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Articles 13711 - 13740 of 24387
Full-Text Articles in Entire DC Network
Ethanol And Opioids Do Not Act Synergistically To Depress Excitation In Carotid Body Type I Cells, Ryan J. Rakoczy, Kajal Kamra, Yoon-Jae Yi, Christopher N. Wyatt
Ethanol And Opioids Do Not Act Synergistically To Depress Excitation In Carotid Body Type I Cells, Ryan J. Rakoczy, Kajal Kamra, Yoon-Jae Yi, Christopher N. Wyatt
Neuroscience, Cell Biology & Physiology Faculty Publications
The combination of opioids and ethanol can synergistically depress breathing and the acute ventilatory response to hypoxia. Multiple studies have shown that the underlying mechanisms for this may involve calcium channel inhibition in central neurons. But we have previously identified opioid receptors in the carotid bodies and shown that their activation inhibits calcium influx into the chemosensitive cells. Given that the carotid bodies contribute to the drive to breathe and underpin the acute hypoxic ventilatory response, we hypothesized that ethanol and opioids may act synergistically in these peripheral sensory organs to further inhibit calcium influx and therefore inhibit ventilation.
Methods …
Mirna-30e Downregulation Increases Cancer Cell Proliferation, Invasion And Tumor Growth Through Targeting Rps6kb1, Lin Wang, Xiang-Bo Ji, Li-Hong Wang, Zhong-Kun Xia, Yun-Xia Xie, Wen-Jing Liu, Jian-Ge Qiu, Bing-Hua Jiang, Ling-Zhi Liu
Mirna-30e Downregulation Increases Cancer Cell Proliferation, Invasion And Tumor Growth Through Targeting Rps6kb1, Lin Wang, Xiang-Bo Ji, Li-Hong Wang, Zhong-Kun Xia, Yun-Xia Xie, Wen-Jing Liu, Jian-Ge Qiu, Bing-Hua Jiang, Ling-Zhi Liu
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Human esophagus carcinoma (EC) is one of the most common malignant tumors, especially in Africa and Asia including China. In EC initiation and progression, genetic and epigenetic aberrations have been reported to play a major role, but the underlying molecular mechanisms are largely unknown. In this study, the miR-30e levels were analyzed in human EC tissues and TCGA databases, and the results demonstrated that miR-30e expression in EC tissues was significantly decreased compared to adjacent normal tissues. To further investigate the role of miR-30e in cancer cells, we found that forced expression of miR-30e dramatically inhibited cell proliferation, invasion, tube …
Contact Normalization And The Role Of Maackia Amurensis Seed Lectin As A Novel Chemotherapeutic And Antiviral Agent, Stephanie A. Sheehan
Contact Normalization And The Role Of Maackia Amurensis Seed Lectin As A Novel Chemotherapeutic And Antiviral Agent, Stephanie A. Sheehan
Graduate School of Biomedical Sciences Theses and Dissertations
Cells communicate with each other to coordinate tissue function and homeostasis. Diseases including cancer, arthritis, and acute respiratory disease syndrome (ARDS) require a breakdown in this intercellular communication. For example, cancer progression is suppressed by junctional communication between nontransformed and transformed cells. This process is called contact normalization. Junctional communication must be disrupted to enable transformed cells to grow into malignancies. However, the junctions and mechanisms by which nontransformed cells normalize cell behavior have not been clearly defined. My project aimed to identify junctions and elucidate mechanisms underlying contact normalization. We discovered that cadherins, specifically N-cadherin, form junctions that enable …
The Sulfur Microbial Diet Is Associated With Increased Risk Of Early-Onset Colorectal Cancer Precursors, Long H. Nguyen, Yin Cao, Jinhee Hur, Raaj S. Mehta, Daniel R. Sikavi, Yiqing Wang, Wenjie Ma, Kana Wu, Mingyang Song, Edward L. Giovannucci, Eric B. Rimm, Walter C. Willett, Wendy S. Garrett, Jacques Izard, Curtis Huttenhower, Andrew T. Chan
The Sulfur Microbial Diet Is Associated With Increased Risk Of Early-Onset Colorectal Cancer Precursors, Long H. Nguyen, Yin Cao, Jinhee Hur, Raaj S. Mehta, Daniel R. Sikavi, Yiqing Wang, Wenjie Ma, Kana Wu, Mingyang Song, Edward L. Giovannucci, Eric B. Rimm, Walter C. Willett, Wendy S. Garrett, Jacques Izard, Curtis Huttenhower, Andrew T. Chan
Food for Health: Publications
Background and aims: Diet may contribute to the increasing incidence of colorectal cancer (CRC) before age 50 (early-onset CRC). Microbial metabolism of dietary sulfur produces hydrogen sulfide (H2S), a gastrointestinal carcinogen that cannot be easily measured at scale. As a result, evidence supporting its role in early neoplasia is lacking.
Methods: We evaluated long-term adherence to the sulfur microbial diet, a dietary index defined a priori based on increased abundance of 43 bacterial species involved with sulfur metabolism, with risk of CRC precursors among 59,013 individuals who underwent lower endoscopy in the Nurses’ Health Study II …
An Investigative Analysis Of Underlying Alzheimer’S Disease Pathology: Understanding The Pathology Of Neurofibril Tangles, William Barker
An Investigative Analysis Of Underlying Alzheimer’S Disease Pathology: Understanding The Pathology Of Neurofibril Tangles, William Barker
Senior Honors Theses
Researchers familiar with Alzheimer’s Disease (AD) refer to two common pathological hallmarks: β-amyloid plaques and Neurofibril Tangles (NFTs). The development of these pathologies are the leading theory to explain the cause of cognitive decline and dementia-like symptoms of individuals with AD. The literature supports the theory that NFTs are caused by the hyperphosphorylation of the precursor tau protein. However, the mechanism that causes this hyperphosphorylation is still unknown. This review seeks to evaluate the normal function of tau then analyze and expound upon the current research concerning the underlying mechanisms for the hyperphosphorylation of tau observed in Neurofibril Tangles pathologies. …
Modulatory Actions Of The Glycine Receptor Β Subunit On The Positive Allosteric Modulation Of Ethanol In Α2 Containing Receptors, Braulio Muñoz, Trinidad Mariqueo, Pablo Murath, Christian Peters, Gonzalo E. Yevenes, Gustavo Moraga-Cid, Robert W. Peoples, Luis G. Aguayo
Modulatory Actions Of The Glycine Receptor Β Subunit On The Positive Allosteric Modulation Of Ethanol In Α2 Containing Receptors, Braulio Muñoz, Trinidad Mariqueo, Pablo Murath, Christian Peters, Gonzalo E. Yevenes, Gustavo Moraga-Cid, Robert W. Peoples, Luis G. Aguayo
Biomedical Sciences Faculty Research and Publications
Alpha1-containing glycine receptors (GlyRs) are major mediators of synaptic inhibition in the spinal cord and brain stem. Recent studies reported the presence of α2-containing GlyRs in other brain regions, such as nucleus accumbens and cerebral cortex. GlyR activation decreases neuronal excitability associated with sensorial information, motor control, and respiratory functions; all of which are significantly altered during ethanol intoxication. We evaluated the role of β GlyR subunits and of two basic amino acid residues, K389 and R390, located in the large intracellular loop (IL) of the α2 GlyR subunit, which are important for binding and functional modulation by Gβγ, the …
The Molecular Mechanisms Of Estrogen Receptor Α On Two Single Nucleotide Polymorphisms To Regulate Wnt Signaling In Osteoblasts, Sarocha Suthon
The Molecular Mechanisms Of Estrogen Receptor Α On Two Single Nucleotide Polymorphisms To Regulate Wnt Signaling In Osteoblasts, Sarocha Suthon
Theses and Dissertations (ETD)
Osteoporosis is the most common bone metabolic disorder, affecting over 200 million people globally. It is characterized by bone mass depletion and microarchitectural deterioration, leading to bone fragility and susceptibility to bone fracture. Genetic factors, estrogen deficiency, and dysregulation of the WNT signaling pathway contribute to the development of this disease. Genome-wide association studies have predicted that the single nucleotide polymorphisms (SNPs) rs2887571 and rs9921222 associate with low bone mass, but the mechanism of these SNPs has remained unknown. Analysis of osteoblasts from 112 different joint replacement patients reveals that the genotype of rs2887571 correlates with WNT5B expression, and the …
Advancing Rna Virus Discovery And Biology With Whole Genome Sequencing, Mariah Katherine Taylor
Advancing Rna Virus Discovery And Biology With Whole Genome Sequencing, Mariah Katherine Taylor
Theses and Dissertations (ETD)
Two RNA virus families that pose a threat to human and animal health are Hantaviridae and Coronaviridae. These RNA viruses which originate in wildlife continue and will continue to cause disease, and hence, it is critical that scientific research define the mechanisms as to how these viruses spillover and adapt to new hosts to become endemic. One gap in our ability to define these mechanisms is the lack of whole genome sequences for many of these viruses. To address this specific gap, I developed a versatile amplicon-based whole-genome sequencing (WGS) approach to identify viral genomes of hantaviruses and severe acute …
Role Of Smad2 And Smad3 On Adipose Tissue Development And Function, Roshan Kumari
Role Of Smad2 And Smad3 On Adipose Tissue Development And Function, Roshan Kumari
Theses and Dissertations (ETD)
Introduction: Obesity and its associated metabolic syndrome are major medical problems worldwide including United States. Adipose tissue is the primary site of energy storage, playing important roles in health. Adipose tissue also has other critical functions, producing adipocytokines and contributing to normal nutrient metabolism, which in turn play important roles in satiety, inflammation, and total energy homeostasis. Activin A and activin B play important roles in maintaining body composition and energy homeostasis. This dissertation highlights the role of activin/SMADs signaling in adipose tissue development, function, and maintenance.
SMAD2/3 proteins are downstream mediators of transforming growth factor-β (TGFβ) family signaling, including …
Citalopram For Treatment Of Cocaine Use Disorder: A Bayesian Drop-The-Loser Randomized Clinical Trial, Robert Suchting, Charles E Green, Constanza De Dios, Jessica Vincent, F Gerard Moeller, Scott D Lane, Joy M Schmitz
Citalopram For Treatment Of Cocaine Use Disorder: A Bayesian Drop-The-Loser Randomized Clinical Trial, Robert Suchting, Charles E Green, Constanza De Dios, Jessica Vincent, F Gerard Moeller, Scott D Lane, Joy M Schmitz
Faculty, Staff and Student Publications
BACKGROUND: Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the 'best efficacy' dose.
METHODS: A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits …
Simultaneous Brain And Intramedullary Spinal Abscesses In A Patient With Streptococcus Intermedius Infection, David P. Friedman, Joseph Desimone Jr, Aaron Christensen, Matthew Pettengill
Simultaneous Brain And Intramedullary Spinal Abscesses In A Patient With Streptococcus Intermedius Infection, David P. Friedman, Joseph Desimone Jr, Aaron Christensen, Matthew Pettengill
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
A male patient in his thirties presented to the hospital with meningismus and altered mental status. Cerebrospinal fluid (CSF) analysis confirmed meningitis, but no microorganisms were identified. Head imaging (MRI) revealed multiple brain abscesses. Surgically-collected brain specimens revealed Gram-positive cocci and subsequently grew Streptococcus intermedius. MRI of the thoracic spine subsequently also identified an intramedullary spinal abscess. While brain abscesses and spinal abscesses caused by S. intermedius have been previously reported, the extent of disseminated disease in the patient was noteworthy.
Mitophagy In Depression: Pathophysiology And Treatment Targets, Ashutosh Tripathi, Giselli Scaini, Tatiana Barichello, João Quevedo, Anilkumar Pillai
Mitophagy In Depression: Pathophysiology And Treatment Targets, Ashutosh Tripathi, Giselli Scaini, Tatiana Barichello, João Quevedo, Anilkumar Pillai
Faculty, Staff and Student Publications
Mitochondria, the 'powerhouse' of eukaryotic cells, play a key role in cellular homeostasis. However, defective mitochondria increase mitochondrial ROS (mtROS) production and cell-free mitochondrial DNA (mtDNA) release, leading to increased inflammation. Mitophagy is a vital pathway, which selectively removes defective mitochondria through the process of autophagy. Thus, an impairment in the mitophagy pathway might trigger the gradual accumulation of defective mitochondria. Accumulating evidence suggest that inflammation and mitochondrial dysfunction are linked to the pathogenesis of depression. In this article, we have reviewed the role of impaired mitophagy as a contributing factor in depression pathophysiology. Further, we have discussed the potential …
Analysis Of Covid-19 Infection And Mortality Among Patients With Psychiatric Disorders, 2020, Antonio L Teixeira, Trudy Millard Krause, Lopita Ghosh, Lokesh Shahani, Rodrigo Machado-Vieira, Scott D Lane, Eric Boerwinkle, Jair C Soares
Analysis Of Covid-19 Infection And Mortality Among Patients With Psychiatric Disorders, 2020, Antonio L Teixeira, Trudy Millard Krause, Lopita Ghosh, Lokesh Shahani, Rodrigo Machado-Vieira, Scott D Lane, Eric Boerwinkle, Jair C Soares
Faculty, Staff and Student Publications
IMPORTANCE: People with major psychiatric disorders are more likely to have comorbidities associated with worse outcomes of COVID-19. This fact alone could determine greater vulnerability of people with major psychiatric disorders to COVID-19.
OBJECTIVE: To assess the odds of testing positive for and mortality from COVID-19 among and between patients with schizophrenia, mood disorders, anxiety disorders and a reference group in a large national database.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used an electronic health record data set aggregated from many national sources in the United States and licensed from Optum with current and historical data on patients tested …
Attenuated Bacteria Potentiate The Outcome Of Immunotherapy With Pd-L1 Blockade In A Pre-Clinical Model Of Colorectal Cancer, Besan Haytham Mohammad Al-Saafeen
Attenuated Bacteria Potentiate The Outcome Of Immunotherapy With Pd-L1 Blockade In A Pre-Clinical Model Of Colorectal Cancer, Besan Haytham Mohammad Al-Saafeen
Theses
After more than a century of investigation, it has become evident that cancer development and progression occur at the expense of a dysfunctional immune system. This realization has ushered cancer immunotherapy as a new modality of treatment. In the last decade, the use of immune checkpoint inhibitors to treat cancer patients resulted in unprecedented and durable clinical benefits. However, the response rate in many cancers remains rather modest, with colorectal cancer being at the lower end of the spectrum. Previous work from our laboratory demonstrated the efficacy of using attenuated bacteria as immunomodulatory anti-cancer agents. The current study investigated the …
The Role Of The Filifactor Alocis Hypothetical Protein Fa519 In Oxidative Stress Resistance, Ezinne Rebecca Aja
The Role Of The Filifactor Alocis Hypothetical Protein Fa519 In Oxidative Stress Resistance, Ezinne Rebecca Aja
Loma Linda University Electronic Theses, Dissertations & Projects
Filifactor alocis, a fastidious, Gram-positive, obligate anaerobic bacterium, is a newly appreciated member of the periodontal community, which is now proposed to be a diagnostic indicator of periodontal disease. Its pathogenic characteristics are highlighted by its ability to survive in the oxidative-stress rich environment of the periodontal pocket and to significantly alter the microbial community dynamics by forming biofilms and interacting with several oral bacteria. Currently, there is incomplete information on the pathogenic mechanism(s) and a possible dynamic functional role of F. alocis in the dysbiotic microbial community. Because the stress response of this bacterium to the oxidative environment …
Comparison Of Culture With Antibiogram To Next-Generation Sequencing Using Bacterial Isolates And Formalin-Fixed, Paraffin-Embedded Gastric Biopsies, Kristina G Hulten, Robert M Genta, Ira N Kalfus, Yi Zhou, Hongjun Zhang, David Y Graham
Comparison Of Culture With Antibiogram To Next-Generation Sequencing Using Bacterial Isolates And Formalin-Fixed, Paraffin-Embedded Gastric Biopsies, Kristina G Hulten, Robert M Genta, Ira N Kalfus, Yi Zhou, Hongjun Zhang, David Y Graham
Faculty, Staff and Students Publications
BACKGROUND & AIMS: The decline in Helicobacter pylori cure rates emphasizes the need for readily available methods to determine antimicrobial susceptibility. Our aim was to compare targeted next-generation sequencing (NGS) and culture-based H pylori susceptibility testing using clinical isolates and paired formalin-fixed, paraffin-embedded (FFPE) gastric biopsies.
METHODS: H pylori isolates and FFPE tissues were tested for susceptibility to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin using agar dilution and NGS targeted to 23S rRNA, gyrA, 16S rRNA, pbp1, rpoB and rdxA. Agreement was quantified using κ statistics.
RESULTS: Paired comparisons included 170 isolates and FFPE tissue for amoxicillin, clarithromycin, metronidazole, …
Ckb Inhibits Epithelial-Mesenchymal Transition And Prostate Cancer Progression By Sequestering And Inhibiting Akt Activation, Zheng Wang, Mohit Hulsurkar, Lijuan Zhuo, Jinbang Xu, Han Yang, Samira Naderinezhad, Lin Wang, Guoliang Zhang, Nanping Ai, Linna Li, Jeffrey T Chang, Songlin Zhang, Ladan Fazli, Chad J Creighton, Fang Bai, Michael M Ittmann, Martin E Gleave, Wenliang Li
Ckb Inhibits Epithelial-Mesenchymal Transition And Prostate Cancer Progression By Sequestering And Inhibiting Akt Activation, Zheng Wang, Mohit Hulsurkar, Lijuan Zhuo, Jinbang Xu, Han Yang, Samira Naderinezhad, Lin Wang, Guoliang Zhang, Nanping Ai, Linna Li, Jeffrey T Chang, Songlin Zhang, Ladan Fazli, Chad J Creighton, Fang Bai, Michael M Ittmann, Martin E Gleave, Wenliang Li
Faculty, Staff and Students Publications
Epithelial-mesenchymal transition (EMT) contributes to tumor invasion, metastasis and drug resistance. AKT activation is key in a number of cellular processes. While many positive regulators for either EMT or AKT activation have been reported, few negative regulators are established. Through kinase cDNA screen, we identified brain-type creatine kinase (CKB or BCK) as a potent suppressor for both. As a ubiquitously expressed kinase in normal tissues, CKB is significantly downregulated in several solid cancer types. Lower CKB expression is significantly associated with worse prognosis. Phenotypically, CKB overexpression suppresses, while its silencing promotes, EMT and cell migration, xenograft tumor growth and metastasis …
Drivers Of Transcriptional Variance In Human Intestinal Epithelial Organoids, Zachary K Criss, Nobel Bhasin, Sara C Di Rienzi, Anubama Rajan, Kali Deans-Fielder, Ganesh Swaminathan, Nabiollah Kamyabi, Xi-Lei Zeng, Harsha Doddapaneni, Vipin K Menon, Deepavali Chakravarti, Clarissa Estrella, Xiaomin Yu, Ketki Patil, Joseph F Petrosino, James C Fleet, Michael P Verzi, Sylvia Christakos, Michael A Helmrath, Sumimasa Arimura, Ronald A Depinho, Robert A Britton, Anthony W Maresso, K Jane Grande-Allen, Sarah E Blutt, Sue E Crawford, Mary K Estes, Sasirekha Ramani, Noah F Shroyer
Drivers Of Transcriptional Variance In Human Intestinal Epithelial Organoids, Zachary K Criss, Nobel Bhasin, Sara C Di Rienzi, Anubama Rajan, Kali Deans-Fielder, Ganesh Swaminathan, Nabiollah Kamyabi, Xi-Lei Zeng, Harsha Doddapaneni, Vipin K Menon, Deepavali Chakravarti, Clarissa Estrella, Xiaomin Yu, Ketki Patil, Joseph F Petrosino, James C Fleet, Michael P Verzi, Sylvia Christakos, Michael A Helmrath, Sumimasa Arimura, Ronald A Depinho, Robert A Britton, Anthony W Maresso, K Jane Grande-Allen, Sarah E Blutt, Sue E Crawford, Mary K Estes, Sasirekha Ramani, Noah F Shroyer
Faculty, Staff and Students Publications
Human intestinal epithelial organoids (enteroids and colonoids) are tissue cultures used for understanding the physiology of the human intestinal epithelium. Here, we explored the effect on the transcriptome of common variations in culture methods, including extracellular matrix substrate, format, tissue segment, differentiation status, and patient heterogeneity. RNA-sequencing datasets from 276 experiments performed on 37 human enteroid and colonoid lines from 29 patients were aggregated from several groups in the Texas Medical Center. DESeq2 and gene set enrichment analysis (GSEA) were used to identify differentially expressed genes and enriched pathways. PERMANOVA, Pearson's correlation, and dendrogram analysis of the data originally indicated …
Zebrafish Paralogs Brd2a And Brd2b Are Needed For Proper Circulatory, Excretory And Central Nervous System Formation And Act As Genetic Antagonists During Development, Gregory L Branigan, Kelly S Olsen, Isabella Burda, Matthew W Haemmerle, Jason Ho, Alexandra Venuto, Nicholas D D'Antonio, Ian E Briggs, Angela J Dibenedetto
Zebrafish Paralogs Brd2a And Brd2b Are Needed For Proper Circulatory, Excretory And Central Nervous System Formation And Act As Genetic Antagonists During Development, Gregory L Branigan, Kelly S Olsen, Isabella Burda, Matthew W Haemmerle, Jason Ho, Alexandra Venuto, Nicholas D D'Antonio, Ian E Briggs, Angela J Dibenedetto
Department of Biochemistry and Molecular Biology Faculty Papers
Brd2 belongs to the BET family of epigenetic transcriptional co-regulators that act as adaptor-scaffolds for the assembly of chromatin-modifying complexes and other factors at target gene promoters. Brd2 is a protooncogene and candidate gene for juvenile myoclonic epilepsy in humans, a homeobox gene regulator in Drosophila, and a maternal-zygotic factor and cell death modulator that is necessary for normal development of the vertebrate central nervous system (CNS). As two copies of Brd2 exist in zebrafish, we use antisense morpholino knockdown to probe the role of paralog Brd2b, as a comparative study to Brd2a, the ortholog of human Brd2. A deficiency …
The Role Of Hgf/Met Signaling In Metastatic Uveal Melanoma, Ryota Tanaka, Mizue Terai, Eric R Londin, Takami Sato
The Role Of Hgf/Met Signaling In Metastatic Uveal Melanoma, Ryota Tanaka, Mizue Terai, Eric R Londin, Takami Sato
Department of Medical Oncology Faculty Papers
Hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signaling promotes tumorigenesis and tumor progression in various types of cancer, including uveal melanoma (UM). The roles of HGF/MET signaling have been studied in cell survival, proliferation, cell motility, and migration. Furthermore, HGF/MET signaling has emerged as a critical player not only in the tumor itself but also in the tumor microenvironment. Expression of MET is frequently observed in metastatic uveal melanoma and is associated with poor prognosis. It has been reported that HGF/MET signaling pathway activation is the major mechanism of treatment resistance in metastatic UM (MUM). To achieve maximal therapeutic benefit …
Multifunctionality Of Prostatic Acid Phosphatase In Prostate Cancer Pathogenesis, Evgenia Alpert, Armin Akhavan, Arie Gruzman, William J. Hansen, Joshua Lehrer-Graiwer, Steven C. Hall, Eric Johansen, Sean Mcallister, Mittul Gulati, Ming-Fong Lin, Vishwanath R Lingappa
Multifunctionality Of Prostatic Acid Phosphatase In Prostate Cancer Pathogenesis, Evgenia Alpert, Armin Akhavan, Arie Gruzman, William J. Hansen, Joshua Lehrer-Graiwer, Steven C. Hall, Eric Johansen, Sean Mcallister, Mittul Gulati, Ming-Fong Lin, Vishwanath R Lingappa
Journal Articles: Biochemistry & Molecular Biology
The role of human prostatic acid phosphatase (PAcP, P15309|PPAP_HUMAN) in prostate cancer was investigated using a new proteomics tool termed signal sequence swapping (replacement of domains from the native cleaved amino terminal signal sequence of secretory/membrane proteins with corresponding regions of functionally distinct signal sequence subtypes). This manipulation preferentially redirects proteins to different pathways of biogenesis at the endoplasmic reticulum (ER), magnifying normally difficult to detect subsets of the protein of interest. For PAcP, this technique reveals three forms identical in amino acid sequence but profoundly different in physiological functions, subcellular location, and biochemical properties. These three forms of PAcP …
Ptsd As An Endothelial Disease: Insights From Covid-19, Adonis Sfera, Carolina Osorio, Leah Rahman, Carlos M. Zapata Martín Del Campo, Jose Campo Maldonado, Nyla Jafri, Michael Cummings, Steve Maurer, Zisis Kozlakidis
Ptsd As An Endothelial Disease: Insights From Covid-19, Adonis Sfera, Carolina Osorio, Leah Rahman, Carlos M. Zapata Martín Del Campo, Jose Campo Maldonado, Nyla Jafri, Michael Cummings, Steve Maurer, Zisis Kozlakidis
School of Medicine Publications
SARS-CoV-2 virus, the etiologic agent of COVID-19, has affected almost every aspect of human life, precipitating stress-related pathology in vulnerable individuals. As the prevalence rate of posttraumatic stress disorder in pandemic survivors exceeds that of the general and special populations, the virus may predispose to this disorder by directly interfering with the stress-processing pathways. The SARS-CoV-2 interactome has identified several antigens that may disrupt the blood-brain-barrier by inducing premature senescence in many cell types, including the cerebral endothelial cells. This enables the stress molecules, including angiotensin II, endothelin-1 and plasminogen activator inhibitor 1, to aberrantly activate the amygdala, hippocampus, and …
Untargeted Lipidomics Of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes In Cancer Vs. Non-Cancer Tissue, Joshua M. Mitchell, Robert M. Flight, Hunter N. B. Moseley
Untargeted Lipidomics Of Non-Small Cell Lung Carcinoma Demonstrates Differentially Abundant Lipid Classes In Cancer Vs. Non-Cancer Tissue, Joshua M. Mitchell, Robert M. Flight, Hunter N. B. Moseley
Molecular and Cellular Biochemistry Faculty Publications
Lung cancer remains the leading cause of cancer death worldwide and non-small cell lung carcinoma (NSCLC) represents 85% of newly diagnosed lung cancers. In this study, we utilized our untargeted assignment tool Small Molecule Isotope Resolved Formula Enumerator (SMIRFE) and ultra-high-resolution Fourier transform mass spectrometry to examine lipid profile differences between paired cancerous and non-cancerous lung tissue samples from 86 patients with suspected stage I or IIA primary NSCLC. Correlation and co-occurrence analysis revealed significant lipid profile differences between cancer and non-cancer samples. Further analysis of machine-learned lipid categories for the differentially abundant molecular formulas identified a high abundance sterol, …
The Ratio Method: Addressing Complex Tort Liability In The Fourth Industrial Revolution, Harrison C. Margolin, Grant H. Frazier
The Ratio Method: Addressing Complex Tort Liability In The Fourth Industrial Revolution, Harrison C. Margolin, Grant H. Frazier
St. Mary's Law Journal
Emerging technologies of the Fourth Industrial Revolution show fundamental promise for improving productivity and quality of life, though their misuse may also cause significant social disruption. For example, while artificial intelligence will be used to accelerate society’s processes, it may also displace millions of workers and arm cybercriminals with increasingly powerful hacking capabilities. Similarly, human gene editing shows promise for curing numerous diseases, but also raises significant concerns about adverse health consequences related to the corruption of human and pathogenic genomes.
In most instances, only specialists understand the growing intricacies of these novel technologies. As the complexity and speed of …
The Effects Of Environmental Copper Exposure On The Behavior And Morphology Of Developing Zebrafish, Christina Kaucic
The Effects Of Environmental Copper Exposure On The Behavior And Morphology Of Developing Zebrafish, Christina Kaucic
The Journal of Purdue Undergraduate Research
No abstract provided.
Replication Stress Response Defects Are Associated With Response To Immune Checkpoint Blockade In Nonhypermutated Cancers, Daniel J Mcgrail, Patrick G Pilié, Hui Dai, Truong Nguyen Anh Lam, Yulong Liang, Leonie Voorwerk, Marleen Kok, Xiang H-F Zhang, Jeffrey M Rosen, Amy B Heimberger, Christine B Peterson, Eric Jonasch, Shiaw-Yih Lin
Replication Stress Response Defects Are Associated With Response To Immune Checkpoint Blockade In Nonhypermutated Cancers, Daniel J Mcgrail, Patrick G Pilié, Hui Dai, Truong Nguyen Anh Lam, Yulong Liang, Leonie Voorwerk, Marleen Kok, Xiang H-F Zhang, Jeffrey M Rosen, Amy B Heimberger, Christine B Peterson, Eric Jonasch, Shiaw-Yih Lin
Faculty, Staff and Students Publications
Treatment with immune checkpoint blockade (ICB) has resulted in durable responses for a subset of patients with cancer, with predictive biomarkers for ICB response originally identified largely in the context of hypermutated cancers. Although recent clinical data have demonstrated clinical responses to ICB in certain patients with nonhypermutated cancers, previously established ICB response biomarkers have failed to accurately identify which of these patients may benefit from ICB. Here, we demonstrated that a replication stress response (RSR) defect gene expression signature, but not other proposed biomarkers, is associated with ICB response in 12 independent cohorts of patients with nonhypermutated cancer across …
Mitochondrial Phenotypes In Purified Human Immune Cell Subtypes And Cell Mixtures, Shannon Rausser, Caroline Trumpff, Marlon A. Mcgill, Alex Junker, Wei Wang, Siu-Hong Ho, Anika Mitchell, Kalpita R. Karan, Catherine Monk, Suzanne C. Segerstrom, Rebecca G. Reed, Martin Picard
Mitochondrial Phenotypes In Purified Human Immune Cell Subtypes And Cell Mixtures, Shannon Rausser, Caroline Trumpff, Marlon A. Mcgill, Alex Junker, Wei Wang, Siu-Hong Ho, Anika Mitchell, Kalpita R. Karan, Catherine Monk, Suzanne C. Segerstrom, Rebecca G. Reed, Martin Picard
Psychology Faculty Publications
Using a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly defined immune cell subtypes, we quantify the natural variation in mitochondrial DNA copy number (mtDNAcn), citrate synthase, and respiratory chain enzymatic activities in human neutrophils, monocytes, B cells, and naïve and memory T lymphocyte subtypes. In mixed peripheral blood mononuclear cells (PBMCs) from the same individuals, we show to what extent mitochondrial measures are confounded by both cell type distributions and contaminating platelets. Cell subtype-specific measures among women and men spanning four decades of life indicate potential age- and sex-related differences, including an age-related elevation in mtDNAcn, …
Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom
Physiological Roles Of Mammalian Transmembrane Adenylyl Cyclase Isoforms, Katrina F. Ostrom, Justin E. Lavigne, Tarsis F. Brust, Roland Seifert, Carmen Dessauer, Val J. Watts, Rennolds S. Ostrom
Pharmacy Faculty Articles and Research
Adenylyl cyclases (ACs) catalyze the conversion of ATP to the ubiquitous second messenger cAMP. Mammals possess nine isoforms of transmembrane ACs, dubbed AC1-9, that serve as major effector enzymes of G protein-coupled receptors. The transmembrane ACs display varying expression patterns across tissues, giving potential for them having a wide array of physiologic roles. Cells express multiple AC isoforms, implying that ACs have redundant functions. Furthermore, all transmembrane ACs are activated by Gαs so it was long assumed that all ACs are activated by Gαs-coupled GPCRs. AC isoforms partition to different microdomains of the plasma membrane and form …
Energy Compensation And Adiposity In Humans, Vincent Careau, Lewis G Halsey, Herman Pontzer, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Graeme L Close, Jamie A Cooper, Sai Krupa Das, Richard Cooper, Lara R Dugas, Simon D Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, John J Reilly, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Amy H Luke, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, William W Wong, Yosuke Yamada, John R Speakman, Iaea Dlw Database Group
Energy Compensation And Adiposity In Humans, Vincent Careau, Lewis G Halsey, Herman Pontzer, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Graeme L Close, Jamie A Cooper, Sai Krupa Das, Richard Cooper, Lara R Dugas, Simon D Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, John J Reilly, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Amy H Luke, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, William W Wong, Yosuke Yamada, John R Speakman, Iaea Dlw Database Group
Children’s Nutrition Research Center Staff Publications
Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.
Intouch October 25, 2021, New York Medical College