Digital Commons Network^™

Loss Of A 20s Proteasome Activator In Saccharomyces Cerevisiae Downregulates Genes Important For Genomic Integrity, Increases Dna Damage, And Selectively Sensitizes Cells To Agents With Diverse Mechanisms Of Action, Kevin M. Doherty, Leah D. Pride, James Lukose, Brian E. Snydsman, Ronald Charles, Ajay Pramanik, Eric G. Muller, David Botstein, Carol Wood Moore

Publications and Research

Cytoprotective functions of a 20S proteasome activator were investigated. Saccharomyces cerevisiae Blm10 and human 20S proteasome activator 200 (PA200) are homologs. Comparative genome-wide analyses of untreated diploid cells lacking Blm10 and growing at steady state at defined growth rates revealed downregulation of numerous genes required for accurate chromosome structure, assembly and repair, and upregulation of a specific subset of genes encoding protein-folding chaperones. Blm10 loss or truncation of the Ubp3/Blm3 deubiquitinating enzyme caused massive chromosomal damage and cell death in homozygous diploids after phleomycin treatments, indicating that Blm10 and Ubp3/Blm3 function to stabilize the genome and protect against cell death. …

Spatial Variability In Levels Of Benzene, Formaldehyde, And Total Benzene, Toluene, Ethylbenzene And Xylenes In New York City: A Land-Use Regression Study, Iyad Kheirbek, Sarah Johnson, Zev Ross, Grant Pezeshki, Kazuhiko Ito, Holger Eisl, Thomas Matte

Publications and Research

Background Hazardous air pollutant exposures are common in urban areas contributing to increased risk of cancer and other adverse health outcomes. While recent analyses indicate that New York City residents experience significantly higher cancer risks attributable to hazardous air pollutant exposures than the United States as a whole, limited data exist to assess intra-urban variability in air toxics exposures. Methods To assess intra-urban spatial variability in exposures to common hazardous air pollutants, street-level air sampling for volatile organic compounds and aldehydes was conducted at 70 sites throughout New York City during the spring of 2011. Land-use regression models were developed …

Detecting The Immune System Response Of A 500 Year-Old Inca Mummy, Angelique Corthals, Antonius Koller, Dwight W. Martin, Robert Rieger, Emily I. Chen, Mario Bernaski, Gabriella Recagno, Liliana M. Dávalos

Publications and Research

Disease detection in historical samples currently relies on DNA extraction and amplification, or immunoassays. These techniques only establish pathogen presence rather than active disease. We report the first use of shotgun proteomics to detect the protein expression profile of buccal swabs and cloth samples from two 500-year-old Andean mummies. The profile of one of the mummies is consistent with immune system response to severe pulmonary bacterial infection at the time of death. Presence of a probably pathogenic Mycobacterium sp. in one buccal swab was confirmed by DNA amplification, sequencing, and phylogenetic analyses. Our study provides positive evidence of active pathogenic …

Hunter-Gatherer Energetics And Human Obesity, Herman Pontzer, David A. Raichlen, Brian M. Wood, Audax Z. P. Mabulla, Susan B. Racette, Frank W. Marlowe

Publications and Research

Western lifestyles differ markedly from those of our hunter-gatherer ancestors, and these differences in diet and activity level are often implicated in the global obesity pandemic. However, few physiological data for hunter-gatherer populations are available to test these models of obesity. In this study, we used the doubly-labeled water method to measure total daily energy expenditure (kCal/day) in Hadza hunter-gatherers to test whether foragers expend more energy each day than their Western counterparts. As expected, physical activity level, PAL, was greater among Hadza foragers than among Westerners. Nonetheless, average daily energy expenditure of traditional Hadza foragers was no different than …

Correlation Of Trpgly And Glytrp Rotamer Structure With W7 And W10 Uv Resonance Raman Modes And Fluorescence Emission Shifts, Azaria Solomon Eisenberg, Laura J. Juszczak

Publications and Research

Tryptophyl glycine (TrpGly) and glycyl tryptophan (GlyTrp) dipeptides at pH 5.5 and pH 9.3 show a pattern of fluorescence emission shifts with the TrpGly zwitterion emission solely blue shifted. This pattern is matched by shifts in the UV resonance Raman (UVRR) W10 band position and the W7 Fermi doublet band ratio. Ab initio calculations show that the 1340 cm−1 band of the W7 doublet is composed of three modes, two of which determine the W7 band ratios for the dipeptides. Molecular dynamics simulations show that the dipeptides take on two conformations: one with the peptide backbone extended; one with the …

A New Body Shape Index Predicts Mortality Hazard Independently Of Body Mass Index, Nir Y. Krakauer, Jesse C. Krakauer

Publications and Research

Background Obesity, typically quantified in terms of Body Mass Index (BMI) exceeding threshold values, is considered a leading cause of premature death worldwide. For given body size (BMI), it is recognized that risk is also affected by body shape, particularly as a marker of abdominal fat deposits. Waist circumference (WC) is used as a risk indicator supplementary to BMI, but the high correlation of WC with BMI makes it hard to isolate the added value of WC. Methods and Findings We considered a USA population sample of 14,105 non-pregnant adults () from the National Health and Nutrition Examination Survey (NHANES) …

Reaction-Diffusion Modeling In The Neuron Simulator, Robert A. Mcdougal, Yosef Skolnick, James C. Schaff, William W. Lytton, Michael L. Hines

Publications and Research

No abstract provided.

Inhibition Of Pokeweed Antiviral Protein (Pap) By Turnip Mosaic Virus Genome-Linked Protein (Vpg), Artem V. Domashevskiy, Hiroshi Miyoshi, Dixie J. Goss

Publications and Research

Pokeweed antiviral protein (PAP) from Phytolacca americana is a ribosome-inactivating protein (RIP) and an RNA N-glycosidase that removes specific purine residues from the sarcin/ricin loop of large rRNA, arresting protein synthesis at the translocation step. PAP is also a cap-binding protein and is a potent antiviral agent against many plant, animal, and human viruses. To elucidate the mechanism of RNA depurination, and to understand how PAP recognizes and targets various RNAs, the interactions between PAP and turnip mosaic virus genomelinked protein (VPg) were investigated. VPg can function as a cap analog in cap-independent translation and potentially target PAP to uncapped …

Halogen Activation Via Interactions With Environmental Ice And Snow In The Polar Lower Troposphere And Other Regions, J. P. D. Abbatt, J. L. Thomas, K. Abrahamsson, Chris Boxe, A. Granfors, A. E. Jones, M. D. King, A. Saiz-Lopez, P. B. Shepson, J. Sodeau, D. W. Toohey, C. Toubin, R. Von Glasow, S. N. Wren, X. Yang

Publications and Research

The role of ice in the formation of chemically active halogens in the environment requires a full understanding because of its role in atmospheric chemistry, including controlling the regional atmospheric oxidizing capacity in specific situations. In particular, ice and snow are important for facilitating multiphase oxidative chemistry and as media upon which marine algae live. This paper reviews the nature of environmental ice substrates that participate in halogen chemistry, describes the reactions that occur on such substrates, presents the field evidence for ice-mediated halogen activation, summarizes our best understanding of ice-halogen activation mechanisms, and describes the current state of modeling …

Comparing Unique Title Coverage Of Web Of Science And Scopus In Earth And Atmospheric Sciences, Philip Barnett, Claudia Lascar

Publications and Research

No abstract provided.

Temporal Changes In Collagen Cross-Links In Spontaneous Articular Cartilage Repair, Masahiko Terajima, Sheela Damle, Madhuri Penmatsa, Paul West, Mathias Bostrom, Chisa Hidaka, Mitsuo Yamauchi, Nancy Pleshko

Publications and Research

Objective: Little is known about how the biochemical properties of collagen change during tissue regeneration following cartilage damage. In the current study, temporal changes in cartilage repair tissue biochemistry were assessed in a rabbit osteochondral defect. Design: Bilateral full-thickness 3-mm osteochondral trochlear groove defects were created in 54 adult male skeletally mature New Zealand white rabbits, and tissue repair was monitored over 16 weeks. Collagen content, cross-links, lysyl hydroxylation, gene expression, histological grading, and Fourier transform infrared analyses were performed at 2, 4, 6, 8, 12, and 16 weeks. Results: Defect fill occurred at ~4 weeks postinjury; however, histological grading …

Genome Plasticity And Systems Evolution In Streptomyces, Zhan Zhou, Jianying Gu, Yong-Quan Li, Yufeng Wang

Publications and Research

Background Streptomycetes are filamentous soil-dwelling bacteria. They are best known as the producers of a great variety of natural products such as antibiotics, antifungals, antiparasitics, and anticancer agents and the decomposers of organic substances for carbon recycling. They are also model organisms for the studies of gene regulatory networks, morphological differentiation, and stress response. The availability of sets of genomes from closely related Streptomyces strains makes it possible to assess the mechanisms underlying genome plasticity and systems adaptation. Results We present the results of a comprehensive analysis of the genomes of five Streptomyces species with distinct phenotypes. These streptomycetes have …

Production Of Mycobacterial Cell Wall Glycopeptidolipids Requires A Member Of The Mbth-Like Protein Family, Elizabeth Tatham, Sivagami Sundaram Chavadi, Poornima Mohandas, Uthamaphani R. Edupuganti, Shiva K. Angala, Delphi Chatterjee, Luis E N Quadri

Publications and Research

Background Glycopeptidolipids (GPLs) are among the major free glycolipid components of the outer membrane of several saprophytic and clinically-relevant Mycobacterium species. The architecture of GPLs is based on a constant tripeptide-amino alcohol core of nonribosomal peptide synthetase origin that is N-acylated with a 3-hydroxy/methoxy acyl chain synthesized by a polyketide synthase and further decorated with variable glycosylation patterns built from methylated and acetylated sugars. GPLs have been implicated in many aspects of mycobacterial biology, thus highlighting the significance of gaining an understanding of their biosynthesis. Our bioinformatics analysis revealed that every GPL biosynthetic gene cluster known to date contains a …

Cannabis-Dependence Risk Relates To Synergism Between Neuroticism And Proenkephalin Snps Associated With Amygdala Gene Expression: Case-Control Study, Didier Jutras-Aswad, Michelle M. Jacobs, Georgia Yiannoulos, Panos Roussos, Panos Bitsios, Yoko Nomura, Xun Liu, Yasmin L. Hurd

Publications and Research

Background Many young people experiment with cannabis, yet only a subgroup progress to dependence suggesting individual differences that could relate to factors such as genetics and behavioral traits. Dopamine receptor D2 (DRD2) and proenkephalin (PENK) genes have been implicated in animal studies with cannabis exposure. Whether polymorphisms of these genes are associated with cannabis dependence and related behavioral traits is unknown. Methodology/Principal Findings Healthy young adults (18–27 years) with cannabis dependence and without a dependence diagnosis were studied (N = 50/group) in relation to a priori-determined single nucleotide polymorphisms (SNPs) of the DRD2 and PENK genes. Negative affect, Impulsive Risk …

Coordination Between Proteasome Impairment And Caspase Activation Leading To Tau Pathology: Neuroprotection By Camp, M. J. Metcalfe, Q. Huang, Maria E. Figueiredo-Pereira

Publications and Research

Neurofibrillary tangles (NFTs) are hallmarks of Alzheimer’s disease (AD). The main component of NFTs is TAU, a highly soluble microtubule-associated protein. However, when TAU is cleaved at Asp421 by caspases it becomes prone to aggregation leading to NFTs. What triggers caspase activation resulting in TAU cleavage remains unclear. We investigated in rat cortical neurons a potential coordination between proteasome impairment and caspase activation. We demonstrate that upon proteasome inhibition, the early accumulation of detergent-soluble ubiquitinated (SUb) proteins paves the way to caspase activation and TAU pathology. This occurs with two drugs that inhibit the proteasome by different means: the product …

Composition Of The Adult Digestive Tract Bacterial Microbiome Based On Seven Mouth Surfaces, Tonsils, Throat And Stool Samples, Nicola Segata, Susan Kinder Haake, Peter Mannon, Katherine P. Lemon, Levi Waldron, Dirk Gevers, Curtis Huttenhower, Jacques Izard

Publications and Research

Background: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body’s greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites.

Results: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub- and supra-gingival plaques; and stool. …

Trends In Mortality From Septicaemia And Pneumonia With Economic Development: An Age-Period-Cohort Analysis, Irene O.L. Wong, Benjamin J. Cowling, Gabriel M. Leung, Mary Schooling

Publications and Research

Background
Hong Kong population has experienced drastic changes in its economic development in the 1940s. Taking advantage of Hong Kong’s unique demographic and socioeconomic history, characterized by massive, punctuated migration waves from Southern China, and recent, rapid transition from a pre-industrialized society to the first ethnic Chinese community reaching ‘‘first world’’ status over the last 60 years (i.e., in two or three generations), we examined the longitudinal trends in infection related mortality including septicemia compared to trends in non-bacterial pneumonia to generate hypotheses for further testing in other recently transitioned economies and to provide generalized aetiological insights on how economic …

Collective Behavior In The Spatial Spreading Of Obesity, Lazaros K. Gallos, Pablo Barttfeld, Shlomo Havlin, Mariano Sigman, Hernán A. Makse

Publications and Research

Obesity prevalence is increasing in many countries at alarming levels. A difficulty in the conception of policies to reverse these trends is the identification of the drivers behind the obesity epidemics. Here, we implement a spatial spreading analysis to investigate whether obesity shows spatial correlations, revealing the effect of collective and global factors acting above individual choices. We find a regularity in the spatial fluctuations of their prevalence revealed by a pattern of scale-free long-range correlations. The fluctuations are anomalous, deviating in a fundamental way from the weaker correlations found in the underlying population distribution indicating the presence of collective …

Mechanisms For Sweetness123, John D. Fernstrom, Steven D. Munger, Anthony Sclafani, Ivan E. De Araujo, Ashley Roberts, Samuel Molinary

Publications and Research

A remarkable amount of information has emerged in the past decade regarding sweet taste physiology. This article reviews these data, with a particular focus on the elucidation of the sweet taste receptor, its location and actions in taste transduction in the mouth, its nontaste functions in the gastrointestinal tract (e.g., in enteroendocrine cells), and the brain circuitry involved in the sensory processing of sweet taste. Complications in the use of rodents to model human sweet taste perception and responses are also considered. In addition, information relating to low-calorie sweeteners (LCS) is discussed in the context of these issues. Particular consideration …

Association Of Adherence Support And Outreach Services With Total Attrition, Loss To Follow-Up, And Death Among Art Patients In Sub-Saharan Africa, Matthew R. Lamb, Wafaa M. El-Sadr, Elvin Geng, Denis Nash

Publications and Research

Background Loss to follow-up (LTF) after antiretroviral therapy (ART) initiation is common in HIV clinics. We examined the effect of availability of adherence support and active patient outreach services on patient attrition following ART initiation. Methods and Findings This ecologic study examined clinic attrition rates (total attrition, LTF, and death) among 232,389 patients initiating ART at 349 clinics during 2004–2008 in 10 sub-Saharan African countries, and cohort attrition (proportion retained at 6 and 12 months after ART initiation) among a subset of patients with follow-up information (n = 83,389). Log-linear regression compared mean rates of attrition, LTF, and death between …

Multi-Locus Phylogeographic And Population Genetic Analysis Of Anolis Carolinensis: Historical Demography Of A Genomic Model Species, Marc Tollis, Gavriel Ausubel, Dhruba Ghimire, Stéphane Boissinot

Publications and Research

The green anole (Anolis carolinensis) has been widely used as an animal model in physiology and neurobiology but has recently emerged as an important genomic model. The recent sequencing of its genome has shed new light on the evolution of vertebrate genomes and on the process that govern species diversification. Surprisingly, the patterns of genetic diversity within natural populations of this widespread and abundant North American lizard remain relatively unknown. In the present study, we use 10 novel nuclear DNA sequence loci (N = 62 to 152) and one mitochondrial locus (N = 226) to delimit green anole populations and …

Fundamental Limits On Wavelength, Efficiency And Yield Of The Charge Separation Triad, Alexander Punnoose, Liza Mcconnell, Wei Liu, Andrew C. Mutter, Ronald Koder

Publications and Research

In an attempt to optimize a high yield, high efficiency artificial photosynthetic protein we have discovered unique energy and spatial architecture limits which apply to all light-activated photosynthetic systems. We have generated an analytical solution for the time behavior of the core three cofactor charge separation element in photosynthesis, the photosynthetic cofactor triad, and explored the functional consequences of its makeup including its architecture, the reduction potentials of its components, and the absorption energy of the light absorbing primary-donor cofactor. Our primary findings are two: First, that a high efficiency, high yield triad will have an absorption frequency more than …

Squalicorax Chips A Tooth: A Consequence Of Feeding-Related Behavior From The Lowermost Navesink Formation (Late Cretaceous: Campanian-Maastrichtian) Of Monmouth County, New Jersey, Usa, Martin A. Becker, John A. Chamberlain Jr.

Publications and Research

Chipped and broken functional teeth are common in modern sharks with serrated tooth shape. Tooth damage consists of splintering, cracking, and flaking near the cusp apex where the enameloid is broken and exposes the osteodentine and orthodentine. Such damage is generally viewed as the result of forces applied during feeding as the cusp apex impacts the skeletal anatomy of prey. Damage seen in serrated functional teeth from sharks Squalicorax kaupi [1] and Squalicorax pristodontus [1] from the late Cretaceous lowermost Navesink Formation of New Jersey resembles that occurring in modern sharks and suggests similar feeding behavior. Tumbling experiments using serrated …

Dynamic Gene Expression In The Human Cerebral Cortex Distinguishes Children From Adults, Kirstin N. Sterner, Amy Weckle, Harry T. Chugani, Adi L. Tarca, Chet C. Sherwood, Patrick R. Hof, Christopher W. Kuzawa, Amy M. Boddy, Asad Abbas, Ryan L. Raaum, Lucie Grégoire, Leonard Lipovich, Lawrence I. Grossman, Monica Uddin, Morris Goodman, Derek E. Wildman

Publications and Research

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR>0). Moreover, genes known to …

Crossing Over…Markov Meets Mendel, Saad Mneimneh

Publications and Research

Chromosomal crossover is a biological mechanism to combine parental traits. It is perhaps the first mechanism ever taught in any introductory biology class. The formulation of crossover, and resulting recombination, came about 100 years after Mendel's famous experiments. To a great extent, this formulation is consistent with the basic genetic findings of Mendel. More importantly, it provides a mathematical insight for his two laws (and corrects them). From a mathematical perspective, and while it retains similarities, genetic recombination guarantees diversity so that we do not rapidly converge to the same being. It is this diversity that made the study of …

Mapping Populations At Risk: Improving Spatial Demographic Data For Infectious Disease Modeling And Metric Derivation, Andrew J. Tatem, Susana Adamo, Nita Bharti, Clara R. Burgert, Marcia Castro, Audrey Dorelien, Gunter Fink, Catherine Linard, Mendelsohn John, Livia Montana, Mark R. Montgomery, Andrew Nelson, Abdisalan M. Noor, Deepa Pindolia, Greg Yetman, Deborah Balk

Publications and Research

The use of Global Positioning Systems (GPS) and Geographical Information Systems (GIS) in disease surveys and reporting is becoming increasingly routine, enabling a better understanding of spatial epidemiology and the improvement of surveillance and control strategies. In turn, the greater availability of spatially referenced epidemiological data is driving the rapid expansion of disease mapping and spatial modeling methods, which are becoming increasingly detailed and sophisticated, with rigorous handling of uncertainties. This expansion has, however, not been matched by advancements in the development of spatial datasets of human population distribution that accompany disease maps or spatial models. Where risks are heterogeneous …

A Comparative Genomics Screen Identifies A Sinorhizobium Meliloti 1021 Sodm-Like Gene Strongly Expressed Within Host Plant Nodules, Clothilde Queiroux, Brian K. Washburn, Olivia M. Davis, Jamie Stewart, Tess E. Brewer, Michael R. Lyons, Kathryn M. Jones

Publications and Research

Background We have used the genomic data in the Integrated Microbial Genomes system of the Department of Energy’s Joint Genome Institute to make predictions about rhizobial open reading frames that play a role in nodulation of host plants. The genomic data was screened by searching for ORFs conserved in α-proteobacterial rhizobia, but not conserved in closely-related non-nitrogen-fixing α-proteobacteria. Results Using this approach, we identified many genes known to be involved in nodulation or nitrogen fixation, as well as several new candidate genes. We knocked out selected new genes and assayed for the presence of nodulation phenotypes and/or nodule-specific expression. One …

Magecomet—Web Application For Harmonizing Existing Large-Scale Experiment Descriptions, Vincent Xue, Tony Burdett, Margus Lukk, Julie Taylor, Alvis Brazma, Helen Parkinson

Publications and Research

Motivation: Meta-analysis of large gene expression datasets obtained from public repositories requires consistently annotated data. Curation of such experiments, however, is an expert activity which involves repetitive manipulation of text. Existing tools for automated curation are few, which bottleneck the analysis pipeline. Results: We present MageComet, a web application for biologists and annotators that facilitates the re-annotation of gene expression experiments in MAGE-TAB format. It incorporates data mining, automatic annotation, use of ontologies and data validation to improve the consistency and quality of experimental meta-data from the ArrayExpress Repository. Availability and implementation: Source and tutorials for MageComet are openly available …

Posttraumatic Stress And Myocardial Infarction Risk Perceptions In Hospitalized Acute Coronary Syndrome Patients, Donald Edmondson, Jonathan A. Shaffer, Ellen-Ge Denton, Daichi Shimbo, Lynn Clemow

Publications and Research

Posttraumatic stress disorder (PTSD) is related to acute coronary syndrome (ACS; i.e., myocardial infarction or unstable angina) recurrence and poor post-ACS adherence to medical advice. Since risk perceptions are a primary motivator of adherence behaviors, we assessed the relationship of probable PTSD to ACS risk perceptions in hospitalized ACS patients (n = 420). Participants completed a brief PTSD screen 3-7 days post-ACS, and rated their 1-year ACS recurrence risk relative to other men or women their age. Most participants exhibited optimistic bias (mean recurrence risk estimate between "average" and "below average"). Further, participants who screened positive for current PTSD (n …

A Chemical Specialty Semantic Network For The Unified Medical Language System, C Paul Morrey, Yehoshua Perl, Michael Halper, Ling Chen, Huanying “Helen” Gu

Publications and Research

Background Terms representing chemical concepts found the Unified Medical Language System (UMLS) are used to derive an expanded semantic network with mutually exclusive semantic types. The UMLS Semantic Network (SN) is composed of a collection of broad categories called semantic types (STs) that are assigned to concepts. Within the UMLS’s coverage of the chemical domain, we find a great deal of concepts being assigned more than one ST. This leads to the situation where the extent of a given ST may contain concepts elaborating variegated semantics. A methodology for expanding the chemical subhierarchy of the SN into a finer-grained categorization …