Biochemistry, Biophysics, and Structural Biology Commons^™

Hydroxamic Acid-Based Histone Deacetylase (Hdac) Inhibitors Can Mediate Neuroprotection Independent Of Hdac Inhibition, Sama Sleiman, Yan-Ling Zhang, Jennifer Gale, Manuela Basso, Giovanni Coppola, John T. Pinto, Rajiv Ratan

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibition improves function and extends survival in rodent models of a host of neurological conditions, including stroke, and neurodegenerative diseases. Our understanding, however, of the contribution of individual HDAC isoforms to neuronal death is limited. In this study, we used selective chemical probes to assess the individual roles of the Class I HDAC isoforms in protecting Mus musculus primary cortical neurons from oxidative death. We demonstrated that the selective HDAC8 inhibitor PCI-34051 is a potent neuroprotective agent; and by taking advantage of both pharmacological and genetic tools, we established that HDAC8 is not critically involved in PCI-34051's …

Hdac8 And Stat3 Repress Bmf Gene Activity In Colon Cancer Cells, Y Kang, Hui Nian, P Rajendran, W Dashwood, John T. Pinto, E Ho, R Dashwood

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein …

Aerosol Emissions From Prescribed Fires In The United States: A Synthesis Of Laboratory And Aircraft Measurements, A. A. May, G. R. Mcmeeking, T. Lee, J. W. Taylor, J. S. Craven, I. R. Burling, A. P. Sullivan, Sheryl Kashi Akagi, J. L. Collett Jr., M. Flynn, H. Coe, S. P. Urbanski, J. H. Seinfeld, Robert Yokelson, S. M. Kreidenweis

Chemistry and Biochemistry Faculty Publications

Aerosol emissions from prescribed fires can affect air quality on regional scales. Accurate representation of these emissions in models requires information regarding the amount and composition of the emitted species.Wemeasured a suite of submicron particulatematter species in young plumes emitted from prescribed fires (chaparral and montane ecosystems in California; coastal plain ecosystem in South Carolina) and from open burning of over 15 individual plant species in the laboratory. We report emission ratios and emission factors for refractory black carbon (rBC) and submicron nonrefractory aerosol and compare field and laboratory measurements to assess the representativeness of our laboratory-measured emissions. Laboratory measurements …

Egfr Phosphorylates And Inhibits Lung Tumor Suppressor Gprc5a In Lung Cancer, Xiaofeng Lin, Shuangshuang Zhong, Xiaofeng Ye, Yueling Liao, Feng Yao, Xiaohua Yang, Beibei Sun, Jie Zhang, Qi Li, Yong Gao, Yifan Wang, Jingyi Liu, Baohui Han, Y. Eugene Chin, Binhua P. Zhou, Jiong Deng

Molecular and Cellular Biochemistry Faculty Publications

BACKGROUND: GPRC5A is a retinoic acid inducible gene that is preferentially expressed in lung tissue. Gprc5a- knockout mice develop spontaneous lung cancer, indicating Gprc5a is a lung tumor suppressor gene. GPRC5A expression is frequently suppressed in majority of non-small cell lung cancers (NSCLCs), however, elevated GPRC5A is still observed in a small portion of NSCLC cell lines and tumors, suggesting that the tumor suppressive function of GPRC5A is inhibited in these tumors by an unknown mechanism.

METHODS: In this study, we examined EGF receptor (EGFR)-mediated interaction and tyrosine phosphorylation of GPRC5A by immunoprecipitation (IP)-Westernblot. Tyrosine phosphorylation of GPRC5A by EGFR …

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.

Dietary Carbohydrates Influence The Structure And Function Of The Intestinal Alpha-Glucosidases, Mohammad Chegeni

Open Access Dissertations

As the primary products of starch digestion by pancreatic α-amylase, maltooligosaccharides (including maltose) are the main substrates for the α-glucosidases at the intestinal brush border. Here, maltose was shown to induce the formation of a higher molecular weight (HMW) sucrase-isomaltase (SI) species in Caco-2 cells that sorts more quickly to the enterocyte surface to act as a digestive enzyme. As this finding suggested a maltose sensing ability of small intestinal enterocytes, molecular mechanisms associated with the maturation and trafficking of HMW SI were further investigated. A pulse-chase experiment using [ ³⁵S]-methionine revealed a higher rate of early trafficking and …

New Experimental And Theoretical Tools For Studying Protein Systems With Elements Of Structural Disorder, Tairan Yuwen

Open Access Dissertations

Disordered proteins are one class of proteins which do not possess well-folded three-dimensional structures as their native conformations. Many eukaryotic proteins have been found to be fully disordered or contain certain disordered regions. Disordered proteins usually display several characteristic properties, such as increased motional freedom and the conformational heterogeneity caused by that. The elements of structural disorder are commonly involved in many important biological functions and are implicated in many diseases. Therefore, the study of disordered proteins has become one of the most important research topics in recent years. This thesis presents results from three different research projects; the common …

Airborne Characterization Of Smoke Marker Ratios From Prescribed Burning, A. P. Sullivan, A. A. May, T. Lee, G. R. Mcmeeking, S. M. Kreidenweis, S. K. Akagi, Robert Yokelson, S. P. Urbanski, J. L. Collett Jr.

Chemistry and Biochemistry Faculty Publications

A Particle-Into-Liquid Sampler – Total Organic Carbon (PILS-TOC) and fraction collector system was flown aboard a Twin Otter aircraft sampling prescribed burning emissions in South Carolina in November 2011 to obtain smoke marker measurements. The fraction collector provided 2 min time-integrated offline samples for carbohydrate (i.e., smoke markers levoglucosan, mannosan, and galactosan) analysis by high-performance anion-exchange chromatography with pulsed amperometric detection. Each fire location appeared to have a unique 1levoglucosan /1water-soluble organic carbon (WSOC) ratio (RF01/RF02/RF03/RF05 = 0.163± 0.007 μg C μg−1 C, RF08 = 0.115 ± 0.011 μg C μg−1 C, RF09A = 0.072 ± 0.028 μgC μg−1 C, …

Effects Of Altered Expression Of The Sumo Conjugating Enzyme, Ubc9 On Mitosis, Meiosis And Conjugation In Tetrahymena Thermophila, Qianyi Yang

Open Access Dissertations

SUMOylation is a critical posttranslational modification in eukaryotic species. Ubc9p is the E2-conjugating enzyme for SUMOylation and consequently it influences multiple cellular pathways. Nuclear proteins are common targets of SUMOylation and regulate nuclear events such as transcription, DNA repair and mitosis. The segregation of the Tetrahymena thermophila genome into two different nuclear compartments provides an unusual context for the analysis of SUMOylation. Each cell contains a transcriptionally silent, diploid germ line micronucleus (MIC) that divides by mitosis and a polyploid transcriptionally active somatic macronucleus (MAC) that divides by an amitotic mechanism. With the long-term goal to exploit these opportunities we …

Overexpression Of Patatin-Related Phospholipase Aiiiβ Altered The Content And Composition Of Sphingolipids In Arabidopsis, Maoyin Li, Jennifer E. Markham, Xuemin Wang

Department of Biochemistry: Faculty Publications

In plants, fatty acids are primarily synthesized in plastids and then transported to the endoplasmic reticulum (ER) for synthesis of most of the complex membrane lipids, including glycerolipids and sphingolipids. The first step of sphingolipid synthesis, which uses a fatty acid and a serine as substrates, is critical for sphingolipid homeostasis; its disruption leads to an altered plant growth. Phospholipase As have been implicated in the trafficking of fatty acids from plastids to the ER. Previously, we found that overexpression of a patatin-related phospholipase, pPLAIIIβ, resulted in a smaller plant size and altered anisotropic cell expansion. Here, we determined the …

New Strategies To Reveal Protein Candidates In Protein-Protein Interactome Study, Meng-Chieh Chen

Open Access Theses

Comprehensive protein-protein interaction network analysis can help reveal protein functions in a system-wide manner. A reliable knowledgebase of interaction networks is not only important for selecting the candidates for drug therapies, but also for evaluating the disease risk. In current interaction databases, 322579 interactions comprised of 56460 proteins have been reported (statistical analysis from APID: Agile Protein Interaction DataAnalyzer; http://bioinfow.dep.usal.es/apid/index.htm). The huge datasets are contributed mainly by yeast -two -hybrid (Y2H) screening and affinity-purification followed by mass spectrometry (AP-MS). High false positive rates and failing to cover certain interaction categories are the limitations of these two methods. Here, we developed …

Hierarchical Cell Fluid Extracellular Matrix Interaction In Cell Microenvironment, Soham Ghosh

Open Access Dissertations

Hierarchical structural interactions between components of cell microenvironment, the extracellular matrix (ECM), cytoplasm, nucleus and fluid, are important phenomena that decide cell level physiological process and tissue engineering applications. One of those tissue engineering modalities is freezing of biomaterials, important in a wide variety of biomedical applications including cryopreservation and cryosurgeries. In order to design these applications, freezing-induced changes of the cells and tissues and corresponding biophysical mechanisms need to be well understood. Although the effects of freezing on cells in suspension have been extensively studied, the intracellular mechanics of cells embedded in the extracellular matrix (ECM) during freezing are …

Intranuclear Strain Measured By Iterative Warping In Cells Under Mechanical And Osmotic Stress, Jonathan T Henderson

Open Access Dissertations

The nucleus is a membrane bound organelle and regulation center for gene expression in the cell. Mechanical forces transfer to the nucleus directly and indirectly through specific cellular cytoskeletal structures and pathways. There is increasing evidence that the transferred forces to the nucleus orchestrate gene expression activity. Methods to characterize nuclear mechanics typically study isolated cells or cells embedded in 3D gel matrices. Often report only aspect ratio and volume changes, measures that oversimplify the inherent complexity of internal strain patterns. This presents technical challenges to simultaneously observe small scale nuclear mechanics and gene expression levels inside the nuclei of …

Towards A Paradigm Shift In The Modeling Of Soil Organic Carbon Decomposition For Earth System Models, Yujie He

Open Access Dissertations

Soils are the largest terrestrial carbon pools and contain approximately 2200 Pg of carbon. Thus, the dynamics of soil carbon plays an important role in the global carbon cycle and climate system. Earth System Models are used to project future interactions between terrestrial ecosystem carbon dynamics and climate. However, these models often predict a wide range of soil carbon responses and their formulations have lagged behind recent soil science advances, omitting key biogeochemical mechanisms. In contrast, recent mechanistically-based biogeochemical models that explicitly account for microbial biomass pools and enzyme kinetics that catalyze soil carbon decomposition produce notably different results and …

Quantum Mechanics In Complex Systems, Ross Douglas Hoehn

Open Access Dissertations

This document should be considered in its separation; there are three distinct topics contained within and three distinct chapters within the body of works. In a similar fashion, this abstract should be considered in three parts. Firstly, we explored the existence of multiply-charged atomic ions by having developed a new set of dimensional scaling equations as well as a series of relativistic augmentations to the standard dimensional scaling procedure and to the self-consistent field calculations. Secondly, we propose a novel method of predicting drug efficacy in hopes to facilitate the discovery of new small molecule therapeutics by modeling the agonist-protein …

The Modification Of Brucine Derivatives As Chiral Ligands And Its Application In The Asymmetric Synthesis, Jian-Yuan Li

Open Access Dissertations

The modification of brucine derivatives as chiral ligands and the use of a multifaceted chiral ligand, brucine diol, under different reaction conditions to produce various optical isomers is described. In Chapter 1, the generation of a number of brucine derivatives is described. Taking the advantage of brucine-diol's excellent molecular recognition capability for multiple organic functional groups, we focused on the synthetic modifications of brucine-diol and the synthesis of brucine N-oxide. We also produced various brucine derivatives with different functional moieties in good yields and selectivities. ^ In Chapter 2, we described the investigation of brucine N-oxide catalyzed Morita-Baylis-Hillman …

Theory For Diffusional Encounters In Heterogeneous Environments And Multivalent Electrolyte Screening Of Charged Interface, Ran Li

Open Access Dissertations

We develop a theory for encounter rates in a three-dimensional system of connected compartments. The model of connected compartments exhibits the length-scale dependent diffusion that is observed in many heterogeneous environments, such as porous catalysts and biological environments. We discovered a dimensionless number that is the dominant scaling variable and obtained, for the first time, an analytical expression for the encounter rate. The new theory generalizes the classic Smoluchowski diffusion limit to the case of heterogeneous environments. The new theory is tested using Brownian dynamics simulations.^ We also experimentally investigated the behavior of multivalent electrolyte near a charged solid-liquid interface. …

Structure-Functionality Relationship Of Collagen Scaffolds For Tissue Engineering, Seungman Park

Open Access Dissertations

Tissue engineering is a promising technology that enables scientists to create artificial organs or replace damaged tissues using animal cells and other components. For successful tissue regeneration, many factors should be taken into account, however, three components are most crucial: cell, scaffold, and soluble factor(s). In order to check the functionality after regeneration of desired tissues, various approaches have been attempted, depending on the physical, biological, and chemical properties of the tissues. Recently, the importance of the extracellular matrix (ECM) microstructure is being considered to be important in this regard. The ECM is closely associated with various functional properties of …

Understanding Preferred Leg Stiffness And Layered Control Strategies For Locomotion, Zhuohua H. Shen

Open Access Dissertations

Despite advancement in the field of robotics, current legged robots still cannot achieve the kind of locomotion stability animals and humans have. In order to develop legged robots with greater stability, we need to better understand general locomotion dynamics and control principles. Here we demonstrate that a mathematical modeling approach could greatly enable the discovery and understanding of general locomotion principles. ^ It is found that animal leg stiffness when scaled by its weight and leg length falls in a narrow region between 7 and 27. Rarely in biology does such a universal preference exist. It is not known completely …

Host Cell Death In Legionella Pneumophila Pathogenesis And Immunity, Wenhan Zhu

Open Access Dissertations

Legionella pneumophila is an intracellular pathogen that causes a severe, atypical pneumonia termed Legionnaires' disease. Upon entering the host cell, L. pneumophila resides in a membrane-bound vacuole, in which the bacterium evades lysosomal fusion and replicates. The establishment of the vacuole requires the Dot/Icm (Defect in organelle trafficking/ intracellular multiplication) transport system, which translocates a large number of substrates into host cells to re-orchestrate various cellular processes, such as intracellular trafficking, protein synthesis and host cell death pathways. Therefore, a key step in understanding the biology of Legionella is to dissect the mechanisms of action of the Dot/Icm substrates. By …