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Simultaneous Monitoring Cytoplasmic Calcium Ion And Cell Surface Phosphatidylserine In The Necrotic Touch Neurons Of Caenorhabditis Elegans, Yoshitaka Furuta, Zheng Zhou Oct 2021

Simultaneous Monitoring Cytoplasmic Calcium Ion And Cell Surface Phosphatidylserine In The Necrotic Touch Neurons Of Caenorhabditis Elegans, Yoshitaka Furuta, Zheng Zhou

Faculty, Staff and Students Publications

Calcium ions trigger many cellular events, including the release of neurotransmitters at the synaptic terminal and excitotoxic cell death. Recently, we have discovered that a transient increase in the level of cytoplasmic Ca2+ triggers the exposure of phosphatidylserine (PS) on the surfaces of necrotic cells in the nematode Caenorhabditis elegans. PS serves as an “eat me” signal that attracts engulfing cells to engulf and degrade necrotic cells. During the above study, we developed a microscopic imaging protocol for real-time monitoring the levels of cytoplasmic Ca2+ and cell surface PS in Caenorhabditis elegans touch neurons. Previously, Ca2+ dynamics was monitored …


Immunometabolic Dysregulation At The Intersection Of Obesity And Covid-19, Collins N. Khwatenge, Marquette Pate, Laura C. Miller, Yongming Sang Oct 2021

Immunometabolic Dysregulation At The Intersection Of Obesity And Covid-19, Collins N. Khwatenge, Marquette Pate, Laura C. Miller, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

Obesity prevails worldwide to an increasing effect. For example, up to 42% of American adults are considered obese. Obese individuals are prone to a variety of complications of metabolic disorders including diabetes mellitus, hypertension, cardiovascular disease, and chronic kidney disease. Recent meta-analyses of clinical studies in patient cohorts in the ongoing coronavirus-disease 2019 (COVID-19) pandemic indicate that the presence of obesity and relevant disorders is linked to a more severe prognosis of COVID-19. Given the significance of obesity in COVID-19 progression, we provide a review of host metabolic and immune responses in the immunometabolic dysregulation exaggerated by obesity and the …


Precision Food Parenting: A Proposed Conceptual Model And Research Agenda, Tom Baranowski, Debbe Thompson, Sheryl O Hughes, Teresia M O'Connor Oct 2021

Precision Food Parenting: A Proposed Conceptual Model And Research Agenda, Tom Baranowski, Debbe Thompson, Sheryl O Hughes, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

Precision medicine, nutrition and behavioral interventions are attempting to move beyond the specification of therapies applied to groups, since some people benefit, some do not and some are harmed by the same therapy. Instead, precision therapies are attempting to employ diverse sets of data to individualize or tailor interventions to optimize the benefits for the receiving individuals. The benefits to be achieved are mostly in the distant future, but the research needs to start now. While precision pediatric nutrition will combine diverse demographic, behavioral and biological variables to specify the optimal foods a child should eat to optimize health, precision …


Nsaids Naproxen, Ibuprofen, Salicylate, And Aspirin Inhibit Trpm7 Channels By Cytosolic Acidification, Rikki Chokshi, Orville Bennett, Tetyana Zhelay, J. Ashot Kozak Oct 2021

Nsaids Naproxen, Ibuprofen, Salicylate, And Aspirin Inhibit Trpm7 Channels By Cytosolic Acidification, Rikki Chokshi, Orville Bennett, Tetyana Zhelay, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for relieving pain and inflammation accompanying numerous disease states. The primary therapeutic mechanism of these widely used drugs is the inhibition of cyclooxygenase 1 and 2 (COX1, 2) enzymes that catalyze the conversion of arachidonic acid into prostaglandins. At higher doses, NSAIDs are used for prevention of certain types of cancer and as experimental treatments for Alzheimer’s disease. In the immune system, various NSAIDs have been reported to influence neutrophil function and lymphocyte proliferation, and affect ion channels and cellular calcium homeostasis. Transient receptor potential melastatin 7 (TRPM7) cation channels are highly expressed in …


M6a Associated Tsuc7 Inhibition Contributed To Erlotinib Resistance In Lung Adenocarcinoma Through A Notch Signaling Activation Dependent Way, Kai Li, Zi-Yang Peng, Shan Gao, Qing-Shi Wang, Rui Wang, Xiang Li, Guo-Dong Xiao, Jing Zhang, Hong Ren, Shou-Ching Tang, Xin Sun Oct 2021

M6a Associated Tsuc7 Inhibition Contributed To Erlotinib Resistance In Lung Adenocarcinoma Through A Notch Signaling Activation Dependent Way, Kai Li, Zi-Yang Peng, Shan Gao, Qing-Shi Wang, Rui Wang, Xiang Li, Guo-Dong Xiao, Jing Zhang, Hong Ren, Shou-Ching Tang, Xin Sun

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: The small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects.

Methods: Multiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections.

Results: We explored the specific gene features of candidates in association with resistance, and found that m6A controlled the stemness of EMT features through METTL3 and YTHDF2. The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 …


Identification And Characterization Of Cyps Induced In The Drosophila Antenna By Exposure To A Plant Odorant, Shane R Baldwin, Pratyajit Mohapatra, Monica Nagalla, Rhea Sindvani, Desiree Amaya, Hope A Dickson, Karen Menuz Oct 2021

Identification And Characterization Of Cyps Induced In The Drosophila Antenna By Exposure To A Plant Odorant, Shane R Baldwin, Pratyajit Mohapatra, Monica Nagalla, Rhea Sindvani, Desiree Amaya, Hope A Dickson, Karen Menuz

Department of Medicine Faculty Papers

Degrading Enzymes (ODEs). However, their contribution to olfactory signaling in vivo is poorly understood. This is due in part to the challenge of identifying which of the dozens of antennal-expressed CYPs might inactivate a given odorant. Here, we tested a high-throughput deorphanization strategy in Drosophila to identify CYPs that are transcriptionally induced by exposure to odorants. We discovered three CYPs selectively upregulated by geranyl acetate using transcriptional profiling. Although these CYPs are broadly expressed in the antenna in non-neuronal cells, electrophysiological recordings from CYP mutants did not reveal any changes in olfactory neuron responses to this odorant. Neurons were desensitized …


Global Gene Expression Analysis Of Systemic Sclerosis Myofibroblasts Demonstrates A Marked Increase In The Expression Of Multiple Nbpf Genes, Giuseppina Abignano, Heidi Hermes, Sonsoles Piera-Velazquez, Sankar Addya, Francesco Del Galdo, Sergio A. Jimenez Oct 2021

Global Gene Expression Analysis Of Systemic Sclerosis Myofibroblasts Demonstrates A Marked Increase In The Expression Of Multiple Nbpf Genes, Giuseppina Abignano, Heidi Hermes, Sonsoles Piera-Velazquez, Sankar Addya, Francesco Del Galdo, Sergio A. Jimenez

Kimmel Cancer Center Faculty Papers

Myofibroblasts are the key effector cells responsible for the exaggerated tissue fibrosis in Systemic Sclerosis (SSc). Despite their importance to SSc pathogenesis, the specific transcriptome of SSc myofibroblasts has not been described. The purpose of this study was to identify transcriptome differences between SSc myofibroblasts and non-myofibroblastic cells. Alpha smooth muscle actin (α-SMA) expressing myofibroblasts and α-SMA negative cells were isolated employing laser capture microdissection from dermal cell cultures from four patients with diffuse SSc of recent onset. Total mRNA was extracted from both cell populations, amplified and analyzed employing microarrays. Results for specific genes were validated by Western blots …


A Selective Antibiotic For Lyme Disease, Nadja Leimer, Xiaoqian Wu, Yu Imai, Madeleine Morrissette, Norman Pitt, Quentin Favre-Godal, Akira Iinishi, Samta Jain, Mariaelena Caboni, Inga V Leus, Vincent Bonifay, Samantha Niles, Rachel Bargabos, Meghan Ghiglieri, Rachel Corsetti, Megan Krumpoch, Gabriel Fox, Sangkeun Son, Dorota Klepacki, Yury S Polikanov, Cecily A Freliech, Julie E Mccarthy, Diane G Edmondson, Steven J Norris, Anthony D'Onofrio, Linden T Hu, Helen I Zgurskaya, Kim Lewis Oct 2021

A Selective Antibiotic For Lyme Disease, Nadja Leimer, Xiaoqian Wu, Yu Imai, Madeleine Morrissette, Norman Pitt, Quentin Favre-Godal, Akira Iinishi, Samta Jain, Mariaelena Caboni, Inga V Leus, Vincent Bonifay, Samantha Niles, Rachel Bargabos, Meghan Ghiglieri, Rachel Corsetti, Megan Krumpoch, Gabriel Fox, Sangkeun Son, Dorota Klepacki, Yury S Polikanov, Cecily A Freliech, Julie E Mccarthy, Diane G Edmondson, Steven J Norris, Anthony D'Onofrio, Linden T Hu, Helen I Zgurskaya, Kim Lewis

Faculty, Staff and Student Publications

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining …


Norovirus Protease Structure And Antivirals Development, Boyang Zhao, Liya Hu, Yongcheng Song, Ketki Patil, Sasirekha Ramani, Robert L Atmar, Mary K Estes, B V Venkataram Prasad Oct 2021

Norovirus Protease Structure And Antivirals Development, Boyang Zhao, Liya Hu, Yongcheng Song, Ketki Patil, Sasirekha Ramani, Robert L Atmar, Mary K Estes, B V Venkataram Prasad

Faculty, Staff and Students Publications

Human norovirus (HuNoV) infection is a global health and economic burden. Currently, there are no licensed HuNoV vaccines or antiviral drugs available. The protease encoded by the HuNoV genome plays a critical role in virus replication by cleaving the polyprotein and is an excellent target for developing small-molecule inhibitors. The current strategy for developing HuNoV protease inhibitors is by targeting the enzyme's active site and designing inhibitors that bind to the substrate-binding pockets located near the active site. However, subtle differential conformational flexibility in response to the different substrates in the polyprotein and structural differences in the active site and …


Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis Oct 2021

Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis

Pharmacy Practice and Science Faculty Publications

Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznań, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period …


Biophysical Evaluation Of Rhesus Macaque Fc Gamma Receptors Reveals Similar Igg Fc Glycoform Preferences To Human Receptors, Andrew R. Crowley, Nana Yaw Osei-Owusu, Gillian Dekkers, Wenda Gao, Manfred Wuhrer, Diogo M. Magnani, Keith A. Reimann, Seth H. Pincus, Gestur Vidarsson, Margaret E. Ackerman Oct 2021

Biophysical Evaluation Of Rhesus Macaque Fc Gamma Receptors Reveals Similar Igg Fc Glycoform Preferences To Human Receptors, Andrew R. Crowley, Nana Yaw Osei-Owusu, Gillian Dekkers, Wenda Gao, Manfred Wuhrer, Diogo M. Magnani, Keith A. Reimann, Seth H. Pincus, Gestur Vidarsson, Margaret E. Ackerman

School of Medicine Faculty Publications

Rhesus macaques are a common non-human primate model used in the evaluation of human monoclonal antibodies, molecules whose effector functions depend on a conserved N-linked glycan in the Fc region. This carbohydrate is a target of glycoengineering efforts aimed at altering antibody effector function by modulating the affinity of Fcγ receptors. For example, a reduction in the overall core fucose content is one such strategy that can increase antibody-mediated cellular cytotoxicity by increasing Fc-FcγRIIIa affinity. While the position of the Fc glycan is conserved in macaques, differences in the frequency of glycoforms and the use of an alternate monosaccharide in …


Congenital Epulis: A Two-Case Report, Monica Ivanov, Bianca Stroe, Valeriu Ardeleanu, Razvan Hainarosie, Vlad Denis Constantin, Anca Silvia Dumitriu, Stana Paunica, Anna Kadar Oct 2021

Congenital Epulis: A Two-Case Report, Monica Ivanov, Bianca Stroe, Valeriu Ardeleanu, Razvan Hainarosie, Vlad Denis Constantin, Anca Silvia Dumitriu, Stana Paunica, Anna Kadar

Journal of Mind and Medical Sciences

Congenital epulis is a rare benign tumor of the newborn that could be detected in the prenatal period. Females are more often affected than males and the premaxillary region is usually the predilection site for this oral mass. Excision is the treatment of choice and no recurrences have been reported so far.

We present our experience with two cases of congenital epulis, detected in the second trimester of gestation and treated shortly after birth with no further complications. Histopathology should differentiate between congenital epulis and other congenital oral tumors even if its clinical appearance is usually enough to make a …


Collagen-Based Biomaterials With Possible Therapeutic Effects, Ramona Mihaela Nedelcuţă, Gigi Călin, Mihai Cristian Nedelcuţă, Vlad Dumitru Baleanu, Dragos Virgil Davitoiu, Bogdan Socea, Bogdan-Petre Stănoiu Oct 2021

Collagen-Based Biomaterials With Possible Therapeutic Effects, Ramona Mihaela Nedelcuţă, Gigi Călin, Mihai Cristian Nedelcuţă, Vlad Dumitru Baleanu, Dragos Virgil Davitoiu, Bogdan Socea, Bogdan-Petre Stănoiu

Journal of Mind and Medical Sciences

Epidermolysis bullosa (EB) is a rare, serious genetic disease, incurable through the current means. Apart from this initial definition, there was later some ease in the definition of the disease, including the manifestations of toxic epidermal necrolysis and Stevens Johnson syndrome in this entity. In medical practice, there are cases that do not overlap with the description in the literature, thus the treatment must be adapted and personalized to the particularities. We present the case of a female new-born, with "de novo" mutation for the early-onset antenatal epidermolysis and our personalized therapeutic management, based on collagen from bovine corneas by …


Periaortic Venous Necklace And Renal Right Double Arteries; Case Report, Petru Bordei, Constantin Andrei Rusali, Constantin Ionescu, Dragos Serban, Valeriu Ardeleanu Oct 2021

Periaortic Venous Necklace And Renal Right Double Arteries; Case Report, Petru Bordei, Constantin Andrei Rusali, Constantin Ionescu, Dragos Serban, Valeriu Ardeleanu

Journal of Mind and Medical Sciences

The case was found on an organic sample consisting of the two kidneys with the renal pedicles and the corresponding segments of the abdominal aorta and inferior vena cava. From the inferior face of the left renal vein, on the lower side of the aorta, a venous branch with an upward path of 8.02 mm was detached, passing on the anterior face of the aorta, passing before its right side, in order to end on the left side of the inferior vena cava, 13.9 mm above the end of the left renal vein in the inferior vena cava, this branch …


Analysis Of Potentially Toxic Contaminants In Milk Powder, Magdalena Mititelu, Lucian Hîncu, Emma Adriana Ozon, Daniela Luiza Baconi, Ioana Paunica, Oana Denisa Bălălău Oct 2021

Analysis Of Potentially Toxic Contaminants In Milk Powder, Magdalena Mititelu, Lucian Hîncu, Emma Adriana Ozon, Daniela Luiza Baconi, Ioana Paunica, Oana Denisa Bălălău

Journal of Mind and Medical Sciences

The aim of this study was to identify potentially toxic contaminants in milk powder. Powdered milk contains a range of toxic and non-toxic substances that are present in a wide variety, also having very different origins. A number of seven milk powder samples from different producers sold on the Romanian market were analyzed, the samples that were collected from the original packaging: P1, P 2, P3, P4, P5, P6 and P7. The concentration of the following elements was analyzed using the X-ray (XRF) fluorescence method: potassium (K), chlorine (Cl), calcium (Ca), phosphorus (P) and aluminum (Al). The vast majority of …


Intestinal Dysbiosis – A New Treatment Target In The Prevention Of Colorectal Cancer, Florinela-Andrada Dumitru, Sergiu Ioan Micu, Roxana Emanuela Popoiag, Marilena Musat, Andreea Daniela Caloian, Valentin Calu, Vlad Denis Constantin, Daniela Gabriela Balan, Cornelia Nitipir, Florin Enache Oct 2021

Intestinal Dysbiosis – A New Treatment Target In The Prevention Of Colorectal Cancer, Florinela-Andrada Dumitru, Sergiu Ioan Micu, Roxana Emanuela Popoiag, Marilena Musat, Andreea Daniela Caloian, Valentin Calu, Vlad Denis Constantin, Daniela Gabriela Balan, Cornelia Nitipir, Florin Enache

Journal of Mind and Medical Sciences

The gastrointestinal microbiome contains at least 100 trillion microorganisms (bacteria, viruses, fungi), whose distribution varies from the mouth to the rectum spatially and temporally throughout one's lifetime. The microbiome benefits from advancing research due to its major role in human health. Studies indicate that its functions are immunity, metabolic processes and mucosal barrier. The disturbances of these functions, dysbiosis, influence physiology, lead to diabetes, inflammatory bowel disease, obesity and colon tumorigenesis. The third most common form of cancer, colorectal cancer, is the result of many factors and genes, and although the link between dysbiosis and this type of cancer is …


How Opportune Is Multigene Testing In Metastatic Colorectal Cancer? A Review, Cristina Orlov-Slavu, Andreea Parosanu, Mihaela Olaru, Dragos Serban, Ioana Paunica, Cornelia Nitipir Oct 2021

How Opportune Is Multigene Testing In Metastatic Colorectal Cancer? A Review, Cristina Orlov-Slavu, Andreea Parosanu, Mihaela Olaru, Dragos Serban, Ioana Paunica, Cornelia Nitipir

Journal of Mind and Medical Sciences

Personalized treatment in oncology is the most innovative method of care. The best method to establish personalized treatment is by genetic characterization of the malignant cell.

Theoretically, the more detailed the characterization, the more effective the choice of treatment becomes. Currently, there are fast and relatively low-cost options that allow such genetic characterization. However, test results sometimes do not detect targetable alterations and, even if they do detect, the use of the treatment-alteration combination does not always generate a satisfactory oncological response.

The present paper aims to answer two questions. First, how targetable can the most common gene alterations in …


Therapeutic Efficacy Of Mesenchymal Stem Cells For Cardiovascular Diseases, Dragana Radoje Miloradovic, Dragica Radoje Pavlovic, Miodrag Bozidar Stojkovic, Sanja Bratislav Bojic, Vladislav Bogdan Volarevic, Marina Milosav Gazdic Jankovic, Biljana Tomislav Ljujic Oct 2021

Therapeutic Efficacy Of Mesenchymal Stem Cells For Cardiovascular Diseases, Dragana Radoje Miloradovic, Dragica Radoje Pavlovic, Miodrag Bozidar Stojkovic, Sanja Bratislav Bojic, Vladislav Bogdan Volarevic, Marina Milosav Gazdic Jankovic, Biljana Tomislav Ljujic

Journal of Mind and Medical Sciences

Despite the improvements in pharmacological and surgical treatments, cardiovascular diseases (CVDs) are the number one cause of death worldwide. During the last two decades, the search for new therapies has been revolutionized with the growing knowledge of stem cell biology. Due to their huge differentiation capacity and paracrine effects, mesenchymal stem cells (MSCs) are a promising tool for the treatment of CVDs. The encouraging outcomes of preclinical studies using MSCs as a treatment for diseased myocardium have set the scene for worldwide clinical trials. In this review, we overview either complete or ongoing clinical trials using MSCs for the therapy …


Epc-Exs Improve Neuronal Survival And Oxidative Stress Through Different Uptaking Pathways In Diabetic Hypoxia Condition, Manasi Suchit Halurkar, Jinju Wang, Shuzhen Chen, Ji Chen Bihl Oct 2021

Epc-Exs Improve Neuronal Survival And Oxidative Stress Through Different Uptaking Pathways In Diabetic Hypoxia Condition, Manasi Suchit Halurkar, Jinju Wang, Shuzhen Chen, Ji Chen Bihl

Pharmacology and Toxicology Faculty Publications

Background: Hyperglycemia contributes to cardiovascular complications in patients with type 2 diabetes. We confirmed that high glucose (HG) induces endothelial dysfunction and cerebral ischemic injury is enlarged in diabetic mice. Stem cell-released exosomes have been shown to protect the brain from ischemic stroke. We have previously shown that endothelial progenitor cells (EPCs)-released exosomes (EPC-EXs) can protect endothial cells from hypoxia/reoxygenation (H/R) and HG-induced injury. Here, we aim to investigate the effects of EPC-EXs on astrocytes under H/R and HG-induced injury and whether miR-126 enriched EPC-EXs (EPC-EXsmiR126) have enhanced efficacy. Methods: EPC-EX uptake and co-localization were measured by fluorescent microscopy using …


Cell-Based Therapies For Retinal Diseases: A Review Of Clinical Trials And Direct To Consumer "Cell Therapy" Clinics, John Hinkle, Raziyeh Mahmoudzadeh, Ajay E. Kuriyan Oct 2021

Cell-Based Therapies For Retinal Diseases: A Review Of Clinical Trials And Direct To Consumer "Cell Therapy" Clinics, John Hinkle, Raziyeh Mahmoudzadeh, Ajay E. Kuriyan

Wills Eye Hospital Papers

Background: The retinal pigment epithelium (RPE) is implicated in the pathophysiology of many retinal degenerative diseases. This cell layer is also an ideal target for cell-based therapies. Several early phase clinical trials evaluating cell therapy approaches for diseases involving the RPE, such as age-related macular degeneration and Stargardt's macular dystrophy have been published. However, there have also been numerous reports of complications from unproven "cell therapy" treatments marketed by "cell therapy" clinics. This review aims to outline the particular approaches in the different published clinical trials for cell-based therapies for retinal diseases. Additionally, the controversies surrounding experimental treatments offered outside …


Intouch October 11, 2021, New York Medical College Oct 2021

Enhancing Mask Activity In Dopaminergic Neurons Extends Lifespan In Flies, Xiaolin Tian Oct 2021

Enhancing Mask Activity In Dopaminergic Neurons Extends Lifespan In Flies, Xiaolin Tian

School of Medicine Faculty Publications

Dopaminergic neurons (DANs) are essential modulators for brain functions involving memory formation, reward processing, and decision-making. Here I demonstrate a novel and important function of the DANs in regulating aging and longevity. Overexpressing the putative scaffolding protein Mask in two small groups of DANs in flies can significantly extend the lifespan in flies and sustain adult locomotor and fecundity at old ages. This Mask-induced beneficial effect requires dopaminergic transmission but cannot be recapitulated by elevating dopamine production alone in the DANs. Independent activation of Gαs in the same two groups of DANs via the drug-inducible DREADD system also extends fly …


Cellular Origins Of Egfr-Driven Lung Cancer Cells Determine Sensitivity To Therapy, Fan Chen, Jinpeng Liu, Robert M. Flight, Kassandra J. Naughton, Alexsandr Lukyanchuk, Abigail R Edgin, Xiulong Song, Haikuo Zhang, Kwok-Kin Wong, Hunter N. B. Moseley, Chi Wang, Christine F. Brainson Oct 2021

Cellular Origins Of Egfr-Driven Lung Cancer Cells Determine Sensitivity To Therapy, Fan Chen, Jinpeng Liu, Robert M. Flight, Kassandra J. Naughton, Alexsandr Lukyanchuk, Abigail R Edgin, Xiulong Song, Haikuo Zhang, Kwok-Kin Wong, Hunter N. B. Moseley, Chi Wang, Christine F. Brainson

Toxicology and Cancer Biology Faculty Publications

Targeting the epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) is one of the major precision medicine treatment options for lung adenocarcinoma. Due to common development of drug resistance to first- and second-generation TKIs, third-generation inhibitors, including osimertinib and rociletinib, have been developed. A model of EGFR-driven lung cancer and a method to develop tumors of distinct epigenetic states through 3D organotypic cultures are described here. It is discovered that activation of the EGFR T790M/L858R mutation in lung epithelial cells can drive lung cancers with alveolar or bronchiolar features, which can originate from alveolar type 2 (AT2) cells …


Free-Floating Immunostaining Of Mouse Brains, Longlong Tu, Nan Zhang, Kristine M Conde, Jonathan C Bean, Chunmei Wang, Yong Xu Oct 2021

Free-Floating Immunostaining Of Mouse Brains, Longlong Tu, Nan Zhang, Kristine M Conde, Jonathan C Bean, Chunmei Wang, Yong Xu

Children’s Nutrition Research Center Staff Publications

Immunohistochemical staining of mouse brains is a routine technique commonly used in neuroscience to investigate central mechanisms underlying the regulation of energy metabolism and other neurobiological processes. However, the quality, reliability, and reproducibility of brain histology results may vary among laboratories. For each staining experiment, it is necessary to optimize the key procedures based on differences in species, tissues, targeted proteins, and the working conditions of the reagents. This paper demonstrates a reliable workflow in detail, including intra-aortic perfusion, brain sectioning, free-floating immunostaining, tissue mounting, and imaging, which can be followed easily by researchers in this field.

Also discussed are …


The Novel Orfv Protein Orfv113 Activates Lpa-P38 Signaling, Sushil Khatiwad, Gustavo Delho, Sabal Chaulagai, Daniel L. Rock Oct 2021

The Novel Orfv Protein Orfv113 Activates Lpa-P38 Signaling, Sushil Khatiwad, Gustavo Delho, Sabal Chaulagai, Daniel L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA1). Consistent with its interaction with LPA1, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113. Infection of cells with virus lacking ORFV113 (OVIA82Δ113) significantly decreased p38 phosphorylation and viral plaque size. …


Neutrophil Dynamics Affect Mycobacterium Tuberculosis Granuloma Outcomes And Dissemination, Caitlin Hult, Joshua T. Mattila, Hannah P. Gideon, Jennifer J. Linderman, Denise E. Kischner Oct 2021

Neutrophil Dynamics Affect Mycobacterium Tuberculosis Granuloma Outcomes And Dissemination, Caitlin Hult, Joshua T. Mattila, Hannah P. Gideon, Jennifer J. Linderman, Denise E. Kischner

Math Faculty Publications

Neutrophil infiltration into tuberculous granulomas is often associated with higher bacteria loads and severe disease but the basis for this relationship is not well understood. To better elucidate the connection between neutrophils and pathology in primate systems, we paired data from experimental studies with our next generation computational model GranSim to identify neutrophil-related factors, including neutrophil recruitment, lifespan, and intracellular bacteria numbers, that drive granuloma-level outcomes. We predict mechanisms underlying spatial organization of neutrophils within granulomas and identify how neutrophils contribute to granuloma dissemination. We also performed virtual deletion and depletion of neutrophils within granulomas and found that neutrophils play …


Serotonin 5-Ht2a Receptor Activity Mediates Adipocyte Differentiation Through Control Of Adipogenic Gene Expression, Bangning Yu, Diana M. Battaglia, Timothy P. Foster, Charles D. Nichols Oct 2021

Serotonin 5-Ht2a Receptor Activity Mediates Adipocyte Differentiation Through Control Of Adipogenic Gene Expression, Bangning Yu, Diana M. Battaglia, Timothy P. Foster, Charles D. Nichols

School of Medicine Faculty Publications

Serotonin 5-HT2 receptors are expressed in many tissues and play important roles in biological processes. Although the 5-HT2A receptor is primarily known for its role in central nervous system, it is also expressed in peripheral tissues. We have found that 5-HT2A receptor antagonists inhibit human subcutaneous primary adipocyte differentiation. We also show that siRNA knockdown of the 5-HT2A receptor blocks differentiation. Using gene expression analysis in combination with receptor antagonists we found that activity of 5-HT2A receptors is necessary very early in the differentiation process to mediate expression of adipogenic genes, including peroxisome proliferator-activated receptor gamma (ppar-γ), adipocyte protein 2 …


Phds/Cpt1b/Vdac1 Axis Regulates Long-Chain Fatty Acid Oxidation In Cardiomyocytes, Aude Angelini, Pradip K Saha, Antrix Jain, Sung Yun Jung, Randall L Mynatt, Xinchun Pi, Liang Xie Oct 2021

Phds/Cpt1b/Vdac1 Axis Regulates Long-Chain Fatty Acid Oxidation In Cardiomyocytes, Aude Angelini, Pradip K Saha, Antrix Jain, Sung Yun Jung, Randall L Mynatt, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

Cardiac metabolism is a high-oxygen-consuming process, showing a preference for long-chain fatty acid (LCFA) as the fuel source under physiological conditions. However, a metabolic switch (favoring glucose instead of LCFA) is commonly reported in ischemic or late-stage failing hearts. The mechanism regulating this metabolic switch remains poorly understood. Here, we report that loss of PHD2/3, the cellular oxygen sensors, blocks LCFA mitochondria uptake and β-oxidation in cardiomyocytes. In high-fat-fed mice, PHD2/3 deficiency improves glucose metabolism but exacerbates the cardiac defects. Mechanistically, we find that PHD2/3 bind to CPT1B, a key enzyme of mitochondrial LCFA uptake, promoting CPT1B-P295 hydroxylation. Further, we …


Expanding The Horizon Of Research Into The Pathogenesis Of The White Matter Diseases Proceedings Of The 2021 Annual Workshop Of The Albert Research Institute For White Matter And Cognition, Shawn N. Whitehead, Askiel Bruno, Jeffrey M. Burns, S. Thomas Carmichael, Anna Csiszar, Jodi D. Edwards, Fanny Elahi, Giuseppe Faraco, Douglas B. Goulding, Deborah R. Gustafson, Vladimir Hachinski, Gary A. Rosenberg, Farzaneh A. Sorond, Andy Y. Shih, Kai Hei Tse, Zoltan Ungvari, Donna M. Wilcock, Kristen L. Zuloaga, Frank C. Barone Oct 2021

Expanding The Horizon Of Research Into The Pathogenesis Of The White Matter Diseases Proceedings Of The 2021 Annual Workshop Of The Albert Research Institute For White Matter And Cognition, Shawn N. Whitehead, Askiel Bruno, Jeffrey M. Burns, S. Thomas Carmichael, Anna Csiszar, Jodi D. Edwards, Fanny Elahi, Giuseppe Faraco, Douglas B. Goulding, Deborah R. Gustafson, Vladimir Hachinski, Gary A. Rosenberg, Farzaneh A. Sorond, Andy Y. Shih, Kai Hei Tse, Zoltan Ungvari, Donna M. Wilcock, Kristen L. Zuloaga, Frank C. Barone

Sanders-Brown Center on Aging Faculty Publications

White matter pathologies are critically involved in the etiology of vascular cognitive impairment–dementia (VCID), Alzheimer’s disease (AD), and Alzheimer’s disease and related diseases (ADRD), and therefore need to be considered a treatable target (Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793–4, [1]. To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of “The Albert Research Institute for White Matter and Cognition” in 2020. The first annual “Institute” meeting …


A Guide For Authors And Readers Of The American Society For Nutrition Journals On The Proper Use Of P Values And Strategies That Promote Transparency And Improve Research Reproducibility, John D Sorkin, Mark Manary, Paul A M Smeets, Amanda J Macfarlane, Arne Astrup, Ronald L Prigeon, Beth B Hogans, Jack Odle, Teresa A Davis, Katherine L Tucker, Christopher P Duggan, Deirdre K Tobias Oct 2021

A Guide For Authors And Readers Of The American Society For Nutrition Journals On The Proper Use Of P Values And Strategies That Promote Transparency And Improve Research Reproducibility, John D Sorkin, Mark Manary, Paul A M Smeets, Amanda J Macfarlane, Arne Astrup, Ronald L Prigeon, Beth B Hogans, Jack Odle, Teresa A Davis, Katherine L Tucker, Christopher P Duggan, Deirdre K Tobias

Children’s Nutrition Research Center Staff Publications

Two questions regarding the scientific literature have become grist for public discussion: 1) what place should P values have in reporting the results of studies? 2) How should the perceived difficulty in replicating the results reported in published studies be addressed? We consider these questions to be 2 sides of the same coin; failing to address them can lead to an incomplete or incorrect message being sent to the reader. If P values (which are derived from the estimate of the effect size and a measure of the precision of the estimate of the effect) are used improperly, for example …