Digital Commons Network^™

Elimination Of The Nlrp3-Asc Inflammasome Protects Against Chronic Obesity-Induced Pancreatic Damage, Yun Hee Youm, Ayinuer Adijiang, Bolormaa Vandanmagsar, David Burk, Anthony Ravussin, Vishwa Deep Dixit

Faculty Publications

Clinical evidence that the blockade of IL-1β in type-2 diabetic patients improves glycemia is indicative of an autoinflammatory mechanism that may trigger adiposity-driven pancreatic damage. IL-1β is a key contributor to the obesity-induced inflammation and subsequent insulin resistance, pancreatic β-cell dysfunction, and the onset of type 2 diabetes. Our previous studies demonstrated that the ceramides activate the Nod-like receptor family, pyrin domain containing 3 (Nlrp3) inflammasome to cause the generation of mature IL-1β and ablation of the Nlrp3 inflammasome in diet-induced obesity improves insulin signaling. However, it remains unclear whether the post-translational processing of active IL-1β in pancreas is regulated …

Genome-Wide Association Study Identifies Loci Influencing Concentrations Of Liver Enzymes In Plasma, J. C. Chambers, W. Zhang, J. Sehmi, X. Li, M. N. Wass, P. Van Der Harst, H. Holm, S. Sanna, M. Kavousi, S. E. Baumeister, L. J. Coin, G. Deng, C. Gieger, N. L. Heard-Costa, J. J. Hottenga, B. Kühnel, V. Kumar, V. Lagou, L. Liang, J. Luan, P. M. Vidal, I. Mateo Leach, P. F. O'Reilly, J. F. Peden, N. Rahmioglu, P. Soininen, E. K. Speliotes, X. Yuan, G. Thorleifsson, B. Z. Alizadeh, L. D. Atwood, I. B. Borecki, M. J. Brown

Faculty Publications

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10-8 to P = 10-190). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis …

The Efficacy Of Detecting Variants With Small Effects On The Affymetrix 6.0 Platform Using Pooled Dna, Charleston W.K. Chiang, Zofia K.Z. Gajdos, Joshua M. Korn, Johannah L. Butler, Rachel Hackett, Candace Guiducci, Thutrang T. Nguyen, Rainford Wilks, Terrence Forrester, Katherine D. Henderson, Loic Le Marchand, Brian E. Henderson, Christopher A. Haiman, Richard S. Cooper, Helen N. Lyon, Xiaofeng Zhu, Colin A. Mckenzie, Mark R. Palmert, Joel N. Hirschhorn

Faculty Publications

Genome-wide genotyping of a cohort using pools rather than individual samples has long been proposed as a cost-saving alternative for performing genome-wide association (GWA) studies. However, successful disease gene mapping using pooled genotyping has thus far been limited to detecting common variants with large effect sizes, which tend not to exist for many complex common diseases or traits. Therefore, for DNA pooling to be a viable strategy for conducting GWA studies, it is important to determine whether commonly used genome-wide SNP array platforms such as the Affymetrix 6.0 array can reliably detect common variants of small effect sizes using pooled …

The Remarkable Evolutionary History Of Endornaviruses, Marilyn J. Roossinck, Sead Sabanadzovic, Ryo Okada, Rodrigo A. Valverde

Faculty Publications

The family Endornaviridae contains several members from diverse hosts, including plants, fungi and oomycetes. They are found as large dsRNA elements with a nick in the coding strand. All members encode a conserved RNA-dependent RNA polymerase, but no other domain that is conserved among all members. Based on the conserved domain database comparison the various domains have different origins, indicating a highly modular evolutionary history. In some cases, domains with similar putative functions are found that are derived from different protein families, indicating convergent evolution for a required function. © 2011 SGM.

Trace Metals In Porewater Of Surface Sediments And Their Bioavailability In Jiaozhou Bay, Qingdao, China, Siyuan Ye, Edward A. Laws, Xigui Ding, Hongming Yuan, Guangming Zhao, Jin Wang

Faculty Publications

Samples of porewater and the edible tissue of mottled clams, Ruditapes variegatus, were collected simultaneously at each of 12 stations from Jiaozhou Bay near Qingdao, China, in June of 2003. Chemical analysis focused on trace metals and major elements. Porewater concentrations of Cd, Cr, Pb, and Zn were distributed in a bimodal fashion among the 12 stations, with mean concentrations at six of the stations being 8-32 times mean values at the other six stations. The concentrations of the same metals in clams were remarkably similar among stations, the coefficients of variation being only 12-37%. Calculations performed with the computer …

The Nuclear Pore Complex Mediates Binding Of The Mig1 Repressor To Target Promoters, Nayan J. Sarma, Thomas D. Buford, Terry Haley, Kellie Barbara-Haley, George M. Santangelo, Kristine A. Willis

Faculty Publications

All eukaryotic cells alter their transcriptional program in response to the sugar glucose. In Saccharomyces cerevisiae, the best-studied downstream effector of this response is the glucose-regulated repressor Mig1. We show here that nuclear pore complexes also contribute to glucose-regulated gene expression. NPCs participate in glucose-responsive repression by physically interacting with Mig1 and mediating its function independently of nucleocytoplasmic transport. Surprisingly, despite its abundant presence in the nucleus of glucose-grown nup120Δ or nup133Δ cells, Mig1 has lost its ability to interact with target promoters. The glucose repression defect in the absence of these nuclear pore components therefore appears …

Functional Dissection Of The Glucose Signaling Pathways That Regulate The Yeast Glucose Transporter Gene (Hxt) Repressor Rgt1, David J. Jouandot Ii, Adhiraj Roy, Jeong-Ho Kim

Faculty Publications

The yeast Rgt1 repressor is a bifunctional protein that acts as a transcriptional repressor and activator. Under glucose-limited conditions, Rgt1 induces transcriptional repression by forming a repressive complex with its corepressors Mth1 and Std1. Here, we show that Rgt1 is converted from a transcriptional repressor into an activator under high glucose conditions and this occurs through two independent but consecutive events mediated by two glucose signaling pathways: (1) disruption of the repressive complex by the Rgt2/Snf3 pathway; (2) phosphorylation of Rgt1 by the cAMP-dependent protein kinase (cAMP-PKA) pathway. Rgt1 is phosphorylated by PKA at four serine residues within its amino-terminal …

A Draft Genome Of Yersinia Pestis From Victims Of The Black Death, Kirsten I. Bos, Verena J. Schuenemann, G. Brian Golding, Hernán A. Burbano, Nicholas Waglechner, Brian K. Coombes, Joseph B. Mcphee, Sharon Dewitte, Matthias Meyer, Sarah Schmedes, James Wood, David J. D. Earn, D. Ann Herring, Peter Bauer, Hendrik N. Poinar, Johannes Krause

Faculty Publications

Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard1. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348–1350. Genetic architecture and phylogenetic analysis indicate …

Influence Of Substrate Modification And C-Terminal Truncation On The Active Site Structure Of Substrate-Bound Heme Oxygenase From Neisseriae Meningitidis. A 1H Nmr Study, Dungeng Peng, James D. Satterlee, Li Hua Ma, Jerry L. Dallas, Kevin M. Smith, Xuhong Zhang, Michihiko Sato, Gerd N. La Mar

Faculty Publications

Heme oxygenase (HO), from the pathogenic bacterium N. meningitidis(NmHO), which secures host iron, shares many properties with mammalian HOs but also exhibits some key differences. The crystal structure appears more compact, and the crystal-undetected C-terminus interacts with substrate in solution. The unique nature of substrate-protein, specifically pyrrole-I/II-helix-2, peripheral interactions in NmHO are probed by 2D 1H NMR to reveal unique structural features controlling substrate orientation. The thermodynamics of substrate orientational isomerism are mapped for substrates with individual vinyl → methyl → hydrogen substitutions and with enzyme C-terminal deletions. NmHO exhibits significantly stronger orientational preference, reflecting much stronger and selective pyrrole-I/II …

Why Not Consider A Spherical Protein? Implications Of Backbone Hydrogen Bonding For Protein Structure And Function, Michal Brylinski, Mu Gao, Jeffrey Skolnick

Faculty Publications

The intrinsic ability of protein structures to exhibit the geometric features required for molecular function in the absence of evolution is examined in the context of three systems: the reference set of real, single domain protein structures, a library of computationally generated, compact homopolypeptides, artificial structures with protein-like secondary structural elements, and quasi-spherical random proteins packed at the same density as proteins but lacking backbone secondary structure and hydrogen bonding. Without any evolutionary selection, the library of artificial structures has similar backbone hydrogen bonding, global shape, surface to volume ratio and statistically significant structural matches to real protein global structures. …

Viral Double-Strand Rna-Binding Proteins Can Enhance Innate Immune Signaling By Toll-Like Receptor 3, Yvonne Lai, Guanghui Yi, Alice Chen, Kanchan Bhardwaj, Brady J. Tragesser, Rodrigo A. Valverde, Adam Zlotnick, Suchetana Mukhopadhyay, C. T. Ranjith-Kumar, C. Cheng Kao

Faculty Publications

Toll-like Receptor 3 (TLR3) detects double-stranded (ds) RNAs to activate innate immune responses. While poly(I:C) is an excellent agonist for TLR3 in several cell lines and in human peripheral blood mononuclear cells, viral dsRNAs tend to be poor agonists, leading to the hypothesis that additional factor(s) are likely required to allow TLR3 to respond to viral dsRNAs. TLR3 signaling was examined in a lung epithelial cell line by quantifying cytokine production and in human embryonic kidney cells by quantifying luciferase reporter levels. Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells …

Genetic Variants In Novel Pathways Influence Blood Pressure And Cardiovascular Disease Risk, Georg B. Ehret, Patricia B. Munroe, Kenneth M. Rice, Murielle Bochud, Andrew D. Johnson, Daniel I. Chasman, Albert V. Smith, Martin D. Tobin, Germaine C. Verwoert, Shih Jen Hwang, Vasyl Pihur, Peter Vollenweider, Paul F. O'Reilly, Najaf Amin, Jennifer L. Bragg-Gresham, Alexander Teumer, Nicole L. Glazer, Lenore Launer, Jing Hua Zhao, Yurii Aulchenko, Simon Heath, Siim Sober, Afshin Parsa, Jian'an Luan, Pankaj Arora, Abbas Dehghan, Feng Zhang, Gavin Lucas, Andrew A. Hicks, Anne U. Jackson, John F. Peden, Toshiko Tanaka, Sarah H. Wild

Faculty Publications

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten …

Rumi Functions As Both A Protein O-Glucosyltransferase And A Protein O-Xylosyltransferase, Hideyuki Takeuchi, Rodrigo C. Fernańdez-Valdivia, Devin S. Caswell, Aleksandra Nita-Lazar, Nadia A. Rana, Thomas P. Garner, Thomas K. Weldeghiorghis, Megan A. Macnaughtan, Hamed Jafar-Nejad, Robert S. Haltiwanger

Faculty Publications

Mutations in rumi result in a temperature-sensitive loss of Notch signaling in Drosophila. Drosophila Rumi is a soluble, endoplasmic reticulum-retained protein with a CAP10 domain that functions as a protein O-glucosyltransferase. In human and mouse genomes, three potential Rumi homologues exist: one with a high degree of identity to Drosophila Rumi (52%), and two others with lower degrees of identity but including a CAP10 domain (KDELC1 and KDELC2). Here we show that both mouse and human Rumi, but not KDELC1 or KDELC2, catalyze transfer of glucose from UDPglucose to an EGF repeat from human factor VII. Similarly, human Rumi, but …

Shaping A Lfe Of Significance For Retirement By R. Jack Hansen And Jerry P. Haas, E Michael Brady Phd

Faculty Publications

The article reviews the book Shaping a Life of Significance for Retirement, by R. Jack Hansen and Jerry P. Haas.

The Rice Miniature Inverted Repeat Transposable Element Mping Is An Effective Insertional Mutagen In Soybean, C. Nathan Hancock, Feng Zhang, Kristen Floyd, Aaron O. Richardson, Peter Lafayette, Donna Tucker, Susan R. Wessler, Wayne A. Parrott

Faculty Publications

Insertional mutagenesis of legume genomes such as soybean (Glycine max) should aid in identifying genes responsible for key traits such as nitrogen fixation and seed quality. The relatively low throughput of soybean transformation necessitates the use of a transposon-tagging strategy where a single transformation event will produce many mutations over a number of generations. However, existing transposon-tagging tools being used in legumes are of limited utility because of restricted transposition (Ac/Ds: soybean) or the requirement for tissue culture activation (Tnt1: Medicago truncatula). A recently discovered transposable element from rice (Oryza …

Dietary-Resistant Starch Improves Maternal Glycemic Control In Goto-Kakizaki Rat, Li Shen, Michael J. Keenan, Anne Raggio, Cathy Williams, Roy J. Martin

Faculty Publications

Scope: Dietary prebiotics show potential in anti-diabetes. Dietary resistant starch (RS) has a favorable impact on gut hormone profiles, including glucagon-like peptide-1 (GLP-1) consistently released, a potent anti-diabetic incretin. Also RS reduced body fat and improved glucose tolerance in rats and mice. In the current project, we hypothesize that dietary-resistant starch can improve insulin sensitivity and pancreatic β cell mass in a type 2 diabetic rat model. Altered gut fermentation and microbiota are the initial mechanisms, and enhancement in serum GLP-1 is the secondary mechanism. Methods and results: In this study, GK rats were fed an RS diet with 30% …

Dietary-Resistant Starch Improves Maternal Glycemic Control In Goto-Kakizaki Rat, Li Shen, Michael J. Keenan, Anne Raggio, Cathy Williams, Roy J. Martin

Faculty Publications

Scope: Dietary prebiotics show potential in anti-diabetes. Dietary resistant starch (RS) has a favorable impact on gut hormone profiles, including glucagon-like peptide-1 (GLP-1) consistently released, a potent anti-diabetic incretin. Also RS reduced body fat and improved glucose tolerance in rats and mice. In the current project, we hypothesize that dietary-resistant starch can improve insulin sensitivity and pancreatic β cell mass in a type 2 diabetic rat model. Altered gut fermentation and microbiota are the initial mechanisms, and enhancement in serum GLP-1 is the secondary mechanism. Methods and results: In this study, GK rats were fed an RS diet with 30% …

Identification, Replication, And Fine-Mapping Of Loci Associated With Adult Height In Individuals Of African Ancestry, Amidou N'Diaye, Gary K. Chen, Cameron D. Palmer, Bing Ge, Bamidele Tayo, Rasika A. Mathias, Jingzhong Ding, Michael A. Nalls, Adebowale Adeyemo, Véronique Adoue, Christine B. Ambrosone, Larry Atwood, Elisa V. Bandera, Lewis C. Becker, Sonja I. Berndt, Leslie Bernstein, William J. Blot, Eric Boerwinkle, Angela Britton, Graham Casey, Stephen J. Chanock, Ellen Demerath, Sandra L. Deming, W. Ryan Diver, Caroline Fox, Tamara B. Harris, Dena G. Hernandez, Jennifer J. Hu, Sue A. Ingles, Esther M. John, Craig Johnson, Brendan Keating, Rick A. Kittles

Faculty Publications

Adult height is a classic polygenic trait of high heritability (h 2 ~0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ~10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = …

Relative Humidity Preference And Survival Of Starved Formosan Subterranean Termites (Isoptera: Rhinotermitidae) At Various Temperature And Relative Humidity Conditions, Bal K. Gautam, Gregg Henderson

Faculty Publications

Foraging groups of Formosan subterranean termites, Coptotermes formosanus Shiraki were tested for their relative humidity (RH) preference in a humidity gradient arena in the laboratory at a constant temperature of 26°G Five RH levels (9%, 33%, 53%, 75%, and 98%) were maintained in the test arena comprising of a series of closed containers by using dry silica gel, saturated salt solutions, or distilled water alone. Termites gradually aggregated to the highest RH chamber in the arena. After 1h, a significantly greater percentage of termites (≈46%) aggregated to the highest RH chamber (98%) than to the lower RH chambers (≤75%). After …

Lineage Diversification And Morphological Evolution In A Large-Scale Continental Radiation: The Neotropical Ovenbirds And Woodcreepers (Aves: Furnariidae), Elizabeth P. Derryberry, Santiago Claramunt, Graham Derryberry, R. Terry Chesser, Joel Cracraft, Alexandre Aleixo, Jorge Pérez-Emán, J. V. Remsen, Robb T. Brumfield

Faculty Publications

Patterns of diversification in species-rich clades provide insight into the processes that generate biological diversity. We tested different models of lineage and phenotypic diversification in an exceptional continental radiation, the ovenbird family Furnariidae, using the most complete species-level phylogenetic hypothesis produced to date for a major avian clade (97% of 293 species). We found that the Furnariidae exhibit nearly constant rates of lineage accumulation but show evidence of constrained morphological evolution. This pattern of sustained high rates of speciation despite limitations on phenotypic evolution contrasts with the results of most previous studies of evolutionary radiations, which have found a pattern …

Endurance And Resistance Training Lowers C-Reactive Protein In Young, Healthy Females, Laura A. Daray, Tara M. Henagan, Michael Zanovec, Conrad P. Earnest, Lisa G. Johnson, Jason Winchester, Georgianna Tuuri, Laura K. Stewart

Faculty Publications

The purpose of this study was to determine whether endurance (E) or endurance + resistance (ER) training affects C-reactive protein (CRP) and if these changes are related to alterations in fitness and (or) body composition in young females. Thirty-eight females (aged 18-24 years) were assigned to 1 of 3 groups: (1) E, (2) ER or (3) active control (AC). The E and ER groups completed 15 weeks of marathon training. The ER group performed additional resistance training and the AC group maintained their usual exercise routine. Primary outcomes were measured pre- and post-training and included anthropometric indices, dual-energy x-ray absorption …

Effect Of School Racial Composition On Trajectories Of Depressive Symptoms From Adolescence Through Early Adulthood, Katrina M. Walsemann, Bethany A. Bell, Bridget J. Goosby

Faculty Publications

Introduction: We investigate the effect of high school racial composition, measured as percent of non-Hispanic White students, on trajectories of depressive symptoms from adolescence to early adulthood. We also explore whether the effect of school racial composition varies by respondent race/ethnicity and if adult socio-economic status mediates this relationship.

Methods: We analyzed four waves of data from the National Longitudinal Study of Adolescent Health using 3-level linear growth models. We restricted our sample to respondents enrolled in grades 9-12 in 1994/5 who were interviewed at a minimum in Waves I and IV. This resulted in 10,350 respondents enrolled in 80 …

A Modified Stokes-Einstein Equation For A Beta Aggregation, Srisairam Achuthan, Bong Jae Chung, Preetam Ghosh, Vijayaraghavan Rangachari, Ashwin Vaidya

Faculty Publications

Background: In all amyloid diseases, protein aggregates have been implicated fully or partly, in the etiology of the disease. Due to their significance in human pathologies, there have been unprecedented efforts towards physiochemical understanding of aggregation and amyloid formation over the last two decades. An important relation from which hydrodynamic radii of the aggregate is routinely measured is the classic Stokes-Einstein equation. Here, we report a modification in the classical Stokes-Einstein equation using a mixture theory approach, in order to accommodate the changes in viscosity of the solvent due to the changes in solute size and shape, to implement a …

Population Structure, Long-Term Connectivity, And Effective Size Of Mutton Snapper (Lutjanus Analis) In The Caribbean Sea And Florida Keys, Evan W. Carson, Eric A. Saillant, Mark A. Renshaw, Nancie J. Cummings, John R. Gold

Faculty Publications

Genetic structure and average long-term connectivity and effective size of mutton snapper (Lutjanus analis) sampled from offshore localities in the U.S. Caribbean and the Florida Keys were assessed by using nuclear-encoded microsatellites and a fragment of mitochondrial DNA. No significant differences in allele, genotype (microsatellites), or haplotype (mtDNA) distributions were detected; tests of selective neutrality (mtDNA) were nonsignificant after Bonferroni correction. Heuristic estimates of average long-term rate of migration (proportion of migrant individuals/generation) between geographically adjacent localities varied from 0.0033 to 0.0054, indicating that local subpopulations could respond independently of environmental perturbations. Estimates of average long-term effective population sizes varied …

Problem Profiles Of At-Risk Youth In Two Service Programs: A Multigroup Exploratory Latent Class Analysis, Richard Dembo, Rhissa Briones-Robinson, Rocío Aracelis Ungaro, Lora M. Karas, Laura M. Gulledge, Paul Greenbaum, James Schmeidler, Ken C. Winters, Steven Belenko

Faculty Publications

Baseline data collected in two brief intervention projects (BI-Court and Truancy Project) were used to assess similarities and differences in subgroups of at-risk youth. Classifications of these subgroups were based on their psychosocial characteristics (e. g., substance use). Multigroup latent class analysis identified two BI-Court subgroups of youth and three truant subgroups. These classes can be viewed as differing along two dimensions, substance use involvement and emotional and behavioral issues. Equality tests of means across the latent classes for BI-Court and Truancy Project youths found significant differences that were consistent with their problem group classification. These findings highlight the importance …

A Once And Future Gulf Of Mexico Ecosystem: Restoration Recommendations Of An Expert Working Group, Charles H. Peterson, Felicia C. Coleman, Jeremy B. C. Jackson, R. Eugene Turner, Gilbert T. Rowe, Richard T. Barber, Karen A. Bjorndal, Robert S. Carney, Robert K. Cowen, Jonathan M. Hoekstra, James T. Hollibaugh, Shirley B. Laska, Richard A. Luettich, Jr., Craig W. Osenberg, Stephen E. Roady, Stanley Senner, John M. Teal, Ping Wong

Faculty Publications

The Deepwater Horizon (DWH) well blowout released more petroleum hydrocarbons into the marine environment than any previous U.S. oil spill (4.9 million barrels), fouling marine life, damaging deep sea and shoreline habitats and causing closures of economically valuable fisheries in the Gulf of Mexico. A suite of pollutants—liquid and gaseous petroleum compounds plus chemical dispersants—poured into ecosystems that had already been stressed by overfishing, development and global climate change. Beyond the direct effects that were captured in dramatic photographs of oiled birds in the media, it is likely that there are subtle, delayed, indirect and potentially synergistic impacts of these …

Tracking Spectral Shapes And Temporal Dynamics Along A Femtosecond Filament, Emilia Schulz, Daniel S. Steingrube, Thomas Binhammer, Mette B. Gaarde, Arnaud Couairon, Uwe Morgner, Milutin Kovačev

Faculty Publications

The spectral evolution of a high-intensity light channel formed by filamentation is investigated in a detailed experimental study. We also track the spatio-temporal dynamics by high-order harmonic generation along the filament. Both the spectral and temporal diagnostics are performed as a function of propagation distance, by extracting the light pulses directly from the hot filament core into vacuum via pinholes that terminate the nonlinear propagation. We compare the measured spectral shapes to simulations and analyze numerically the temporal dynamics inside the filament. © 2011 Optical Society of America.

Cryopreservation Of Spin-Dried Mammalian Cells, Nilay Chakraborty, Michael A. Menze, Jason Malsam, Alptekin Aksan, Steven C. Hand, Mehmet Toner

Faculty Publications

This study reports an alternative approach to achieve vitrification where cells are pre-desiccated prior to cooling to cryogenic temperatures for storage. Chinese Hamster Ovary (CHO) cells suspended in a trehalose solution were rapidly and uniformly desiccated to a low moisture content (< 0.12 g of water per g of dry weight) using a spin-drying technique. Trehalose was also introduced into the cells using a high-capacity trehalose transporter (TRET1). Fourier Transform Infrared Spectroscopy (FTIR) was used to examine the uniformity of water concentration distribution in the spin-dried samples. 62% of the cells were shown to survive spin-drying in the presence of trehalose following immediate rehydration. The spin-dried samples were stored in liquid nitrogen (LN 2) at a vitrified state. It was shown that following re-warming to room temperature and re-hydration with a fully complemented cell culture medium, 51% of the spin-dried and vitrified cells survived and demonstrated normal growth characteristics. Spin-drying is a novel strategy that can be used to improve cryopreservation outcome by promoting rapid vitrification. © 2011 Chakraborty et al.

Structure-Based Development Of Small Molecule Pfkfb3 Inhibitors: A Framework For Potential Cancer Therapeutic Agents Targeting The Warburg Effect, Minsuh Seo, Jeong Do Kim, David Neau, Inder Sehgal, Yong Hwan Lee

Faculty Publications

Cancer cells adopt glycolysis as the major source of metabolic energy production for fast cell growth. The HIF-1-induced PFKFB3 plays a key role in this adaptation by elevating the concentration of Fru-2,6-BP, the most potent glycolysis stimulator. As this metabolic conversion has been suggested to be a hallmark of cancer, PFKFB3 has emerged as a novel target for cancer chemotherapy. Here, we report that a small molecular inhibitor, N4A, was identified as an initial lead compound for PFKFB3 inhibitor with therapeutic potential. In an attempt to improve its potency, we determined the crystal structure of the PFKFB3•N4A complex to 2.4 …

Landscapes Of Wealth & Desire, Ryan B. Anderson

Faculty Publications

This paper explores the historical background to a proposed study of political disputes over the value of large-scale tourism development in Baja California Sur. The paper starts with a review of anthropological discussions of value — focusing on the work of Kluckhohn, Graeber, Elyachar and Appadurai. The aim is to use an anthropological approach to value to place current conflicts over land and resources arising from recent developments within a historical perspective. The paper then investigates how actors in different time periods have contributed to collective and often contradictory constructions of the area as a place of subsistence, adventure, possibilities, …