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Articles 1 - 29 of 29
Full-Text Articles in Life Sciences
Glycocalyx Mechanotransduction Mechanisms Are Involved In Renal Cancer Metastasis, Heriberto Moran, Limary M. Cancel, Peigen Huang, Sylvie Roberge, Tuoye Xu, John M. Tarbell, Lance L. Munn
Glycocalyx Mechanotransduction Mechanisms Are Involved In Renal Cancer Metastasis, Heriberto Moran, Limary M. Cancel, Peigen Huang, Sylvie Roberge, Tuoye Xu, John M. Tarbell, Lance L. Munn
Publications and Research
Mammalian cells, including cancer cells, are covered by a surface layer containing cell bound proteoglycans, glycoproteins, associated glycosaminoglycans and bound proteins that is commonly referred to as the glycocalyx. Solid tumors also have a dynamic fluid microenvironment with elevated interstitial flow. In the present work we further investigate the hypothesis that interstitial flow is sensed by the tumor glycocalyx leading to activation of cell motility and metastasis. Using a highly metastatic renal carcinoma cell line (SN12L1) and its low metastatic counterpart (SN12C) we demonstrate in vitro that the small molecule Suberoylanilide Hydroxamic Acid (SAHA) inhibits the heparan sulfate synthesis enzyme …
High-Resolution Cryo-Electron Microscopy Structure Of Photosystem Ii From The Mesophilic Cyanobacterium, Synechocystis Sp. Pcc 6803, Christopher J. Gisriel, Jimin Wang, Jinchan Liu, David A. Flesher, Krystle M. Reiss, Hao-Li Huang, Ke R. Yang, William H. Armstrong, M. R. Gunner, Victor S. Batista, Richard J. Debus, Gary W. Brudvig
High-Resolution Cryo-Electron Microscopy Structure Of Photosystem Ii From The Mesophilic Cyanobacterium, Synechocystis Sp. Pcc 6803, Christopher J. Gisriel, Jimin Wang, Jinchan Liu, David A. Flesher, Krystle M. Reiss, Hao-Li Huang, Ke R. Yang, William H. Armstrong, M. R. Gunner, Victor S. Batista, Richard J. Debus, Gary W. Brudvig
Publications and Research
Photosystem II (PSII) enables global-scale, light-driven water oxidation. Genetic manipulation of PSII from the mesophilic cyanobacterium Synechocystis sp. PCC 6803 has provided insights into the mechanism of water oxidation; however, the lack of a highresolution structure of oxygen-evolving PSII from this organism has limited the interpretation of biophysical data to models based on structures of thermophilic cyanobacterial PSII. Here, we report the cryo-electron microscopy structure of PSII from Synechocystis sp. PCC 6803 at 1.93-Å resolution. A number of differences are observed relative to thermophilic PSII structures, including the following: the extrinsic subunit PsbQ is maintained, the C terminus of the …
Cryptococcus Neoformans Melanization Incorporates Multiple Catecholamines To Produce Polytypic Melanin, Rosanna P. Baker, Christine Chrissian, Ruth E. Stark, Arturo Casadevall
Cryptococcus Neoformans Melanization Incorporates Multiple Catecholamines To Produce Polytypic Melanin, Rosanna P. Baker, Christine Chrissian, Ruth E. Stark, Arturo Casadevall
Publications and Research
Melanin is a major virulence factor in pathogenic fungi that enhances the ability of fungal cells to resist immune clearance. Cryptococcus neoformans is an important human pathogenic fungus that synthesizes melanin from exogenous tissue catecholamine precursors during infection, but the type of melanin made in cryptococcal meningoencephalitis is unknown. We analyzed the efficacy of various catecholamines found in brain tissue in supporting melanization using animal brain tissue and synthetic catecholamine mixtures reflecting brain tissue proportions. Solid-state NMR spectra of the melanin pigment produced from such mixtures yielded more melanin than expected if only the preferred constituent dopamine had been incorporated, …
Structure Of A Monomeric Photosystem Ii Core Complex From A Cyanobacterium Acclimated To Far-Red Light Reveals The Functions Of Chlorophylls D And F, Christopher J. Gisriel, Gaozhong Shen, Ming-Yang Ho, Vasily Kurashov, David A. Flesher, Jimin Wang, William H. Armstrong, John H. Golbeck, Marilyn R. Gunner, David J. Vinyard, Richard J. Debus, Gary W. Brudvig, Donald A. Bryant
Structure Of A Monomeric Photosystem Ii Core Complex From A Cyanobacterium Acclimated To Far-Red Light Reveals The Functions Of Chlorophylls D And F, Christopher J. Gisriel, Gaozhong Shen, Ming-Yang Ho, Vasily Kurashov, David A. Flesher, Jimin Wang, William H. Armstrong, John H. Golbeck, Marilyn R. Gunner, David J. Vinyard, Richard J. Debus, Gary W. Brudvig, Donald A. Bryant
Publications and Research
Far-red light (FRL) photoacclimation in cyanobacteria provides a selective growth advantage for some terrestrial cyanobacteria by expanding the range of photosynthetically active radiation to include far-red/near-infrared light (700–800 nm). During this photoacclimation process, photosystem II (PSII), the water:plastoquinone photooxidoreductase involved in oxygenic photosynthesis, is modified. The resulting FRL-PSII is comprised of FRL-specific core subunits and binds chlorophyll (Chl) d and Chl f molecules in place of several of the Chl a molecules found when cells are grown in visible light. These new Chls effectively lower the energy canonically thought to define the “red limit” for light required to drive photochemical …
Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo
Cryo-Em Structure Of Mechanosensitive Channel Ynai Using Sma2000: Challenges And Opportunities, Claudio Catalano, Danya Ben-Hail, Weihua Qiu, Paul Blount, Amedee Des Georges, Youzhong Guo
Publications and Research
Mechanosensitive channels respond to mechanical forces exerted on the cell membrane and play vital roles in regulating the chemical equilibrium within cells and their environment. Highresolution structural information is required to understand the gating mechanisms of mechanosensitive channels. Protein-lipid interactions are essential for the structural and functional integrity of mechanosensitive channels, but detergents cannot maintain the crucial native lipid environment for purified mechanosensitive channels. Recently, detergent-free systems have emerged as alternatives for membrane protein structural biology. This report shows that while membrane-active polymer, SMA2000, could retain some native cell membrane lipids on the transmembrane domain of the mechanosensitive-like YnaI channel, …
A Conserved Structural Role For The Walker-A Lysine In P-Loop Containing Kinases, Fatlum Hajredini, Ranajeet Ghose
A Conserved Structural Role For The Walker-A Lysine In P-Loop Containing Kinases, Fatlum Hajredini, Ranajeet Ghose
Publications and Research
Bacterial tyrosine kinases (BY-kinases) and shikimate kinases (SKs) comprise two structurally divergent P-loop containing enzyme families that share similar catalytic site geometries, most notably with respect to their Walker-A, Walker-B, and DxD motifs. We had previously demonstrated that in BY-kinases, a specific interaction between the Walker-A and Walker-B motifs, driven by the conserved “catalytic” lysine housed on the former, leads to a conformation that is unable to efficiently coordinate Mg2+•ATP and is therefore incapable of chemistry. Here, using enhanced sampling molecular dynamics simulations, we demonstrate that structurally similar interactions between the Walker-A and Walker-B motifs, also mediated by …
Aurora Kinase A Inhibition Reverses The Warburg Effect And Elicits Unique Metabolic Vulnerabilities In Glioblastoma, Trang T. T. Nguyen, Enyuan Shang, Chang Shu, Sungsoo Kim, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Hee Won Yang, Hasan Orhan Akman, Catarina M. Quinzii, Guoan Zhang, Mike-Andrew Westhoff, Georg Karpel-Massler, Jeffrey N. Bruce, Peter Canoll, Markus D. Siegelin
Aurora Kinase A Inhibition Reverses The Warburg Effect And Elicits Unique Metabolic Vulnerabilities In Glioblastoma, Trang T. T. Nguyen, Enyuan Shang, Chang Shu, Sungsoo Kim, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Hee Won Yang, Hasan Orhan Akman, Catarina M. Quinzii, Guoan Zhang, Mike-Andrew Westhoff, Georg Karpel-Massler, Jeffrey N. Bruce, Peter Canoll, Markus D. Siegelin
Publications and Research
Aurora kinase A (AURKA) has emerged as a drug target for glioblastoma (GBM). However, resistance to therapy remains a critical issue. By integration of transcriptome, chromatin immunoprecipitation sequencing (CHIP-seq), Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq), proteomic and metabolite screening followed by carbon tracing and extracellular flux analyses we show that genetic and pharmacological AURKA inhibition elicits metabolic reprogramming mediated by inhibition of MYC targets and concomitant activation of Peroxisome Proliferator Activated Receptor Alpha (PPARA) signaling. While glycolysis is suppressed by AURKA inhibition, we note an increase in the oxygen consumption rate fueled by enhanced fatty acid oxidation (FAO), which was …
Decoding The Roles Of Astrocytes And Hedgehog Signaling In Medulloblastoma, Terence Teixeira Duarte, Silvia Aparecida Teixeira, Luis Gonzalez-Reyes, Rui Manuel Reis
Decoding The Roles Of Astrocytes And Hedgehog Signaling In Medulloblastoma, Terence Teixeira Duarte, Silvia Aparecida Teixeira, Luis Gonzalez-Reyes, Rui Manuel Reis
Publications and Research
The molecular evolution of medulloblastoma is more complex than previously imagined, as emerging evidence suggests that multiple interactions between the tumor cells and components of the tumor microenvironment (TME) are important for tumor promotion and progression. The identification of several molecular networks within the TME, which interact with tumoral cells, has provided new clues to understand the tumorigenic roles of many TME components as well as potential therapeutic targets. In this review, we discuss the most recent studies regarding the roles of astrocytes in supporting sonic hedgehog (SHH) subgroup medulloblastoma (MB) and provide an overview of MB progression through SHH …
Protein Motifs For Proton Transfers That Build The Transmembrane Proton Gradient, Divya Kaur, Umesh Khaniya, Yingying Zhang, M. R. Gunner
Protein Motifs For Proton Transfers That Build The Transmembrane Proton Gradient, Divya Kaur, Umesh Khaniya, Yingying Zhang, M. R. Gunner
Publications and Research
Biological membranes are barriers to polar molecules, so membrane embedded proteins control the transfers between cellular compartments. Protein controlled transport moves substrates and activates cellular signaling cascades. In addition, the electrochemical gradient across mitochondrial, bacterial and chloroplast membranes, is a key source of stored cellular energy. This is generated by electron, proton and ion transfers through proteins. The gradient is used to fuel ATP synthesis and to drive active transport. Here the mechanisms by which protons move into the buried active sites of Photosystem II (PSII), bacterial RCs (bRCs) and through the proton pumps, Bacteriorhodopsin (bR), Complex I and Cytochrome …
Lighting The Way: Recent Insights Into The Structure And Regulation Of Phototropin Blue Light Receptors, Jaynee E. Hart, Kevin H. Gardner
Lighting The Way: Recent Insights Into The Structure And Regulation Of Phototropin Blue Light Receptors, Jaynee E. Hart, Kevin H. Gardner
Publications and Research
The phototropins (phots) are light-activated kinases that are critical for plant physiology and the many diverse optogenetic tools that they have inspired. Phototropins combine two bluelight- sensing Light–Oxygen–Voltage (LOV) domains (LOV1 and LOV2) and a C-terminal serine/threonine kinase domain, using the LOV domains to control the catalytic activity of the kinase. While much is known about the structure and photochemistry of the light-perceiving LOV domains, particularly in how activation of the LOV2 domain triggers the unfolding of alpha helices that communicate the light signal to the kinase domain, many questions about phot structure and mechanism remain. Recent studies have made …
Unconventional Constituents And Shared Molecular Architecture Of The Melanized Cell Wall Of C. Neoformans And Spore Wall Of S. Cerevisiae, Christine Chrissian, Coney Pei-Chin Lin, Emma Camacho, Arturo Casadevall, Aaron M. Neiman, Ruth E. Stark
Unconventional Constituents And Shared Molecular Architecture Of The Melanized Cell Wall Of C. Neoformans And Spore Wall Of S. Cerevisiae, Christine Chrissian, Coney Pei-Chin Lin, Emma Camacho, Arturo Casadevall, Aaron M. Neiman, Ruth E. Stark
Publications and Research
The fungal cell wall serves as the interface between the cell and the environment. Fungal cell walls are composed largely of polysaccharides, primarily glucans and chitin, though in many fungi stress-resistant cell types elaborate additional cell wall structures. Here, we use solid-state nuclear magnetic resonance spectroscopy to compare the architecture of cell wall fractions isolated from Saccharomyces cerevisiae spores and Cryptococcus neoformans melanized cells. The specialized cell walls of these two divergent fungi are highly similar in composition. Both use chitosan, the deacetylated derivative of chitin, as a scaffold on which a polyaromatic polymer, dityrosine and melanin, respectively, is assembled. …
Two And Three-Dimensional Radiographic Imaging Of Contrast Agents In Heterogeneous Live Cell Media To Understand Contrast-Induced Toxicity, Fahaneda Hassan, Aldona Gjoni, Subhendra Sarkar
Two And Three-Dimensional Radiographic Imaging Of Contrast Agents In Heterogeneous Live Cell Media To Understand Contrast-Induced Toxicity, Fahaneda Hassan, Aldona Gjoni, Subhendra Sarkar
Publications and Research
Radiographic imaging was done using low and high energy radiography equipment. The test hypothesis that macromolecular aggregation changes sample noise in imaging samples for optical imaging methods. Inorganic complexes scatter radiation at the molecular level and may increase the sample noise locally. At high and low photon energies in various x-ray machines, sample and background noise were gathered and compared with those from mammography systems from mammography researchers. The samples with high macromolecular aggregates were prepared using various animal cell compositions and imaged under different conditions that produced different macromolecular dynamics within the samples and thus different image-based sample noise. …
Retrieving Functional Pathways Of Biomolecules From Single-Particle Snapshots, Ali Dashti, Ghoncheh Mashayekhi, Mrinal Shekhar, Danya Ben Hail, Salah Salah, Peter Schwander, Amedee Des Georges, Abhishek Singharoy, Joachim Frank, Abbas Ourmazd
Retrieving Functional Pathways Of Biomolecules From Single-Particle Snapshots, Ali Dashti, Ghoncheh Mashayekhi, Mrinal Shekhar, Danya Ben Hail, Salah Salah, Peter Schwander, Amedee Des Georges, Abhishek Singharoy, Joachim Frank, Abbas Ourmazd
Publications and Research
A primary reason for the intense interest in structural biology is the fact that knowledge of structure can elucidate macromolecular functions in living organisms. Sustained effort has resulted in an impressive arsenal of tools for determining the static structures. But under physiological conditions, macromolecules undergo continuous conformational changes, a subset of which are functionally important. Techniques for capturing the continuous conformational changes underlying function are essential for further progress. Here, we present chemically-detailed conformational movies of biological function, extracted data-analytically from experimental single-particle cryo-electron microscopy (cryo-EM) snapshots of ryanodine receptor type 1 (RyR1), a calcium-activated calcium channel engaged in the …
Metabolic Reprogramming By C-Met Inhibition As A Targetable Vulnerability In Glioblastoma, Trang Thi Thu Nguyen, Enyuan Shang, Georg Karpel-Massler, Markus D. Siegelin
Metabolic Reprogramming By C-Met Inhibition As A Targetable Vulnerability In Glioblastoma, Trang Thi Thu Nguyen, Enyuan Shang, Georg Karpel-Massler, Markus D. Siegelin
Publications and Research
The elucidation of better treatments for solid tumors and especially malignant glial tumors is a priority. Better understanding of the molecular underpinnings of treatment response and resistance are critical determinants in the success for this endeavor. Recently, a battery of novel tools have surfaced that allow to interrogate tumor cell metabolism to more precise extent than this was possible in the earlier days. At the forefront of these developments are the extracellular flux and carbon tracing analyses. Through utilization of these techniques our group made the recent observation that acute and chronic c-MET inhibition drives fatty acid oxidation that in …
Bright Green Biofluorescence In Sharks Derives From Bromo-Kynurenine Metabolism, Hyun Bong Park, Yick Chong Lam, Jean P. Gaffney, James C. Weaver, Sara Rose Krivoshik, Randy Hamchand, Vincent Pieribone, David F. Gruber, Jason M. Crawford
Bright Green Biofluorescence In Sharks Derives From Bromo-Kynurenine Metabolism, Hyun Bong Park, Yick Chong Lam, Jean P. Gaffney, James C. Weaver, Sara Rose Krivoshik, Randy Hamchand, Vincent Pieribone, David F. Gruber, Jason M. Crawford
Publications and Research
Although in recent years there has been an increased awareness of the widespread nature of biofluorescence in the marine environment, the diversity of the molecules responsible for this luminescent phenotype has been mostly limited to green fluorescent proteins (GFPs), GFP-like proteins, and fluorescent fatty acid-binding proteins (FABPs). In the present study, we describe a previously undescribed group of brominated tryptophan-kynurenine small molecule metabolites responsible for the green biofluorescence in two species of sharks and provide their structural, antimicrobial, and spectral characterization. Multi-scale fluorescence microscopy studies guided the discovery of metabolites that were differentially produced in fluorescent versus non-fluorescent skin, as …
Inhibition Of Mitochondrial Permeability Transition By Deletion Of The Ant Family And Cypd, Jason Karch, Michael J. Bround, Hadi Khalil, Michelle A. Sargent, Nadina Latchman, Naohiro Terada, Pablo M. Peixoto, Jeffery D. Molkentin
Inhibition Of Mitochondrial Permeability Transition By Deletion Of The Ant Family And Cypd, Jason Karch, Michael J. Bround, Hadi Khalil, Michelle A. Sargent, Nadina Latchman, Naohiro Terada, Pablo M. Peixoto, Jeffery D. Molkentin
Publications and Research
The mitochondrial permeability transition pore (MPTP) has resisted molecular identification. The original model of the MPTP that proposed the adenine nucleotide translocator (ANT) as the inner membrane pore-forming component was challenged when mitochondria from Ant1/2 double null mouse liver still had MPTP activity. Because mice express three Ant genes, we reinvestigated whether the ANTs comprise the MPTP. Liver mitochondria from Ant1, Ant2, and Ant4 deficient mice were highly refractory to Ca2+-induced MPTP formation, and when also given cyclosporine A (CsA), the MPTP was completely inhibited. Moreover, liver mitochondria from mice with quadruple deletion of Ant1, Ant2, Ant4, and Ppif (cyclophilin …
Endothelial Iqgap1 Regulates Leukocyte Transmigration By Directing The Lbrc To The Site Of Diapedesis, David P. Sullivan, Prarthana J. Dalal, Fanny Jaulin, David B. Sacks, Geri Kreitzer, William A. Muller
Endothelial Iqgap1 Regulates Leukocyte Transmigration By Directing The Lbrc To The Site Of Diapedesis, David P. Sullivan, Prarthana J. Dalal, Fanny Jaulin, David B. Sacks, Geri Kreitzer, William A. Muller
Publications and Research
Transendothelial migration (TEM) of leukocytes across the endothelium is critical for inflammation. In the endothelium, TEM requires the coordination of membrane movements and cytoskeletal interactions, including, prominently, recruitment of the lateral border recycling compartment (LBRC). The scaffold protein IQGAP1 was recently identified in a screen for LBRC-interacting proteins. Knockdown of endothelial IQGAP1 disrupted the directed movement of the LBRC and substantially reduced leukocyte TEM. Expression of truncated IQGAP1 constructs demonstrated that the calponin homology domain is required for IQGAP1 localization to endothelial borders and that the IQ domain, on the same IQGAP1 polypeptide, is required for its function in TEM. …
Arabinose Substitution Effect On Xylan Rigidity And Self-Aggregation, Utsab Shrestha, Sydney Smith, Sai Venkatesh Pingali, Hui Yang, Mai Zahran, Llyod Breunig, Liza Wilson, Daniel Cosgrove, Hugh O'Neill, Loukas Petridis
Arabinose Substitution Effect On Xylan Rigidity And Self-Aggregation, Utsab Shrestha, Sydney Smith, Sai Venkatesh Pingali, Hui Yang, Mai Zahran, Llyod Breunig, Liza Wilson, Daniel Cosgrove, Hugh O'Neill, Loukas Petridis
Publications and Research
Substituted xylans play an important role in the structure and mechanics of the primary cell wall of plants. Arabinoxylans (AX) consist of a xylose backbone substituted with arabinose, while glucuronoarabinoxylans (GAX) also contain glucuronic acid substitutions and ferulic acid esters on some of the arabinoses. We provide a molecular-level description on the dependence of xylan conformational, selfaggregation properties and binding to cellulose on the degree of arabinose substitution. Molecular dynamics simulations reveal fully solubilized xylans with a low degree of arabinose substitution (lsAX) to be stiffer than their highly substituted (hsAX) counterparts. Small-angle neutron scattering experiments indicate that both wild-type …
Deletion Of Mgr2p Affects The Gating Behavior Of The Tim23 Complex, Oygul Mirzalieva, Shinhye Jeon, Kevin Damri, Ruth Hartke, Layla Drwesh, Keren Demishtein-Zohary, Abdussalam Azem, Cory D. Dunn, Pablo M. Peixoto
Deletion Of Mgr2p Affects The Gating Behavior Of The Tim23 Complex, Oygul Mirzalieva, Shinhye Jeon, Kevin Damri, Ruth Hartke, Layla Drwesh, Keren Demishtein-Zohary, Abdussalam Azem, Cory D. Dunn, Pablo M. Peixoto
Publications and Research
The TIM23 complex is a hub for translocation of preproteins into or across the mitochondrial inner membrane. This dual sorting mechanism is currently being investigated, and in yeast appears to be regulated by a recently discovered subunit, the Mgr2 protein. Deletion of Mgr2p has been found to delay protein translocation into the matrix and accumulation in the inner membrane. This result and other findings suggested that Mgr2p controls the lateral release of inner membrane proteins harboring a stop-transfer signal that follows an N-terminal amino acid signal. However, the mechanism of lateral release is unknown. Here, we used patch clamp electrophysiology …
Cryptic Diversity In The Mexican Highlands: Thousands Of Uce Loci Help Illuminate Phylogenetic Relationships, Species Limits And Divergence Times Of Montane Rattlesnakes (Viperidae: Crotalus ), Christopher Blair, Robert W. Bryson Jr, Charles W. Linkem, David Lazcano, John Klicka, John E. Mccormack
Cryptic Diversity In The Mexican Highlands: Thousands Of Uce Loci Help Illuminate Phylogenetic Relationships, Species Limits And Divergence Times Of Montane Rattlesnakes (Viperidae: Crotalus ), Christopher Blair, Robert W. Bryson Jr, Charles W. Linkem, David Lazcano, John Klicka, John E. Mccormack
Publications and Research
With the continued adoption of genome‐scale data in evolutionary biology comes the challenge of adequately harnessing the information to make accurate phylogenetic inferences. Coalescent‐based methods of species tree inference have become common, and concatenation has been shown in simulation to perform well, particularly when levels of incomplete lineage sorting are low. However, simulation conditions are often overly simplistic, leaving empiricists with uncertainty regarding analytical tools. We use a large ultraconserved element data set (>3,000 loci) from rattlesnakes of the Crotalus triseriatus group to delimit lineages and estimate species trees using concatenation and several coalescent‐based methods. Unpartitioned and partitioned maximum …
Water Pharmacophore: Designing Ligands Using Molecular Dynamics Simulations With Water, Sang Won Jung, Minsup Kim, Steven Ramsey, Tom Kurtzman, Art E. Cho
Water Pharmacophore: Designing Ligands Using Molecular Dynamics Simulations With Water, Sang Won Jung, Minsup Kim, Steven Ramsey, Tom Kurtzman, Art E. Cho
Publications and Research
In this study, we demonstrate a method to construct a water-based pharmacophore model which can be utilized in the absence of known ligands. This method utilizes waters found in the binding pocket, sampled through molecular dynamics. Screening of compound databases against this water-based pharmacophore model reveals that this approach can successfully identify known binders to a target protein. The method was tested by enrichment studies of 7 therapeutically important targets and compared favourably to screening-by-docking with Glide. Our results suggest that even without experimentally known binders, pharmacophore models can be generated using molecular dynamics with waters and used for virtual …
Phase Diagram Of Water Confined By Graphene, Zhenghan Gao, Nicolas Giovambattista, Ozgur Sahin
Phase Diagram Of Water Confined By Graphene, Zhenghan Gao, Nicolas Giovambattista, Ozgur Sahin
Publications and Research
The behavior of water confined at the nanoscale plays a fundamental role in biological processes and technological applications, including protein folding, translocation of water across membranes, and filtration and desalination. Remarkably, nanoscale confinement drastically alters the properties of water. Using molecular dynamics simulations, we determine the phase diagram of water confined by graphene sheets in slab geometry, at T = 300 K and for a wide range of pressures. We find that, depending on the confining dimension D and density σ, water can exist in liquid and vapor phases, or crystallize into monolayer and bilayer square ices, as observed in …
Engineered Aptamers To Probe Molecular Interactions On The Cell Surface, Sana Batool, Sanam Bhandari, Shanell George, Precious Okeoma, Nabeela Van, Hazan E. Zümrüt, Prabodhika Mallikaratchy
Engineered Aptamers To Probe Molecular Interactions On The Cell Surface, Sana Batool, Sanam Bhandari, Shanell George, Precious Okeoma, Nabeela Van, Hazan E. Zümrüt, Prabodhika Mallikaratchy
Publications and Research
Significant progress has been made in understanding the nature of molecular interactions on the cell membrane. To decipher such interactions, molecular scaffolds can be engineered as a tool to modulate these events as they occur on the cell membrane. To guarantee reliability, scaffolds that function as modulators of cell membrane events must be coupled to a targeting moiety with superior chemical versatility. In this regard, nucleic acid aptamers are a suitable class of targeting moieties. Aptamers are inherently chemical in nature, allowing extensive site-specific chemical modification to engineer sensing molecules. Aptamers can be easily selected using a simple laboratory-based in …
Thermodynamic And Kinetic Analyses Of Iron Response Element (Ire)-Mrna Binding To Iron Regulatory Protein, Irp1, Mateen A. Khan, William E. Walden, Elizabeth C. Theil, Dixie J. Goss
Thermodynamic And Kinetic Analyses Of Iron Response Element (Ire)-Mrna Binding To Iron Regulatory Protein, Irp1, Mateen A. Khan, William E. Walden, Elizabeth C. Theil, Dixie J. Goss
Publications and Research
Comparison of kinetic and thermodynamic properties of IRP1 (iron regulatory protein1) binding to FRT (ferritin) and ACO2 (aconitase2) IRE-RNAs, with or without Mn2+, revealed differences specific to each IRE-RNA. Conserved among animal mRNAs, IRE-RNA structures are noncoding and bind Fe2+ to regulate biosynthesis rates of the encoded, iron homeostatic proteins. IRP1 protein binds IRERNA, inhibiting mRNA activity; Fe2+ decreases IRE-mRNA/IRP1 binding, increasing encoded protein synthesis. Here, we observed heat, 5 °C to 30 °C, increased IRP1 binding to IRE-RNA 4-fold (FRT IRE-RNA) or 3-fold (ACO2 IRE-RNA), which was enthalpy driven and entropy favorable. Mn2+ (50 μM, 25 °C) increased IRE-RNA/IRP1 …
Bow-Tie Signaling In C-Di-Gmp: Machine Learning In A Simple Biochemical Network, Jinyuan Yan, Maxime Deforet, Kerry E. Boyle, Rayees Rahman, Raymond Liang, Chinweike Okegbe, Lars E. P. Dietrich, Weigang Qiu, Joao B. Xavier
Bow-Tie Signaling In C-Di-Gmp: Machine Learning In A Simple Biochemical Network, Jinyuan Yan, Maxime Deforet, Kerry E. Boyle, Rayees Rahman, Raymond Liang, Chinweike Okegbe, Lars E. P. Dietrich, Weigang Qiu, Joao B. Xavier
Publications and Research
Bacteria of many species rely on a simple molecule, the intracellular secondary messenger c-di-GMP (Bis-(3'-5')-cyclic dimeric guanosine monophosphate), to make a vital choice: whether to stay in one place and form a biofilm, or to leave it in search of better conditions. The c-di-GMP network has a bow-tie shaped architecture that integrates many signals from the outside worldÐthe input stimuliÐinto intracellular c-di-GMP levels that then regulate genes for biofilm formation or for swarming motilityÐthe output phenotypes. How does the `uninformed' process of evolution produce a network with the right input/output association and enable bacteria to make the right choice? Inspired …
Evolution Of Complex Target Selex To Identify Aptamers Against Mammalian Cell-Surface Antigens, Prabodhika R. Mallikaratchy
Evolution Of Complex Target Selex To Identify Aptamers Against Mammalian Cell-Surface Antigens, Prabodhika R. Mallikaratchy
Publications and Research
The demand has increased for sophisticated molecular tools with improved detection limits. Such molecules should be simple in structure, yet stable enough for clinical applications. Nucleic acid aptamers (NAAs) represent a class of molecules able to meet this demand. In particular, aptamers, a class of small nucleic acid ligands that are composed of single-stranded modified/unmodified RNA/DNA molecules, can be evolved from a complex library using Systematic Evolution of Ligands by EXponential enrichment (SELEX) against almost any molecule. Since its introduction in 1990, in stages, SELEX technology has itself undergone several modifications, improving selection and broadening the repertoire of targets. This …
Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran
Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran
Publications and Research
Syndecans (SDC, SYND) comprise a group of four structurally related type 1 transmembrane heparan sulfate proteoglycans (HSPGs) that play important roles in tumorigenic processes. SDCs exert signaling via their protein cores and their conserved transmembrane and cytoplasmic domains or by forming complexes with growth factors (GFs). In classical Hodgkin's lymphoma (cHL), a lymphoid neoplasm of predominantly B cell origin, SDC1 and SDC4 are the active SDCs, and a number of GF (vascular endothelial growth factor, fibroblast growth factor, etc.) signaling pathways have been studied. However, despite extensive pre-clinical and clinical research on SDC-mediated GF signaling in many cancer types, there …
Antioxidant And Hepatoprotective Effects Of Procyanidins Fromwild Grape (Vitis Amurensis) Seeds In Ethanol-Induced Cells And Rats, Min Ji Bak, Van-Long Truong, Se-Yeon Ko, Xuan Ngan Giang Nguyen, Pajaree Ingkasupart, Mira Jun, Jin Young Shin, Woo-Sik Jeong
Antioxidant And Hepatoprotective Effects Of Procyanidins Fromwild Grape (Vitis Amurensis) Seeds In Ethanol-Induced Cells And Rats, Min Ji Bak, Van-Long Truong, Se-Yeon Ko, Xuan Ngan Giang Nguyen, Pajaree Ingkasupart, Mira Jun, Jin Young Shin, Woo-Sik Jeong
Publications and Research
In the present study, we characterized the antioxidant and hepatoprotective mechanisms underlying of wild grape seed procyanidins (WGP) against oxidative stress damage in ethanol-treated HepG2 cell and Sprague-Dawley (SD)-rat models. In HepG2 cells, WGP not only diminished the ethanol (EtOH, 100 mM)-induced reactive oxygen species (ROS) formation and cytochrome P450 2E1 (CYP2E1) expression, but also renovated both the activity and expression of antioxidant enzymes including catalase, superoxide dismutase, and glutathione peroxidase. Additionally, to investigate the hepatoprotective effect of WGP, rats were orally administered 10 or 50 mg/kg WGP once daily for seven days prior to the single oral administration of …
Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman
Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman
Publications and Research
Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic …