Membrane Protein Nanoparticles: The Shape Of Things To Come, 2018 University of Massachusetts Medical School
Membrane Protein Nanoparticles: The Shape Of Things To Come, Kailene S. Simon, Naomi L. Pollock, Sarah C. Lee
Open Access Articles
The use of styrene-maleic acid (SMA) for the purification of a wide range of membrane proteins (MPs) from both prokaryotic and eukaryotic sources has begun to make an impact in the field of MP biology. This method is growing in popularity as a means to purify and thoroughly investigate the structure and function of MPs and biological membranes. The amphiphilic SMA copolymer can effectively extract MPs directly from a native lipid bilayer to form discs approximately 10 nm in diameter. The resulting lipid particles, or styrene-maleic acid lipid particles (SMALPs), contain SMA, protein and membrane lipid. MPs purified in SMALPs ...
Transcriptional Regulation Of Lipophorin Receptors Supports Neuronal Adaptation To Chronic Elevations Of Activity, 2018 National Institute of Neurological Disorders and Stroke
Transcriptional Regulation Of Lipophorin Receptors Supports Neuronal Adaptation To Chronic Elevations Of Activity, Jun Yin, Mary Gibbs, Caixia Long, Justin Rosenthal, Hyong S. Kim, Anna Kim, Chengyu Sheng, Peng Ding, Uzma Javed, Quan Yuan
Open Access Articles
Activity-dependent modifications strongly influence neural development. However, molecular programs underlying their context and circuit-specific effects are not well understood. To study global transcriptional changes associated with chronic elevation of synaptic activity, we performed cell-type-specific transcriptome profiling of Drosophila ventral lateral neurons (LNvs) in the developing visual circuit and identified activity-modified transcripts that are enriched in neuron morphogenesis, circadian regulation, and lipid metabolism and trafficking. Using bioinformatics and genetic analyses, we validated activity-induced isoform-specific upregulation of Drosophila lipophorin receptors LpR1 and LpR2, the homologs of mammalian low-density lipoprotein receptor (LDLR) family proteins. Furthermore, our morphological and physiological studies uncovered critical functions ...
Fxr And Tgr5 Agonists Ameliorate Liver Injury, Steatosis, And Inflammation After Binge Or Prolonged Alcohol Feeding In Mice, 2018 University of Massachusetts Medical School
Fxr And Tgr5 Agonists Ameliorate Liver Injury, Steatosis, And Inflammation After Binge Or Prolonged Alcohol Feeding In Mice, Arvin Iracheta-Vellve, Charles D. Calenda, Jan Petrasek, Aditya Ambade, Karen Kodys, Luciano Adorini, Gyongyi Szabo
Open Access Articles
Bile acids (BAs) activate various dedicated receptors, including the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). The FXR agonist obeticholic acid (OCA) is licensed for the treatment of primary biliary cholangitis and has shown promising results in NASH patients, whereas TGR5 agonists target inflammation and metabolism. We hypothesized that FXR and/or TGR5 agonists may be therapeutic in early alcoholic liver disease (ALD) in mice, in which hepatic inflammation plays a major role. OCA, INT-777, and INT-767 are BA derivatives with selective agonist properties for FXR, TGR5, or both, respectively. These compounds were tested in ...
Substantial Increase In Compliance With Saturated Fatty Acid Intake Recommendations After One Year Following The American Heart Association Diet, 2018 University of Massachusetts Medical School
Substantial Increase In Compliance With Saturated Fatty Acid Intake Recommendations After One Year Following The American Heart Association Diet, Miaomiao Zhao, David E. Chiriboga, Barbara C. Olendzki, Bin Xie, Yawen Li, Lisa Jo Mcgonigal, Ana Maldonado-Contreras, Yunsheng Ma
Open Access Articles
The American Heart Association (AHA) dietary guidelines recommend 30(-)35% of energy intake (%E) be from total fat, < 7%E from saturated fatty acids (SFA), and < 1%E from trans fatty acid (TFA). This study evaluates the effect of AHA dietary counselling on fat intake. Between 2009 and 2014, 119 obese adults with metabolic syndrome (MetS), (71% women, average 52.5 years of age, and 34.9 kg/m(2) of body mass index), received individual and group counselling on the AHA diet, over a one-year study period. Each participant attended 2 individual sessions (months 1 and 12) and 12 group sessions, at one-month intervals. At baseline and one-year, we collected three random 24-h diet recalls (two weekdays and one weekend day). Fat intake patterns over time were analyzed using paired-t test and linear mixed-effect models. There was significant variation on SFA and TFA intake per meal, being highest at dinner, in restaurants, and on weekends. Over the one-year study period, daily intake of total fat, SFA, and TFA decreased by 27%, 37% and 41%, respectively (p-value < 0.01, each). Correspondingly, the percentage of participants complying with AHA's recommendations, increased from 25.2% to 40.2% for total fat (p-value = 0.02); from 2.5% to 20.7% for SFA (p-value < 0.01); and from 45.4% to 62% for TFA (p-value = 0.02). Additionally, SFA intake for all meal types at home decreased significantly (p-value < 0.05, each). AHA dietary counselling significantly increased the compliance with AHA dietary guidelines, with an eightfold increase in compliance in SFA intake. Nonetheless, ~80% of our participants still exceeded the recommended SFA intake. Substantial efforts are needed to encourage low-SFA and low-TFA food preparation at home, with strong public health policies to decrease SFA and TFA in restaurants and prepared foods.
Health Information Discrepancies Between Internet Media And Scientific Papers Reporting On Omega-3 Supplement Research: Comparative Analysis, 2018 National University of Natural Medicine
Health Information Discrepancies Between Internet Media And Scientific Papers Reporting On Omega-3 Supplement Research: Comparative Analysis, Daryl Nault, Ariel Beccia, Haruka Ito, Sarah Kashdan, Angela Senders
Open Access Articles
BACKGROUND: Dietary supplements are the most used complementary and alternative health modality in the United States, and omega-3 supplements continue to be the most popularly used nonvitamin or nonmineral supplements by adults. Users of dietary supplements report that they obtain health guidance from internet media resources, but there is question as to whether or not these resources provide the necessary evidence to guide health decisions. Current evidence suggests that there is a mistranslation occurring somewhere between researchers and the media.
OBJECTIVE: The aim of this study was to conduct a comparative cross-sectional analysis to identify areas of discordance created when ...
Intestinal P-Glycoprotein Exports Endocannabinoids To Prevent Inflammation And Maintain Homeostasis, 2018 University of Massachusetts Medical School
Intestinal P-Glycoprotein Exports Endocannabinoids To Prevent Inflammation And Maintain Homeostasis, Rose L. Szabady, Christopher Louissaint, Anneke Lubben, Bailu Xie, Shaun Reeksting, Christine Tuohy, Zachary Demma, Sage Foley, Christina S. Faherty, Alejandro Llanos-Chea, Andrew J. Olive, Randall J. Mrsny, Beth A. Mccormick
Open Access Articles
Neutrophil influx into the intestinal lumen is a critical response to infectious agents, but is also associated with severe intestinal damage observed in idiopathic inflammatory bowel disease. The chemoattractant hepoxilin A3, an eicosanoid secreted from intestinal epithelial cells by the apically restricted efflux pump multidrug resistance protein 2 (MRP2), mediates this neutrophil influx. Information about a possible counterbalance pathway that could signal the lack of or resolution of an apical inflammatory signal, however, has yet to be described. We now report a system with such hallmarks. Specifically, we identify endocannabinoids as the first known endogenous substrates of the apically restricted ...
Mass Spectrometry Image Creator (Msic): Ion Mobility / Mass Spectrometry Imaging Workflow In Python, Stephen Creger, Julia Laskin, Daniela Mesa Sanchez
The Summer Undergraduate Research Fellowship (SURF) Symposium
Mass spectrometry (MS) is a powerful characterization technique that enables identification of compounds in complex mixtures. Acquiring mass spectra in a spatially-resolved manner (i.e. over a grid), allows the data to be used to generate images that show the spatial distribution and relative intensities of every compound in a sample. These images can be used to monitor and identify biomarkers, explore the metabolism of compounds within tissues, and much more. However, the limitations of mass spectrometry can result in ambiguous compound identifications. Another characterization tool, ion mobility spectrometry (IM) can be integrated into existing MS routines to address this ...
Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, 2018 University of Massachusetts Medical School
Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, Adilson L. Guilherme, David J. Pedersen, Felipe Henriques, Alexander H. Bedard, Elizabeth Henchey, Mark Kelly, Kamal Rahmouni, Donald A. Morgan, Michael P. Czech
University of Massachusetts Medical School Faculty Publications
White adipose tissue (WAT) secretes factors to communicate with other metabolic organs to maintain energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) causes expansion of sympathetic neurons within white adipose tissue (WAT) and the appearance of beige adipocytes. Here we report evidence that white adipocyte DNL activity is also coupled to neuronal regulation and thermogenesis in brown adipose tissue (BAT). Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. In ...
Children With Type 1 Diabetes Who Experienced A Honeymoon Phase Had Significantly Lower Ldl Cholesterol 5 Years After Diagnosis, 2018 University of Massachusetts Medical School
Children With Type 1 Diabetes Who Experienced A Honeymoon Phase Had Significantly Lower Ldl Cholesterol 5 Years After Diagnosis, Benjamin U. Nwosu, Bo Zhang, Sanaa S. Ayyoub, Stephanie Choi, Tony R. Villalobos-Ortiz, Laura C. Alonso, Bruce A. Barton
Pediatric Publications and Presentations
IMPORTANCE: Landmark studies showed that partial clinical remission in new-onset type 1 diabetes is associated with reduced prevalence of long-term complications, but early clinical indicators of this favorable outcome are poorly characterized.
AIM: To determine if there were any differences in lipid parameters, especially LDL-cholesterol, between remitters and non-remitters 4 to 5 years after the diagnosis of type 1 diabetes after controlling for hemoglobin A1c, body mass index, and pubertal status.
SUBJECTS AND METHODS: A longitudinal retrospective cohort study of 123 subjects of mean age 11.9 +/- 2.9 years, [male 11.7 +/- 2.9 years, (n = 55); female 12 ...
Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, 2018 University of Massachusetts Medical School
Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti
GSBS Dissertations and Theses
Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data.
We established that cholesterol-conjugated siRNAs passively associate ...
Serum Lipidomics Of Bovine Paratuberculosis: Disruption Of Choline-Containing Glycerophospholipids And Sphingolipids, 2018 Lincoln Memorial University
Serum Lipidomics Of Bovine Paratuberculosis: Disruption Of Choline-Containing Glycerophospholipids And Sphingolipids, Paul L. Wood, Erdal Erol, Glen F. Hoffsis, Margaret Steinman, Jeroen Debuck
Veterinary Science Faculty Publications
Objectives: Bovine paratuberculosis is a devastating infection with Mycobacterium avium subspecies paratuberculosis that ultimately results in death from malnutrition. While the infection is characterized by a long (2–4 years) subclinical phase with immune activation, ultimately host defense mechanisms fail and the bacteria spread from the small intestine to other organs. Since both the gastrointestinal tract and liver are essential for the biosynthesis of structural glycerophospholipids, we investigated the circulating levels of these lipids in field infections and experimentally infected cattle.
Methods: Serum lipidomics of control and M. avium subspecies paratuberculosis–infected cattle were performed utilizing high-resolution mass spectrometry.
Effects Of Mitochondrial Nadp+-Dependent Isocitrate Dehydrogenase Deficiency On Fructose-Induced Obesity In Mice, 2018 University of Arkansas, Fayetteville
Effects Of Mitochondrial Nadp+-Dependent Isocitrate Dehydrogenase Deficiency On Fructose-Induced Obesity In Mice, Allison Michelle Montalbano, Kaleigh Elizabeth Beane
Human Nutrition and Hospitality Innovation Undergraduate Honors Theses
Obesity prevalence in the United States continues to increase and is associated with health consequences such as type 2 diabetes, hypertension, atherosclerosis, and hyperlipidemia. Among many contributing factors to obesity, fructose may be one of the major reasons as it disrupts the antioxidant system thereby resulting in an accumulation of reactive oxidative species and leading to obese conditions. The enzyme, isocitrate dehydrogenase 2 (IDH2), reduces nicotinamide adenine dinucleotide phosphate from the TCA Cycle, hence might be implicated with not only energy metabolism but also cellular redox homeostasis. Therefore, the hypothesis was that IDH2 deficiency in mice would exacerbate hepatic lipid ...
Cbx4 Sumoylates Prdm16 To Regulate Adipose Tissue Thermogenesis, 2018 University of Massachusetts Medical School
Cbx4 Sumoylates Prdm16 To Regulate Adipose Tissue Thermogenesis, Qingbo Chen, Lei Huang, Dongning Pan, Lihua (Julie) Zhu, Yong-Xu Wang
Open Access Articles
Transcriptional co-activator Prdm16 controls brown fat development and white fat browning, but how this thermogenic function is modulated post-translationally is poorly understood. Here, we report that Cbx4, a Polycomb group protein, is a SUMO E3 ligase for Prdm16 and that Cbx4-mediated sumoylation of Prdm16 is required for thermogenic gene expression. Cbx4 expression is enriched in brown fat and is induced in adipose tissue by acute cold exposure. Sumoylation of Prdm16 at lysine 917 by Cbx4 blocks its ubiquitination-mediated degradation, thereby augmenting its stability and thermogenic function. Moreover, this sumoylation event primes Prdm16 to be further stabilized by methyltransferase Ehmt1. Heterozygous ...
Cerebral Organoids Derived From Sandhoff Disease-Induced Pluripotent Stem Cells Exhibit Impaired Neurodifferentiation, 2018 National Institutes of Health
Cerebral Organoids Derived From Sandhoff Disease-Induced Pluripotent Stem Cells Exhibit Impaired Neurodifferentiation, Maria L. Allende, Emily K. Cook, Bridget C. Larman, Adrienne Nugent, Jacqueline M. Brady, Diane Golebiowski, Miguel Sena-Esteves, Cynthia J. Tifft, Richard L. Proia
Open Access Articles
Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of beta-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease ...
An Exome-Wide Sequencing Study Of Lipid Response To High-Fat Meal And Fenofibrate In Caucasians From The Goldn Cohort, 2018 The University of Texas Health Science Center at Houston
An Exome-Wide Sequencing Study Of Lipid Response To High-Fat Meal And Fenofibrate In Caucasians From The Goldn Cohort, Xin Geng, Marguerite R. Irvin, Bertha Hidalgo, Stella Aslibekyan, Vinodh Srinivasasainagendra, Ping An, Alexis C. Frazier-Wood, Hemant K. Tiwari, Tushar Dave, Kathleen Ryan, Jose M. Ordovas, Robert J. Straka, Mary F. Feitosa, Paul N. Hopkins, Ingrid Borecki, Michael A. Province, Braxton D. Mitchell, Donna K. Arnett, Degui Zhi
Epidemiology Faculty Publications
Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial AUI response to FFB ...
Dynamic Cycling Of T-Snare Acylation Regulates Platelet Exocytosis, 2018 University of Kentucky
Dynamic Cycling Of T-Snare Acylation Regulates Platelet Exocytosis, Jinchao Zhang, Yunjie Huang, Jing Chen, Haining Zhu, Sidney W. Whiteheart
Molecular and Cellular Biochemistry Faculty Publications
Platelets regulate vascular integrity by secreting a host of molecules that promote hemostasis and its sequelae. Given the importance of platelet exocytosis, it is critical to understand how it is controlled. The t-SNAREs, SNAP-23 and syntaxin-11, lack classical transmembrane domains (TMDs), yet both are associated with platelet membranes and redistributed into cholesterol-dependent lipid rafts when platelets are activated. Using metabolic labeling and hydroxylamine (HA)/HCl treatment, we showed that both contain thioester-linked acyl groups. Mass spectrometry mapping further showed that syntaxin-11 was modified on cysteine 275, 279, 280, 282, 283, and 285, and SNAP-23 was modified on cysteine 79, 80 ...
Novel Function Of Ceramide For Regulation Of Mitochondrial Atp Release In Astrocytes, 2018 Augusta University
Novel Function Of Ceramide For Regulation Of Mitochondrial Atp Release In Astrocytes, Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B. Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D. Spassieva, Erhard Bieberich
Physiology Faculty Publications
We reported that amyloid β peptide (Aβ42) activated neutral SMase 2 (nSMase2), thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Aβ42 induced mitochondrial fragmentation in wild-type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria. Using immunocytochemistry and super-resolution microscopy, we detected ceramide-enriched and mitochondria-associated membranes (CEMAMs) that were codistributed with microtubules. Interaction of ceramide with tubulin was confirmed by cross-linking to N-[9-(3-pent-4-ynyl-3-H-diazirine-3-yl ...
The Forensic Characterization Of Bacterial And Fungal Organisms In Traditional Chinese Medicine, 2018 Virginia Commonwealth University
The Forensic Characterization Of Bacterial And Fungal Organisms In Traditional Chinese Medicine, Julia Grzymkowski, Christopher J. Ehrhardt, Justin L. Poklis, Michelle R. Peace
Undergraduate Research Posters
There has been an increase in use of Traditional Chinese Medicine (TCM) in the United States because they are less expensive and believed to be more effective with less adverse effects in comparison to traditional pharmaceutics. Therefore, sales have increased in the US, despite articles and case studies demonstrating the dangers, such as injury and death, related to TCM, stemming from improper labelling, toxic contaminants, and, in some cases, the presence of pathogenic bacteria. The aim of this study was to perform a survival experiment to demonstrate the importance of proper herbal brewing technique and to conduct a molecular and ...
The Role Of Ceramide In Neutrophil Elastase Induced Inflammation In The Lungs, 2018 Virginia Commonwealth University
The Role Of Ceramide In Neutrophil Elastase Induced Inflammation In The Lungs, Sophia Karandashova
Theses and Dissertations
Alterations to sphingolipid metabolism are associated with increased pulmonary inflammation, but the impact of inflammatory mediators, such as neutrophil elastase (NE), on airway sphingolipid homeostasis remains unknown. NE is a protease associated CF lung disease progression, and can be found in up to micromolar concentrations in patient airways. While sphingolipids have been investigated in the context of CF, the focus has been on loss of cystic fibrosis transmembrane conductance regulator (CFTR) function. Here, we present a novel observation: oropharyngeal aspiration of NE increases airway ceramides in mice. Using a previously characterized mouse model of NE-induced inflammation, we demonstrate that NE ...
Naturally Occurring 3rs, 7r, 11r-Phytanic Acid Suppresses In Vitro T-Cell Production Of Interferon-Gamma, 2018 Hebrew Theological College
Naturally Occurring 3rs, 7r, 11r-Phytanic Acid Suppresses In Vitro T-Cell Production Of Interferon-Gamma, Tomonori Nakanishi, Ibuki Motoba, Mayuko Anraku, Ryoji Suzuki, Yuto Yamaguchi, Laurie Erickson, Satoshi Kawahara
Hebrew Theological College Publications and Research
Background: Among the eight stereoisomers of phytanic acid (PA), the 3RS, 7R, 11R-isomer is naturally occurring and is present in foods and the human body. PA is considered to have possible health benefits in the immune system. However, it remains undetermined whether these effects are elicited by the 3RS, 7R, 11R-PA isomer, because previous studies used a commercially available PA whose isomer configuration is unknown. In this study, we synthesized a preparation of 3RS, 7R, 11R-PA, and investigated its in vitro immunomodulatory effects, especially the T-cell production of interferon (IFN)-γ, which is associated with various autoimmune diseases. This study ...