for the role of EBV in autoimmune diseases. In this article, the development of autoimmune diseases is proposed as a simple two‐step process: specific autoimmune initiators may cause irreversible changes to genetic materials that increase autoimmune risks, and autoimmune promoters promote autoimmune disease formation once cells are susceptible to autoimmunity. EBV has several types of latencies including type III latency with higher proliferation potential. EBV could serve as autoimmune initiators for some autoimmune diseases. At the same time, EBV may play …


The Effects Of Deleting Lrb E3 Ligase Region 2 On Red Light Responses In Arabidopsis Thaliana, Sabina Liskey Nov 2022

The Effects Of Deleting Lrb E3 Ligase Region 2 On Red Light Responses In Arabidopsis Thaliana, Sabina Liskey

Masters Theses

The ability of plants to absorb light through photoreceptors is essential for successful plant development. Phytochromes are important plant photoreceptors that detect and absorb red and far-red light and must function properly for plant survival. The Light Response BTB proteins (LRB) play an important role in a plant’s response to red light by degrading phytochrome B (PhyB) via the ubiquitin proteasome system (UPS). Although there has been a successful investigation into understanding the function of the LRBs, the function of a few regions within LRB proteins remains unknown, including a portion located on the N-terminal end of the protein, termed …


Il-33 Promotes Increased Replication Of Theiler’S Murine Encephalomyelitis Virus In Raw264.7 Macrophage Cells With An Irf3-Dependent Response, Ahmed Esmael, Thomas M. Petro Nov 2022

Il-33 Promotes Increased Replication Of Theiler’S Murine Encephalomyelitis Virus In Raw264.7 Macrophage Cells With An Irf3-Dependent Response, Ahmed Esmael, Thomas M. Petro

Nebraska Center for Virology: Faculty Publications

Interleukin-33 (IL-33), which promotes M2 macrophage development, may influence the control of viruses, such as Theiler’s Murine Encephalomyelitis Virus (TMEV) that infect macrophages. Because Interferon Regulatory Factor-3 (IRF3) is also critical to control of TMEV infection in macrophages, information on the relationship between IL-33 and IRF3 is important. Thus, RAW264.7 Lucia murine macrophage lineage cells with an endogenous IRF3-ISRE promoter driving secreted luciferase and IRF3KO RAW Lucia, a subline deficient in IRF3, were challenged with TMEV. After the challenge, considerable TMEV RNA detected at 18 and 24 h in RAW cells was significantly elevated in IRF3KO RAW cells. TMEV induction …


Il-33 Promotes Increased Replication Of Theiler’S Murine Encephalomyelitis Virus In Raw264.7 Macrophage Cells With An Irf3-Dependent Response, Ahmed Esmael, Thomas M. Petro Nov 2022

Il-33 Promotes Increased Replication Of Theiler’S Murine Encephalomyelitis Virus In Raw264.7 Macrophage Cells With An Irf3-Dependent Response, Ahmed Esmael, Thomas M. Petro

Nebraska Center for Virology: Faculty Publications

Interleukin-33 (IL-33), which promotes M2 macrophage development, may influence the control of viruses, such as Theiler’s Murine Encephalomyelitis Virus (TMEV) that infect macrophages. Because Interferon Regulatory Factor-3 (IRF3) is also critical to control of TMEV infection in macrophages, information on the relationship between IL-33 and IRF3 is important. Thus, RAW264.7 Lucia murine macrophage lineage cells with an endogenous IRF3-ISRE promoter driving secreted luciferase and IRF3KO RAW Lucia, a subline deficient in IRF3, were challenged with TMEV. After the challenge, considerable TMEV RNA detected at 18 and 24 h in RAW cells was significantly elevated in IRF3KO RAW cells. TMEV induction …


A Single Amino Acid Substitution In Porcine Reproductive And Respiratory Syndrome Virus Glycoprotein 2 Significantly Impairs Its Infectivity In Macrophages, Jayeshbhai Chaudhari, Raquel Arruda Leme, Kassandra Durazo-Martinez, Sarah Vitosh-Sillman, Aspen M. Workman, Hiep Vu Nov 2022

A Single Amino Acid Substitution In Porcine Reproductive And Respiratory Syndrome Virus Glycoprotein 2 Significantly Impairs Its Infectivity In Macrophages, Jayeshbhai Chaudhari, Raquel Arruda Leme, Kassandra Durazo-Martinez, Sarah Vitosh-Sillman, Aspen M. Workman, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) has a restricted tropism for macrophages and CD163 is a key receptor for infection. In this study, the PRRSV strain NCV1 was passaged on MARC-145 cells for 95 passages, and two plaque-clones (C1 and C2) were randomly selected for further analysis. The C1 virus nearly lost the ability to infect porcine alveolar macrophages (PAMs), as well as porcine kidney cells expressing porcine CD163 (PK15-pCD163), while the C2 virus replicates well in these two cell types. Pretreatment of MARC-145 cells with an anti-CD163 antibody nearly blocked C1 virus infection, indicating that the virus still …


Molecular Basis For Integrin Adhesion Receptor Binding To P21-Activated Kinase 4 (Pak4), Byung Hak Ha, Sezin Yigit, Nailini Natarajan, Elizabeth M. Luoma, David A. Calderwood, Titus J. Boggon Nov 2022

Molecular Basis For Integrin Adhesion Receptor Binding To P21-Activated Kinase 4 (Pak4), Byung Hak Ha, Sezin Yigit, Nailini Natarajan, Elizabeth M. Luoma, David A. Calderwood, Titus J. Boggon

SHU Faculty Publications

Integrin adhesion receptors provide links between extracellular ligands and cytoplasmic signaling. Multiple kinases have been found to directly engage with integrin β tails, but the molecular basis for these interactions remain unknown. Here, we assess the interaction between the kinase domain of p21-activated kinase 4 (PAK4) and the cytoplasmic tail of integrin β5. We determine three crystal structures of PAK4-β5 integrin complexes and identify the PAK-binding site. This is a region in the membrane-proximal half of the β5 tail and confirmed by site-directed mutagenesis. The β5 tail engages the kinase substrate-binding groove and positions the non-phosphorylatable integrin residue Glu767 at …


Regulation Of Parkinson’S Disease-Associated Genes By Pumilio Proteins And Micrornas In The Human Neuroblastoma Cell Line Sh-Sy5y, Lisa J. Snoderly-Foster Nov 2022

Regulation Of Parkinson’S Disease-Associated Genes By Pumilio Proteins And Micrornas In The Human Neuroblastoma Cell Line Sh-Sy5y, Lisa J. Snoderly-Foster

Dissertations

Parkinson’s disease (PD) is the second most common age-related, neurodegenerative disease. A small collection of genes has been linked to PD, including SNCA encoding the protein alpha-synuclein that aggregates in Lewy bodies, a hallmark of PD. Overexpression of these genes can lead to pathogenesis, yet the regulatory mechanisms that control protein production of the genes are not fully understood. The SH-SY5Y neuronal cell line is a common model for the study of neurodegenerative diseases, including PD. However, SH-SY5Y cells are difficult to transfect, a process necessary for genetic manipulations and downstream analysis of RNA and protein. Herein, I describe the …


Polyphenolics, Glucosinolates And Isothiocyanates Profiling Of Aerial Parts Of Nasturtium Officinale (Watercress), Sotiris Kyriakou, Kyriaki Michailidou, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis Nov 2022

Polyphenolics, Glucosinolates And Isothiocyanates Profiling Of Aerial Parts Of Nasturtium Officinale (Watercress), Sotiris Kyriakou, Kyriaki Michailidou, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

Nebraska Center for Virology: Faculty Publications

Watercress (Nasturtium officinale) is a rich source of secondary metabolites with disease-preventing and/or health-promoting properties. Herein, we have utilized extraction procedures to isolate fractions of polyphenols, glucosinolates and isothiocyanates to determine their identification, and quantification. In doing so, we have utilized reproducible analytical methodologies based on liquid chromatography with tandem mass spectrometry by either positive or negative ion mode. Due to the instability and volatility of isothiocyanates, we followed an ammonia derivatization protocol which converts them into respective ionizable thiourea derivatives. The analytes’ content distribution map was created on watercress flowers, leaves and stems. We have demonstrated that …


Polyphenolics, Glucosinolates And Isothiocyanates Profiling Of Aerial Parts Of Nasturtium Officinale (Watercress), Sotiris Kyriakou, Kyriaki Michailidou, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis Nov 2022

Polyphenolics, Glucosinolates And Isothiocyanates Profiling Of Aerial Parts Of Nasturtium Officinale (Watercress), Sotiris Kyriakou, Kyriaki Michailidou, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Watercress (Nasturtium officinale) is a rich source of secondary metabolites with disease-preventing and/or health-promoting properties. Herein, we have utilized extraction procedures to isolate fractions of polyphenols, glucosinolates and isothiocyanates to determine their identification, and quantification. In doing so, we have utilized reproducible analytical methodologies based on liquid chromatography with tandem mass spectrometry by either positive or negative ion mode. Due to the instability and volatility of isothiocyanates, we followed an ammonia derivatization protocol which converts them into respective ionizable thiourea derivatives. The analytes’ content distribution map was created on watercress flowers, leaves and stems. We have demonstrated that …


A Pooling Strategy For Detecting Carbapenem Resistance Genes By The Xpert Carba-R Test In Rectal Swab Specimens, Fred C. Tenover, Peng Zhang, Qi Wang, Chaoe Zhou, Feifei Zhang, Xinghui Gao, Yi-Wei Tang, Hui Wang Nov 2022

A Pooling Strategy For Detecting Carbapenem Resistance Genes By The Xpert Carba-R Test In Rectal Swab Specimens, Fred C. Tenover, Peng Zhang, Qi Wang, Chaoe Zhou, Feifei Zhang, Xinghui Gao, Yi-Wei Tang, Hui Wang

Biology Faculty Publications

Rapid and accurate detection of carriers of carbapenemase-producing organisms (CPO) in hospitalized patients is critical for infection control and prevention. This study aimed to evaluate a pooling strategy for the detection of carbapenem resistance genes (CRG) in multiple specimens using the Xpert Carba-R test. Two rectal swabs each were collected from 415 unique patients. One swab was tested by Carba-R on the five specimen-pooled strategy. The other swab was tested individually by culture followed by DNA sequence analysis for CRG as the reference. At the first 5:1 pooling testing, 22 of 83 pools were positive, which yielded 34 positives from …


Canalization And Other Design Principles Of Gene Regulatory Networks, Claus Kadelka Nov 2022

Canalization And Other Design Principles Of Gene Regulatory Networks, Claus Kadelka

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.


Cardiac Myosin-Specific Autoimmune T Cells Contribute To Immune-Checkpoint-Inhibitor-Associated Myocarditis, Johns Hopkins University School Of Medicine, Johns Hopkins University Bloomberg School Of Public Health, Johns Hopkins University Whiting School Of Engineering, Ninaad Lasrado, Jay Reddy, Daniela Ciháková Nov 2022

Cardiac Myosin-Specific Autoimmune T Cells Contribute To Immune-Checkpoint-Inhibitor-Associated Myocarditis, Johns Hopkins University School Of Medicine, Johns Hopkins University Bloomberg School Of Public Health, Johns Hopkins University Whiting School Of Engineering, Ninaad Lasrado, Jay Reddy, Daniela Ciháková

School of Veterinary and Biomedical Sciences: Faculty Publications

Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear. Here, we show the development of myocarditis in A/J mice induced by anti-PD-1 monoclonal antibody (mAb) administration alone without tumor cell inoculation, immunization, or viral infection. Mice with myocarditis have increased cardiac infiltration, elevated cardiac troponin levels, and arrhythmia. Anti-PD-1 mAb treatment also causes irAEs in other organs. Autoimmune T cells recognizing cardiac myosin are activated and increased …


Cardiac Myosin-Specific Autoimmune T Cells Contribute To Immune-Checkpoint-Inhibitor-Associated Myocarditis, Taejoon Won, Hannah M. Kalinoski, Megan K. Wood, David M. Hughes, Camille M. Jaime, Paul Delgado, Monica V. Talor, Ninaad Lasrado, Jay Reddy, Daniela Čiháková Nov 2022

Cardiac Myosin-Specific Autoimmune T Cells Contribute To Immune-Checkpoint-Inhibitor-Associated Myocarditis, Taejoon Won, Hannah M. Kalinoski, Megan K. Wood, David M. Hughes, Camille M. Jaime, Paul Delgado, Monica V. Talor, Ninaad Lasrado, Jay Reddy, Daniela Čiháková

Jay Reddy Publications

Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear. Here, we show the development of myocarditis in A/J mice induced by anti-PD-1 monoclonal antibody (mAb) administration alone without tumor cell inoculation, immunization, or viral infection. Mice with myocarditis have increased cardiac infiltration, elevated cardiac troponin levels, and arrhythmia. Anti-PD-1 mAb treatment also causes irAEs in other organs. Autoimmune T cells recognizing cardiac myosin are activated and increased …


The “Big Six”: Hidden Emerging Foodborne Bacterial Pathogens, Mona G. Alharbi, Rashad R. Al-Hindi, Ahmed Esmael, Ibrahim A. Alotibi, Sheren A. Azhari, Mazen S. Alseghayer, Addisu D. Teklemariam Nov 2022

The “Big Six”: Hidden Emerging Foodborne Bacterial Pathogens, Mona G. Alharbi, Rashad R. Al-Hindi, Ahmed Esmael, Ibrahim A. Alotibi, Sheren A. Azhari, Mazen S. Alseghayer, Addisu D. Teklemariam

Nebraska Center for Virology: Faculty Publications

Non-O157 Shiga toxin-producing Escherichia coli (STEC) are emerging serogroups that often result in diseases ranging from diarrhea to severe hemorrhagic colitis in humans. The most common non-O157 STEC are O26, O45, O103, O111, O121, and O145. These serogroups are known by the name “big six” because they cause severe illness and death in humans and the United States Department of Agriculture declared these serogroups as food contaminants. The lack of fast and efficient diagnostic methods exacerbates the public impact of the disease caused by these serogroups. Numerous outbreaks have been reported globally and most of these outbreaks were caused by …


Ferrocenium Salt Aided Substitution Reactions And Synthesis Of Glycosylated Curcumin Derivatives, Deva Saroja Talasila Nov 2022

Ferrocenium Salt Aided Substitution Reactions And Synthesis Of Glycosylated Curcumin Derivatives, Deva Saroja Talasila

Dissertations

Organic synthesis has been significantly advanced with the employment of transition metal complexes. The discovery of transition metal catalysts provided the synthetic community with powerful tools for accelerating reactions and making them more selective and efficient. Many chemical reactions do not happen without a catalyst.

Iron-based catalysts have several advantages for the chemical industry because it is a non-toxic and ecologically friendly metal. Our group previously found that ferrocenium cations with a 3+ oxidation state of iron-catalyzed propargylic substitution reactions at low temperatures. The sandwich structure of ferrocenes allows substituents to be introduced on the cyclopentadienyl rings, which allows for …


Cell Size Control Mechanisms In The Multiple Fission Cell Cycle Of Chlamydomonas, Dianyi Liu Nov 2022

Cell Size Control Mechanisms In The Multiple Fission Cell Cycle Of Chlamydomonas, Dianyi Liu

Dissertations

Size homeostasis is achieved by a balance between cell growth and cell division, but the underlying mechanisms are yet fully understood. Green alga Chlamydomonas reinhardtii (Chlamydomonas) is a unique model for size control. Instead of the canonical binary fission cell cycle, Chlamydomonas uses a multiple fission cell cycle where a prolonged G1 phase is followed by rapid alternative n rounds of S/M (DNA synthesis and mitosis) cycles to produce 2n daughter cells. Two size checkpoints show size-dependence: the Commitment checkpoint governs a minimum size for a cell to divide at least once, and the S/M checkpoint governs the division …


Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R. Deshotels, Caroline Sun, Vijay Nambi, Salim S. Virani, Kunihiro Matsushita, Bing Yu, Christie . M. Ballantyne, Ron C. Hoogeveen Nov 2022

Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R. Deshotels, Caroline Sun, Vijay Nambi, Salim S. Virani, Kunihiro Matsushita, Bing Yu, Christie . M. Ballantyne, Ron C. Hoogeveen

Office of the Provost

Background: Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person's life is sufficient for cardiovascular risk assessment in all adults.
Methods and Results: Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline …