Hepatic Dysfunction Caused By Consumption Of A High-Fat Diet, 2017 Massachusetts Institute of Technology
Hepatic Dysfunction Caused By Consumption Of A High-Fat Diet, Anthony R. Soltis, Norman J. Kennedy, Xiaofeng Xin, Feng Zhou, Scott B. Ficarro, Yoon Sing Yap, Bryan J. Matthews, Douglas A. Lauffenburger, Forest M. White, Jarrod A. Marto, Roger J. Davis, Ernest Fraenkel
University of Massachusetts Medical School Faculty Publications
Obesity is a major human health crisis that promotes insulin resistance and, ultimately, type 2 diabetes. The molecular mechanisms that mediate this response occur across many highly complex biological regulatory levels that are incompletely understood. Here, we present a comprehensive molecular systems biology study of hepatic responses to high-fat feeding in mice. We interrogated diet-induced epigenomic, transcriptomic, proteomic, and metabolomic alterations using high-throughput omic methods and used a network modeling approach to integrate these diverse molecular signals. Our model indicated that disruption of hepatic architecture and enhanced hepatocyte apoptosis are among the numerous biological processes that contribute to early liver ...
Structural Determination Of The Broadly Reactive Anti-Ighv1-69 Anti-Idiotypic Antibody G6 And Its Idiotope, 2017 Harvard Medical School
Structural Determination Of The Broadly Reactive Anti-Ighv1-69 Anti-Idiotypic Antibody G6 And Its Idiotope, Yuval Avnir, Kristina L. Prachanronarong, Shurong Hou, Brendan J. Hilbert, Markus-Frederik Bohn, Timothy F. Kowalik, Robert W. Finberg, Jennifer P. Wang, Nese Kurt Yilmaz, Celia A. Schiffer, Wayne A. Marasco
Schiffer Lab Publications
The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-69 heavy chain germline gene 51p1 alleles that have been implicated in these Ab responses and disease processes. Here, we determine the co-crystal structure of humanized G6 (hG6.3) in complex with anti-influenza hemagglutinin stem-directed broadly neutralizing Ab D80. The core of the hG6.3 idiotope is a continuous string of CDR-H2 ...
The Alpha6beta4 Integrin Promotes Resistance To Ferroptosis, 2017 University of Massachusetts Medical School
The Alpha6beta4 Integrin Promotes Resistance To Ferroptosis, Caitlin W. Brown, John J. Amante, Hira Lal Goel, Arthur M. Mercurio
UMass Metabolic Network Publications
Increases in lipid peroxidation can cause ferroptosis, a form of cell death triggered by inhibition of glutathione peroxidase 4 (GPX4), which catalyzes the reduction of lipid peroxides and is a target of ferroptosis inducers, such as erastin. The alpha6beta4 integrin protects adherent epithelial and carcinoma cells from ferroptosis induced by erastin. In addition, extracellular matrix (ECM) detachment is a physiologic trigger of ferroptosis, which is evaded by alpha6beta4. The mechanism that enables alpha6beta4 to evade ferroptosis involves its ability to protect changes in membrane lipids that are proferroptotic. Specifically, alpha6beta4-mediated activation of Src and STAT3 suppresses expression of ACSL4, an ...
Characterization Of Notch1 And Pi3k-Pten-Akt/Mtor Pathway Interaction In Head And Neck Squamous Cell Carcinoma, 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Characterization Of Notch1 And Pi3k-Pten-Akt/Mtor Pathway Interaction In Head And Neck Squamous Cell Carcinoma, Kyriante' Henry
UT GSBS Dissertations and Theses (Open Access)
Head and neck squamous cell carcinoma (HNSCC) affects various mucosal sites of the upper aerodigestive tract, including the nasal and oral cavities, the nasopharynx, and the oropharynx. More than five hundred thousand new cases of HNSCC occurred in 2011 alone, with 50,000 reported cases in the United States. This trend made HNSCC the seventh most common non-skin cancer worldwide (Ferlay et al., 2015). Although significant epidemiological and pathological advancements have been made, survival rates have not improved much over the last 40 years, leaving a mortality rate that remains at approximately 50%. An unbiased drug screen demonstrated that HNSCC ...
Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, 2017 University of Arkansas, Fayetteville
Developing Algorithms For Quantifying The Super Resolution Microscopic Data: Applications To The Quantification Of Protein-Reorganization In Bacteria Responding To Treatment By Silver Ions, Sai Divya Challapalli
Theses and Dissertations
Histone-like nucleoid structuring proteins (HNS) play significant roles in shaping the chromosomal DNA, regulation of transcriptional networks in microbes, as well as bacterial responses to environmental changes such as temperature fluctuations. In this work, the intracellular organization of HNS proteins in E. coli bacteria was investigated utilizing super-resolution fluorescence microscopy, which surpasses conventional microscopy by 10–20 fold in spatial resolution. More importantly, the changes of the spatial distribution of HNS proteins in E. coli, by addition of silver ions into the growth medium were explored. To quantify the spatial distribution of HNS in bacteria and its changes, an automatic ...
Temporal Regulation Of Chromatin During Myoblast Differentiation, 2017 Kyushu University, Japan
Temporal Regulation Of Chromatin During Myoblast Differentiation, Akihito Harada, Yasuyuki Ohkawa, Anthony N. Imbalzano
UMass Metabolic Network Publications
The commitment to and execution of differentiation programmes involves a significant change in gene expression in the precursor cell to facilitate development of the mature cell type. In addition to being regulated by lineage-determining and auxiliary transcription factors that drive these changes, the structural status of the chromatin has a considerable impact on the transcriptional competence of differentiation-specific genes, which is clearly demonstrated by the large number of cofactors and the extraordinary complex mechanisms by which these genes become activated. The terminal differentiation of myoblasts to myotubes and mature skeletal muscle is an excellent system to illustrate these points. The ...
Determination Of The Effects Of Different Maillard Reaction Products On The Taxonomic Composition Of The Gut Microbiota, 2017 University of Arkansas, Fayetteville
Determination Of The Effects Of Different Maillard Reaction Products On The Taxonomic Composition Of The Gut Microbiota, Nesreen Hamdan Aljahdali
Theses and Dissertations
The Maillard Reaction (MR) is a non-enzymatic chemical reaction which results in linkage between the amino group of amino acids and the carbonyl group of reduced sugars. This reaction generates Maillard reaction products (MRPs) which are not present naturally in foods, and are responsible for a range of colors, odors, flavors, and other sensory properties. Conflicting reports of MRPs impacts on human health are probably due to the fact that bioconversion of these digestible molecules by the gut microbiota has been marginally taken into account. This study aimed to determine the effects of different MRPs on rodent’s gut microbiota ...
Piglet Gut Microbiota Responses To Exposure To Outdoor Simulated Environment And Formula Feeding, 2017 University of Arkansas, Fayetteville
Piglet Gut Microbiota Responses To Exposure To Outdoor Simulated Environment And Formula Feeding, Nguyen Vo
Theses and Dissertations
Several lines of evidence suggest that early-life gut microbiota composition is a crucial determinant of the susceptibility to diseases later in life. Understanding the evolution of early-life gut microbiota and critical factors that can modify this microbial community will espouse the prevention or reversion of health risk originating from dysbiosis of the gut microbiota in the early stage. In this research, we hypothesized that alterations in the environment (simulation of rural conditions by soil exposure) and feeding mode (breastmilk versus formula milk) will have significant impacts on the establishment of the gut microbiota in early life. At first, in literature ...
Role Of Incompatibility Group 1 (Inci1) Plasmid-Encoded Factors On Salmonella Enterica Antimicrobial Resistance And Virulence, 2017 University of Arkansas, Fayetteville
Role Of Incompatibility Group 1 (Inci1) Plasmid-Encoded Factors On Salmonella Enterica Antimicrobial Resistance And Virulence, Pravin Raghunath Kaldhone
Theses and Dissertations
Foodborne illnesses are a leading cause of infectious diseases in the world. Among enteric organisms Salmonella is a key pathogen. It’s high prevalence in poultry and other food-animal sources make it imperative to study. Salmonella has the ability to modify its genetic content with help of mobile genetic elements such as plasmids. Incompatibiltiy group 1 (IncI1) plasmids are commonly reported in Salmonella. This study evaluates role on IncI1 plasmids in antimicrobial resistance and virulence in Salmonella. Genetic determinants of resistance and virulence are noted among our IncI1-containing Salmonella isolates. These genetic elements are also transferable and reported to carry ...
Detection Of Survival And Proliferation Of Sulfate Reducers Under Simulated Martian Atmospheric And Soil Conditions, 2017 University of Arkansas, Fayetteville
Detection Of Survival And Proliferation Of Sulfate Reducers Under Simulated Martian Atmospheric And Soil Conditions, Sergio Mosquera Mora
Theses and Dissertations
Numerous studies have tried to determine the survivability and proliferation of microorganisms under simulated Martian conditions. Furthermore, most of them have been focused on the ability of these microbes to cope with high brines’ salt (NaCl) concentrations inherent of the Martian surface. However, there are not studies related to the ability of bacteria to survive on subsurface environments that have increasing concentrations of sulfate compounds. For this research, a group of microorganisms known as sulfate-reducing bacteria or simply sulfate reducers were chosen due to their ability to use sulfate compounds as terminal electron acceptors to produce metabolic energy, their tolerance ...
Tea Induction Of Cyp6a8 Promoter In Drosophila Melanogaster, 2017 University of Tennessee, Knoxville
Tea Induction Of Cyp6a8 Promoter In Drosophila Melanogaster, Fiona Retzer
University of Tennessee Honors Thesis Projects
No abstract provided.
Complete Sequencing And Comparative Analysis Of The Genomes Of The First Magnetotactic Gammaproteobacteria Isolated In Pure Culture: Strains Bw-2 And Ss-5, Corey Geurink
UNLV Theses, Dissertations, Professional Papers, and Capstones
The genomes of the first two discovered magnetotactic bacteria (MTB) belonging to the ammaproteobacteria, strains BW-2 and SS-51, were sequenced, sealed, annotated and compared to MTB of other phylogenetic groups. Cells of both strains are rod-shaped and biomineralize cuboctahedral and elongated octahedral crystals of magnetite, respectively, that are enveloped in a protein-embedded, lipid-bilayer membrane referred to as the magnetosome membrane or vesicle. The crystals and their associated membranes are known as magnetosomes. Magnetosome crystals consist of either magnetite (Fe3O4) or greigite (Fe3S4) and, because of their specific mineral compositions, crystal morphologies and sizes, the biomineralization processes involved in magnetosome formation ...
Type Ix Secretion System : Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru
Electronic Theses and Dissertations
Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the propensity ...
Robust Expression Of Tumor Suppressor Mirna's Let-7 And Mir-195 Detected In Plasma Of Saudi Female Breast Cancer Patients., 2017 George Washington University
Robust Expression Of Tumor Suppressor Mirna's Let-7 And Mir-195 Detected In Plasma Of Saudi Female Breast Cancer Patients., Amal Qattan, Haya Intabli, Wafa Alkhayal, Chafica Eltabache, Taher Tweigieri, Suad Bin Amer
Biochemistry and Molecular Medicine Faculty Publications
Female breast cancer is frequently diagnosed at a later stage and the leading cause of cancer deaths world-wide. Levels of cell-free circulating microRNAs (miRNAs) can potentially be used as biomarkers to measure disease progression in breast cancer patients in a non-invasive way and are therefore of high clinical value.
Using quantitative RT-PCR, circulating miRNAs were measured in blood samples collected from disease-free individuals (n = 34), triple-negative breast tumours (TNBC) (n = 36) and luminal tumours (n = 57). In addition to intergroup comparisons, plasma miRNA expression levels of all groups were analyzed against RNASeq data from cancerous breast tissue via ...
Validation Of A Hairy Roots System To Study Soybean-Soybean Aphid Interactions, 2017 Iowa State University
Validation Of A Hairy Roots System To Study Soybean-Soybean Aphid Interactions, Stephanie C. Morriss, Matthew E. Studham, Gregory L. Tylka, Gustavo C. Macintosh
The soybean aphid (Aphis glycines) is one of the main insect pests of soybean (Glycine max) worldwide. Genomics approaches have provided important data on transcriptome changes, both in the insect and in the plant, in response to the plant-aphid interaction. However, the difficulties to transform soybean and to rear soybean aphid on artificial media have hindered our ability to systematically test the function of genes identified by those analyses as mediators of plant resistance to the insect. An efficient approach to produce transgenic soybean material is the production of transformed hairy roots using Agrobacterium rhizogenes; however, soybean aphids colonize leaves ...
Role Of Heat Shock Transcription Factor 1 In Ovarian Cancer Epithelial-Mesenchymal Transition And Drug Sensitivity, 2017 University of South Florida
Role Of Heat Shock Transcription Factor 1 In Ovarian Cancer Epithelial-Mesenchymal Transition And Drug Sensitivity, Chase David Powell
Graduate Theses and Dissertations
The heat shock response (HSR) is a robust cellular reaction to mitigate protein damage from heat and other challenges to the proteome. This protective molecular program in humans is controlled by heat shock transcription factor 1 (HSF1). Activation of HSF1 leads to the induction of an array of cytoprotective genes, many of which code for chaperones. These chaperones, known as heat shock proteins (HSPs), are responsible for maintaining the functional integrity of the proteome. HSPs achieve this by promoting proper folding and assembly of nascent proteins, refolding denatured proteins, and processing for degradation proteins and aggregates which cannot be returned ...
Protein Loop Dynamics Are Complex And Depend On The Motions Of The Whole Protein, 2017 Iowa State University
Protein Loop Dynamics Are Complex And Depend On The Motions Of The Whole Protein, Michael T. Zimmermann, Robert L. Jernigan
We investigate the relationship between the motions of the same peptide loop segment incorporated within a protein structure and motions of free or end-constrained peptides. As a reference point we also compare against alanine chains having the same length as the loop. Both the analysis of atomic molecular dynamics trajectories and structure-based elastic network models, reveal no general dependence on loop length or on the number of solvent exposed residues. Rather, the whole structure affects the motions in complex ways that depend strongly and specifically on the tertiary structure of the whole protein. Both the Elastic Network Models and Molecular ...
Factors Correlating With Significant Differences Between X-Ray Structures Of Myoglobin, 2017 BioChemComp Inc
Factors Correlating With Significant Differences Between X-Ray Structures Of Myoglobin, Alexander A. Rashin, Marcin J. Domagalski, Michael T. Zimmermann, Wladek Minor, Maksymilian Chruszcz, Robert L. Jernigan
Validation of general ideas about the origins of conformational differences in proteins is critical in order to arrive at meaningful functional insights. Here, principal component analysis (PCA) and distance difference matrices are used to validate some such ideas about the conformational differences between 291 myoglobin structures from sperm whale, horse and pig. Almost all of the horse and pig structures form compact PCA clusters with only minor coordinate differences and outliers that are easily explained. The 222 whale structures form a few dense clusters with multiple outliers. A few whale outliers with a prominent distortion of the GH loop are ...
Protein Flexibility: Coordinate Uncertainties And Interpretation Of Structural Differences, Alexander A. Rashin, Abraham H. L. Rashin, Robert L. Jernigan
Valid interpretations of conformational movements in protein structures determined by X-ray crystallography require that the movement magnitudes exceed their uncertainty threshold. Here, it is shown that such thresholds can be obtained from the distance difference matrices (DDMs) of 1014 pairs of independently determined structures of bovine ribonuclease A and sperm whale myoglobin, with no explanations provided for reportedly minor coordinate differences. The smallest magnitudes of reportedly functional motions are just above these thresholds. Uncertainty thresholds can provide objective criteria that distinguish between true conformational changes and apparent `noise', showing that some previous interpretations of protein coordinate changes attributed to external ...
Jnk Promotes Epithelial Cell Anoikis By Transcriptional And Post-Translational Regulation Of Bh3-Only Proteins, 2017 University of Massachusetts Medical School
Jnk Promotes Epithelial Cell Anoikis By Transcriptional And Post-Translational Regulation Of Bh3-Only Proteins, Nomeda Girnius, Roger J. Davis
UMass Metabolic Network Publications
Developmental morphogenesis, tissue injury, and oncogenic transformation can cause the detachment of epithelial cells. These cells are eliminated by a specialized form of apoptosis (anoikis). While the processes that contribute to this form of cell death have been studied, the underlying mechanisms remain unclear. Here, we tested the role of the cJUN NH2-terminal kinase (JNK) signaling pathway using murine models with compound JNK deficiency in mammary and kidney epithelial cells. These studies demonstrated that JNK is required for efficient anoikis in vitro and in vivo. Moreover, JNK-promoted anoikis required pro-apoptotic members of the BCL2 family of proteins. We show that ...