Biased and unbiased strategies to identify biologically active small molecules.

PubMed

Abet, Valentina; Mariani, Angelica; Truscott, Fiona R; Britton, Sébastien; Rodriguez, Raphaël

2014-08-15

Small molecules are central players in chemical biology studies. They promote the perturbation of cellular processes underlying diseases and enable the identification of biological targets that can be validated for therapeutic intervention. Small molecules have been shown to accurately tune a single function of pluripotent proteins in a reversible manner with exceptional temporal resolution. The identification of molecular probes and drugs remains a worthy challenge that can be addressed by the use of biased and unbiased strategies. Hypothesis-driven methodologies employs a known biological target to synthesize complementary hits while discovery-driven strategies offer the additional means of identifying previously unanticipated biological targets. This review article provides a general overview of recent synthetic frameworks that gave rise to an impressive arsenal of biologically active small molecules with unprecedented cellular mechanisms. Copyright © 2014. Published by Elsevier Ltd.

Proteomic analysis of Medulloblastoma reveals functional biology with translational potential.

PubMed

Rivero-Hinojosa, Samuel; Lau, Ling San; Stampar, Mojca; Staal, Jerome; Zhang, Huizhen; Gordish-Dressman, Heather; Northcott, Paul A; Pfister, Stefan M; Taylor, Michael D; Brown, Kristy J; Rood, Brian R

2018-06-07

Genomic characterization has begun to redefine diagnostic classifications of cancers. However, it remains a challenge to infer disease phenotypes from genomic alterations alone. To help realize the promise of genomics, we have performed a quantitative proteomics investigation using Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and 41 tissue samples spanning the 4 genomically based subgroups of medulloblastoma and control cerebellum. We have identified and quantitated thousands of proteins across these groups and find that we are able to recapitulate the genomic subgroups based upon subgroup restricted and differentially abundant proteins while also identifying subgroup specific protein isoforms. Integrating our proteomic measurements with genomic data, we calculate a poor correlation between mRNA and protein abundance. Using EPIC 850 k methylation array data on the same tissues, we also investigate the influence of copy number alterations and DNA methylation on the proteome in an attempt to characterize the impact of these genetic features on the proteome. Reciprocally, we are able to use the proteome to identify which genomic alterations result in altered protein abundance and thus are most likely to impact biology. Finally, we are able to assemble protein-based pathways yielding potential avenues for clinical intervention. From these, we validate the EIF4F cap-dependent translation pathway as a novel druggable pathway in medulloblastoma. Thus, quantitative proteomics complements genomic platforms to yield a more complete understanding of functional tumor biology and identify novel therapeutic targets for medulloblastoma.

DEIsoM: a hierarchical Bayesian model for identifying differentially expressed isoforms using biological replicates

PubMed Central

Peng, Hao; Yang, Yifan; Zhe, Shandian; Wang, Jian; Gribskov, Michael; Qi, Yuan

2017-01-01

Abstract Motivation High-throughput mRNA sequencing (RNA-Seq) is a powerful tool for quantifying gene expression. Identification of transcript isoforms that are differentially expressed in different conditions, such as in patients and healthy subjects, can provide insights into the molecular basis of diseases. Current transcript quantification approaches, however, do not take advantage of the shared information in the biological replicates, potentially decreasing sensitivity and accuracy. Results We present a novel hierarchical Bayesian model called Differentially Expressed Isoform detection from Multiple biological replicates (DEIsoM) for identifying differentially expressed (DE) isoforms from multiple biological replicates representing two conditions, e.g. multiple samples from healthy and diseased subjects. DEIsoM first estimates isoform expression within each condition by (1) capturing common patterns from sample replicates while allowing individual differences, and (2) modeling the uncertainty introduced by ambiguous read mapping in each replicate. Specifically, we introduce a Dirichlet prior distribution to capture the common expression pattern of replicates from the same condition, and treat the isoform expression of individual replicates as samples from this distribution. Ambiguous read mapping is modeled as a multinomial distribution, and ambiguous reads are assigned to the most probable isoform in each replicate. Additionally, DEIsoM couples an efficient variational inference and a post-analysis method to improve the accuracy and speed of identification of DE isoforms over alternative methods. Application of DEIsoM to an hepatocellular carcinoma (HCC) dataset identifies biologically relevant DE isoforms. The relevance of these genes/isoforms to HCC are supported by principal component analysis (PCA), read coverage visualization, and the biological literature. Availability and implementation The software is available at https

Identifying biological concepts from a protein-related corpus with a probabilistic topic model

PubMed Central

Zheng, Bin; McLean, David C; Lu, Xinghua

2006-01-01

Background Biomedical literature, e.g., MEDLINE, contains a wealth of knowledge regarding functions of proteins. Major recurring biological concepts within such text corpora represent the domains of this body of knowledge. The goal of this research is to identify the major biological topics/concepts from a corpus of protein-related MEDLINE© titles and abstracts by applying a probabilistic topic model. Results The latent Dirichlet allocation (LDA) model was applied to the corpus. Based on the Bayesian model selection, 300 major topics were extracted from the corpus. The majority of identified topics/concepts was found to be semantically coherent and most represented biological objects or concepts. The identified topics/concepts were further mapped to the controlled vocabulary of the Gene Ontology (GO) terms based on mutual information. Conclusion The major and recurring biological concepts within a collection of MEDLINE documents can be extracted by the LDA model. The identified topics/concepts provide parsimonious and semantically-enriched representation of the texts in a semantic space with reduced dimensionality and can be used to index text. PMID:16466569

Dynamical compensation and structural identifiability of biological models: Analysis, implications, and reconciliation

PubMed Central

2017-01-01

The concept of dynamical compensation has been recently introduced to describe the ability of a biological system to keep its output dynamics unchanged in the face of varying parameters. However, the original definition of dynamical compensation amounts to lack of structural identifiability. This is relevant if model parameters need to be estimated, as is often the case in biological modelling. Care should we taken when using an unidentifiable model to extract biological insight: the estimated values of structurally unidentifiable parameters are meaningless, and model predictions about unmeasured state variables can be wrong. Taking this into account, we explore alternative definitions of dynamical compensation that do not necessarily imply structural unidentifiability. Accordingly, we show different ways in which a model can be made identifiable while exhibiting dynamical compensation. Our analyses enable the use of the new concept of dynamical compensation in the context of parameter identification, and reconcile it with the desirable property of structural identifiability. PMID:29186132

Dynamical compensation and structural identifiability of biological models: Analysis, implications, and reconciliation.

PubMed

Villaverde, Alejandro F; Banga, Julio R

2017-11-01

The concept of dynamical compensation has been recently introduced to describe the ability of a biological system to keep its output dynamics unchanged in the face of varying parameters. However, the original definition of dynamical compensation amounts to lack of structural identifiability. This is relevant if model parameters need to be estimated, as is often the case in biological modelling. Care should we taken when using an unidentifiable model to extract biological insight: the estimated values of structurally unidentifiable parameters are meaningless, and model predictions about unmeasured state variables can be wrong. Taking this into account, we explore alternative definitions of dynamical compensation that do not necessarily imply structural unidentifiability. Accordingly, we show different ways in which a model can be made identifiable while exhibiting dynamical compensation. Our analyses enable the use of the new concept of dynamical compensation in the context of parameter identification, and reconcile it with the desirable property of structural identifiability.

Regenerative Chemical Biology: Current Challenges and Future Potential

PubMed Central

Ao, Ada; Hao, Jijun; Hong, Charles C.

2011-01-01

The enthusiasm surrounding the clinical potential of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is tempered by the fact that key issues regarding their safety, efficacy, and long-term benefits have thus far been suboptimal. Small molecules can potentially relieve these problems at major junctions of stem cell biology and regenerative therapy. In this review, we will introduce recent advances in these important areas and the first-generation of small molecules used in the regenerative context. Current chemical biology studies will provide the archetype for future interdisciplinary collaborations, and improve clinical benefits of cell-based therapies. PMID:21513877

Kantorovich-Wasserstein Distance for Identifying the Dynamic of Some Compartmental Models in Biology

NASA Astrophysics Data System (ADS)

Pousin, Jérôme

2008-09-01

Determining the influence of a biological species to the evolution of an other one strongly depends on the choice of mathematical models in biology. In this work we consider the case of distribution of lipids (docosahexaenoic acid (DHA)) in two compartments of the plasma, the platelets and the erythrocytes, and we compare three different mathematical approaches. The first one, consists of a system of differential equations the coefficients of which are identified through a least square procedure. The second one is made of a system of differential equations on a graph, the adjacency matrix of which represents the interplay between the species. The third one consists of mapping the provider curves to the target curves. Thus we have a distance between two families of curves, the curves of providers and the curves of targets, and by comparing the distances, we are able to decide which provider delivers preferentially to a target according to cumulative species mass curves. Numerical results are presented, and we show that the ordinary differential least square model provides qualitatively the same result as the Kantorovich-Wasserstein distance strategy. Finally, we discuss the potential ability of the presented Kantorovich-Wasserstein distance to perform the biological properties of a system.

Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples.

PubMed

Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Eric; Banzet, Nathalie; Defoort, Catherine; Bott, Romain; Dublineau, Isabelle; Aigueperse, Jocelyne; Gourmelon, Patrick; Martin, Jean-Charles; Souidi, Maâmar

2013-01-01

Because uranium is a natural element present in the earth's crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions. The aim of this study was to assess the biological changes in rats caused by ingestion of natural uranium in drinking water with a mean daily intake of 2.7 mg/kg for 9 months and to identify potential biomarkers related to such a contamination. Subsequently, we observed no pathology and standard clinical tests were unable to distinguish between treated and untreated animals. Conversely, LC-MS metabolomics identified urine as an appropriate biofluid for discriminating the experimental groups. Of the 1,376 features detected in urine, the most discriminant were metabolites involved in tryptophan, nicotinate, and nicotinamide metabolic pathways. In particular, N -methylnicotinamide, which was found at a level seven times higher in untreated than in contaminated rats, had the greatest discriminating power. These novel results establish a proof of principle for using metabolomics to address chronic low-dose uranium contamination. They open interesting perspectives for understanding the underlying biological mechanisms and designing a diagnostic test of exposure.

Biological treatment strategies for disc degeneration: potentials and shortcomings

PubMed Central

Nerlich, Andreas G.; Boos, Norbert

2006-01-01

Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient. PMID:16983559

Identifying DNA-binding proteins using structural motifs and the electrostatic potential

PubMed Central

Shanahan, Hugh P.; Garcia, Mario A.; Jones, Susan; Thornton, Janet M.

2004-01-01

Robust methods to detect DNA-binding proteins from structures of unknown function are important for structural biology. This paper describes a method for identifying such proteins that (i) have a solvent accessible structural motif necessary for DNA-binding and (ii) a positive electrostatic potential in the region of the binding region. We focus on three structural motifs: helix–turn-helix (HTH), helix–hairpin–helix (HhH) and helix–loop–helix (HLH). We find that the combination of these variables detect 78% of proteins with an HTH motif, which is a substantial improvement over previous work based purely on structural templates and is comparable to more complex methods of identifying DNA-binding proteins. Similar true positive fractions are achieved for the HhH and HLH motifs. We see evidence of wide evolutionary diversity for DNA-binding proteins with an HTH motif, and much smaller diversity for those with an HhH or HLH motif. PMID:15356290

Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology.

PubMed

Theophilou, Georgios; Paraskevaidi, Maria; Lima, Kássio M G; Kyrgiou, Maria; Martin-Hirsch, Pierre L; Martin, Francis L

2015-05-01

The complex processes driving cancer have so far impeded the discovery of dichotomous biomarkers associated with its initiation and progression. Reductionist approaches utilizing 'omics' technologies have met some success in identifying molecular alterations associated with carcinogenesis. Systems biology is an emerging science that combines high-throughput investigation techniques to define the dynamic interplay between regulatory biological systems in response to internal and external cues. Vibrational spectroscopy has the potential to play an integral role within systems biology research approaches. It is capable of examining global models of carcinogenesis by scrutinizing chemical bond alterations within molecules. The application of infrared or Raman spectroscopic approaches coupled with computational analysis under the systems biology umbrella can assist the transition of biomarker research from the molecular level to the system level. The comprehensive representation of carcinogenesis as a multilevel biological process will inevitably revolutionize cancer-related healthcare by personalizing risk prediction and prevention.

Biology of Leptoypha hospita (Hemiptera: Tingidae), a Potential Biological Control Agent of Chinese Privet

Treesearch

Yanzhuo Zhang; James L. Hanula; Scott Horn; Kristine Braman; Jianghua Sun

2011-01-01

The biology of Leptoypha hospita Drake et Poor (Hemiptera: Tingidae), a potential biological control agent from China for Chinese privet, Ligustrum sinense Lour., was studied in quarantine in the United States. Both nymphs and adults feed on Chinese privet mesophyll cells that lead to a bleached appearance of leaves and dieback of branch tips. L. hospita has five...

Identifying relevant data for a biological database: handcrafted rules versus machine learning.

PubMed

Sehgal, Aditya Kumar; Das, Sanmay; Noto, Keith; Saier, Milton H; Elkan, Charles

2011-01-01

With well over 1,000 specialized biological databases in use today, the task of automatically identifying novel, relevant data for such databases is increasingly important. In this paper, we describe practical machine learning approaches for identifying MEDLINE documents and Swiss-Prot/TrEMBL protein records, for incorporation into a specialized biological database of transport proteins named TCDB. We show that both learning approaches outperform rules created by hand by a human expert. As one of the first case studies involving two different approaches to updating a deployed database, both the methods compared and the results will be of interest to curators of many specialized databases.

Potential biological activities and bioavailability of alfrutamide and caffedymine

USDA-ARS?s Scientific Manuscript database

Alfrutamide and caffedymine are clovamide-type phenolic amides whose analogues are found in numerous plants including garlic and cocoa. However, potential health effects of the amides are largely unknown. For last ten years, several amides have been synthesized and their potential biological activi...

Biology and preliminary host range assessment of two potential kudzu biological control agents

Treesearch

Matthew J. Fyre; Judith Hough-Goldstein; Jiang-Hua Sun

2007-01-01

Two insect species from China, Gonioctena tredecimmaclliata (Jacoby) (Coleoptera: Chrysomelidae) and Ornatalcides (Mesalcidodes) trifidus (Pascoe) (Coleoptera: Curculionidae), were studied in quarantine in the United States as potential biological control agents for kudzu, Pueraria nwntana variety Zobata (Willd.) Maesen and S. Almeida...

Can the vector space model be used to identify biological entity activities?

PubMed Central

2011-01-01

Background Biological systems are commonly described as networks of entity interactions. Some interactions are already known and integrate the current knowledge in life sciences. Others remain unknown for long periods of time and are frequently discovered by chance. In this work we present a model to predict these unknown interactions from a textual collection using the vector space model (VSM), a well known and established information retrieval model. We have extended the VSM ability to retrieve information using a transitive closure approach. Our objective is to use the VSM to identify the known interactions from the literature and construct a network. Based on interactions established in the network our model applies the transitive closure in order to predict and rank new interactions. Results We have tested and validated our model using a collection of patent claims issued from 1976 to 2005. From 266,528 possible interactions in our network, the model identified 1,027 known interactions and predicted 3,195 new interactions. Iterating the model according to patent issue dates, interactions found in a given past year were often confirmed by patent claims not in the collection and issued in more recent years. Most confirmation patent claims were found at the top 100 new interactions obtained from each subnetwork. We have also found papers on the Web which confirm new inferred interactions. For instance, the best new interaction inferred by our model relates the interaction between the adrenaline neurotransmitter and the androgen receptor gene. We have found a paper that reports the partial dependence of the antiapoptotic effect of adrenaline on androgen receptor. Conclusions The VSM extended with a transitive closure approach provides a good way to identify biological interactions from textual collections. Specifically for the context of literature-based discovery, the extended VSM contributes to identify and rank relevant new interactions even if these

Measuring job stress among hospital nurses: an attempt to identify biological markers.

PubMed

Kawaguchi, Yoshichika; Toyomasu, Kouji; Yoshida, Noriko; Baba, Kaori; Uemoto, Masaharu; Minota, Shoichi

2007-02-01

The purpose of this study was to identify biological markers corresponding to job stress among hospital nurses. The subjects of this study were 128 nurses working at a university hospital. The NIOSH job stress questionnaire and the Miki Nurse Stressor 35-item Scale measured their job stress levels. The GHQ28 was also used to measure the subjects' general mental health status. Blood analyses for neuroendocrine function and immunity reaction were performed in order to identify biological markers of job stress. Stress is related to the plasma levels of catecholamine, cortisol, adrenocorticotrophic hormone, and natural killer cell activity, therefore these factors were measured accordingly. In consideration to circadian rhythms, blood was collected from the subjects prior to the start of the day shift. The nurses filled out the questionnaires on the day of the blood tests. In order to investigate the correlation between job stress reactions indicated by the questionnaires and the results of the blood tests, we utilized Pearson's correlation coefficient and partial correlation coefficient for which other affected items were controlled. In this study, significant correlations were found between job stress and biological factors; however, the correlations were not strong. Thus, it can be said that the biological markers associated with a specific kind of job stress remain unclear. In the future, rather than implementing a simple cross-sectional study, a longitudinal study including follow-up research will be more effective in establishing biological markers for job stress.

Methods of identifying potential vanpool riders.

DOT National Transportation Integrated Search

1977-01-01

Identifying potential vanpool riders and matching them to form pools are fundamental tasks in the initiation of a vanpool program. The manner in which these tasks are done will determine the costs and benefits of the program. This report presents the...

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.

PubMed

Warren, Helen R; Evangelou, Evangelos; Cabrera, Claudia P; Gao, He; Ren, Meixia; Mifsud, Borbala; Ntalla, Ioanna; Surendran, Praveen; Liu, Chunyu; Cook, James P; Kraja, Aldi T; Drenos, Fotios; Loh, Marie; Verweij, Niek; Marten, Jonathan; Karaman, Ibrahim; Lepe, Marcelo P Segura; O'Reilly, Paul F; Knight, Joanne; Snieder, Harold; Kato, Norihiro; He, Jiang; Tai, E Shyong; Said, M Abdullah; Porteous, David; Alver, Maris; Poulter, Neil; Farrall, Martin; Gansevoort, Ron T; Padmanabhan, Sandosh; Mägi, Reedik; Stanton, Alice; Connell, John; Bakker, Stephan J L; Metspalu, Andres; Shields, Denis C; Thom, Simon; Brown, Morris; Sever, Peter; Esko, Tõnu; Hayward, Caroline; van der Harst, Pim; Saleheen, Danish; Chowdhury, Rajiv; Chambers, John C; Chasman, Daniel I; Chakravarti, Aravinda; Newton-Cheh, Christopher; Lindgren, Cecilia M; Levy, Daniel; Kooner, Jaspal S; Keavney, Bernard; Tomaszewski, Maciej; Samani, Nilesh J; Howson, Joanna M M; Tobin, Martin D; Munroe, Patricia B; Ehret, Georg B; Wain, Louise V

2017-03-01

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

PubMed Central

Ntalla, Ioanna; Surendran, Praveen; Liu, Chunyu; Cook, James P; Kraja, Aldi T; Drenos, Fotios; Loh, Marie; Verweij, Niek; Marten, Jonathan; Karaman, Ibrahim; Segura Lepe, Marcelo P; O’Reilly, Paul F; Knight, Joanne; Snieder, Harold; Kato, Norihiro; He, Jiang; Tai, E Shyong; Said, M Abdullah; Porteous, David; Alver, Maris; Poulter, Neil; Farrall, Martin; Gansevoort, Ron T; Padmanabhan, Sandosh; Mägi, Reedik; Stanton, Alice; Connell, John; Bakker, Stephan J L; Metspalu, Andres; Shields, Denis C; Thom, Simon; Brown, Morris; Sever, Peter; Esko, Tõnu; Hayward, Caroline; van der Harst, Pim; Saleheen, Danish; Chowdhury, Rajiv; Chambers, John C; Chasman, Daniel I; Chakravarti, Aravinda; Newton-Cheh, Christopher; Lindgren, Cecilia M; Levy, Daniel; Kooner, Jaspal S; Keavney, Bernard; Tomaszewski, Maciej; Samani, Nilesh J; Howson, Joanna M M; Tobin, Martin D; Munroe, Patricia B; Ehret, Georg B; Wain, Louise V

2017-01-01

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. Combined with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure raising genetic variants on future cardiovascular disease risk. PMID:28135244

Synthesis of novel (-)-epicatechin derivatives as potential endothelial GPER agonists: Evaluation of biological effects.

PubMed

Sarmiento, Viviana; Ramirez-Sanchez, Israel; Moreno-Ulloa, Aldo; Romero-Perez, Diego; Chávez, Daniel; Ortiz, Miguel; Najera, Nayelli; Correa-Basurto, Jose; Villarreal, Francisco; Ceballos, Guillermo

2018-02-15

To potentially identify proteins that interact (i.e. bind) and may contribute to mediate (-)-epicatechin (Epi) responses in endothelial cells we implemented the following strategy: 1) synthesis of novel Epi derivatives amenable to affinity column use, 2) in silico molecular docking studies of the novel derivatives on G protein-coupled estrogen receptor (GPER), 3) biological assessment of the derivatives on NO production, 4) implementation of an immobilized Epi derivative affinity column and, 5) affinity column based isolation of Epi interacting proteins from endothelial cell protein extracts. For these purposes, the Epi phenol and C3 hydroxyl groups were chemically modified with propargyl or mesyl groups. Docking studies of the novel Epi derivatives on GPER conformers at 14 ns and 70 ns demostrated favorable thermodynamic interactions reaching the binding site. Cultures of bovine coronary artery endothelial cells (BCAEC) treated with Epi derivatives stimulated NO production via Ser1179 phosphorylation of eNOS, effects that were attenuated by the use of the GPER blocker, G15. Epi derivative affinity columns yielded multiple proteins from BCAEC. Proteins were electrophoretically separated and inmmunoblotting analysis revealed GPER as an Epi derivative binding protein. Altogether, these results validate the proposed strategy to potentially isolate and identify novel Epi receptors that may account for its biological activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Systems biology combining human- and animal-data miRNA and mRNA data identifies new targets in ureteropelvic junction obstruction.

PubMed

Papadopoulos, Theofilos; Casemayou, Audrey; Neau, Eric; Breuil, Benjamin; Caubet, Cécile; Calise, Denis; Thornhill, Barbara A; Bachvarova, Magdalena; Belliere, Julie; Chevalier, Robert L; Moulos, Panagiotis; Bachvarov, Dimcho; Buffin-Meyer, Benedicte; Decramer, Stéphane; Auriol, Françoise Conte; Bascands, Jean-Loup; Schanstra, Joost P; Klein, Julie

2017-03-01

Although renal fibrosis and inflammation have shown to be involved in the pathophysiology of obstructive nephropathies, molecular mechanisms underlying evolution of these processes remain undetermined. In an attempt towards improved understanding of obstructive nephropathy and improved translatability of the results to clinical practice we have developed a systems biology approach combining omics data of both human and mouse obstructive nephropathy. We have studied in parallel the urinary miRNome of infants with ureteropelvic junction obstruction and the kidney tissue miRNome and transcriptome of the corresponding neonatal partial unilateral ureteral obstruction (UUO) mouse model. Several hundreds of miRNAs and mRNAs displayed changed abundance during disease. Combination of miRNAs in both species and associated mRNAs let to the prioritization of five miRNAs and 35 mRNAs associated to disease. In vitro and in vivo validation identified consistent dysregulation of let-7a-5p and miR-29-3p and new potential targets, E3 ubiquitin-protein ligase (DTX4) and neuron navigator 1 (NAV1), potentially involved in fibrotic processes, in obstructive nephropathy in both human and mice that would not be identified otherwise. Our study is the first to correlate a mouse model of neonatal partial UUO with human UPJ obstruction in a comprehensive systems biology analysis. Our data revealed let-7a and miR-29b as molecules potentially involved in the development of fibrosis in UPJ obstruction via the control of DTX4 in both man and mice that would not be identified otherwise.

Identifying the underlying causes of biological instability in a full-scale drinking water supply system.

PubMed

Nescerecka, Alina; Juhna, Talis; Hammes, Frederik

2018-05-15

Changes in bacterial concentration and composition in drinking water during distribution are often attributed to biological (in)stability. Here we assessed temporal biological stability in a full-scale distribution network (DN) supplied with different types of source water: treated and chlorinated surface water and chlorinated groundwater produced at three water treatment plants (WTP). Monitoring was performed weekly during 12 months in two locations in the DN. Flow cytometric total and intact cell concentration (ICC) measurements showed considerable seasonal fluctuations, which were different for two locations. ICC varied between 0.1-3.75 × 10 5  cells mL -1 and 0.69-4.37 × 10 5  cells mL -1 at two locations respectively, with ICC increases attributed to temperature-dependent bacterial growth during distribution. Chlorinated water from the different WTP was further analysed with a modified growth potential method, identifying primary and secondary growth limiting compounds. It was observed that bacterial growth in the surface water sample after chlorination was primarily inhibited by phosphorus limitation and secondly by organic carbon limitation, while carbon was limiting in the chlorinated groundwater samples. However, the ratio of available nutrients changed during distribution, and together with disinfection residual decay, this resulted in higher bacterial growth potential detected in the DN than at the WTP. In this study, bacterial growth was found to be higher (i) at higher water temperatures, (ii) in samples with lower chlorine residuals and (iii) in samples with less nutrient (carbon, phosphorus, nitrogen, iron) limitation, while this was significantly different between the samples of different origin. Thus drinking water microbiological quality and biological stability could change during different seasons, and the extent of these changes depends on water temperature, the water source and treatment. Furthermore, differences in primary

Genetic studies of plasma analytes identify novel potential biomarkers for several complex traits

PubMed Central

Deming, Yuetiva; Xia, Jian; Cai, Yefei; Lord, Jenny; Del-Aguila, Jorge L.; Fernandez, Maria Victoria; Carrell, David; Black, Kathleen; Budde, John; Ma, ShengMei; Saef, Benjamin; Howells, Bill; Bertelsen, Sarah; Bailey, Matthew; Ridge, Perry G.; Hefti, Franz; Fillit, Howard; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Carrillo, Maria; Fleisher, Adam; Reeder, Stephanie; Trncic, Nadira; Burke, Anna; Tariot, Pierre; Reiman, Eric M.; Chen, Kewei; Sabbagh, Marwan N.; Beiden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Green, Robert C.; Marshall, Gad; Johnson, Keith A.; Sperling, Reisa A.; Snyder, Peter; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Bernick, Charles; Munic, Donna; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Relkin, Norman; Chaing, Gloria; Ravdin, Lisa; Paul, Steven; Flashman, Laura A.; Seltzer, Marc; Hynes, Mary L.; Santulli, Robert B.; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Friedl, Karl; Murali Doraiswamy, P.; Petrella, Jeffrey R.; Borges-Neto, Salvador; James, Olga; Wong, Terence; Coleman, Edward; Schwartz, Adam; Cellar, Janet S.; Levey, Allan L.; Lah, James J.; Behan, Kelly; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Tatsuoka, Curtis; Fatica, Parianne; Farlow, Martin R.; Saykin, Andrew J.; Foroud, Tatiana M.; Shen, Li; Faber, Kelly; Kim, Sungeun; Nho, Kwangsik; Marie Hake, Ann; Matthews, Brandy R.; Brosch, Jared R.; Herring, Scott; Hunt, Cynthia; Albert, Marilyn; Onyike, Chiadi; D’Agostino, Daniel; Kielb, Stephanie; Graff-Radford, Neill R; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Petersen, Ronald; Jack, Clifford R.; Bernstein, Matthew; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Chertkow, Howard; Hosein, Chris; Mintzer, Jacob; Spicer, Kenneth; Bachman, David; Grossman, Hillel; Mitsis, Effie; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Potter, William; Buckholtz, Neil; Hsiao, John; Kittur, Smita; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Pogorelec, Dana M.; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Johnson, Nancy; Chuang-Kuo; Kerwin, Diana; Bonakdarpour, Borna; Weintraub, Sandra; Grafman, Jordan; Lipowski, Kristine; Mesulam, Marek-Marsel; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Kaye, Jeffrey; Quinn, Joseph; Silbert, Lisa; Lind, Betty; Carter, Raina; Dolen, Sara; Borrie, Michael; Lee, T-Y; Bartha, Rob; Martinez, Walter; Villena, Teresa; Sadowsky, Carl; Khachaturian, Zaven; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Frank, Richard; Fleischman, Debra; Arfanakis, Konstantinos; Shah, Raj C.; deToledo-Morrell, Leyla; Sorensen, Greg; Finger, Elizabeth; Pasternack, Stephen; Rachinsky, Irina; Drost, Dick; Rogers, John; Kertesz, Andrew; Furst, Ansgar J.; Chad, Stevan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Mudge, Benita; Assaly, Michele; Fox, Nick; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Ekstam Smith, Karen; Burns, Jeffrey M.; Swerdlow, Russell H.; Brooks, William M.; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Natelson Love, Marissa; DeCarli, Charles; Carmichael, Owen; Olichney, John; Maillard, Pauline; Fletcher, Evan; Nguyen, Dana; Preda, Andrian; Potkin, Steven; Mulnard, Ruth A.; Thai, Gaby; McAdams-Ortiz, Catherine; Landau, Susan; Jagust, William; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H.S.; Lu, Po H.; Bartzokis, George; Thompson, Paul; Donohue, Michael; Thomas, Ronald G.; Walter, Sarah; Gessert, Devon; Brewer, James; Vanderswag, Helen; Sather, Tamie; Jiminez, Gus; Balasubramanian, Archana B.; Mason, Jennifer; Sim, Iris; Aisen, Paul; Davis, Melissa; Morrison, Rosemary; Harvey, Danielle; Thal, Lean; Beckett, Laurel; Neylan, Thomas; Finley, Shannon; Weiner, Michael W.; Hayes, Jacqueline; Rosen, Howard J.; Miller, Bruce L.; Perry, David; Massoglia, Dino; Brawman-Mentzer, Olga; Schuff, Norbert; Smith, Charles D.; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Koeppe, Robert A.; Lord, Joanne L.; Heidebrink, Judith L.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Clark, Christopher M.; Trojanowki, John Q.; Shaw, Leslie M.; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Foster, Norm; Montine, Tom; Fruehling, J. Jay; Harding, Sandra; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Petrie, Eric C.; Peskind, Elaine; Li, Gail; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Smith, Amanda; Ashok Raj, Balebail; Fargher, Kristin; Kuller, Lew; Mathis, Chet; Ann Oakley, Mary; Lopez, Oscar L.; Simpson, Donna M.; Sink, Kaycee M.; Gordineer, Leslie; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Cairns, Nigel J.; Raichle, Marc; Morris, John C.; Householder, Erin; Taylor-Reinwald, Lisa; Holtzman, David; Ances, Beau; Carroll, Maria; Creech, Mary L.; Franklin, Erin; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Varma, Pradeep; MacAvoy, Martha G.; Carson, Richard E.; van Dyck, Christopher H.; Davies, Peter; Holtzman, David; Morris, John C.; Bales, Kelly; Pickering, Eve H.; Lee, Jin-Moo; Heitsch, Laura; Kauwe, John; Goate, Alison; Piccio, Laura; Cruchaga, Carlos

2016-01-01

Genome-wide association studies of 146 plasma protein levels in 818 individuals revealed 56 genome-wide significant associations (28 novel) with 47 analytes. Loci associated with plasma levels of 39 proteins tested have been previously associated with various complex traits such as heart disease, inflammatory bowel disease, Type 2 diabetes, and multiple sclerosis. These data suggest that these plasma protein levels may constitute informative endophenotypes for these complex traits. We found three potential pleiotropic genes: ABO for plasma SELE and ACE levels, FUT2 for CA19-9 and CEA plasma levels, and APOE for ApoE and CRP levels. We also found multiple independent signals in loci associated with plasma levels of ApoH, CA19-9, FetuinA, IL6r, and LPa. Our study highlights the power of biological traits for genetic studies to identify genetic variants influencing clinically relevant traits, potential pleiotropic effects, and complex disease associations in the same locus.

Six Siderophore-Producing Microorganisms Identified in Biological Soil Crusts

NASA Astrophysics Data System (ADS)

Noonan, K.; Anbar, A. D.; Garcia-Pichel, F.; Poret-peterson, A. T.; Hartnett, H. E.

2011-12-01

Biological soil crusts (BSCs) are diverse microbial communities that colonize soils in arid and semi-arid environments. Cyanobacteria in BSCs are pioneer organisms that increase ecosystem habitability by providing fixed carbon (C) and nitrogen (N) as well as by reducing water run-off and increasing infiltration. Photosynthesis and N fixation, in particular, require a variety of metals in large quantities, and yet, metals are predominantly insoluble in the environments where BSCs thrive. Therefore, BSC organisms must have efficient strategies for extracting metals from soil minerals. We hypothesized that BSC microbes, particularly the cyanobacteria, produce siderophores to serve their metal-acquisition needs. Siderophores are small organic compounds that bind Fe with high affinity and are produced by a variety of microorganisms, including cyanobacteria. Most siderophores bind Fe, primarily; however, some can also bind Mo, V, and Cu. Soil siderophores are released by microbes to increase the solubility of metals from minerals and to facilitate microbial uptake. Thus, siderophores serve as chemical weathering agents and provide a direct link between soil microbes and minerals. Studying siderophore production in BSCs provides insight into how BSCs tackle the challenge of acquiring insoluble metals, and may help conservationists determine useful fertilizers for BSC growth by facilitating metal acquisition. Biological soil crusts were collected near Moab, UT. Soil slurries were prepared in deionized water and transferred to modified BG-11 agar plates. The O-CAS agar plate assay was used to screen organisms for siderophore production. Siderophore producing microbes were isolated and identified by16S rRNA gene sequencing. Cultures were then grown in 3 L batch cultures under metal limitation, and siderophore presence was monitored using the traditional liquid CAS assay. After siderophore detection, cells were removed by centrifugation, organic compounds were separated using

Synthetic biology approaches to biological containment: pre-emptively tackling potential risks

PubMed Central

Krüger, Antje; Csibra, Eszter; Gianni, Edoardo

2016-01-01

Biocontainment comprises any strategy applied to ensure that harmful organisms are confined to controlled laboratory conditions and not allowed to escape into the environment. Genetically engineered microorganisms (GEMs), regardless of the nature of the modification and how it was established, have potential human or ecological impact if accidentally leaked or voluntarily released into a natural setting. Although all evidence to date is that GEMs are unable to compete in the environment, the power of synthetic biology to rewrite life requires a pre-emptive strategy to tackle possible unknown risks. Physical containment barriers have proven effective but a number of strategies have been developed to further strengthen biocontainment. Research on complex genetic circuits, lethal genes, alternative nucleic acids, genome recoding and synthetic auxotrophies aim to design more effective routes towards biocontainment. Here, we describe recent advances in synthetic biology that contribute to the ongoing efforts to develop new and improved genetic, semantic, metabolic and mechanistic plans for the containment of GEMs. PMID:27903826

Synthetic biology approaches to biological containment: pre-emptively tackling potential risks.

PubMed

Torres, Leticia; Krüger, Antje; Csibra, Eszter; Gianni, Edoardo; Pinheiro, Vitor B

2016-11-30

Biocontainment comprises any strategy applied to ensure that harmful organisms are confined to controlled laboratory conditions and not allowed to escape into the environment. Genetically engineered microorganisms (GEMs), regardless of the nature of the modification and how it was established, have potential human or ecological impact if accidentally leaked or voluntarily released into a natural setting. Although all evidence to date is that GEMs are unable to compete in the environment, the power of synthetic biology to rewrite life requires a pre-emptive strategy to tackle possible unknown risks. Physical containment barriers have proven effective but a number of strategies have been developed to further strengthen biocontainment. Research on complex genetic circuits, lethal genes, alternative nucleic acids, genome recoding and synthetic auxotrophies aim to design more effective routes towards biocontainment. Here, we describe recent advances in synthetic biology that contribute to the ongoing efforts to develop new and improved genetic, semantic, metabolic and mechanistic plans for the containment of GEMs. © 2016 The Author(s).

Proteomic analysis of first trimester maternal serum to identify candidate biomarkers potentially predictive of spontaneous preterm birth.

PubMed

D'Silva, Arlene M; Hyett, Jon A; Coorssen, Jens R

2018-04-30

Spontaneous preterm birth (sPTB) remains a major clinical dilemma; current diagnostics and interventions have not reduced the rate of this serious healthcare burden. This study characterizes differential protein profiles and post-translational modifications (PTMs) in first trimester maternal serum using a refined top-down approach coupling two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to directly compare subsequent term and preterm labour events and identify marked protein differences. 30 proteoforms were found to be significantly increased or decreased in the sPTB group including 9 phosphoproteins and 11 glycoproteins. Changes occurred in proteins associated with immune and defence responses. We identified protein species that are associated with several clinically relevant biological processes, including interrelated biological networks linked to regulation of the complement cascade and coagulation pathways, immune modulation, metabolic processes and cell signalling. The finding of altered proteoforms in maternal serum from pregnancies that delivered preterm suggests these as potential early biomarkers of sPTB and also possible mediators of the disorder. Identifying changes in protein profiles is critical in the study of cell biology, and disease treatment and prevention. Identifying consistent changes in the maternal serum proteome during early pregnancy, including specific protein PTMs (e.g. phosphorylation, glycosylation), is likely to provide better opportunities for prediction, intervention and prevention of preterm birth. This is the first study to examine first trimester maternal serum using a highly refined top-down proteomic analytical approach based on high resolution 2DE coupled with mass spectrometry to directly compare preterm (<37 weeks) and preterm (≥37 weeks) events and identify select protein differences between these conditions. As such, the data present a promising avenue for translation of biomarker discovery to a

Identifying the role of conservation biology for solving the environmental crisis.

PubMed

Dalerum, Fredrik

2014-11-01

Humans are altering their living environment to an extent that could cause environmental collapse. Promoting change into environmental sustainability is therefore urgent. Despite a rapid expansion in conservation biology, appreciation of underlying causes and identification of long-term solutions have largely been lacking. I summarized knowledge regarding the environmental crisis, and argue that the most important contributions toward solutions come from economy, political sciences, and psychology. Roles of conservation biology include providing environmental protection until sustainable solutions have been found, evaluating the effectiveness of implemented solutions, and providing societies with information necessary to align effectively with environmental values. Because of the potential disciplinary discrepancy between finding long-term solutions and short-term protection, we may face critical trade-offs between allocations of resources toward achieving sustainability. Since biological knowledge is required for such trade-offs, an additional role for conservation biologists may be to provide guidance toward finding optimal strategies in such trade-offs.

The potential of standards-based agriculture biology as an alternative to traditional biology in California

NASA Astrophysics Data System (ADS)

Sellu, George Sahr

schools. Thoron & Meyer (2011) suggested that research into the contribution of integrated science courses toward higher test scores yielded mixed results. This finding may have been due in part to the fact that integrated science courses only incorporate select topics into agriculture education courses. In California, however, agriculture educators have developed standards-based courses such as Agriculture Biology (AgBio) that cover the same content standards as core traditional courses such as traditional biology. Students in both AgBio and traditional biology take the same standardized biology test. This is the first time there has been an opportunity for a fair comparison and a uniform metric for an agriscience course such as AgBio to be directly compared to traditional biology. This study will examine whether there are differences between AgBio and traditional biology with regard to standardized test scores in biology. Furthermore, the study examines differences in perception between teachers and students regarding teaching and learning activities associated with higher achievement in science. The findings of the study could provide a basis for presenting AgBio as a potential alternative to traditional biology. The findings of this study suggest that there are no differences between AgBio and traditional biology students with regard to standardized biology test scores. Additionally, the findings indicate that co-curricular activities in AgBio could contribute higher student achievement in biology. However, further research is required to identify specific activities in AgBio that contribute to higher achievement in science.

Identifying non-point sources of endocrine active compounds and their biological impacts in freshwater lakes

USGS Publications Warehouse

Baker, Beth H.; Martinovic-Weigelt, Dalma; Ferrey, Mark L.; Barber, Larry B.; Writer, Jeffrey H.; Rosenberry, Donald O.; Kiesling, Richard L.; Lundy, James R.; Schoenfuss, Heiko L.

2014-01-01

Contaminants of emerging concern, particularly endocrine active compounds (EACs), have been identified as a threat to aquatic wildlife. However, little is known about the impact of EACs on lakes through groundwater from onsite wastewater treatment systems (OWTS). This study aims to identify specific contributions of OWTS to Sullivan Lake, Minnesota, USA. Lake hydrology, water chemistry, caged bluegill sunfish (Lepomis macrochirus), and larval fathead minnow (Pimephales promelas) exposures were used to assess whether EACs entered the lake through OWTS inflow and the resultant biological impact on fish. Study areas included two OWTS-influenced near-shore sites with native bluegill spawning habitats and two in-lake control sites without nearby EAC sources. Caged bluegill sunfish were analyzed for plasma vitellogenin concentrations, organosomatic indices, and histological pathologies. Surface and porewater was collected from each site and analyzed for EACs. Porewater was also collected for laboratory exposure of larval fathead minnow, before analysis of predator escape performance and gene expression profiles. Chemical analysis showed EACs present at low concentrations at each study site, whereas discrete variations were reported between sites and between summer and fall samplings. Body condition index and liver vacuolization of sunfish were found to differ among study sites as did gene expression in exposed larval fathead minnows. Interestingly, biological exposure data and water chemistry did not match. Therefore, although results highlight the potential impacts of seepage from OWTS, further investigation of mixture effects and life history factor as well as chemical fate is warranted.

Identifying biologically meaningful hot-weather events using threshold temperatures that affect life-history.

PubMed

Cunningham, Susan J; Kruger, Andries C; Nxumalo, Mthobisi P; Hockey, Philip A R

2013-01-01

Increases in the frequency, duration and intensity of heat waves are frequently evoked in climate change predictions. However, there is no universal definition of a heat wave. Recent, intense hot weather events have caused mass mortalities of birds, bats and even humans, making the definition and prediction of heat wave events that have the potential to impact populations of different species an urgent priority. One possible technique for defining biologically meaningful heat waves is to use threshold temperatures (T(thresh)) above which known fitness costs are incurred by species of interest. We set out to test the utility of this technique using T(thresh) values that, when exceeded, affect aspects of the fitness of two focal southern African bird species: the southern pied babbler Turdiodes bicolor (T(thresh) = 35.5 °C) and the common fiscal Lanius collaris (T(thresh) = 33 °C). We used these T(thresh) values to analyse trends in the frequency, duration and intensity of heat waves of magnitude relevant to the focal species, as well as the annual number of hot days (maximum air temperature > T(thresh)), in north-western South Africa between 1961 and 2010. Using this technique, we were able to show that, while all heat wave indices increased during the study period, most rapid increases for both species were in the annual number of hot days and in the maximum intensity (and therefore intensity variance) of biologically meaningful heat waves. Importantly, we also showed that warming trends were not uniform across the study area and that geographical patterns in warming allowed both areas of high risk and potential climate refugia to be identified. We discuss the implications of the trends we found for our focal species, and the utility of the T(thresh) technique as a conservation tool.

Identifying Biologically Meaningful Hot-Weather Events Using Threshold Temperatures That Affect Life-History

PubMed Central

Cunningham, Susan J.; Kruger, Andries C.; Nxumalo, Mthobisi P.

2013-01-01

Increases in the frequency, duration and intensity of heat waves are frequently evoked in climate change predictions. However, there is no universal definition of a heat wave. Recent, intense hot weather events have caused mass mortalities of birds, bats and even humans, making the definition and prediction of heat wave events that have the potential to impact populations of different species an urgent priority. One possible technique for defining biologically meaningful heat waves is to use threshold temperatures (Tthresh) above which known fitness costs are incurred by species of interest. We set out to test the utility of this technique using Tthresh values that, when exceeded, affect aspects of the fitness of two focal southern African bird species: the southern pied babbler Turdiodes bicolor (Tthresh = 35.5°C) and the common fiscal Lanius collaris (Tthresh = 33°C). We used these Tthresh values to analyse trends in the frequency, duration and intensity of heat waves of magnitude relevant to the focal species, as well as the annual number of hot days (maximum air temperature > Tthresh), in north-western South Africa between 1961 and 2010. Using this technique, we were able to show that, while all heat wave indices increased during the study period, most rapid increases for both species were in the annual number of hot days and in the maximum intensity (and therefore intensity variance) of biologically meaningful heat waves. Importantly, we also showed that warming trends were not uniform across the study area and that geographical patterns in warming allowed both areas of high risk and potential climate refugia to be identified. We discuss the implications of the trends we found for our focal species, and the utility of the Tthresh technique as a conservation tool. PMID:24349296

Biological and molecular characterization of cellular differentiation in Tetrahymena vorax: a potential biocontrol protozoan.

PubMed

Green, M M; LeBoeuf, R D; Churchill, P F

2000-01-01

Tetrahymena vorax (T. vorax) is an indigenous fresh water protozoan with the natural biological potential to maintain a specific aquatic microbial flora by ingesting and eliminating specific microorganism. To investigate the molecular mechanisms controlling Tetrahymena vorax (T. vorax) cellular differentiation from a small-mouth vegetative cell to a voracious large-mouth carnivore capable of ingesting prey ciliates and bacteria from aquatic environments, we use DNA subtraction and gene discovery techniques to identify and isolate T. vorax differentiation-specific genes. The physiological necessity for one newly discovered gene, SUBII-TG, was determined in vivo using an antisense oligonucleotide directed against the 5' SUBII-TG DNA sequence. The barriers to delivering antisense oligonucleotides to the cytoplasm of T. vorax were circumvented by employing a new but simple procedure of processing the oligonucleotide with the differentiation stimulus, stomatin. In these studies, the antisense oligonucleotide down-regulated SUBII-TG mRNA expression, and blocked differentiation and ingestion of prey ciliates. The ability to down-regulate SUBII-TG expression with the antisense oligonucleotide suggests that the molecular mechanisms controlling the natural biological activities of T. vorax can be manipulated to further study its cellular differentiation and potential as a biocontrol microorganism.

Systems Biology in Animal Breeding: Identifying relationships among markers, genes, and phenotypes

USDA-ARS?s Scientific Manuscript database

The Breeding and Genetics Symposium titled “Systems Biology in Animal Breeding: Identifying relationships among markers, genes, and phenotypes” was held at the Joint Annual Meeting of the American Dairy Science Association and the American Society of Animal Science in Phoenix, AZ, July 15 to 19, 201...

Cold tolerance of Trissolcus japonicus and T. cultratus, potential biological control agents of Halyomorpha halys, the brown marmorated stink bug

Treesearch

Erica Nystrom Santacruz; Robert C. Venette; Christine Dieckhoff; Kim Hoelmer; Robert L. Koch

2017-01-01

Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) is native to Asia and has become a severe agricultural and nuisance pest in the U.S. Therefore, foreign exploration was conducted in Asia to identify potential classical biological control agents. Several Trissolcus spp. (Hymenoptera: Scelionidae) parasitize H. halys...

Genetic regulation of gene expression in the lung identifies CST3 and CD22 as potential causal genes for airflow obstruction.

PubMed

Lamontagne, Maxime; Timens, Wim; Hao, Ke; Bossé, Yohan; Laviolette, Michel; Steiling, Katrina; Campbell, Joshua D; Couture, Christian; Conti, Massimo; Sherwood, Karen; Hogg, James C; Brandsma, Corry-Anke; van den Berge, Maarten; Sandford, Andrew; Lam, Stephen; Lenburg, Marc E; Spira, Avrum; Paré, Peter D; Nickle, David; Sin, Don D; Postma, Dirkje S

2014-11-01

COPD is a complex chronic disease with poorly understood pathogenesis. Integrative genomic approaches have the potential to elucidate the biological networks underlying COPD and lung function. We recently combined genome-wide genotyping and gene expression in 1111 human lung specimens to map expression quantitative trait loci (eQTL). To determine causal associations between COPD and lung function-associated single nucleotide polymorphisms (SNPs) and lung tissue gene expression changes in our lung eQTL dataset. We evaluated causality between SNPs and gene expression for three COPD phenotypes: FEV(1)% predicted, FEV(1)/FVC and COPD as a categorical variable. Different models were assessed in the three cohorts independently and in a meta-analysis. SNPs associated with a COPD phenotype and gene expression were subjected to causal pathway modelling and manual curation. In silico analyses evaluated functional enrichment of biological pathways among newly identified causal genes. Biologically relevant causal genes were validated in two separate gene expression datasets of lung tissues and bronchial airway brushings. High reliability causal relations were found in SNP-mRNA-phenotype triplets for FEV(1)% predicted (n=169) and FEV(1)/FVC (n=80). Several genes of potential biological relevance for COPD were revealed. eQTL-SNPs upregulating cystatin C (CST3) and CD22 were associated with worse lung function. Signalling pathways enriched with causal genes included xenobiotic metabolism, apoptosis, protease-antiprotease and oxidant-antioxidant balance. By using integrative genomics and analysing the relationships of COPD phenotypes with SNPs and gene expression in lung tissue, we identified CST3 and CD22 as potential causal genes for airflow obstruction. This study also augmented the understanding of previously described COPD pathways. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Mast cells: potential positive and negative roles in tumor biology.

PubMed

Marichal, Thomas; Tsai, Mindy; Galli, Stephen J

2013-11-01

Mast cells are immune cells that reside in virtually all vascularized tissues. Upon activation by diverse mechanisms, mast cells can secrete a broad array of biologically active products that either are stored in the cytoplasmic granules of the cells (e.g., histamine, heparin, various proteases) or are produced de novo upon cell stimulation (e.g., prostaglandins, leukotrienes, cytokines, chemokines, and growth factors). Mast cells are best known for their effector functions during anaphylaxis and acute IgE-associated allergic reactions, but they also have been implicated in a wide variety of processes that maintain health or contribute to disease. There has been particular interest in the possible roles of mast cells in tumor biology. In vitro studies have shown that mast cells have the potential to influence many aspects of tumor biology, including tumor development, tumor-induced angiogenesis, and tissue remodeling, and the shaping of adaptive immune responses to tumors. Yet, the actual contributions of mast cells to tumor biology in vivo remain controversial. Here, we review some basic features of mast cell biology with a special emphasis on those relevant to their potential roles in tumors. We discuss how using in vivo tumor models in combination with models in which mast cell function can be modulated has implicated mast cells in the regulation of host responses to tumors. Finally, we summarize data from studies of human tumors that suggest either beneficial or detrimental roles for mast cells in tumors. ©2013 AACR.

Identifying novel glioma associated pathways based on systems biology level meta-analysis.

PubMed

Hu, Yangfan; Li, Jinquan; Yan, Wenying; Chen, Jiajia; Li, Yin; Hu, Guang; Shen, Bairong

2013-01-01

With recent advances in microarray technology, including genomics, proteomics, and metabolomics, it brings a great challenge for integrating this "-omics" data to analysis complex disease. Glioma is an extremely aggressive and lethal form of brain tumor, and thus the study of the molecule mechanism underlying glioma remains very important. To date, most studies focus on detecting the differentially expressed genes in glioma. However, the meta-analysis for pathway analysis based on multiple microarray datasets has not been systematically pursued. In this study, we therefore developed a systems biology based approach by integrating three types of omics data to identify common pathways in glioma. Firstly, the meta-analysis has been performed to study the overlapping of signatures at different levels based on the microarray gene expression data of glioma. Among these gene expression datasets, 12 pathways were found in GeneGO database that shared by four stages. Then, microRNA expression profiles and ChIP-seq data were integrated for the further pathway enrichment analysis. As a result, we suggest 5 of these pathways could be served as putative pathways in glioma. Among them, the pathway of TGF-beta-dependent induction of EMT via SMAD is of particular importance. Our results demonstrate that the meta-analysis based on systems biology level provide a more useful approach to study the molecule mechanism of complex disease. The integration of different types of omics data, including gene expression microarrays, microRNA and ChIP-seq data, suggest some common pathways correlated with glioma. These findings will offer useful potential candidates for targeted therapeutic intervention of glioma.

Integration analysis of quantitative proteomics and transcriptomics data identifies potential targets of frizzled-8 protein-related antiproliferative factor in vivo.

PubMed

Yang, Wei; Kim, Yongsoo; Kim, Taek-Kyun; Keay, Susan K; Kim, Kwang Pyo; Steen, Hanno; Freeman, Michael R; Hwang, Daehee; Kim, Jayoung

2012-12-01

What's known on the subject? and What does the study add? Interstitial cystitis (IC) is a prevalent and debilitating pelvic disorder generally accompanied by chronic pain combined with chronic urinating problems. Over one million Americans are affected, especially middle-aged women. However, its aetiology or mechanism remains unclear. No efficient drug has been provided to patients. Several urinary biomarker candidates have been identified for IC; among the most promising is antiproliferative factor (APF), whose biological activity is detectable in urine specimens from >94% of patients with both ulcerative and non-ulcerative IC. The present study identified several important mediators of the effect of APF on bladder cell physiology, suggesting several candidate drug targets against IC. In an attempt to identify potential proteins and genes regulated by APF in vivo, and to possibly expand the APF-regulated network identified by stable isotope labelling by amino acids in cell culture (SILAC), we performed an integration analysis of our own SILAC data and the microarray data of Gamper et al. (2009) BMC Genomics 10: 199. Notably, two of the proteins (i.e. MAPKSP1 and GSPT1) that are down-regulated by APF are involved in the activation of mTORC1, suggesting that the mammalian target of rapamycin (mTOR) pathway is potentially a critical pathway regulated by APF in vivo. Several components of the mTOR pathway are currently being studied as potential therapeutic targets in other diseases. Our analysis suggests that this pathway might also be relevant in the design of diagnostic tools and medications targeting IC. • To enhance our understanding of the interstitial cystitis urine biomarker antiproliferative factor (APF), as well as interstitial cystitis biology more generally at the systems level, we reanalyzed recently published large-scale quantitative proteomics and in vivo transcriptomics data sets using an integration analysis tool that we have developed. • To

Identifying niche-mediated regulatory factors of stem cell phenotypic state: a systems biology approach.

PubMed

Ravichandran, Srikanth; Del Sol, Antonio

2017-02-01

Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and nonlinear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants). This view offers a new basis for the development of single cell-based computational approaches for identifying niche determinants, which has potential applications in regenerative medicine and tissue engineering. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation.

PubMed

Godec, Jernej; Tan, Yan; Liberzon, Arthur; Tamayo, Pablo; Bhattacharya, Sanchita; Butte, Atul J; Mesirov, Jill P; Haining, W Nicholas

2016-01-19

Gene-expression profiling has become a mainstay in immunology, but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets. For instance, conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial. To improve transcriptional analysis in immunology, we created ImmuneSigDB: a manually annotated compendium of ∼5,000 gene-sets from diverse cell states, experimental manipulations, and genetic perturbations in immunology. Analysis using ImmuneSigDB identified signatures induced in activated myeloid cells and differentiating lymphocytes that were highly conserved between humans and mice. Sepsis triggered conserved patterns of gene expression in humans and mouse models. However, we also identified species-specific biological processes in the sepsis transcriptional response: although both species upregulated phagocytosis-related genes, a mitosis signature was specific to humans. ImmuneSigDB enables granular analysis of transcriptomic data to improve biological understanding of immune processes of the human and mouse immune systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Robust global identifiability theory using potentials--Application to compartmental models.

PubMed

Wongvanich, N; Hann, C E; Sirisena, H R

2015-04-01

This paper presents a global practical identifiability theory for analyzing and identifying linear and nonlinear compartmental models. The compartmental system is prolonged onto the potential jet space to formulate a set of input-output equations that are integrals in terms of the measured data, which allows for robust identification of parameters without requiring any simulation of the model differential equations. Two classes of linear and non-linear compartmental models are considered. The theory is first applied to analyze the linear nitrous oxide (N2O) uptake model. The fitting accuracy of the identified models from differential jet space and potential jet space identifiability theories is compared with a realistic noise level of 3% which is derived from sensor noise data in the literature. The potential jet space approach gave a match that was well within the coefficient of variation. The differential jet space formulation was unstable and not suitable for parameter identification. The proposed theory is then applied to a nonlinear immunological model for mastitis in cows. In addition, the model formulation is extended to include an iterative method which allows initial conditions to be accurately identified. With up to 10% noise, the potential jet space theory predicts the normalized population concentration infected with pathogens, to within 9% of the true curve. Copyright © 2015 Elsevier Inc. All rights reserved.

A theoretical framework for biological control of soil-borne plant pathogens: Identifying effective strategies.

PubMed

Cunniffe, Nik J; Gilligan, Christopher A

2011-06-07

We develop and analyse a flexible compartmental model of the interaction between a plant host, a soil-borne pathogen and a microbial antagonist, for use in optimising biological control. By extracting invasion and persistence thresholds of host, pathogen and biological control agent, performing an equilibrium analysis, and numerical investigation of sensitivity to parameters and initial conditions, we determine criteria for successful biological control. We identify conditions for biological control (i) to prevent a pathogen entering a system, (ii) to eradicate a pathogen that is already present and, if that is not possible, (iii) to reduce the density of the pathogen. Control depends upon the epidemiology of the pathogen and how efficiently the antagonist can colonise particular habitats (i.e. healthy tissue, infected tissue and/or soil-borne inoculum). A sharp transition between totally effective control (i.e. eradication of the pathogen) and totally ineffective control can follow slight changes in biologically interpretable parameters or to the initial amounts of pathogen and biological control agent present. Effective biological control requires careful matching of antagonists to pathosystems. For preventative/eradicative control, antagonists must colonise susceptible hosts. However, for reduction in disease prevalence, the range of habitat is less important than the antagonist's bulking-up efficiency. Copyright © 2011 Elsevier Ltd. All rights reserved.

Synthetic Biology and Human Health: Potential Applications for Spaceflight

NASA Technical Reports Server (NTRS)

Karouia, Fathi; Carr, Christopher; Cai, Yizhi; Chen, Y.; Grenon, Marlene; Larios-Sanz, Maia; Jones, Jeffrey A.; Santos, Orlando

2011-01-01

Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. Spaceflight-related changes have been reported in the musculo-skeletal, cardiovascular, neurovestibular, endocrine, and immune systems. The spacecraft environment further subjects the traveler to noise and gravitational forces, as well as airborne chemical, microbiological contaminants, and radiation exposure. As humans prepare for longer duration missions effective countermeasures must be developed, verified, and implemented to ensure mission success. Over the past ten years, synthetic biology has opened new avenues for research and development in areas such as biological control, biomaterials, sustainable energy production, bioremediation, and biomedical therapies. The latter in particular is of great interest to the implementation of long-duration human spaceflight capabilities. This article discusses the effects of spaceflight on humans, and reviews current capabilities and potential needs associated with the health of the astronauts where synthetic biology could play an important role in the pursuit of space exploration.

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

PubMed

Chasman, Daniel I; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary F; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid B; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Kao, W H Linda; Fox, Caroline S; Köttgen, Anna

2012-12-15

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function

PubMed Central

Chasman, Daniel I.; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A.; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary F.; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S.; van Duijn, Cornelia M.; Borecki, Ingrid B.; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Kao, W.H. Linda; Fox, Caroline S.; Köttgen, Anna

2012-01-01

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10−9) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10−4–2.2 × 10−7. Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general. PMID:22962313

Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

PubMed

Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

2017-11-01

Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

Identifying potential academic leaders

PubMed Central

White, David; Krueger, Paul; Meaney, Christopher; Antao, Viola; Kim, Florence; Kwong, Jeffrey C.

2016-01-01

Objective To identify variables associated with willingness to undertake leadership roles among academic family medicine faculty. Design Web-based survey. Bivariate and multivariable analyses (logistic regression) were used to identify variables associated with willingness to undertake leadership roles. Setting Department of Family and Community Medicine at the University of Toronto in Ontario. Participants A total of 687 faculty members. Main outcome measures Variables related to respondents’ willingness to take on various academic leadership roles. Results Of all 1029 faculty members invited to participate in the survey, 687 (66.8%) members responded. Of the respondents, 596 (86.8%) indicated their level of willingness to take on various academic leadership roles. Multivariable analysis revealed that the predictors associated with willingness to take on leadership roles were as follows: pursuit of professional development opportunities (odds ratio [OR] 3.79, 95% CI 2.29 to 6.27); currently holding at least 1 leadership role (OR 5.37, 95% CI 3.38 to 8.53); a history of leadership training (OR 1.86, 95% CI 1.25 to 2.78); the perception that mentorship is important for one’s current role (OR 2.25, 95% CI 1.40 to 3.60); and younger age (OR 0.97, 95% CI 0.95 to 0.99). Conclusion Willingness to undertake new or additional leadership roles was associated with 2 variables related to leadership experiences, 2 variables related to perceptions of mentorship and professional development, and 1 demographic variable (younger age). Interventions that support opportunities in these areas might expand the pool and strengthen the academic leadership potential of faculty members. PMID:27331226

Systemic analysis of genome-wide expression profiles identified potential therapeutic targets of demethylation drugs for glioblastoma.

PubMed

Ning, Tongbo; Cui, Hao; Sun, Feng; Zou, Jidian

2017-09-05

Glioblastoma represents one of the most aggressive malignant brain tumors with high morbidity and motility. Demethylation drugs have been developed for its treatment with little efficacy has been observed. The purpose of this study was to screen therapeutic targets of demethylation drugs or bioactive molecules for glioblastoma through systemic bioinformatics analysis. We firstly downloaded genome-wide expression profiles from the Gene Expression Omnibus (GEO) and conducted the primary analysis through R software, mainly including preprocessing of raw microarray data, transformation between probe ID and gene symbol and identification of differential expression genes (DEGs). Secondly, functional enrichment analysis was conducted via the Database for Annotation, Visualization and Integrated Discovery (DAVID) to explore biological processes involved in the development of glioblastoma. Thirdly, we constructed protein-protein interaction (PPI) network of interested genes and conducted cross analysis for multi datasets to obtain potential therapeutic targets for glioblastoma. Finally, we further confirmed the therapeutic targets through real-time RT-PCR. As a result, biological processes that related to cancer development, amino metabolism, immune response and etc. were found to be significantly enriched in genes that differential expression in glioblastoma and regulated by 5'aza-dC. Besides, network and cross analysis identified ACAT2, UFC1 and CYB5R1 as novel therapeutic targets of demethylation drugs which also confirmed by real time RT-PCR. In conclusions, our study identified several biological processes and genes that involved in the development of glioblastoma and regulated by 5'aza-dC, which would be helpful for the treatment of glioblastoma. Copyright © 2017 Elsevier B.V. All rights reserved.

A transatlantic perspective on 20 emerging issues in biological engineering

PubMed Central

Rhodes, Catherine; Molloy, Jennifer C; Millett, Piers; Adam, Laura; Breitling, Rainer; Carlson, Rob; Casagrande, Rocco; Dando, Malcolm; Doubleday, Robert; Drexler, Eric; Edwards, Brett; Ellis, Tom; Evans, Nicholas G; Hammond, Richard; Haseloff, Jim; Kahl, Linda; Kuiken, Todd; Lichman, Benjamin R; Matthewman, Colette A; Napier, Johnathan A; ÓhÉigeartaigh, Seán S; Patron, Nicola J; Perello, Edward; Shapira, Philip; Tait, Joyce; Takano, Eriko; Sutherland, William J

2017-01-01

Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment. PMID:29132504

A transatlantic perspective on 20 emerging issues in biological engineering.

PubMed

Wintle, Bonnie C; Boehm, Christian R; Rhodes, Catherine; Molloy, Jennifer C; Millett, Piers; Adam, Laura; Breitling, Rainer; Carlson, Rob; Casagrande, Rocco; Dando, Malcolm; Doubleday, Robert; Drexler, Eric; Edwards, Brett; Ellis, Tom; Evans, Nicholas G; Hammond, Richard; Haseloff, Jim; Kahl, Linda; Kuiken, Todd; Lichman, Benjamin R; Matthewman, Colette A; Napier, Johnathan A; ÓhÉigeartaigh, Seán S; Patron, Nicola J; Perello, Edward; Shapira, Philip; Tait, Joyce; Takano, Eriko; Sutherland, William J

2017-11-14

Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment.

Chemical and Biological Defense: Designated Entity Needed to Identify, Align, and Manage DOD’s Infrastructure

DTIC Science & Technology

2015-06-01

Designated Leader, GAO-10-645 (Washington, D.C.: June 30, 2010). 35See GAO, Biological Defense: DOD Has Strengthened Coordination on Medical... on track to be designated a Leadership in Energy and Environmental Design facility. metabolic poisons, and pulmonary toxicants; nerve agent...CHEMICAL AND BIOLOGICAL DEFENSE Designated Entity Needed to Identify, Align, and Manage DOD’s Infrastructure

Magnetic nanoparticles as potential candidates for biomedical and biological applications.

PubMed

Zeinali Sehrig, Fatemeh; Majidi, Sima; Nikzamir, Nasrin; Nikzamir, Nasim; Nikzamir, Mohammad; Akbarzadeh, Abolfazl

2016-05-01

Magnetic iron oxide nanoparticles have become the main candidates for biomedical and biological applications, and the application of small iron oxide nanoparticles in in vitro diagnostics has been practiced for about half a century. Magnetic nanoparticles (MNPs), in combination with an external magnetic field and/or magnetizable grafts, allow the delivery of particles to the chosen target area, fix them at the local site while the medication is released, and act locally. In this review, we focus mostly on the potential use of MNPs for biomedical and biotechnological applications, and the improvements made in using these nanoparticles (NPs) in biological applications.

An outlook review: mechanochromic materials and their potential for biological and healthcare applications.

PubMed

Jiang, Ying

2014-12-01

Macroscopic mechanical perturbations have been observed to result in optical changes for certain compounds and composite materials. This phenomenon could originate from chemical and physical changes across various length scales, from the rearrangement of chemical bonds to alteration of molecular domains on the order of several hundred nanometers. This review classifies the mechanisms and surveys of how each class of mechanochromic materials has been, and can potentially be applied in biological and healthcare innovations. The study of cellular and molecular responses to mechanical forces in biological systems is an emerging field; there is potential in applying mechanochromic principles and material systems for probing biological systems. On the other hand, application of mechanochromic materials for medical and healthcare consumer products has been described in a wide variety of concepts and inventions. It is hopeful that further understanding of mechanochromism and material innovations would initiate concrete, impactful studies in biological systems soon. Copyright © 2014 Elsevier B.V. All rights reserved.

Identifying Affordances of 3D Printed Tangible Models for Understanding Core Biological Concepts

ERIC Educational Resources Information Center

Davenport, Jodi L.; Silberglitt, Matt; Boxerman, Jonathan; Olson, Arthur

2014-01-01

3D models derived from actual molecular structures have the potential to transform student learning in biology. We share findings related to our research questions: 1) what types of interactions with a protein folding kit promote specific learning objectives?, and 2) what features of the instructional environment (e.g., peer interactions, teacher…

Preliminary nutritional and biological potential of Artocarpus heterophyllus L. shell powder.

PubMed

Sharma, Anubhuti; Gupta, Priti; Verma, A K

2015-03-01

Artocarpus heterophyllus shell powder was investigated in terms of its nutritional and biological potential. A thorough examination of shell powder demonstrated its potential as a source of minerals, β carotene and dietary fiber, which were assessed gravimetrically & spectrophotometrically. This showed 3.05 ± 0.19 g 100 g(-1) DW of alkaloids followed by saponins and tannins. Three different extracts; acetone, methanol, & mix solvent were used to evaluate phenolic & flavonoid content, antioxidant & antimicrobial activity, GC/MS screening and quantitative analysis of polyphenols. Among all, the methanol extract showed highest antioxidant activity evaluated by DPPH, FRAP & ABTS assays and was significantly correlated with phenolic and flavonoid contents. Phenolic & flavonoid content was found to be 158 ± 0.34 mg (GAE) and 10.0 ± 0.64 mg (CE) respectively. The results of antimicrobial activity showed that L. monocytogenes was more susceptible to all extracts followed by other microorganisms. Catechin, ascorbic & chlorogenic acids were identified as major polyphenols analyzed by LC-MS/MS. GC/MS analysis showed that it contains a variety of compounds with different therapeutic activities. The study revealed that A. heterophyllus shell is a good source of natural antioxidants & other bioactive compounds and can be used in cosmetics, medicines and functional food application.

Biological Activities and Potential Oral Applications of N-Acetylcysteine: Progress and Prospects

PubMed Central

Pei, Yanping; Liu, Huan; Yang, Yi; Yang, Yanwei

2018-01-01

N-Acetylcysteine (NAC), a cysteine prodrug and glutathione (GSH) precursor, has been used for several decades in clinical therapeutic practices as a mucolytic agent and for the treatment of disorders associated with GSH deficiency. Other therapeutic activities of NAC include inhibition of inflammation/NF-κB signaling and expression of proinflammatory cytokines. N-Acetylcysteine is also a nonantibiotic compound possessing antimicrobial property and exerts anticarcinogenic and antimutagenic effects against certain types of cancer. Recently, studies describing potentially important biological and pharmacological activities of NAC have stimulated interests in using NAC-based therapeutics for oral health care. The present review focused on the biological activities of NAC and its potential oral applications. The potential side effects of NAC and formulations for drug delivery were also discussed, with the intent of advancing NAC-associated treatment modalities in oral medicine. PMID:29849877

Creating biological nanomaterials using synthetic biology.

PubMed

Rice, MaryJoe K; Ruder, Warren C

2014-02-01

Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

The Biology of the Glutamatergic System and Potential Role in Migraine

PubMed Central

Gasparini, C. F.; Griffiths, L. R.

2013-01-01

Migraine is a common genetically linked neurovascular disorder. Approximately ∼12% of the Caucasian population are affected including 18% of adult women and 6% of adult men (1, 2). A notable female bias is observed in migraine prevalence studies with females affected ∼3 times more than males and is credited to differences in hormone levels arising from reproductive achievements. Migraine is extremely debilitating with wide-ranging socioeconomic impact significantly affecting people’s health and quality of life. A number of neurotransmitter systems have been implicated in migraine, the most studied include the serotonergic and dopaminergic systems. Extensive genetic research has been carried out to identify genetic variants that may alter the activity of a number of genes involved in synthesis and transport of neurotransmitters of these systems. The biology of the Glutamatergic system in migraine is the least studied however there is mounting evidence that its constituents could contribute to migraine. The discovery of antagonists that selectively block glutamate receptors has enabled studies on the physiologic role of glutamate, on one hand, and opened new perspectives pertaining to the potential therapeutic applications of glutamate receptor antagonists in diverse neurologic diseases. In this brief review, we discuss the biology of the Glutamatergic system in migraine outlining recent findings that support a role for altered Glutamatergic neurotransmission from biochemical and genetic studies in the manifestation of migraine and the implications of this on migraine treatment. PMID:23675283

Human Papillomavirus Biology, Pathogenesis, and Potential for Drug Discovery: A Literature Review for HIV Nurse Clinical Scientists.

PubMed

Walhart, Tara

2015-01-01

Persistent oncogenic human papillomavirus (HPV) infection increases the probability that precancerous anal high-grade squamous intraepithelial lesions will progress to invasive anal cancer. Anal neoplasia associated with HPV disproportionately affects HIV-infected individuals, especially men who have sex with men. Prevention is limited to HPV vaccine recommendations, highlighting the need for new treatments. The purpose of this review is to provide HIV information to nurse clinical scientists about HPV-related cancer to highlight the connection between: (a) HPV biology and pathogenesis and (b) the development of drugs and novel therapeutic methods using high-throughput screening. PubMed and CINAHL were used to search the literature to determine HPV-related epidemiology, biology, and use of high-throughput screening for drug discovery. Several events in the HPV life cycle have the potential to be developed into biologic targets for drug discovery using the high-throughput screening technique, which has been successfully used to identify compounds to inhibit HPV infections. Copyright © 2015 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Using consumption rate to assess potential predators for biological control of white perch

USGS Publications Warehouse

Gosch, N.J.C.; Pope, K.L.

2011-01-01

Control of undesirable fishes is important in aquatic systems, and using predation as a tool for biological control is an attractive option to fishery biologists. However, determining the appropriate predators for biological control is critical for success. The objective of this study was to evaluate the utility of consumption rate as an index to determine the most effective predators for biological control of an invasive fish. Consumption rate values were calculated for nine potential predators that prey on white perch Morone americana in Branched Oak and Pawnee reservoirs, Nebraska. The consumption rate index provided a unique and insightful means of determining the potential effectiveness of each predator species in controlling white perch. Cumulative frequency distributions facilitated interpretation by providing a graphical presentation of consumption rates by all individuals within each predator species. Largemouth bass Micropterus salmoides, walleye Sander vitreus and sauger S. canadensis were the most efficient white perch predators in both reservoirs; however, previous attempts to increase biomass of these predators have failed suggesting that successful biological control is unlikely using existing predator species in these Nebraska reservoirs. ?? 2011 ONEMA.

Identifying Potential Kidney Donors Using Social Networking Websites

PubMed Central

Chang, Alexander; Anderson, Emily E.; Turner, Hang T.; Shoham, David; Hou, Susan H.; Grams, Morgan

2013-01-01

Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation. They allow for wide dissemination of information and discussion, and could lessen anxiety associated with a face-to-face request for donation. However, sparse data exist on the use of social media for this purpose. We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested. In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2–69); 88% were U.S. residents. Other posted information included the individual’s photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%). Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live donor kidney transplant. Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic. Facebook is already being used to identify potential kidney donors. Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation. PMID:23600791

Biological Control Potential of Neoaplectanid Nematodes

PubMed Central

Gaugler, Randy

1981-01-01

The neoaplectanids are among the most studied of all entomogenous nematodes. Because these nematodes kill their insect hosts, they are regarded as having excellent potential as biological control agents. While the host specificity of most entontogenous nematodes tends to limit their potential usefulness, the broad host range and high virulence of neoaplectanids make them attractive candidates for industrial development. Also, recent development of economical mass rearing procedures appears to make production on a commercial basis feasible. Infective stages may be stored for years trader various laboratory conditions. Although entomogenous nematodes, as parasites, are exempt from govermnent registration requirements, the mutualistic association of neoaplectanid nematodes with a bacterium will likely necessitate a detailed safety evaluation. Studies conducted to date indicate a lack of pathogenicity to mammals. Field trial success has been limited by the intolerance of infective stages to mffavorable environmental conditions, particularly low moisture. Applications against pests on exposed plant foliage have been especially disappointing. More encouraging anti consistent results have been obtained in more favorable environments, including soil and aquatic habitats, but the most promising treatment sites ntay be cryptic habitats where infective stages are shehered from environmental extremes. Cryptic habitats also exploit the ability of neoaplectanids to actively seek out hosts in recessed places where conventional insecticide applications are intpractical. PMID:19300757

Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects.

PubMed

Vassar, Robert; Kuhn, Peer-Hendrik; Haass, Christian; Kennedy, Matthew E; Rajendran, Lawrence; Wong, Philip C; Lichtenthaler, Stefan F

2014-07-01

The β-site APP cleaving enzymes 1 and 2 (BACE1 and BACE2) were initially identified as transmembrane aspartyl proteases cleaving the amyloid precursor protein (APP). BACE1 is a major drug target for Alzheimer's disease because BACE1-mediated cleavage of APP is the first step in the generation of the pathogenic amyloid-β peptides. BACE1, which is highly expressed in the nervous system, is also required for myelination by cleaving neuregulin 1. Several recent proteomic and in vivo studies using BACE1- and BACE2-deficient mice demonstrate a much wider range of physiological substrates and functions for both proteases within and outside of the nervous system. For BACE1 this includes axon guidance, neurogenesis, muscle spindle formation, and neuronal network functions, whereas BACE2 was shown to be involved in pigmentation and pancreatic β-cell function. This review highlights the recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism-based liabilities, in particular for BACE inhibitors in Alzheimer's disease. The protease BACE1 is a major drug target in Alzheimer disease. Together with its homolog BACE2, both proteases have an increasing number of functions within and outside of the nervous system. This review highlights recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism-based liabilities, in particular for BACE inhibitors in Alzheimer disease. © 2014 International Society for Neurochemistry.

3D-printed biological organs: medical potential and patenting opportunity.

PubMed

Yoo, Seung-Schik

2015-05-01

Three-dimensional (3D) bioprinting has emerged as a new disruptive technology that may address the ever-increasing demand for organ transplants. 3D bioprinting offers many technical features that allow for building functional biological tissue constructs by dispensing the individual or group of cells into specific locations along with various types of bio-scaffold materials and extracellular matrices, and thus, may provide flexibility needed for on-demand individualized construction of biological organs. Several key classes of 3D bioprinting techniques are reviewed, including potential medical and industrial applications. Several unanswered engineering components for the ultimate creation of printed biological organs are also discussed. The complicated nature of the human organs, in addition to the legal and ethical requirements for safe implantation into the human body, would require significant research and development to produce marketable bioprinted organs. This also suggests the possibility for further patenting and licensing opportunities from different sectors of the economy.

Potentials of single-cell biology in identification and validation of disease biomarkers.

PubMed

Niu, Furong; Wang, Diane C; Lu, Jiapei; Wu, Wei; Wang, Xiangdong

2016-09-01

Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location. We headline the important role of single-cell biology in the discovery and development of disease-specific biomarkers with a special emphasis on understanding single-cell biological functions, e.g. mechanical phenotypes, single-cell biology, heterogeneity and organization of genome function. We have reason to believe that such multi-dimensional, multi-layer, multi-crossing and stereoscopic single-cell biology definitely benefits the discovery and development of disease-specific biomarkers. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Biological data warehousing system for identifying transcriptional regulatory sites from gene expressions of microarray data.

PubMed

Tsou, Ann-Ping; Sun, Yi-Ming; Liu, Chia-Lin; Huang, Hsien-Da; Horng, Jorng-Tzong; Tsai, Meng-Feng; Liu, Baw-Juine

2006-07-01

Identification of transcriptional regulatory sites plays an important role in the investigation of gene regulation. For this propose, we designed and implemented a data warehouse to integrate multiple heterogeneous biological data sources with data types such as text-file, XML, image, MySQL database model, and Oracle database model. The utility of the biological data warehouse in predicting transcriptional regulatory sites of coregulated genes was explored using a synexpression group derived from a microarray study. Both of the binding sites of known transcription factors and predicted over-represented (OR) oligonucleotides were demonstrated for the gene group. The potential biological roles of both known nucleotides and one OR nucleotide were demonstrated using bioassays. Therefore, the results from the wet-lab experiments reinforce the power and utility of the data warehouse as an approach to the genome-wide search for important transcription regulatory elements that are the key to many complex biological systems.

Synthetic Biology Expands the Industrial Potential of Yarrowia lipolytica.

PubMed

Markham, Kelly A; Alper, Hal S

2018-06-04

The oleaginous yeast Yarrowia lipolytica is quickly emerging as the most popular non-conventional (i.e., non-model organism) yeast in the bioproduction field. With a high propensity for flux through tricarboxylic acid (TCA) cycle intermediates and biological precursors such as acetyl-CoA and malonyl-CoA, this host is especially well suited to meet our industrial chemical production needs. Recent progress in synthetic biology tool development has greatly enhanced our ability to rewire this organism, with advances in genetic component design, CRISPR technologies, and modular cloning strategies. In this review we investigate recent developments in metabolic engineering and describe how the new tools being developed help to realize the full industrial potential of this host. Finally, we conclude with our vision of the developments that will be necessary to enhance future engineering efforts. Copyright © 2018 Elsevier Ltd. All rights reserved.

Using SCOPE to identify potential regulatory motifs in coregulated genes.

PubMed

Martyanov, Viktor; Gross, Robert H

2011-05-31

SCOPE is an ensemble motif finder that uses three component algorithms in parallel to identify potential regulatory motifs by over-representation and motif position preference. Each component algorithm is optimized to find a different kind of motif. By taking the best of these three approaches, SCOPE performs better than any single algorithm, even in the presence of noisy data. In this article, we utilize a web version of SCOPE to examine genes that are involved in telomere maintenance. SCOPE has been incorporated into at least two other motif finding programs and has been used in other studies. The three algorithms that comprise SCOPE are BEAM, which finds non-degenerate motifs (ACCGGT), PRISM, which finds degenerate motifs (ASCGWT), and SPACER, which finds longer bipartite motifs (ACCnnnnnnnnGGT). These three algorithms have been optimized to find their corresponding type of motif. Together, they allow SCOPE to perform extremely well. Once a gene set has been analyzed and candidate motifs identified, SCOPE can look for other genes that contain the motif which, when added to the original set, will improve the motif score. This can occur through over-representation or motif position preference. Working with partial gene sets that have biologically verified transcription factor binding sites, SCOPE was able to identify most of the rest of the genes also regulated by the given transcription factor. Output from SCOPE shows candidate motifs, their significance, and other information both as a table and as a graphical motif map. FAQs and video tutorials are available at the SCOPE web site which also includes a "Sample Search" button that allows the user to perform a trial run. Scope has a very friendly user interface that enables novice users to access the algorithm's full power without having to become an expert in the bioinformatics of motif finding. As input, SCOPE can take a list of genes, or FASTA sequences. These can be entered in browser text fields, or read from

Reactions of copper macrocycles with antioxidants and HOCl: potential for biological redox sensing.

PubMed

Sowden, Rebecca J; Trotter, Katherine D; Dunbar, Lynsey; Craig, Gemma; Erdemli, Omer; Spickett, Corinne M; Reglinski, John

2013-02-01

A series of simple copper N(2)S(2) macrocycles were examined for their potential as biological redox sensors, following previous characterization of their redox potentials and crystal structures. The divalent species were reduced by glutathione or ascorbate at a biologically relevant pH in aqueous buffer. A less efficient reduction was also achieved by vitamin E in DMSO. Oxidation of the corresponding univalent copper species by sodium hypochlorite resulted in only partial (~65 %) recovery of the divalent form. This was concluded to be due to competition between metal oxidation and ligand oxidation, which is believed to contribute to macrocycle demetallation. Electrospray mass spectrometry confirmed that ligand oxidation had occurred. Moreover, the macrocyclic complexes could be demetallated by incubation with EDTA and bovine serum albumin, demonstrating that they would be inappropriate for use in biological systems. The susceptibility to oxidation and demetallation was hypothesized to be due to oxidation of the secondary amines. Consequently these were modified to incorporate additional oxygen donor atoms. This modification led to greater resistance to demetallation and ligand oxidation, providing a better platform for further development of copper macrocycles as redox sensors for use in biological systems.

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes

PubMed Central

Kuang, Zheng; Ji, Zhicheng

2018-01-01

Abstract Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. PMID:29325176

Biological agents with potential for misuse: a historical perspective and defensive measures.

PubMed

Bhalla, Deepak K; Warheit, David B

2004-08-15

Biological and chemical agents capable of producing serious illness or mortality have been used in biowarfare from ancient times. Use of these agents has progressed from crude forms in early and middle ages, when snakes and infected cadavers were used as weapons in battles, to sophisticated preparations for use during and after the second World War. Cults and terrorist organizations have attempted the use of biological agents with an aim to immobilize populations or cause serious harm. The reasons for interest in these agents by individuals and organizations include relative ease of acquisition, potential for causing mass casualty or panic, modest financing requirement, availability of technology, and relative ease of delivery. The Centers for Disease Control and Prevention has classified Critical Biological Agents into three major categories. This classification was based on several criteria, which include severity of impact on human health, potential for delivery in a weapon, capacity to cause panic and special needs for development, and stockpiling of medication. Agents that could cause the greatest harm following deliberate use were placed in category A. Category B included agents capable of producing serious harm and significant mortality but of lower magnitude than category A agents. Category C included emerging pathogens that could be developed for mass dispersion in future and their potential as a major health threat. A brief description of the category A bioagents is included and the pathophysiology of two particularly prominent agents, namely anthrax and smallpox, is discussed in detail. The potential danger from biological agents and their ever increasing threat to human populations have created a need for developing technologies for their early detection, for developing treatment strategies, and for refinement of procedures to ensure survival of affected individuals so as to attain the ultimate goal of eliminating the threat from intentional use of

Identifying the immunomodulatory components of helminths.

PubMed

Shepherd, C; Navarro, S; Wangchuk, P; Wilson, D; Daly, N L; Loukas, A

2015-06-01

Immunomodulatory components of helminths offer great promise as an entirely new class of biologics for the treatment of inflammatory diseases. Here, we discuss the emerging themes in helminth-driven immunomodulation in the context of therapeutic drug discovery. We broadly define the approaches that are currently applied by researchers to identify these helminth molecules, highlighting key areas of potential exploitation that have been mostly neglected thus far, notably small molecules. Finally, we propose that the investigation of immunomodulatory compounds will enable the translation of current and future research efforts into potential treatments for autoimmune and allergic diseases, while at the same time yielding new insights into the molecular interface of host-parasite biology. © 2015 John Wiley & Sons Ltd.

Phytotoxicity of vulpia residues: III. Biological activity of identified allelochemicals from Vulpia myuros.

PubMed

An, M; Pratley, J E; Haig, T

2001-02-01

Twenty compounds identified in vulpia (Vulpia myuros) residues as allelochemicals were individually and collectively tested for biological activity. Each exhibited characteristic allelochemical behavior toward the test plant, i.e., inhibition at high concentrations and stimulation or no effect at low concentrations, but individual activities varied. Allelopathins present in large quantities, such as syringic, vanillic, and succinic acids, possessed low activity, while those present in small quantities, such as catechol and hydrocinnamic acid, possessed strong inhibitory activity. The concept of a phytotoxic strength index was developed for quantifying the biological properties of each individual allelopathin in a concise, comprehensive, and meaningful format. The individual contribution of each allelopathin, assessed by comparing the phytotoxic strength index to the overall toxicity of vulpia residues, was variable according to structure and was influenced by its relative proportion in the residue. The majority of compounds possessed low or medium biological activity and contributed most of the vulpia phytotoxicity, while compounds with high biological activity were in the minority and only present at low concentration. Artificial mixtures of these pure allelochemicals also produced phytotoxicity. There were additive/synergistic effects evident in the properties of these mixtures. One such mixture, formulated from allelochemicals found in the same proportions as occur in vulpia extract, produced stronger activity than another formulated from the same set of compounds but in equal proportions. These results suggest that the exploration of the relative composition of a cluster of allelopathins may be more important than simply focusing on the identification of one or two compounds with strong biological activity and that synergism is fundamental to the understanding of allelopathy.

Use of Event-Related Potentials to Identify Language and Reading Skills

ERIC Educational Resources Information Center

Molfese, Victoria J.; Molfese, Dennis L.; Beswick, Jennifer L.; Jacobi-Vessels, Jill; Molfese, Peter J.; Molnar, Andrew E.; Wagner, Mary C.; Haines, Brittany L.

2008-01-01

The extent to which oral language and emergent literacy skills are influenced by event-related potential measures of phonological processing was examined. Results revealed that event-related potential responses identify differences in letter naming but not receptive language skills.

Biology, behavior, and larval morphology of Salbia lotanalis (Lepidoptera: Crambidae), a potential biological control agent of Miconia calvescens (Myrtales: Melastomataceae) from Costa Rica

Treesearch

Alexander Castillo; M. Tracy Johnson; Francisco R. Badenes-Pérez

2014-01-01

The leaf roller Salbia lotanalis Druce (Lepidoptera: Crambidae), a potential biological control agent of Miconia calvescens de Candolle (Melastomataceae), was studied in Costa Rica. Larvae were collected from a field site near San Jose and the insect was reared in the laboratory to study its biology and behavior. Chaetotaxy and...

Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and their binding sites driving dynamic biological processes.

PubMed

Kuang, Zheng; Ji, Zhicheng; Boeke, Jef D; Ji, Hongkai

2018-01-09

Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data. In the first step, DynaMO predicts TF binding sites with a random forests approach. Next and uniquely, DynaMO infers dynamic TF binding activities at predicted binding sites using their local chromatin profiles from multiple biological conditions. Another landmark of DynaMO is to identify key TFs in a dynamic process using a clustering and enrichment analysis of dynamic TF binding patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian clock and human neural differentiation exhibits its accuracy and versatility. We anticipate DynaMO will be generally useful for elucidating transcriptional programs in dynamic processes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Consistent design schematics for biological systems: standardization of representation in biological engineering

PubMed Central

Matsuoka, Yukiko; Ghosh, Samik; Kitano, Hiroaki

2009-01-01

The discovery by design paradigm driving research in synthetic biology entails the engineering of de novo biological constructs with well-characterized input–output behaviours and interfaces. The construction of biological circuits requires iterative phases of design, simulation and assembly, leading to the fabrication of a biological device. In order to represent engineered models in a consistent visual format and further simulating them in silico, standardization of representation and model formalism is imperative. In this article, we review different efforts for standardization, particularly standards for graphical visualization and simulation/annotation schemata adopted in systems biology. We identify the importance of integrating the different standardization efforts and provide insights into potential avenues for developing a common framework for model visualization, simulation and sharing across various tools. We envision that such a synergistic approach would lead to the development of global, standardized schemata in biology, empowering deeper understanding of molecular mechanisms as well as engineering of novel biological systems. PMID:19493898

Defining the Synthetic Biology Supply Chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frazar, Sarah L.; Hund, Gretchen E.; Bonheyo, George T.

In this article, a team of experts in synthetic biology, data analytics, and national security describe the overall supply chain surrounding synthetic biology. The team analyzes selected interactions within that network to better understand the risks raised by synthetic biology and identifies opportunities for risk mitigation. To introduce the concept, the article will briefly describe how an understanding of supply chains has been important in promoting nuclear nonproliferation objectives. The article concludes by assessing the structure and networks identified in the supply chains to reveal potential opportunities for future biodefense research and development; options for additional information exchange; and meansmore » to interdict, detect, or deter suspicious activity.« less

Visual event-related potentials to biological motion stimuli in autism spectrum disorders

PubMed Central

Bletsch, Anke; Krick, Christoph; Siniatchkin, Michael; Jarczok, Tomasz A.; Freitag, Christine M.; Bender, Stephan

2014-01-01

Atypical visual processing of biological motion contributes to social impairments in autism spectrum disorders (ASD). However, the exact temporal sequence of deficits of cortical biological motion processing in ASD has not been studied to date. We used 64-channel electroencephalography to study event-related potentials associated with human motion perception in 17 children and adolescents with ASD and 21 typical controls. A spatio-temporal source analysis was performed to assess the brain structures involved in these processes. We expected altered activity already during early stimulus processing and reduced activity during subsequent biological motion specific processes in ASD. In response to both, random and biological motion, the P100 amplitude was decreased suggesting unspecific deficits in visual processing, and the occipito-temporal N200 showed atypical lateralization in ASD suggesting altered hemispheric specialization. A slow positive deflection after 400 ms, reflecting top-down processes, and human motion-specific dipole activation differed slightly between groups, with reduced and more diffuse activation in the ASD-group. The latter could be an indicator of a disrupted neuronal network for biological motion processing in ADS. Furthermore, early visual processing (P100) seems to be correlated to biological motion-specific activation. This emphasizes the relevance of early sensory processing for higher order processing deficits in ASD. PMID:23887808

e-Biologics: Fabrication of Sustainable Electronics with "Green" Biological Materials.

PubMed

Lovley, Derek R

2017-06-27

The growing ubiquity of electronic devices is increasingly consuming substantial energy and rare resources for materials fabrication, as well as creating expansive volumes of toxic waste. This is not sustainable. Electronic biological materials (e-biologics) that are produced with microbes, or designed with microbial components as the guide for synthesis, are a potential green solution. Some e-biologics can be fabricated from renewable feedstocks with relatively low energy inputs, often while avoiding the harsh chemicals used for synthesizing more traditional electronic materials. Several are completely free of toxic components, can be readily recycled, and offer unique features not found in traditional electronic materials in terms of size, performance, and opportunities for diverse functionalization. An appropriate investment in the concerted multidisciplinary collaborative research required to identify and characterize e-biologics and to engineer materials and devices based on e-biologics could be rewarded with a new "green age" of sustainable electronic materials and devices. Copyright © 2017 Lovley.

Uncovering the Biology of Cancers in Adolescents and Young Adults

Cancer.gov

Evidence suggests that some adolescent and young adult cancers may have unique genetic and biological features. Researchers are trying to better understand the biology of these cancers in order to identify potential therapeutic targets.

Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

PubMed

Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

2013-01-01

Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

Chemical and Biological Contract Manufacturing Services: Potential Proliferation Concerns and Impacts on Strategic Trade Controls

DOE PAGES

Carrera, Julie A.; Castiglioni, Andrew J.; Heine, Peter M.

2017-04-01

The use of contract manufacturing services in the chemical, pharmaceutical, and biotechnology industries has grown significantly in recent years, but the potential for such service providers to be exploited for chemical or biological weapons proliferation has garnered relatively little attention, despite the role of contract manufacturers in the A.Q. Khan nuclear proliferation network. Here, we examine the dual-use potential and global spread of chemical and biological contract manufacturing and their ramifications for related strategic trade controls (STCs). Hundreds of providers of dual-use contract services were found worldwide, but they were primarily located in jurisdictions with comprehensive STC regulations. This thenmore » provides some degree of protection against their misuse. However, the results outlined below also suggest that chemical and biological contract manufacturers are a critical community to target for STC outreach activities and efforts to increase industry compliance. Targeted outreach would help prevent contract manufacturing service providers from unwittingly contributing to the production and proliferation of chemical and biological weapons.« less

Chemical and Biological Contract Manufacturing Services: Potential Proliferation Concerns and Impacts on Strategic Trade Controls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carrera, Julie A.; Castiglioni, Andrew J.; Heine, Peter M.

The use of contract manufacturing services in the chemical, pharmaceutical, and biotechnology industries has grown significantly in recent years, but the potential for such service providers to be exploited for chemical or biological weapons proliferation has garnered relatively little attention, despite the role of contract manufacturers in the A.Q. Khan nuclear proliferation network. Here, we examine the dual-use potential and global spread of chemical and biological contract manufacturing and their ramifications for related strategic trade controls (STCs). Hundreds of providers of dual-use contract services were found worldwide, but they were primarily located in jurisdictions with comprehensive STC regulations. This thenmore » provides some degree of protection against their misuse. However, the results outlined below also suggest that chemical and biological contract manufacturers are a critical community to target for STC outreach activities and efforts to increase industry compliance. Targeted outreach would help prevent contract manufacturing service providers from unwittingly contributing to the production and proliferation of chemical and biological weapons.« less

Identifying potential kidney donors using social networking web sites.

PubMed

Chang, Alexander; Anderson, Emily E; Turner, Hang T; Shoham, David; Hou, Susan H; Grams, Morgan

2013-01-01

Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation. They allow for wide dissemination of information and discussion and could lessen anxiety associated with a face-to-face request for donation. However, sparse data exist on the use of social media for this purpose. We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested. In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2-69); 88% were US residents. Other posted information included the individual's photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%). Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live-donor kidney transplant. Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic. Facebook is already being used to identify potential kidney donors. Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation. © 2013 John Wiley & Sons A/S.

Heterapoderopsis bicallosicollis (Coleoptera: Attelabidae): a potential biological control agent for Triadica sebifera.

PubMed

Wang, Yi; Ding, Jianqing; Wheeler, Gregory S; Purcell, Matthew F; Zhang, Guoan

2009-08-01

Native to China, Chinese tallow, Triadica sebifera L. Small (Euphorbiaceae), is an invasive plant in the southeastern United States. The leaf-rolling weevil, Heterapoderopsis bicallosicollis Voss, is a common herbivore attacking this plant in China. To evaluate its potential as a biological control agent of T. sebifera, biology and host specificity of this weevil were studied in China. H. bicallosicollis occurs over a wide, native, geographic range and its immatures successfully develop at 15-35 degrees C, indicating its physiological potential to establish and persist throughout the range of climatic conditions where the target plant grows in the United States. Adults make feeding holes on leaves. Before oviposition, the female makes a sealed leaf roll called a nidus and then lays one to two eggs inside. Eggs, larvae, and pupae develop within nidi, and larvae survive only when they develop inside the nidi. This requirement makes the weevil highly host specific to T. sebifera. In laboratory no-choice tests of 54 species from eight families, adults fed on only 3 plant species, T. sebifera, Sapium chihsinianum S. K. Lee, and Phyllanthus urinaria L. and only oviposited on T. sebifera. These results were confirmed where, in multiple-choice tests, adults only oviposited on T. sebifera. Given that T. sebifera is the only species in the genus Triadica in the United States, the results of this study suggest that H. bicallosicollis is a potential biological control agent of T. sebifera and should be considered to be imported into quarantine in the United States for further tests on native North American species.

Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis.

PubMed

Cheng, Feixiong; Murray, James L; Zhao, Junfei; Sheng, Jinsong; Zhao, Zhongming; Rubin, Donald H

2016-09-01

Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase). Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B) identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline) that may be potential for antiviral indication (e.g. anti-Ebola). In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics.

Hidden treasures in "ancient" microarrays: gene-expression portrays biology and potential resistance pathways of major lung cancer subtypes and normal tissue.

PubMed

Kerkentzes, Konstantinos; Lagani, Vincenzo; Tsamardinos, Ioannis; Vyberg, Mogens; Røe, Oluf Dimitri

2014-01-01

Novel statistical methods and increasingly more accurate gene annotations can transform "old" biological data into a renewed source of knowledge with potential clinical relevance. Here, we provide an in silico proof-of-concept by extracting novel information from a high-quality mRNA expression dataset, originally published in 2001, using state-of-the-art bioinformatics approaches. The dataset consists of histologically defined cases of lung adenocarcinoma (AD), squamous (SQ) cell carcinoma, small-cell lung cancer, carcinoid, metastasis (breast and colon AD), and normal lung specimens (203 samples in total). A battery of statistical tests was used for identifying differential gene expressions, diagnostic and prognostic genes, enriched gene ontologies, and signaling pathways. Our results showed that gene expressions faithfully recapitulate immunohistochemical subtype markers, as chromogranin A in carcinoids, cytokeratin 5, p63 in SQ, and TTF1 in non-squamous types. Moreover, biological information with putative clinical relevance was revealed as potentially novel diagnostic genes for each subtype with specificity 93-100% (AUC = 0.93-1.00). Cancer subtypes were characterized by (a) differential expression of treatment target genes as TYMS, HER2, and HER3 and (b) overrepresentation of treatment-related pathways like cell cycle, DNA repair, and ERBB pathways. The vascular smooth muscle contraction, leukocyte trans-endothelial migration, and actin cytoskeleton pathways were overexpressed in normal tissue. Reanalysis of this public dataset displayed the known biological features of lung cancer subtypes and revealed novel pathways of potentially clinical importance. The findings also support our hypothesis that even old omics data of high quality can be a source of significant biological information when appropriate bioinformatics methods are used.

IDENTIFYING THE "SLOW LEARNER" IN BSCS HIGH SCHOOL BIOLOGY.

ERIC Educational Resources Information Center

GROBMAN, HULDA

THE SUITABILITY OF THE BLUE, GREEN, AND YELLOW VERSION BIOLOGICAL SCIENCES CURRICULUM STUDY (BSCS) FOR THE UPPER 75 PERCENT OF THE STUDENTS TAKING TENTH GRADE BIOLOGY IN THE UNITED STATES IS EXAMINED AND PROCEDURES USED IN ASSIGNING SLOW LEARNERS TO CLASSES USING BSCS SPECIAL MATERIALS ARE SURVEYED. THE SUITABILITY STUDY INVOLVED 12,602 STUDENTS…

Probing nanomechanical interaction at the interface between biological membrane and potentially toxic chemical.

PubMed

Lim, Chanoong; Park, Sohee; Park, Jinwoo; Ko, Jina; Lee, Dong Woog; Hwang, Dong Soo

2018-04-12

Various xenobiotics interact with biological membranes, and precise evaluations of the molecular interactions between them are essential to foresee the toxicity and bioavailability of existing or newly synthesized molecules. In this study, surface forces apparatus (SFA) measurement and Langmuir trough based tensiometry are performed to reveal nanomechanical interaction mechanisms between potential toxicants and biological membranes for ex vivo toxicity evaluation. As a toxicant, polyhexamethylene guanidine (PHMG) was selected because PHMG containing humidifier disinfectant and Vodka caused lots of victims in both S. Korea and Russia, respectively, due to the lack of holistic toxicity evaluation of PHMG. Here, we measured strong attraction (Wad ∼4.2 mJ/m 2 ) between PHMG and head group of biological membranes while no detectable adhesion force between the head group and control molecules was measured. Moreover, significant changes in π-A isotherm of 1,2-Dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) monolayers were measured upon PHMG adsorption. These results indicate PHMG strongly binds to hydrophilic group of lipid membranes and alters the structural and phase behavior of them. More importantly, complementary utilization of SFA and Langmuir trough techniques are found to be useful to predict the potential toxicity of a chemical by evaluating the molecular interaction with biological membranes, the primary protective barrier for living organisms. Copyright © 2018 Elsevier B.V. All rights reserved.

Phytochemistry, biological activities and potential of annatto in natural colorant production for industrial applications – A review

PubMed Central

Shahid-ul-Islam; Rather, Luqman J.; Mohammad, Faqeer

2015-01-01

Bixa orellana commonly known as annatto is one of the oldest known natural dye yielding plants native to Central and South America. Various parts of annatto have been widely used in the traditional medical system for prevention and treatment of a wide number of health disorders. The plethora of traditional uses has encouraged researchers to identify and isolate phytochemicals from all parts of this plant. Carotenoids, apocarotenoids, terpenes, terpenoids, sterols, and aliphatic compounds are main compounds found in all parts of this plant and are reported to exhibit a wide range of pharmacological activities. In recent years annatto has received tremendous scientific interest mainly due to the isolation of yellow–orange natural dye from its seeds which exhibits high biodegradability, low toxicity, and compatibility with the environment. Considerable research work has already been done and is currently underway for its applications in food, textile, leather, cosmetic, solar cells, and other industries. The present review provides up-to-date systematic and organized information on the traditional usage, phytochemistry and pharmacology of annatto. It also highlights its non-food industrial applications in order to bring more interest on this dye plant, identifies the existing gaps and provides potential for future studies. Studies reported in this review have demonstrated that annatto holds a great potential for being exploited as source of drugs and a potential natural dye. However, further efforts are required to identify extract biomolecules and their action mechanisms in exhibiting certain biological activities in order to understand the full phytochemical profile and the complex pharmacological effects of this plant. PMID:27222755

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma.

PubMed

Chow, Yock Ping; Tan, Lu Ping; Chai, San Jiun; Abdul Aziz, Norazlin; Choo, Siew Woh; Lim, Paul Vey Hong; Pathmanathan, Rajadurai; Mohd Kornain, Noor Kaslina; Lum, Chee Lun; Pua, Kin Choo; Yap, Yoke Yeow; Tan, Tee Yong; Teo, Soo Hwang; Khoo, Alan Soo-Beng; Patel, Vyomesh

2017-03-03

In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma

PubMed Central

Chow, Yock Ping; Tan, Lu Ping; Chai, San Jiun; Abdul Aziz, Norazlin; Choo, Siew Woh; Lim, Paul Vey Hong; Pathmanathan, Rajadurai; Mohd Kornain, Noor Kaslina; Lum, Chee Lun; Pua, Kin Choo; Yap, Yoke Yeow; Tan, Tee Yong; Teo, Soo Hwang; Khoo, Alan Soo-Beng; Patel, Vyomesh

2017-01-01

In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies. PMID:28256603

Application of ToxCast to evaluate potential biological effects from organic contaminants in Great Lakes tributaries

EPA Science Inventory

With the development of “high throughput” in-vitro biological assays, screening-level information on potential adverse biological effects is available for a rapidly increasing number of chemicals. The U.S. EPA ToxCast program has now evaluated several thousand chemica...

System and method for preconcentrating, identifying, and quantifying chemical and biological substances

DOEpatents

Yu, Conrad M.; Koo, Jackson C.

2000-01-01

A system and method for preconcentrating, identifying, and quantifying chemical and biological substances is disclosed. An input valve directs a first volume of a sample gas to a surface acoustic wave (SAW) device. The SAW device preconcentrates and detects a mass of a substance within the sample gas. An output valve receives a second volume of the sample gas containing the preconcentrated substance from the SAW device and directs the second volume to a gas chromatograph (GC). The GC identifies the preconcentrated substance within the sample gas. A shunt valve exhausts a volume of the sample gas equal to the first volume minus the second volume away from the SAW device and the GC. The method of the present invention includes the steps of opening an input valve for passing a first volume of a sample gas to a SAW device; preconcentrating and detecting a mass of a substance within the sample gas using the SAW device; opening an output valve for passing a second volume of the sample gas containing the preconcentrated substance to a gas chromatograph (GC); and then identifying the preconcentrated substance within the sample gas using the GC.

e-Biologics: Fabrication of Sustainable Electronics with “Green” Biological Materials

PubMed Central

2017-01-01

ABSTRACT The growing ubiquity of electronic devices is increasingly consuming substantial energy and rare resources for materials fabrication, as well as creating expansive volumes of toxic waste. This is not sustainable. Electronic biological materials (e-biologics) that are produced with microbes, or designed with microbial components as the guide for synthesis, are a potential green solution. Some e-biologics can be fabricated from renewable feedstocks with relatively low energy inputs, often while avoiding the harsh chemicals used for synthesizing more traditional electronic materials. Several are completely free of toxic components, can be readily recycled, and offer unique features not found in traditional electronic materials in terms of size, performance, and opportunities for diverse functionalization. An appropriate investment in the concerted multidisciplinary collaborative research required to identify and characterize e-biologics and to engineer materials and devices based on e-biologics could be rewarded with a new “green age” of sustainable electronic materials and devices. PMID:28655820

Complete Host Range Testing on Common Reed with Potential Biological Control Agents and Investigation into Biological Control for Flowering Rush

DTIC Science & Technology

2016-07-01

ER D C/ EL C R- 16 -5 Aquatic Plant Control Research Program Complete Host Range Testing on Common Reed with Potential Biological...client/default. Aquatic Plant Control Research Program ERDC/EL CR-16-5 July 2016 Complete Host Range Testing on Common Reed with Potential...and started with sequential no-choice oviposition tests. So far, no eggs were found on any of the 22 test plants offered. The authors also found the

Benzoin Schiff Bases: Design, Synthesis, and Biological Evaluation as Potential Antitumor Agents.

PubMed

Sabbah, Dima A; Al-Tarawneh, Fatima; Talib, Wamidh H; Sweidan, Kamal; Bardaweel, Sanaa K; Al-Shalabi, Eveen; Zhong, Haizhen A; Abu Sheikha, Ghassan; Abu Khalaf, Reema; Mubarak, Mohammad S

2018-04-12

Phosphoinositide 3-kinase α (PI3Kα) is an attractive target for anticancer drug design. Target compounds were designed to probe the significance of alcohol and imine moieties tailored on a benzoin scaffold to better understand the structure activity relation (SAR) and improve their biological activity as anticancer compounds. Chemical synthesis of the targeted compounds, biological evaluation tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, as well as Glide docking studies were employed in this investigation. A new series of 1,2-diphenylimino ethanol was successfully synthesized and characterized by means of FT-IR, HRMS, NMR, and by elemental analysis. Biological screening revealed that the newly synthesized compounds inhibit PI3Kα activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines. Results additionally showed that these compounds exhibit selective antiproliferative activity, induce apoptosis, and suppress the VEGF production. Compounds 2b, 2d, and 2g displayed promising inhibitory activity in HCT-116 suggesting that hydrophobic and/or hydrogen bond-acceptor mediate(s) ligand-receptor interaction on o- and m-positions. Furthermore, compounds 2g, 2i, 2j, and 2h, bearing hydrophobic moiety on m- and p-position, exerted high antiproliferative activity in T47D and MCF-7 cells, whereas compound 2e showed selectivity against T47D and MCF-7. Molecular docking studies against PI3Kα and caspase-3 demonstrated a strong correlation between the predicted binding affinity (ΔGobsd) and IC50 values of prepared compounds for the caspase-3 model, implying that the cellulous inhibitory activity was caspase-3-dependent. Moreover, Glide docking against PI3Kα identified Ser774, Lys802, E849, V851, and Asp933 as key binding residues. The series exerted a potential PI3Kα inhibitory activity in human carcinoma cell lines expressing PI3K�

A network-based, integrative study to identify core biological pathways that drive breast cancer clinical subtypes

PubMed Central

Dutta, B; Pusztai, L; Qi, Y; André, F; Lazar, V; Bianchini, G; Ueno, N; Agarwal, R; Wang, B; Shiang, C Y; Hortobagyi, G N; Mills, G B; Symmans, W F; Balázsi, G

2012-01-01

Background: The rapid collection of diverse genome-scale data raises the urgent need to integrate and utilise these resources for biological discovery or biomedical applications. For example, diverse transcriptomic and gene copy number variation data are currently collected for various cancers, but relatively few current methods are capable to utilise the emerging information. Methods: We developed and tested a data-integration method to identify gene networks that drive the biology of breast cancer clinical subtypes. The method simultaneously overlays gene expression and gene copy number data on protein–protein interaction, transcriptional-regulatory and signalling networks by identifying coincident genomic and transcriptional disturbances in local network neighborhoods. Results: We identified distinct driver-networks for each of the three common clinical breast cancer subtypes: oestrogen receptor (ER)+, human epidermal growth factor receptor 2 (HER2)+, and triple receptor-negative breast cancers (TNBC) from patient and cell line data sets. Driver-networks inferred from independent datasets were significantly reproducible. We also confirmed the functional relevance of a subset of randomly selected driver-network members for TNBC in gene knockdown experiments in vitro. We found that TNBC driver-network members genes have increased functional specificity to TNBC cell lines and higher functional sensitivity compared with genes selected by differential expression alone. Conclusion: Clinical subtype-specific driver-networks identified through data integration are reproducible and functionally important. PMID:22343619

Identifying biologically relevant putative mechanisms in a given phenotype comparison

PubMed Central

Hanoudi, Samer; Donato, Michele; Draghici, Sorin

2017-01-01

A major challenge in life science research is understanding the mechanism involved in a given phenotype. The ability to identify the correct mechanisms is needed in order to understand fundamental and very important phenomena such as mechanisms of disease, immune systems responses to various challenges, and mechanisms of drug action. The current data analysis methods focus on the identification of the differentially expressed (DE) genes using their fold change and/or p-values. Major shortcomings of this approach are that: i) it does not consider the interactions between genes; ii) its results are sensitive to the selection of the threshold(s) used, and iii) the set of genes produced by this approach is not always conducive to formulating mechanistic hypotheses. Here we present a method that can construct networks of genes that can be considered putative mechanisms. The putative mechanisms constructed by this approach are not limited to the set of DE genes, but also considers all known and relevant gene-gene interactions. We analyzed three real datasets for which both the causes of the phenotype, as well as the true mechanisms were known. We show that the method identified the correct mechanisms when applied on microarray datasets from mouse. We compared the results of our method with the results of the classical approach, showing that our method produces more meaningful biological insights. PMID:28486531

Using a watershed-centric approach to identify potentially impacted beaches

EPA Science Inventory

Beaches can be affected by a variety of contaminants. Of particular concern are beaches impacted by human fecal contamination and urban runoff. This poster demonstrates a methodology to identify potentially impacted beaches using Geographic Information Systems (GIS). Since h...

Mode of Infection of Metarhizium spp. Fungus and Their Potential as Biological Control Agents

PubMed Central

Aw, Kimberly Moon San; Hue, Seow Mun

2017-01-01

Chemical insecticides have been commonly used to control agricultural pests, termites, and biological vectors such as mosquitoes and ticks. However, the harmful impacts of toxic chemical insecticides on the environment, the development of resistance in pests and vectors towards chemical insecticides, and public concern have driven extensive research for alternatives, especially biological control agents such as fungus and bacteria. In this review, the mode of infection of Metarhizium fungus on both terrestrial and aquatic insect larvae and how these interactions have been widely employed will be outlined. The potential uses of Metarhizium anisopliae and Metarhizium acridum biological control agents and molecular approaches to increase their virulence will be discussed. PMID:29371548

Potential biological targets for bioassay development in drug discovery of Sturge-Weber syndrome.

PubMed

Mohammadipanah, Fatemeh; Salimi, Fatemeh

2017-04-29

Sturge-Weber Syndrome (SWS) is among the neurocutaneous diseases, which has several clinical manifestations of ocular (glaucoma), cutaneous (port-wine stain), neurological (seizures) and vascular problems. Molecular mechanisms of SWS pathogenesis are initiated by the somatic mutation in GNAQ. Therefore, no definite treatments exist for the SWS and treatment options only mitigate the intensity of its clinical manifestations. Biological assay design for drug discovery against this syndrome demands comprehensive knowledge on mechanisms which are involved in its pathogenesis. By analysis of the interrelated molecular targets of SWS, some in vitro bioassay systems can be allotted for drug screening against this syndrome. Development of such platforms of bioassay can bring along the implementation of high throughput screening of natural or synthetic compounds in drug discovery programs. Regarding the fact that study of biological targets and their integration in biological assay design can facilitate the process of effective drug discovery; some potential biological targets and their respective biological assay for SWS drug discovery are propounded in this review. For this purpose, some biological targets for SWS drug discovery such as acetylcholine esterase, alkaline phosphatase, gamma-aminobutyricacidergic, Hypoxia-Inducible Factor (HIF) -1α and 2α are suggested. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Short communication: Development of a direct in vivo screening model to identify potential probiotic bacteria using Caenorhabditis elegans.

PubMed

Park, M R; Yun, H S; Son, S J; Oh, S; Kim, Y

2014-11-01

Caenorhabditis elegans is an accepted model host to study host-bacteria interactions in the gut, in addition to being a simple model with which to study conserved aspects of biological signaling pathways in intestinal environments, because these nematode worms have similar intestinal cells to those of humans. Here, we used C. elegans to develop a new in vivo screening system for potential probiotic lactic acid bacteria (LAB). Initially, critical colonization ability of LAB strains isolated from Korean infant feces was screened in the worm intestinal tract over a period of 5 d. Furthermore, we investigated host health-promoting activities, including longevity-extending effects and immune-enhancing activities against foodborne pathogen infection. We identified 4 LAB strains that were highly persistent in the nematode gut and that significantly prolonged the longevity of C. elegans and improved the survival of C. elegans in response to infection by Staphylococcus aureus. The 4 LAB strains we identified showed resistance to acid and bile conditions, assimilated cholesterol, and were able to attach to a mucus layer. The 4 LAB isolates were identified as Lactobacillus plantarum using 16S rRNA sequencing analysis. Taken together, we developed a direct in vivo screening system using C. elegans to study host health-promoting LAB. Our system is simple, rapid, cost-effective, and reliable, and we anticipate that this system will result in the discovery of many more potential probiotic bacteria for dairy foods. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

An integrated chemical biology approach identifies specific vulnerability of Ewing's sarcoma to combined inhibition of Aurora kinases A and B.

PubMed

Winter, Georg E; Rix, Uwe; Lissat, Andrej; Stukalov, Alexey; Müllner, Markus K; Bennett, Keiryn L; Colinge, Jacques; Nijman, Sebastian M; Kubicek, Stefan; Kovar, Heinrich; Kontny, Udo; Superti-Furga, Giulio

2011-10-01

Ewing's sarcoma is a pediatric cancer of the bone that is characterized by the expression of the chimeric transcription factor EWS-FLI1 that confers a highly malignant phenotype and results from the chromosomal translocation t(11;22)(q24;q12). Poor overall survival and pronounced long-term side effects associated with traditional chemotherapy necessitate the development of novel, targeted, therapeutic strategies. We therefore conducted a focused viability screen with 200 small molecule kinase inhibitors in 2 different Ewing's sarcoma cell lines. This resulted in the identification of several potential molecular intervention points. Most notably, tozasertib (VX-680, MK-0457) displayed unique nanomolar efficacy, which extended to other cell lines, but was specific for Ewing's sarcoma. Furthermore, tozasertib showed strong synergies with the chemotherapeutic drugs etoposide and doxorubicin, the current standard agents for Ewing's sarcoma. To identify the relevant targets underlying the specific vulnerability toward tozasertib, we determined its cellular target profile by chemical proteomics. We identified 20 known and unknown serine/threonine and tyrosine protein kinase targets. Additional target deconvolution and functional validation by RNAi showed simultaneous inhibition of Aurora kinases A and B to be responsible for the observed tozasertib sensitivity, thereby revealing a new mechanism for targeting Ewing's sarcoma. We further corroborated our cellular observations with xenograft mouse models. In summary, the multilayered chemical biology approach presented here identified a specific vulnerability of Ewing's sarcoma to concomitant inhibition of Aurora kinases A and B by tozasertib and danusertib, which has the potential to become a new therapeutic option.

Factors Potentially Influencing Student Acceptance of Biological Evolution

NASA Astrophysics Data System (ADS)

Wiles, Jason R.

This investigation explored scientific, religious, and otherwise nonscientific factors that may influence student acceptance of biological evolution and related concepts, how students perceived these factors to have influenced their levels of acceptance of evolution and changes therein, and what patterns arose among students' articulations of how their levels of acceptance of evolution may have changed. This exploration also measured the extent to which students' levels of acceptance changed following a treatment designed to address factors identified as potentially affecting student acceptance of evolution. Acceptance of evolution was measured using the MATE instrument (Rutledge and Warden, 1999; Rutledge and Sadler, 2007) among participants enrolled in a secondary-level academic program during the summer prior to their final year of high school and as they transitioned to the post-secondary level. Student acceptance of evolution was measured to be significantly higher than pre-treatment levels both immediately following and slightly over one year after treatment. Qualitative data from informal questionnaires, from formal course evaluations, and from semi-structured interviews of students engaged in secondary level education and former students at various stages of post-secondary education confirmed that the suspected factors were perceived by participants to have influenced their levels of acceptance of evolution. Furthermore, participant reports provided insight regarding the relative effects they perceived these factors to have had on their evolution acceptance levels. Additionally, many participants reported that their science teachers in public schools had avoided, omitted, or denigrated evolution during instruction, and several of these students expressed frustration regarding what they perceived to have been a lack of education of an important scientific principle. Finally, no students expressed feelings of being offended by having been taught about

The Power and Potential of Genomics in Weed Biology and Management.

PubMed

Ravet, Karl; Patterson, Eric L; Krähmer, Hansjörg; Hamouzová, Kateřina; Fan, Longjiang; Jasieniuk, Marie; Lawton-Rauh, Amy; Malone, Jenna M; Scott McElroy, J; Merotto, Aldo; Westra, Philip; Preston, Christopher; Vila-Aiub, Martin M; Busi, Roberto; Tranel, Patrick J; Reinhardt, Carl; Saski, Christopher; Beffa, Roland; Neve, Paul; Gaines, Todd A

2018-04-24

There have been previous calls for, and efforts focused on, realizing the power and potential of weed genomics for better understanding of weeds. Sustained advances in genome sequencing and assembly technologies now make it possible for individual research groups to generate reference genomes for multiple weed species at reasonable costs. Here, we present the outcomes from several meetings, discussions, and workshops focused on establishing an International Weed Genomics Consortium (IWGC) for a coordinated international effort in weed genomics. We review the 'state of the art' in genomics and weed genomics, including technologies, applications, and on-going weed genome projects. We also report the outcomes from a workshop and a global survey of the weed science community to identify priority species, key biological questions, and weed management applications that can be addressed through greater availability of, and access to, genomic resources. Major focus areas include the evolution of herbicide resistance and weedy traits, the development of molecular diagnostics, and the identification of novel targets and approaches for weed management. There is increasing interest in, and need for, weed genomics, and the establishment of the IWGC will provide the necessary global platform for communication and coordination of weed genomics research. This article is protected by copyright. All rights reserved.

Potential biological targets for bioassay development in drug discovery of Sturge-Weber syndrome.

PubMed

Mohammadipanah, Fatemeh; Salimi, Fatemeh

2018-02-01

Sturge-Weber Syndrome (SWS) is a neurocutaneous disease with clinical manifestations including ocular (glaucoma), cutaneous (port-wine birthmark), neurologic (seizures), and vascular problems. Molecular mechanisms of SWS pathogenesis are initiated by the somatic mutation in GNAQ. Therefore, no definite treatments exist for SWS and treatment options only mitigate the intensity of its clinical manifestations. Biological assay design for drug discovery against this syndrome demands comprehensive knowledge on mechanisms which are involved in its pathogenesis. By analysis of the interrelated molecular targets of SWS, some in vitro bioassay systems can be allotted for drug screening against its progression. Development of such platforms of bioassay can bring along the implementation of high-throughput screening of natural or synthetic compounds in drug discovery programs. Regarding the fact that study of molecular targets and their integration in biological assay design can facilitate the process of effective drug discovery; some potential biological targets and their respective biological assay for SWS drug discovery are propounded in this review. For this purpose, some biological targets for SWS drug discovery such as acetylcholinesterase, alkaline phosphatase, GABAergic receptors, Hypoxia-Inducible Factor (HIF)-1α and 2α are suggested. © 2017 John Wiley & Sons A/S.

Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats.

PubMed

Kobeissy, Firas H; Guingab-Cagmat, Joy D; Zhang, Zhiqun; Moghieb, Ahmed; Glushakova, Olena Y; Mondello, Stefania; Boutté, Angela M; Anagli, John; Rubenstein, Richard; Bahmad, Hisham; Wagner, Amy K; Hayes, Ronald L; Wang, Kevin K W

2016-01-01

Traumatic brain injury (TBI) represents a critical health problem of which diagnosis, management, and treatment remain challenging. TBI is a contributing factor in approximately one-third of all injury-related deaths in the United States. The Centers for Disease Control and Prevention estimate that 1.7 million people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI) model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1 day) and for the first time, subacute (7 days), post-injury time frame using the established cation-anion exchange chromatography-1D SDS gel electrophoresis LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entity, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day) and subacute (7 days) periods post-TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7 days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is among the

Potential of calcium isotopes to identify fractionations in vegetation: experimental approach

NASA Astrophysics Data System (ADS)

Cobert, F.; Schmitt, A.; Bourgade, P.; Stille, P.; Chabaux, F. J.; Badot, P.; Jaegler, T.

2010-12-01

This study aims to better understand the role of vegetation on the Ca cycle at the level of the critical zone of the Earth, in order to specify the mechanisms controlling the Ca absorption by plants at the rock/plant interface. To do this, we performed experiments using hydroponic plant cultures in a way that we could control the cooccuring geochemical and biological processes and determine the impact of the nutritive solution on the Ca cycle within plants. A dicotyledon and calcicole plant with rapid growth, the French bean (Phaseolus vulgaris L.), has been chosen to have access to one complete growth cycle. Several experiments have been conducted with two Ca concentrations, 5 (L) and 60 (H) ppm and two pH values (4 and 6) in the nutritive solution, for which the Ca concentration was maintained constant, so its Ca content is considered to be infinite. We determined Ca concentrations and isotopic ratios in the nutritive solution and in different organs (main roots, secondary roots, old and young stems, old and young leaves and fruits) at two different growth stages (10 days and 6 weeks). Our results show, in accord with previously published field studies, that the bean organs are all enriched in the light 40Ca isotope compared to the nutritive solution (e.g. Wigand et al., 2005; Page et al., 2008; Cenki-Tok et al., 2009; Holmden and Bélanger, 2010). We identify two fractionation levels. The first occurs during the uptake of the nutrient elements by the lateral roots. This implies that the main mechanisms of light isotope enrichments in the plant are due to electrochemical gradient transport processes taking place at this interface. The second fractionation can be observed within the plant itself and is due to the nature of the considered organ itself. Indeed structural reservoirs (primary roots, stem, reproductive organs) incorporate more the light 40Ca isotope compared to the transfer reservoirs (lateral roots, xylem sap, leaves). This could be linked to ion

Identification of potential drug targets based on a computational biology algorithm for venous thromboembolism.

PubMed

Xie, Ruiqiang; Li, Lei; Chen, Lina; Li, Wan; Chen, Binbin; Jiang, Jing; Huang, Hao; Li, Yiran; He, Yuehan; Lv, Junjie; He, Weiming

2017-02-01

Venous thromboembolism (VTE) is a common, fatal and frequently recurrent disease. Changes in the activity of different coagulation factors serve as a pathophysiological basis for the recurrent risk of VTE. Systems biology approaches provide a better understanding of the pathological mechanisms responsible for recurrent VTE. In this study, a novel computational method was presented to identify the recurrent risk modules (RRMs) based on the integration of expression profiles and human signaling network, which hold promise for achieving new and deeper insights into the mechanisms responsible for VTE. The results revealed that the RRMs had good classification performance to discriminate patients with recurrent VTE. The functional annotation analysis demonstrated that the RRMs played a crucial role in the pathogenesis of VTE. Furthermore, a variety of approved drug targets in the RRM M5 were related to VTE. Thus, the M5 may be applied to select potential drug targets for combination therapy and the extended treatment of VTE.

Biological activities and potential health benefits of polysaccharides from Poria cocos and their derivatives.

PubMed

Sun, Yichun

2014-07-01

Poria cocos has a long history of medicinal use in Asian countries such as China, Japan, Korea and Thailand. It is a kind of edible and pharmaceutical mushroom. The chemical compositions of Poria cocos mainly include triterpenes, polysaccharides, steroids, amino acids, choline, histidine, etc. Great advances have been made in chemical and bioactive studies on Poria cocos polysaccharides (PCP) and their derivatives in recent decades. These PCP and their derivatives exhibit many beneficial biological activities including anticancer, anti-inflammatory, antioxidant and antiviral activities. Therefore, PCP and their derivatives have great potential for further development as therapy or adjuvant therapy for cancer, immune-modulatory and antiviral drugs. This paper presents an overview of biological activities and potential health benefits of PCP and their derivatives. Copyright © 2014 Elsevier B.V. All rights reserved.

Biologic Potential of Calcium Phosphate Biopowders Produced via Decomposition Combustion Synthesis

PubMed Central

Vollmer, N.; King, K.B.; Ayers, R.

2015-01-01

The aim of this research was to evaluate the biologic potential of calcium phosphate (CaP) biopowders produced with a novel reaction synthesis system. Decomposition combustion synthesis (DCS) is a modified combustion synthesis method capable of producing CaP powders for use in bone tissue engineering applications. During DCS, the stoichiometric ratio of reactant salt to fuel was adjusted to alter product chemistry and morphology. In vitro testing methods were utilized to determine the effects of controlling product composition on cytotoxicity, proliferation, biocompatibility and biomineralization. In vitro, human fetal osteoblasts (ATCC, CRL-11372) cultured with CaP powder displayed a flattened morphology, and uniformly encompassed the CaP particulates. Matrix vesicles containing calcium and phosphorous budded from the osteoblast cells. CaP powders produced via DCS are a source of biologically active, synthetic, bone graft substitute materials PMID:26034341

Omics of Brucella: Species-Specific sRNA-Mediated Gene Ontology Regulatory Networks Identified by Computational Biology.

PubMed

Vishnu, Udayakumar S; Sankarasubramanian, Jagadesan; Gunasekaran, Paramasamy; Sridhar, Jayavel; Rajendhran, Jeyaprakash

2016-06-01

Brucella is an intracellular bacterium that causes the zoonotic infectious disease, brucellosis. Brucella species are currently intensively studied with a view to developing novel global health diagnostics and therapeutics. In this context, small RNAs (sRNAs) are one of the emerging topical areas; they play significant roles in regulating gene expression and cellular processes in bacteria. In the present study, we forecast sRNAs in three Brucella species that infect humans, namely Brucella melitensis, Brucella abortus, and Brucella suis, using a computational biology analysis. We combined two bioinformatic algorithms, SIPHT and sRNAscanner. In B. melitensis 16M, 21 sRNA candidates were identified, of which 14 were novel. Similarly, 14 sRNAs were identified in B. abortus, of which four were novel. In B. suis, 16 sRNAs were identified, and five of them were novel. TargetRNA2 software predicted the putative target genes that could be regulated by the identified sRNAs. The identified mRNA targets are involved in carbohydrate, amino acid, lipid, nucleotide, and coenzyme metabolism and transport, energy production and conversion, replication, recombination, repair, and transcription. Additionally, the Gene Ontology (GO) network analysis revealed the species-specific, sRNA-based regulatory networks in B. melitensis, B. abortus, and B. suis. Taken together, although sRNAs are veritable modulators of gene expression in prokaryotes, there are few reports on the significance of sRNAs in Brucella. This report begins to address this literature gap by offering a series of initial observations based on computational biology to pave the way for future experimental analysis of sRNAs and their targets to explain the complex pathogenesis of Brucella.

Matrix metalloproteinase-9, a potential biological marker in invasive pituitary adenomas.

PubMed

Gong, Jian; Zhao, Yunge; Abdel-Fattah, Rana; Amos, Samson; Xiao, Aizhen; Lopes, M Beatriz S; Hussaini, Isa M; Laws, Edward R

2008-01-01

We analyzed MMP-9 expression using mRNA and protein level determinations and explored the possibility that matrix metalloproteinase-9 (MMP-9) is a potential biological marker of pituitary adenoma invasiveness and whether MMP-9 could be used to discriminate the extent of invasiveness among different hormonal subtypes, tumor sizes, growth characteristics, and primary versus recurrent tumors. 73 pituitary tumor specimens were snap frozen in liquid nitrogen immediately after surgical resection. RNA and protein were extracted. MMP-9 mRNA transcripts were analyzed by quantitative RT-PCR. MMP-9 protein activity was analyzed by gelatin zymography and validated by western blot analysis. Immunohistochemistry was performed to identify the presence and localization of MMP-9 in pituitary adenomas. Statistical differences between results were determined using Student's t-test or one way ANOVA. Comparing different hormonal subtypes of noninvasive and invasive pituitary tumors, MMP-9 mRNA expression was significantly increased in the majority of invasive adenomas. Considering the protein levels, our data also showed a significant increase in MMP-9 activity in the majority of invasive adenomas and these differences were confirmed by western blot analysis and immunohistochemistry. In addition, consistent differences in MMP-9 expression levels were found according to tumor subtype, tumor size, tumor extension and primary versus redo-surgery. MMP-9 expression can consistently distinguish invasive pituitary tumors from noninvasive pituitary tumors and would reflect the extent of invasiveness in pituitary tumors according to tumor subtype, size, tumor extension, primary and redo surgery, even at early stages of invasiveness. MMP-9 may be considered a potential biomarker to determine and predict the invasive nature of pituitary tumors.

PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables.

PubMed

Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C; Downing, James R; Lamba, Jatinder

2009-08-15

In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org.

Potential of Neoactinolaimus as a biological control agent of root-knot and reniform nematodes

USDA-ARS?s Scientific Manuscript database

The predatory nematode Neoactinolaimus spp. (family Actinolaimidae) was examined as a potential biological control agent against root-knot (Meloidogyne spp.) and reniform (Rotylenchulus reniformis) nematodes in laboratory conditions. Neoactinolaimus possesses a large odontostylet to puncture the cu...

CASE STUDY DEMONSTRATING THE STRESSOR IDENTIFICATION PROCESS THAT IDENTIFIES CAUSES OF BIOLOGICAL IMPAIRMENT IN THE NATION'S WATER BODIES

EPA Science Inventory

The stressor identification program developed guidance for identifying the causes of biological impairments in the nation's waters:

U.S. EPA. 2000. Stressor identification guidance document. EPA/822/B-00/025. U.S. Environmental Protection Agency, Washington, DC.

The ...

Discovering Potential Pathogens among Fungi Identified as Nonsporulating Molds▿

PubMed Central

Pounder, June I.; Simmon, Keith E.; Barton, Claudia A.; Hohmann, Sheri L.; Brandt, Mary E.; Petti, Cathy A.

2007-01-01

Fungal infections are increasing, particularly among immunocompromised hosts, and a rapid diagnosis is essential to initiate antifungal therapy. Often fungi cannot be identified by conventional methods and are classified as nonsporulating molds (NSM).We sequenced internal transcribed spacer regions from 50 cultures of NSM and found 16 potential pathogens that can be associated with clinical disease. In selected clinical settings, identification of NSM could prove valuable and have an immediate impact on patient management. PMID:17135442

A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

PubMed

Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

2015-02-01

The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

Proteomics-based approach identified differentially expressed proteins with potential roles in endometrial carcinoma.

PubMed

Li, Zhengyu; Min, Wenjiao; Huang, Canhua; Bai, Shujun; Tang, Minghai; Zhao, Xia

2010-01-01

We used proteomic approaches to identify altered expressed proteins in endometrial carcinoma, with the aim of discovering potential biomarkers or therapeutic targets for endometrial carcinoma. The global proteins extracted from endometrial carcinoma and normal endometrial tissues were separated by 2-dimensional electrophoresis and analyzed with PDQuest (Bio-Rad, Hercules, Calif) software. The differentially expressed spots were identified by mass spectrometry and searched against NCBInr protein database. Those proteins with potential roles were confirmed by Western blotting and immunohistochemical assays. Ninety-nine proteins were identified by mass spectrometry, and a cluster diagram analysis indicated that these proteins were involved in metabolism, cell transformation, protein folding, translation and modification, proliferation and apoptosis, signal transduction, cytoskeleton, and so on. In confirmatory immunoblotting and immunohistochemical analyses, overexpressions of epidermal fatty acid-binding protein, calcyphosine, and cyclophilin A were also observed in endometrial carcinoma tissues, which were consistent with the proteomic results. Our results suggested that these identified proteins, including epidermal fatty acid-binding protein, calcyphosine, and cyclophilin A, might be of potential values in the studies of endometrial carcinogenesis or investigations of diagnostic biomarkers or treatment targets for endometrial carcinoma.

Examples of testing global identifiability of biological and biomedical models with the DAISY software.

PubMed

Saccomani, Maria Pia; Audoly, Stefania; Bellu, Giuseppina; D'Angiò, Leontina

2010-04-01

DAISY (Differential Algebra for Identifiability of SYstems) is a recently developed computer algebra software tool which can be used to automatically check global identifiability of (linear and) nonlinear dynamic models described by differential equations involving polynomial or rational functions. Global identifiability is a fundamental prerequisite for model identification which is important not only for biological or medical systems but also for many physical and engineering systems derived from first principles. Lack of identifiability implies that the parameter estimation techniques may not fail but any obtained numerical estimates will be meaningless. The software does not require understanding of the underlying mathematical principles and can be used by researchers in applied fields with a minimum of mathematical background. We illustrate the DAISY software by checking the a priori global identifiability of two benchmark nonlinear models taken from the literature. The analysis of these two examples includes comparison with other methods and demonstrates how identifiability analysis is simplified by this tool. Thus we illustrate the identifiability analysis of other two examples, by including discussion of some specific aspects related to the role of observability and knowledge of initial conditions in testing identifiability and to the computational complexity of the software. The main focus of this paper is not on the description of the mathematical background of the algorithm, which has been presented elsewhere, but on illustrating its use and on some of its more interesting features. DAISY is available on the web site http://www.dei.unipd.it/ approximately pia/. 2010 Elsevier Ltd. All rights reserved.

An automated technique to identify potential inappropriate traditional Chinese medicine (TCM) prescriptions.

PubMed

Yang, Hsuan-Chia; Iqbal, Usman; Nguyen, Phung Anh; Lin, Shen-Hsien; Huang, Chih-Wei; Jian, Wen-Shan; Li, Yu-Chuan

2016-04-01

Medication errors such as potential inappropriate prescriptions would induce serious adverse drug events to patients. Information technology has the ability to prevent medication errors; however, the pharmacology of traditional Chinese medicine (TCM) is not as clear as in western medicine. The aim of this study was to apply the appropriateness of prescription (AOP) model to identify potential inappropriate TCM prescriptions. We used the association rule of mining techniques to analyze 14.5 million prescriptions from the Taiwan National Health Insurance Research Database. The disease and TCM (DTCM) and traditional Chinese medicine-traditional Chinese medicine (TCMM) associations are computed by their co-occurrence, and the associations' strength was measured as Q-values, which often referred to as interestingness or life values. By considering the number of Q-values, the AOP model was applied to identify the inappropriate prescriptions. Afterwards, three traditional Chinese physicians evaluated 1920 prescriptions and validated the detected outcomes from the AOP model. Out of 1920 prescriptions, 97.1% of positive predictive value and 19.5% of negative predictive value were shown by the system as compared with those by experts. The sensitivity analysis indicated that the negative predictive value could improve up to 27.5% when the model's threshold changed to 0.4. We successfully applied the AOP model to automatically identify potential inappropriate TCM prescriptions. This model could be a potential TCM clinical decision support system in order to improve drug safety and quality of care. Copyright © 2016 John Wiley & Sons, Ltd.

Hot spot analysis applied to identify ecosystem services potential in Lithuania

NASA Astrophysics Data System (ADS)

Pereira, Paulo; Depellegrin, Daniel; Misiune, Ieva

2016-04-01

Hot spot analysis are very useful to identify areas with similar characteristics. This is important for a sustainable use of the territory, since we can identify areas that need to be protected, or restored. This is a great advantage in terms of land use planning and management, since we can allocate resources, reduce the economical costs and do a better intervention in the landscape. Ecosystem services (ES) are different according land use. Since landscape is very heterogeneous, it is of major importance understand their spatial pattern and where are located the areas that provide better ES and the others that provide less services. The objective of this work is to use hot-spot analysis to identify areas with the most valuable ES in Lithuania. CORINE land-cover (CLC) of 2006 was used as the main spatial information. This classification uses a grid of 100 m resolution and extracted a total of 31 land use types. ES ranking was carried out based on expert knowledge. They were asked to evaluate the ES potential of each different CLC from 0 (no potential) to 5 (very high potential). Hot spot analysis were evaluated using the Getis-ord test, which identifies cluster analysis available in ArcGIS toolbox. This tool identifies areas with significantly high low values and significant high values at a p level of 0.05. In this work we used hot spot analysis to assess the distribution of providing, regulating cultural and total (sum of the previous 3) ES. The Z value calculated from Getis-ord was used to statistical analysis to access the clusters of providing, regulating cultural and total ES. ES with high Z value show that they have a high number of cluster areas with high potential of ES. The results showed that the Z-score was significantly different among services (Kruskal Wallis ANOVA =834. 607, p<0.001). The Z score of providing services (0.096±2.239) were significantly higher than the total (0.093±2.045), cultural (0.080±1.979) and regulating (0.076±1.961). These

Systems biology for organotypic cell cultures.

PubMed

Grego, Sonia; Dougherty, Edward R; Alexander, Francis J; Auerbach, Scott S; Berridge, Brian R; Bittner, Michael L; Casey, Warren; Cooley, Philip C; Dash, Ajit; Ferguson, Stephen S; Fennell, Timothy R; Hawkins, Brian T; Hickey, Anthony J; Kleensang, Andre; Liebman, Michael N J; Martin, Florian; Maull, Elizabeth A; Paragas, Jason; Qiao, Guilin Gary; Ramaiahgari, Sreenivasa; Sumner, Susan J; Yoon, Miyoung

2017-01-01

Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, "organotypic" cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomic data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data.

Genetic Insights Into ADHD Biology.

PubMed

Hayman, Victoria; Fernandez, Thomas V

2018-01-01

ADHD is a neurobiological disorder with a large worldwide prevalence causing significant impairment in children, adolescents, and adults. While there is general agreement about genetic contributions toward the disorder, progress in leveraging genetics to learn more about the biology and risk factors for ADHD has been limited. In this perspective, we identified 105 genes from the literature showing at least nominal statistical significance in association with ADHD. We analyzed these genes for enrichment in biological pathways and in known interacting biological networks. We also analyzed the expression patterns of candidate genes across brain regions and across periods of human development. From our analysis, we identify 14 genes that cluster within an interactive gene network, with enrichment in nitric oxide synthase and alpha-1 adrenergic pathways. Furthermore, these genes show enrichment for expression in the cerebellum during childhood through young adulthood, and in the cortex in adolescence and young adulthood. Gene discovery holds great potential for elucidating the unknown biological underpinnings of ADHD. Genome-wide sequencing efforts are underway and are likely to provide important insights that can be leveraged for new treatments and interventions.

Service-based analysis of biological pathways

PubMed Central

Zheng, George; Bouguettaya, Athman

2009-01-01

Background Computer-based pathway discovery is concerned with two important objectives: pathway identification and analysis. Conventional mining and modeling approaches aimed at pathway discovery are often effective at achieving either objective, but not both. Such limitations can be effectively tackled leveraging a Web service-based modeling and mining approach. Results Inspired by molecular recognitions and drug discovery processes, we developed a Web service mining tool, named PathExplorer, to discover potentially interesting biological pathways linking service models of biological processes. The tool uses an innovative approach to identify useful pathways based on graph-based hints and service-based simulation verifying user's hypotheses. Conclusion Web service modeling of biological processes allows the easy access and invocation of these processes on the Web. Web service mining techniques described in this paper enable the discovery of biological pathways linking these process service models. Algorithms presented in this paper for automatically highlighting interesting subgraph within an identified pathway network enable the user to formulate hypothesis, which can be tested out using our simulation algorithm that are also described in this paper. PMID:19796403

Whole genome association study identifies regions of the bovine genome and biological pathways involved in carcass trait performance in Holstein-Friesian cattle.

PubMed

Doran, Anthony G; Berry, Donagh P; Creevey, Christopher J

2014-10-01

Four traits related to carcass performance have been identified as economically important in beef production: carcass weight, carcass fat, carcass conformation of progeny and cull cow carcass weight. Although Holstein-Friesian cattle are primarily utilized for milk production, they are also an important source of meat for beef production and export. Because of this, there is great interest in understanding the underlying genomic structure influencing these traits. Several genome-wide association studies have identified regions of the bovine genome associated with growth or carcass traits, however, little is known about the mechanisms or underlying biological pathways involved. This study aims to detect regions of the bovine genome associated with carcass performance traits (employing a panel of 54,001 SNPs) using measures of genetic merit (as predicted transmitting abilities) for 5,705 Irish Holstein-Friesian animals. Candidate genes and biological pathways were then identified for each trait under investigation. Following adjustment for false discovery (q-value < 0.05), 479 quantitative trait loci (QTL) were associated with at least one of the four carcass traits using a single SNP regression approach. Using a Bayesian approach, 46 QTL were associated (posterior probability > 0.5) with at least one of the four traits. In total, 557 unique bovine genes, which mapped to 426 human orthologs, were within 500kbs of QTL found associated with a trait using the Bayesian approach. Using this information, 24 significantly over-represented pathways were identified across all traits. The most significantly over-represented biological pathway was the peroxisome proliferator-activated receptor (PPAR) signaling pathway. A large number of genomic regions putatively associated with bovine carcass traits were detected using two different statistical approaches. Notably, several significant associations were detected in close proximity to genes with a known role in animal growth

Comparative qualitative phosphoproteomics analysis identifies shared phosphorylation motifs and associated biological processes in evolutionary divergent plants.

PubMed

Al-Momani, Shireen; Qi, Da; Ren, Zhe; Jones, Andrew R

2018-06-15

Phosphorylation is one of the most prevalent post-translational modifications and plays a key role in regulating cellular processes. We carried out a bioinformatics analysis of pre-existing phosphoproteomics data, to profile two model species representing the largest subclasses in flowering plants the dicot Arabidopsis thaliana and the monocot Oryza sativa, to understand the extent to which phosphorylation signaling and function is conserved across evolutionary divergent plants. We identified 6537 phosphopeptides from 3189 phosphoproteins in Arabidopsis and 2307 phosphopeptides from 1613 phosphoproteins in rice. We identified phosphorylation motifs, finding nineteen pS motifs and two pT motifs shared in rice and Arabidopsis. The majority of shared motif-containing proteins were mapped to the same biological processes with similar patterns of fold enrichment, indicating high functional conservation. We also identified shared patterns of crosstalk between phosphoserines with enrichment for motifs pSXpS, pSXXpS and pSXXXpS, where X is any amino acid. Lastly, our results identified several pairs of motifs that are significantly enriched to co-occur in Arabidopsis proteins, indicating cross-talk between different sites, but this was not observed in rice. Our results demonstrate that there are evolutionary conserved mechanisms of phosphorylation-mediated signaling in plants, via analysis of high-throughput phosphorylation proteomics data from key monocot and dicot species: rice and Arabidposis thaliana. The results also suggest that there is increased crosstalk between phosphorylation sites in A. thaliana compared with rice. The results are important for our general understanding of cell signaling in plants, and the ability to use A. thaliana as a general model for plant biology. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Beyond patchwork precaution in the dual-use governance of synthetic biology.

PubMed

Kelle, Alexander

2013-09-01

The emergence of synthetic biology holds the potential of a major breakthrough in the life sciences by transforming biology into a predictive science. The dual-use characteristics of similar breakthroughs during the twentieth century have led to the application of benignly intended research in e.g. virology, bacteriology and aerobiology in offensive biological weapons programmes. Against this background the article raises the question whether the precautionary governance of synthetic biology can aid in preventing this techno-science witnessing the same fate? In order to address this question, this paper proceeds in four steps: it firstly introduces the emerging techno-science of synthetic biology and presents some of its potential beneficial applications. It secondly analyses contributions to the bioethical discourse on synthetic biology as well as precautionary reasoning and its application to life science research in general and synthetic biology more specifically. The paper then identifies manifestations of a moderate precautionary principle in the emerging synthetic biology dual-use governance discourse. Using a dual-use governance matrix as heuristic device to analyse some of the proposed measures, it concludes that the identified measures can best be described as "patchwork precaution" and that a more systematic approach to construct a web of dual-use precaution for synthetic biology is needed in order to guard more effectively against the field's future misuse for harmful applications.

Incorporating Allee effects into the potential biological removal level

USGS Publications Warehouse

Hadier, Humza; Oldfield, Sarah; Tu, Tiffany; Moreno, Rosa; Diffendorfer, Jay E.; Eager, Eric A.; Erickson, Richard A.

2017-01-01

Potential biological removal (PBR) is an approach used to calculate sustainable harvest and “take” limits for populations. PBR was originally derived assuming logistic growth while ignoring the effects of small population size (i.e., an Allee effect). We derived a version of PBR that includes an Allee effect (i.e., small population size or densities limiting population growth rates). We found that PBR becomes less conservative when it fails to consider an Allee effect. Specifically, sustainable harvest and take levels based upon PBR with an Allee effect were between approximately 51% and 66% of levels based upon PBR without an Allee effect. Managers and biologists using PBR may need to consider the limitations if an Allee effect may be present in the species being modeled.

Identifying potential impact of lead contamination using a geographic information system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bocco, G.; Sanchez, R.

1997-01-01

The main objective of this research was to identify the potential hazards associated with lead contamination from fixed sources in the city of Tijuana. An exploratory model is presented that describes the potential polluting sources as well as the exposed universe. The results of the analysis provide a clear picture of the geographic distribution of hazards areas for potential lead pollution in Tijuana. The findings are indicative of the dramatic consequences of rapid industrialization and urbanization in a city where there have not been significant planning efforts to mitigate the negative effects of this growth. The approach followed helps tomore » narrow the universe of potential pollution sources, which can help to direct attention, research priorities, and resources to the most critical areas. 16 refs.« less

Sigma receptors: biology and therapeutic potential.

PubMed

Guitart, Xavier; Codony, Xavier; Monroy, Xavier

2004-07-01

More than 20 years after the identification of the sigma receptors as a unique binding site in the brain and in the peripheral organs, several questions regarding this receptor are still open. Only one of the subtypes of the receptor has been cloned to date, but the endogenous ligand still remains unknown, and the possible association of the receptor with a conventional second messenger system is controversial. From the very beginning, the sigma receptors were associated with various central nervous system disorders such as schizophrenia or movement disorders. Today, after hundreds of papers dealing with the importance of sigma receptors in brain function, it is widely accepted that sigma receptors represent a new and different avenue in the possible pharmacological treatment of several brain-related disorders. In this review, what is known about the biology of the sigma receptor regarding its putative structure and its distribution in the central nervous system is summarized first. The role of sigma receptors regulating cellular functions and other neurotransmitter systems is also addressed, as well as a short overview of the possible endogenous ligands. Finally, although no specific sigma ligand has reached the market, different pharmacological approaches to the alleviation and treatment of several central nervous system disorders and deficits, including schizophrenia, pain, memory deficits, etc., are discussed, with an overview of different compounds and their potential therapeutic use.

Common variants identified in genome-wide association studies of testicular germ cell tumour: an update, biological insights and clinical application.

PubMed

Litchfield, K; Shipley, J; Turnbull, C

2015-01-01

Testicular germ cell tumour (TGCT) is the most common cause of cancer in young men (aged 15-45 years) in many populations. Multiple genome-wide association studies (GWAS) of TGCT have now been conducted, yielding over 25 disease-associated single-nucleotide polymorphism (SNP)s at 19 independent loci. The genes at these loci have provided rich biological and genetic insight into possible mechanisms underlying testicular germ cell oncogenesis. In this review, we summarize these mechanisms which can be grouped into five distinct categories: KIT/KITLG signalling, other pathways of male germ cell development/differentiation, telomerase function, microtubule assembly and DNA damage repair. The TGCT risk markers identified through GWAS include individual SNPs carrying per allele odds ratios (OR) in excess of 2.5. These ORs are among the highest reported in GWAS of any cancer type, hence suggesting a potential clinical utility in risk determination. Here, we present analysis of such an approach, using polygenic risk scores to calculate the combined effect of all risk loci on overall TGCT risk and discuss how a potential screening strategy may fit within a broader clinical context. © 2015 American Society of Andrology and European Academy of Andrology.

Potential biological control agents for management of cogongrass (Cyperales: Poaceae) in the southeastern USA

USDA-ARS?s Scientific Manuscript database

Cogongrass, Imperata cylindrica (L.) Palisot de Beauvois (Cyperales: Poaceae), is a noxious invasive weed in the southeastern USA. Surveys for potential biological control agents of cogongrass were conducted in Asia and East Africa from 2013 to 2016. Several insect herbivores were found that may hav...

Conservation biology in Asia: the major policy challenges.

PubMed

McNeely, Jeffrey A; Kapoor-Vijay, Promila; Zhi, Lu; Olsvig-Whittaker, Linda; Sheikh, Kashif M; Smith, Andrew T

2009-08-01

With about half the world's human population and booming economies, Asia faces numerous challenges to its biodiversity. The Asia Section of the Society for Conservation Biology has identified some key policy issues in which significant progress can be made. These include developing new sources of funding for forest conservation; identifying potential impacts of energy alternatives on the conservation of biodiversity; curbing the trade in endangered species of plants and animals; a special focus on the conservation of mountain biodiversity; enhancing relevant research; ensuring that conservation biology contributes to major international conventions and funding mechanisms; using conservation biology to build a better understanding of zoonotic diseases; more effectively addressing human-animal conflicts; enhancing community-based conservation; and using conservation biology to help address the pervasive water-deficit problems in much of Asia. These challenges can be met through improved regional cooperation among the relevant stakeholders.

Systems biology approaches for identifying adverse drug reactions and elucidating their underlying biological mechanisms.

PubMed

Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph D; Moskovitch, Robert; Tatonetti, Nicholas P

2016-01-01

Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. © 2015 Wiley Periodicals, Inc.

Spontaneous swallowing frequency has potential to identify dysphagia in acute stroke.

PubMed

Crary, Michael A; Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael F

2013-12-01

Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. In a cohort of 63 acute stroke cases, swallow frequency rates (swallows per minute [SPM]) were compared with stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with versus without clinically significant dysphagia. Receiver operating characteristic curve analysis was used to identify the optimal threshold in SPM, which was compared with a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was used to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. Receiver operating characteristic curve analysis yielded a threshold of SPM≤0.40 that identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5- to 10-minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel.

Spontaneous Swallowing Frequency [Has Potential to] Identify Dysphagia in Acute Stroke

PubMed Central

Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael

2014-01-01

Background and Purpose Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. Methods In a cohort of 63 acute stroke cases swallow frequency rates (swallows per minute: SPM) were compared to stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with vs. without clinically significant dysphagia. ROC analysis was used to identify the optimal threshold in SPM which was compared to a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was employed to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. Results SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. ROC analysis yielded a threshold of SPM ≤ 0.40 which identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5 to 10 minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Conclusions Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel. PMID:24149008

The growing role of biologics and biosimilars in the United States: Perspectives from the APhA Biologics and Biosimilars Stakeholder Conference.

PubMed

Crespi-Lofton, Judy; Skelton, Jann B

The American Pharmacists Association (APhA) convened the Biologics and Biosimilars Stakeholder Conference on November 30, 2016, in Washington DC. The objectives of the Conference were to determine the key issues and challenges within the marketplace for biologics, follow-on biologics (FOBs), and biosimilars, identify potential roles and responsibilities of pharmacists regarding biologic and biosimilar medications, and identify actions or activities that pharmacists may take to optimize the safe and cost-effective use of biologics and biosimilars. National thought leaders and stakeholder representatives, including individuals from the Food and Drug Administration, Centers for Medicare and Medicaid Services, a private third-party payer, manufacturers, and several national organizations of health care professionals, participated in the conference. Information shared by this group was supplemented with relevant legal and regulatory information and published literature. Biologics play a valuable role in the treatment of numerous health conditions, but their associated costs, which tend to be greater than those of small-molecule drugs, place a burden on the health care system. Biosimilars (both noninterchangeable and interchangeable) are highly similar copies of the originator biologic and offer the potential to reduce costs and improve patient access to biological products by increasing treatment options and creating a more competitive market. Despite the potential benefits of biosimilars, certain factors may limit their uptake. The conference participants explored issues that different stakeholders think influence the use of biologics, including biosimilars, in the United States. Barriers included technology, prescriber-pharmacist communication, legislation and regulations, limited patient and health care practitioner knowledge of biological products, patient and health care practitioner perceptions of biosimilars, and evolving science or lack of long-term data. After

Potential application of SERS for arsenic speciation in biological matrices.

PubMed

Yang, Mingwei; Matulis, Shannon; Boise, Lawrence H; McGoron, Anthony J; Cai, Yong

2017-08-01

Speciation of arsenic is usually carried out using chromatography-based methods coupled with spectroscopic determination; however, the inevitable procedures involving sample preparation and separation could potentially alter the integrity of the arsenic metabolites present in biological samples. Surface-enhanced Raman spectroscopy (SERS) could be a promising alternative for providing a reliable arsenic analysis under the influence of a cellular matrix. A method for arsenic speciation using SERS in cellular matrix was developed in this study and four arsenicals were selected, including arsenite (As III ), arsenate (As V ), monomethylarsonic acid (MMA V ) and dimethylarsinic acid (DMA V ). Silver nanoparticles in the form of colliodal suspension with different surface charges, i.e., coated with citrate (AgNPs-Citrate) and spermine (AgNPs-Spermine) were employed as SERS substrates. Adsorption of arsenicals on nanoparticles in colloidal suspensions and the cellular matrix and the pH, size, and zeta potential of the colloidal suspensions were investigated for a better understanding of the SERS signal response of arsenicals in the colloidal suspensions or under the influence of cellular matrix. Arsenicals showed substantially different SERS responses in the two colloidal suspensions, mainly because of the distinct difference in the interaction between the arsenicals and the nanoparticles. Arsenic speciation in cell lysate could be successfully carried out in AgNPs-Spermine suspension, while AgNPs-Citrate could not yield significant SERS signals under the experimental conditions. This study proved that AgNPs-Spermine colloidal suspension could be a promising SERS substrate for studying arsenic metabolism in a biological matrix, reducing the bias caused by traditional techniques that involve sample extraction and pretreatment.

PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables

PubMed Central

Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R.; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C.; Downing, James R.; Lamba, Jatinder

2009-01-01

Motivation: In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Results: Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Availability: Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org. Contact: stanley.pounds@stjude.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19528086

Identifying Potential Norovirus Epidemics in China via Internet Surveillance

PubMed Central

Chen, Bin; Jiang, Tao; Cai, Gaofeng; Jiang, Zhenggang; Chen, Yongdi; Wang, Zhengting; Gu, Hua; Chai, Chengliang

2017-01-01

Background Norovirus is a common virus that causes acute gastroenteritis worldwide, but a monitoring system for norovirus is unavailable in China. Objective We aimed to identify norovirus epidemics through Internet surveillance and construct an appropriate model to predict potential norovirus infections. Methods The norovirus-related data of a selected outbreak in Jiaxing Municipality, Zhejiang Province of China, in 2014 were collected from immediate epidemiological investigation, and the Internet search volume, as indicated by the Baidu Index, was acquired from the Baidu search engine. All correlated search keywords in relation to norovirus were captured, screened, and composited to establish the composite Baidu Index at different time lags by Spearman rank correlation. The optimal model was chosen and possibly predicted maps in Zhejiang Province were presented by ArcGIS software. Results The combination of two vital keywords at a time lag of 1 day was ultimately identified as optimal (ρ=.924, P<.001). The exponential curve model was constructed to fit the trend of this epidemic, suggesting that a one-unit increase in the mean composite Baidu Index contributed to an increase of norovirus infections by 2.15 times during the outbreak. In addition to Jiaxing Municipality, Hangzhou Municipality might have had some potential epidemics in the study time from the predicted model. Conclusions Although there are limitations with early warning and unavoidable biases, Internet surveillance may be still useful for the monitoring of norovirus epidemics when a monitoring system is unavailable. PMID:28790023

Creative design inspired by biological knowledge: Technologies and methods

NASA Astrophysics Data System (ADS)

Tan, Runhua; Liu, Wei; Cao, Guozhong; Shi, Yuan

2018-05-01

Biological knowledge is becoming an important source of inspiration for developing creative solutions to engineering design problems and even has a huge potential in formulating ideas that can help firms compete successfully in a dynamic market. To identify the technologies and methods that can facilitate the development of biologically inspired creative designs, this research briefly reviews the existing biological-knowledge-based theories and methods and examines the application of biological-knowledge-inspired designs in various fields. Afterward, this research thoroughly examines the four dimensions of key technologies that underlie the biologically inspired design (BID) process. This research then discusses the future development trends of the BID process before presenting the conclusions.

Apparent synergy among defense mechanisms in subterranean termites (Rhinotermitidae) against epizootic events: limits and potential for biological control.

PubMed

Chouvenc, Thomas; Su, Nan-Yao

2010-08-01

The use of entomopathogens for biological control of subterranean termites (Rhinotermitidae) has attracted attention in the past four decades, and several laboratory studies have shown promising results with fungal agents. This approach was based on the concept of classical biological control with the use of a virulent agent that can self-replicate in a termite nest and be transmitted among individuals, resulting in an epizootic to kill the entire colony. However, the absence of positive results in field studies challenged the potential of fungal pathogens as a realistic approach for subterranean termite control, and the relationship between fungi and subterranean termites remains poorly understood. A multimodal approach of the currently identified defense mechanisms allowed us to show that subterranean termites have the ability to prevent an epizootic from occurring. The defense mechanisms involved in such resistance are reviewed and documented. Finally, the interactions among three major defense mechanisms (grooming, cellular encapsulation, and gut antifungal activity) were analyzed, and it is suggested that these mechanisms act synergistically to produce an efficient defense against the infection of the fungus at the individual and group level so as to protect the colony from epizootics.

Biology Myth-Killers

ERIC Educational Resources Information Center

Lampert, Evan

2014-01-01

"Biology Myth-Killers" is an activity designed to identify and correct common misconceptions for high school and college introductory biology courses. Students identify common myths, which double as biology misconceptions, and use appropriate sources to share the "truth" about the myths. This learner-centered activity is a fun…

The acquisition of dangerous biological materials: Technical facts sheets to assist risk assessments of 46 potential BW agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aceto, Donato Gonzalo; Astuto-Gribble, Lisa M.; Gaudioso, Jennifer M.

Numerous terrorist organizations have openly expressed interest in producing and deploying biological weapons. However, a limiting factor for many terrorists has been the acquisition of dangerous biological agents, as evidenced by the very few successful instances of biological weapons use compared to the number of documented hoaxes. Biological agents vary greatly in their ability to cause loss of life and economic damage. Some agents, if released properly, can kill many people and cause an extensive number of secondary infections; other agents will sicken only a small number of people for a short period of time. Consequently, several biological agents canmore » potentially be used to perpetrate a bioterrorism attack but few are likely capable of causing a high consequence event. It is crucial, from a US national security perspective, to more deeply understand the likelihood that terrorist organizations can acquire the range of these agents. Few studies have attempted to comprehensively compile the technical information directly relevant to the acquisition of dangerous bacteria, viruses and toxins. In this report, technical fact sheets were assembled for 46 potentially dangerous biological agents. Much of the information was taken from various research sources which could ultimately and significantly expedite and improve bioterrorism threat assessments. By systematically examining a number of specific agent characteristics included in these fact sheets, it may be possible to detect, target, and implement measures to thwart future terrorist acquisition attempts. In addition, the information in these fact sheets may be used as a tool to help laboratories gain a rudimentary understanding of how attractive a method laboratory theft is relative to other potential acquisition modes.« less

A method to identify and analyze biological programs through automated reasoning

PubMed Central

Yordanov, Boyan; Dunn, Sara-Jane; Kugler, Hillel; Smith, Austin; Martello, Graziano; Emmott, Stephen

2016-01-01

Predictive biology is elusive because rigorous, data-constrained, mechanistic models of complex biological systems are difficult to derive and validate. Current approaches tend to construct and examine static interaction network models, which are descriptively rich, but often lack explanatory and predictive power, or dynamic models that can be simulated to reproduce known behavior. However, in such approaches implicit assumptions are introduced as typically only one mechanism is considered, and exhaustively investigating all scenarios is impractical using simulation. To address these limitations, we present a methodology based on automated formal reasoning, which permits the synthesis and analysis of the complete set of logical models consistent with experimental observations. We test hypotheses against all candidate models, and remove the need for simulation by characterizing and simultaneously analyzing all mechanistic explanations of observed behavior. Our methodology transforms knowledge of complex biological processes from sets of possible interactions and experimental observations to precise, predictive biological programs governing cell function. PMID:27668090

Systems Biology for Organotypic Cell Cultures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grego, Sonia; Dougherty, Edward R.; Alexander, Francis J.

Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, “organotypic” cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomicmore » data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data. This consensus report summarizes the

Progeny Clustering: A Method to Identify Biological Phenotypes

PubMed Central

Hu, Chenyue W.; Kornblau, Steven M.; Slater, John H.; Qutub, Amina A.

2015-01-01

Estimating the optimal number of clusters is a major challenge in applying cluster analysis to any type of dataset, especially to biomedical datasets, which are high-dimensional and complex. Here, we introduce an improved method, Progeny Clustering, which is stability-based and exceptionally efficient in computing, to find the ideal number of clusters. The algorithm employs a novel Progeny Sampling method to reconstruct cluster identity, a co-occurrence probability matrix to assess the clustering stability, and a set of reference datasets to overcome inherent biases in the algorithm and data space. Our method was shown successful and robust when applied to two synthetic datasets (datasets of two-dimensions and ten-dimensions containing eight dimensions of pure noise), two standard biological datasets (the Iris dataset and Rat CNS dataset) and two biological datasets (a cell phenotype dataset and an acute myeloid leukemia (AML) reverse phase protein array (RPPA) dataset). Progeny Clustering outperformed some popular clustering evaluation methods in the ten-dimensional synthetic dataset as well as in the cell phenotype dataset, and it was the only method that successfully discovered clinically meaningful patient groupings in the AML RPPA dataset. PMID:26267476

The pediatric sepsis biomarker risk model: potential implications for sepsis therapy and biology.

PubMed

Alder, Matthew N; Lindsell, Christopher J; Wong, Hector R

2014-07-01

Sepsis remains a major cause of morbidity and mortality in adult and pediatric intensive care units. Heterogeneity of demographics, comorbidities, biological mechanisms, and severity of illness leads to difficulty in determining which patients are at highest risk of mortality. Determining mortality risk is important for weighing the potential benefits of more aggressive interventions and for deciding whom to enroll in clinical trials. Biomarkers can be used to parse patients into different risk categories and can outperform current methods of patient risk stratification based on physiologic parameters. Here we review the Pediatric Sepsis Biomarker Risk Model that has also been modified and applied to estimate mortality risk in adult patients. We compare the two models and speculate on the biological implications of the biomarkers in patients with sepsis.

Identifying biological pathways that underlie primordial short stature using network analysis.

PubMed

Hanson, Dan; Stevens, Adam; Murray, Philip G; Black, Graeme C M; Clayton, Peter E

2014-06-01

Mutations in CUL7, OBSL1 and CCDC8, leading to disordered ubiquitination, cause one of the commonest primordial growth disorders, 3-M syndrome. This condition is associated with i) abnormal p53 function, ii) GH and/or IGF1 resistance, which may relate to failure to recycle signalling molecules, and iii) cellular IGF2 deficiency. However the exact molecular mechanisms that may link these abnormalities generating growth restriction remain undefined. In this study, we have used immunoprecipitation/mass spectrometry and transcriptomic studies to generate a 3-M 'interactome', to define key cellular pathways and biological functions associated with growth failure seen in 3-M. We identified 189 proteins which interacted with CUL7, OBSL1 and CCDC8, from which a network including 176 of these proteins was generated. To strengthen the association to 3-M syndrome, these proteins were compared with an inferred network generated from the genes that were differentially expressed in 3-M fibroblasts compared with controls. This resulted in a final 3-M network of 131 proteins, with the most significant biological pathway within the network being mRNA splicing/processing. We have shown using an exogenous insulin receptor (INSR) minigene system that alternative splicing of exon 11 is significantly changed in HEK293 cells with altered expression of CUL7, OBSL1 and CCDC8 and in 3-M fibroblasts. The net result is a reduction in the expression of the mitogenic INSR isoform in 3-M syndrome. From these preliminary data, we hypothesise that disordered ubiquitination could result in aberrant mRNA splicing in 3-M; however, further investigation is required to determine whether this contributes to growth failure. © 2014 The authors.

Systems Biology to Support Nanomaterial Grouping.

PubMed

Riebeling, Christian; Jungnickel, Harald; Luch, Andreas; Haase, Andrea

2017-01-01

The assessment of potential health risks of engineered nanomaterials (ENMs) is a challenging task due to the high number and great variety of already existing and newly emerging ENMs. Reliable grouping or categorization of ENMs with respect to hazards could help to facilitate prioritization and decision making for regulatory purposes. The development of grouping criteria, however, requires a broad and comprehensive data basis. A promising platform addressing this challenge is the systems biology approach. The different areas of systems biology, most prominently transcriptomics, proteomics and metabolomics, each of which provide a wealth of data that can be used to reveal novel biomarkers and biological pathways involved in the mode-of-action of ENMs. Combining such data with classical toxicological data would enable a more comprehensive understanding and hence might lead to more powerful and reliable prediction models. Physico-chemical data provide crucial information on the ENMs and need to be integrated, too. Overall statistical analysis should reveal robust grouping and categorization criteria and may ultimately help to identify meaningful biomarkers and biological pathways that sufficiently characterize the corresponding ENM subgroups. This chapter aims to give an overview on the different systems biology technologies and their current applications in the field of nanotoxicology, as well as to identify the existing challenges.

NANOSILVER MOVEMENT THROUGH BIOLOGICAL BARRIERS RELATES TO PHYSICOCHEMICAL PROPERTIES

EPA Science Inventory

Linking the physicochemical (PC) properties of engineered nanomaterials (NM) to their biological activity is critical for identifying their (toxic) mode of action, and developing appropriate and effective risk assessment guidelines. Particle surface charge (zeta potential), surfa...

Using Social Media Data to Identify Potential Candidates for Drug Repurposing: A Feasibility Study.

PubMed

Rastegar-Mojarad, Majid; Liu, Hongfang; Nambisan, Priya

2016-06-16

Drug repurposing (defined as discovering new indications for existing drugs) could play a significant role in drug development, especially considering the declining success rates of developing novel drugs. Typically, new indications for existing medications are identified by accident. However, new technologies and a large number of available resources enable the development of systematic approaches to identify and validate drug-repurposing candidates. Patients today report their experiences with medications on social media and reveal side effects as well as beneficial effects of those medications. Our aim was to assess the feasibility of using patient reviews from social media to identify potential candidates for drug repurposing. We retrieved patient reviews of 180 medications from an online forum, WebMD. Using dictionary-based and machine learning approaches, we identified disease names in the reviews. Several publicly available resources were used to exclude comments containing known indications and adverse drug effects. After manually reviewing some of the remaining comments, we implemented a rule-based system to identify beneficial effects. The dictionary-based system and machine learning system identified 2178 and 6171 disease names respectively in 64,616 patient comments. We provided a list of 10 common patterns that patients used to report any beneficial effects or uses of medication. After manually reviewing the comments tagged by our rule-based system, we identified five potential drug repurposing candidates. To our knowledge, this is the first study to consider using social media data to identify drug-repurposing candidates. We found that even a rule-based system, with a limited number of rules, could identify beneficial effect mentions in patient comments. Our preliminary study shows that social media has the potential to be used in drug repurposing.

Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants

PubMed Central

Gala, Manish; Abecasis, Goncalo; Bezieau, Stephane; Brenner, Hermann; Butterbach, Katja; Caan, Bette J.; Carlson, Christopher S.; Casey, Graham; Chang-Claude, Jenny; Conti, David V.; Curtis, Keith R.; Duggan, David; Gallinger, Steven; Haile, Robert W.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hudson, Thomas J.; Jenkins, Mark A.; Küry, Sébastien; Le Marchand, Loic; Leal, Suzanne M.; Newcomb, Polly A.; Nickerson, Deborah A.; Potter, John D.; Schoen, Robert E.; Schumacher, Fredrick R.; Seminara, Daniela; Slattery, Martha L.; Hsu, Li; Chan, Andrew T.; White, Emily; Berndt, Sonja I.; Peters, Ulrike

2016-01-01

Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s). PMID:27379672

Contextual Hub Analysis Tool (CHAT): A Cytoscape app for identifying contextually relevant hubs in biological networks.

PubMed

Muetze, Tanja; Goenawan, Ivan H; Wiencko, Heather L; Bernal-Llinares, Manuel; Bryan, Kenneth; Lynn, David J

2016-01-01

Highly connected nodes (hubs) in biological networks are topologically important to the structure of the network and have also been shown to be preferentially associated with a range of phenotypes of interest. The relative importance of a hub node, however, can change depending on the biological context. Here, we report a Cytoscape app, the Contextual Hub Analysis Tool (CHAT), which enables users to easily construct and visualize a network of interactions from a gene or protein list of interest, integrate contextual information, such as gene expression or mass spectrometry data, and identify hub nodes that are more highly connected to contextual nodes (e.g. genes or proteins that are differentially expressed) than expected by chance. In a case study, we use CHAT to construct a network of genes that are differentially expressed in Dengue fever, a viral infection. CHAT was used to identify and compare contextual and degree-based hubs in this network. The top 20 degree-based hubs were enriched in pathways related to the cell cycle and cancer, which is likely due to the fact that proteins involved in these processes tend to be highly connected in general. In comparison, the top 20 contextual hubs were enriched in pathways commonly observed in a viral infection including pathways related to the immune response to viral infection. This analysis shows that such contextual hubs are considerably more biologically relevant than degree-based hubs and that analyses which rely on the identification of hubs solely based on their connectivity may be biased towards nodes that are highly connected in general rather than in the specific context of interest. CHAT is available for Cytoscape 3.0+ and can be installed via the Cytoscape App Store ( http://apps.cytoscape.org/apps/chat).

Endothelial cell palmitoylproteomics identifies novel lipid modified targets and potential substrates for protein acyl transferases

PubMed Central

Marin, Ethan P.; Derakhshan, Behrad; Lam, TuKiet T.; Davalos, Alberto; Sessa, William C.

2012-01-01

Rationale Protein S-palmitoylation is the post-translational attachment of a saturated 16-carbon palmitic acid to a cysteine side chain via a thioester bond. Palmitoylation can affect protein localization, trafficking, stability, and function. The extent and roles of palmitoylation in endothelial cell (EC) biology is not well understood, in part due to technological limits on palmitoylprotein detection. Objective To develop a method using acyl-biotinyl exchange (ABE) technology coupled with mass spectrometry to globally isolate and identify palmitoylproteins in EC. Methods and Results More than 150 putative palmitoyl proteins were identified in EC using ABE and mass spectrometry. Among the novel palmitoylproteins identified is superoxide dismutase 1 (SOD1), an intensively studied enzyme that protects all cells from oxidative damage. Mutation of cysteine 6 prevents palmitoylation, leads to reduction in SOD1 activity in vivo and in vitro, and inhibits nuclear localization, thereby supporting a functional role for SOD1 palmitoylation. Moreover, we used ABE to search for substrates of particular protein acyl transferases in EC. We found that palmitoylation of the cell adhesion protein PECAM1 is dependent on the protein acyl transferase ZDHHC21. We show that knockdown of ZDHHC21 leads to reduced levels of PECAM1 at the cell surface. Conclusions Our data demonstrate the utility of EC palmitoylproteomics to reveal new insights into the role of this important post-translational lipid modification in EC biology. PMID:22496122

Identifying High Academic Potential in Australian Aboriginal Children Using Dynamic Testing

ERIC Educational Resources Information Center

Chaffey, Graham W.; Bailey, Stan B.; Vine, Ken W.

2015-01-01

The primary purpose of this study was to determine the effectiveness of dynamic testing as a method for identifying high academic potential in Australian Aboriginal children. The 79 participating Aboriginal children were drawn from Years 3-5 in rural schools in northern New South Wales. The dynamic testing method used in this study involved a…

Evaluating Effect of Students' Academic Achievement on Identified Difficult Concepts in Senior Secondary School Biology in Delta State

ERIC Educational Resources Information Center

Agboghoroma, Tim E.; Oyovwi, E. O.

2015-01-01

This study evaluated the effect of students' academic achievement on identified difficult concepts or topics in Senior Secondary School Biology in Delta State, Nigeria. The study was quasi-experimental and the design was a 2X2 factorial non-randomized pretest-posttest control group design. The sample was drawn from intact classes from four…

Ultrashort Phenomena in Biochemistry and Biological Signaling

NASA Astrophysics Data System (ADS)

Splinter, Robert

2014-11-01

In biological phenomena there are indications that within the long pulse-length of the action potential on millisecond scale, there is additional ultrashort perturbation encoding that provides the brain with detailed information about the origin (location) and physiological characteristics. The objective is to identify the mechanism-of-action providing the potential for encoding in biological signal propagation. The actual molecular processes involved in the initiation of the action potential have been identified to be in the femtosecond and pico-second scale. The depolarization process of the cellular membrane itself, leading to the onset of the actionpotential that is transmitted to the brain, however is in the millisecond timeframe. One example of the femtosecond chemical interaction is the photoresponse of bacteriorhodopsin. No clear indication for the spatial encoding has so far been verified. Further research will be required on a cellular signal analysis level to confirm or deny the spatial and physiological encoding in the signal wave-trains of intercellular communications and sensory stimuli. The pathological encoding process for cardiac depolarization is however very pronounced and validated, however this electro-chemical process is in the millisecond amplitude and frequency modulation spectrum.

The Effect of Inkjet Printing over Polymeric Films as Potential Buccal Biologics Delivery Systems.

PubMed

Montenegro-Nicolini, Miguel; Reyes, Patricio E; Jara, Miguel O; Vuddanda, Parameswara R; Neira-Carrillo, Andrónico; Butto, Nicole; Velaga, Sitaram; Morales, Javier O

2018-06-22

The buccal mucosa appears as a promissory route for biologic drug administration, and pharmaceutical films are flexible dosage forms that can be used in the buccal mucosa as drug delivery systems for either a local or systemic effect. Recently, thin films have been used as printing substrates to manufacture these dosage forms by inkjet printing. As such, it is necessary to investigate the effects of printing biologics on films as substrates in terms of their physical and mucoadhesive properties. Here, we explored solvent casting as a conventional method with two biocompatible polymers, hydroxypropyl methylcellulose, and chitosan, and we used electrospinning process as an electrospun film fabrication of polycaprolactone fibers due to its potential to elicit mucoadhesion. Lysozyme was used as biologic drug model and was formulated as a solution for printing by thermal inkjet printing. Films were characterized before and after printing by mechanical and mucoadhesive properties, surface, and ultrastructure morphology through scanning electron microscopy and solid state properties by thermal analysis. Although minor differences were detected in micrographs and thermograms in all polymeric films tested, neither mechanical nor mucoadhesive properties were affected by these differences. Thus, biologic drug printing on films was successful without affecting their mechanical or mucoadhesive properties. These results open way to explore biologics loading on buccal films by inkjet printing, and future efforts will include further in vitro and in vivo evaluations.

Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

DTIC Science & Technology

2015-04-01

step of the Plasmodium mammalian cycle . Inhibiting this step can block malaria at an early step. However, few anti-malarials target liver infection...points in the life cycle of malaria parasites. PLoS Biol 12: e1001806. 2. Falae A, Combe A, Amaladoss A, Carvalho T, Menard R, et al. (2010) Role of...AWARD NUMBER: W81XWH-13-1-0429 TITLE: Using "Click Chemistry" to Identify Potential Drug Targets in Plasmodium PRINCIPAL INVESTIGATOR: Dr. Purnima

The emerging molecular biology toolbox for the study of long noncoding RNA biology.

PubMed

Fok, Ezio T; Scholefield, Janine; Fanucchi, Stephanie; Mhlanga, Musa M

2017-10-01

Long noncoding RNAs (lncRNAs) have been implicated in many biological processes. However, due to the unique nature of lncRNAs and the consequential difficulties associated with their characterization, there is a growing disparity between the rate at which lncRNAs are being discovered and the assignment of biological function to these transcripts. Here we present a molecular biology toolbox equipped to help dissect aspects of lncRNA biology and reveal functionality. We outline an approach that begins with a broad survey of genome-wide, high-throughput datasets to identify potential lncRNA candidates and then narrow the focus on specific methods that are well suited to interrogate the transcripts of interest more closely. This involves the use of imaging-based strategies to validate these candidates and observe the behaviors of these transcripts at single molecule resolution in individual cells. We also describe the use of gene editing tools and interactome capture techniques to interrogate functionality and infer mechanism, respectively. With the emergence of lncRNAs as important molecules in healthy and diseased cellular function, it remains crucial to deepen our understanding of their biology.

How Long Does the Benefit of Biologics Last? An Update on Time To Relapse and Potential for Rebound of Biologic Agents for Psoriasis.

PubMed

Kamaria, Monique; Liao, Wilson; Koo, J Y

2010-01-01

The biologic agents vary considerably in terms of their long-term duration of effect. Using the definitions provided by the National Psoriasis Foundation Medical Board, the objective of this review was to compare all biologic agents with respect to time to relapse and potential for rebound. Overall, alefacept had the longest off-treatment benefit (29.9 weeks in Psoriasis Area and Severity Index [PASI] 75 responders), followed by ustekinumab (22 weeks), infliximab (19.5 weeks), adalimumab (18 weeks), etanercept (12.1 weeks in PASI 50 responders), and, lastly, efalizumab (9.6 weeks). Rebound was reported commonly for efalizumab (14%) and, extremely rarely, for etanercept (0.002%).

Field Characterization of Potential Reference Sediments in the Gulf of Mexico: Chemical and Biological Quality

EPA Science Inventory

Lewis, Michael A., Jed G. Campbell, Peggy S. Harris, Darrin D. Dantin, Steve S. Foss, Robert L. Quarles, James C. Moore and Cynthia A. Chancy. Submitted. Characterization of Potential Reference Areas in the Gulf of Mexico: Near-Coastal Sediment Chemical and Biological Quality. En...

Student Acquisition of Biological Evolution-Related Misconceptions: The Role of Public High School Introductory Biology Teachers

ERIC Educational Resources Information Center

Yates, Tony Brett

2011-01-01

In order to eliminate student misconceptions concerning biological evolution, it is important to identify their sources. The purposes of this study were to: (a) identify biological evolution-related misconceptions held by Oklahoma public high school Biology I teachers; (b) identify biological evolution-related misconceptions held by Oklahoma…

Theory and methodology for utilizing genes as biomarkers to determine potential biological mixtures.

PubMed

Shrestha, Sadeep; Smith, Michael W; Beaty, Terri H; Strathdee, Steffanie A

2005-01-01

Genetically determined mixture information can be used as a surrogate for physical or behavioral characteristics in epidemiological studies examining research questions related to socially stigmatized behaviors and horizontally transmitted infections. A new measure, the probability of mixture discrimination (PMD), was developed to aid mixture analysis that estimates the ability to differentiate single from multiple genomes in biological mixtures. Four autosomal short tandem repeats (STRs) were identified, genotyped and evaluated in African American, European American, Hispanic, and Chinese individuals to estimate PMD. Theoretical PMD frameworks were also developed for autosomal and sex-linked (X and Y) STR markers in potential male/male, male/female and female/female mixtures. Autosomal STRs genetically determine the presence of multiple genomes in mixture samples of unknown genders with more power than the apparently simpler X and Y chromosome STRs. Evaluation of four autosomal STR loci enables the detection of mixtures of DNA from multiple sources with above 99% probability in all four racial/ethnic populations. The genetic-based approach has applications in epidemiology that provide viable alternatives to survey-based study designs. The analysis of genes as biomarkers can be used as a gold standard for validating measurements from self-reported behaviors that tend to be sensitive or socially stigmatizing, such as those involving sex and drugs.

Applying the Nernst equation to simulate redox potential variations for biological nitrification and denitrification processes.

PubMed

Chang, Cheng-Nan; Cheng, Hong-Bang; Chao, Allen C

2004-03-15

In this paper, various forms of Nernst equations have been developed based on the real stoichiometric relationship of biological nitrification and denitrification reactions. Instead of using the Nernst equation based on a one-to-one stoichiometric relation for the oxidizing and the reducing species, the basic Nernst equation is modified into slightly different forms. Each is suitable for simulating the redox potential (ORP) variation of a specific biological nitrification or denitrification process. Using the data published in the literature, the validity of these developed Nernst equations has been verified by close fits of the measured ORP data with the calculated ORP curve. The simulation results also indicate that if the biological process is simulated using an incorrect form of Nernst equation, the calculated ORP curve will not fit the measured data. Using these Nernst equations, the ORP value that corresponds to a predetermined degree of completion for the biochemical reaction can be calculated. Thus, these Nernst equations will enable a more efficient on-line control of the biological process.

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses

PubMed Central

2017-01-01

Introduction Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. Aim The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. Methods A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. Results The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Conclusion Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses.

PubMed

Sultana, Janet; Calabró, Marco; Garcia-Serna, Ricard; Ferrajolo, Carmen; Crisafulli, Concetta; Mestres, Jordi; Trifirò', Gianluca

2017-01-01

Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk

Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates?

PubMed

Gopalakrishnan, Ranganath; Frolov, Andrey I; Knerr, Laurent; Drury, William J; Valeur, Eric

2016-11-10

Over the past decade, foldamers have progressively emerged as useful architectures to mimic secondary structures of proteins. Peptidic foldamers, consisting of various amino acid based backbones, have been the most studied from a therapeutic perspective, while polyaromatic foldamers have barely evolved from their nascency and remain perplexing for medicinal chemists due to their poor drug-like nature. Despite these limitations, this compound class may still offer opportunities to study challenging targets or provide chemical biology tools. The potential of foldamer drug candidates reaching the clinic is still a stretch. Nevertheless, advances in the field have demonstrated their potential for the discovery of next generation therapeutics. In this perspective, the current knowledge of foldamers is reviewed in a drug discovery context. Recent advances in the early phases of drug discovery including hit finding, target validation, and optimization and molecular modeling are discussed. In addition, challenges and focus areas are debated and gaps highlighted.

Marine Isolates of Trichoderma spp. as Potential Halotolerant Agents of Biological Control for Arid-Zone Agriculture ▿ †

PubMed Central

Gal-Hemed, Inbal; Atanasova, Lea; Komon-Zelazowska, Monika; Druzhinina, Irina S.; Viterbo, Ada; Yarden, Oded

2011-01-01

The scarcity of fresh water in the Mediterranean region necessitates the search for halotolerant agents of biological control of plant diseases that can be applied in arid-zone agriculture irrigated with saline water. Among 29 Trichoderma strains previously isolated from Mediterranean Psammocinia sp. sponges, the greatest number of isolates belong to the Trichoderma longibrachiatum-Hypocrea orientalis species pair (9), H. atroviridis/T. atroviride (9), and T. harzianum species complex (7), all of which are known for high mycoparasitic potential. In addition, one isolate of T. asperelloides and two putative new species, Trichoderma sp. O.Y. 14707 and O.Y. 2407, from Longibrachiatum and Strictipilosa clades, respectively, have been identified. In vitro salinity assays showed that the ability to tolerate increasing osmotic pressure (halotolerance) is a strain- or clade-specific property rather than a feature of a species. Only a few isolates were found to be sensitive to increased salinity, while others either were halotolerant or even demonstrated improved growth in increasingly saline conditions. In vitro antibiosis assays revealed strong antagonistic activity toward phytopathogens due to the production of both soluble and volatile metabolites. Two marine-derived Trichoderma isolates, identified as T. atroviride and T. asperelloides, respectively, effectively reduced Rhizoctonia solani damping-off disease on beans and also induced defense responses in cucumber seedlings against Pseudomonas syringae pv. lachrimans. This is the first inclusive evaluation of marine fungi as potential biocontrol agents. PMID:21666030

Occupational exposure to potentially infectious biological material in a dental teaching environment.

PubMed

Machado-Carvalhais, Helenaura P; Ramos-Jorge, Maria L; Auad, Sheyla M; Martins, Laura H P M; Paiva, Saul M; Pordeus, Isabela A

2008-10-01

The aims of this cross-sectional study were to determine the prevalence of occupational accidents with exposure to biological material among undergraduate students of dentistry and to estimate potential risk factors associated with exposure to blood. Data were collected through a self-administered questionnaire (86.4 percent return rate), which was completed by a sample of 286 undergraduate dental students (mean age 22.4 +/-2.4 years). The students were enrolled in the clinical component of the curriculum, which corresponds to the final six semesters of study. Descriptive, bivariate, simple logistic regression and multiple logistic regression (Forward Stepwise Procedure) analyses were performed. The level of statistical significance was set at 5 percent. Percutaneous and mucous exposures to potentially infectious biological material were reported by 102 individuals (35.6 percent); 26.8 percent reported the occurrence of multiple episodes of exposure. The logistic regression analyses revealed that the incomplete use of individual protection equipment (OR=3.7; 95 percent CI 1.5-9.3), disciplines where surgical procedures are carried out (OR=16.3; 95 percent CI 7.1-37.2), and handling sharp instruments (OR=4.4; 95 percent CI 2.1-9.1), more specifically, hollow-bore needles (OR=6.8; 95 percent CI 2.1-19.0), were independently associated with exposure to blood. Policies of reviewing the procedures during clinical practice are recommended in order to reduce occupational exposure.

Application of a phenotypic drug discovery strategy to identify biological and chemical starting points for inhibition of TSLP production in lung epithelial cells

PubMed Central

Orellana, Adelina; García-González, Vicente; López, Rosa; Pascual-Guiral, Sonia; Lozoya, Estrella; Díaz, Julia; Casals, Daniel; Barrena, Antolín; Paris, Stephane; Andrés, Miriam; Segarra, Victor; Vilella, Dolors; Malhotra, Rajneesh; Eastwood, Paul; Planagumà, Anna; Miralpeix, Montserrat

2018-01-01

Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung epithelium in response to external insult. Considered as a master switch in T helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role in allergic diseases including asthma. The aim of this study was to use a phenotypic approach to identify new biological and chemical starting points for inhibition of TSLP production in human bronchial epithelial cells (NHBE), with the objective of reducing Th2-mediated airway inflammation. To this end, a phenotypic screen was performed using poly I:C / IL-4 stimulated NHBE cells interrogated with a 44,974 compound library. As a result, 85 hits which downregulated TSLP protein and mRNA levels were identified and a representative subset of 7 hits was selected for further characterization. These molecules inhibited the activity of several members of the MAPK, PI3K and tyrosine kinase families and some of them have been reported as modulators of cellular phenotypic endpoints like cell-cell contacts, microtubule polymerization and caspase activation. Characterization of the biological profile of the hits suggested that mTOR could be a key activity involved in the regulation of TSLP production in NHBE cells. Among other targeted kinases, inhibition of p38 MAPK and JAK kinases showed different degrees of correlation with TSLP downregulation, while Syk kinase did not seem to be related. Overall, inhibition of TSLP production by the selected hits, rather than resulting from inhibition of single isolated targets, appeared to be due to a combination of activities with different levels of relevance. Finally, a hit expansion exercise yielded additional active compounds that could be amenable to further optimization, providing an opportunity to dissociate TSLP inhibition from other non-desired activities. This study illustrates the potential of phenotypic drug discovery to complement target based approaches by providing new chemistry and biology

Structured methods for identifying and correcting potential human errors in aviation operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, W.R.

1997-10-01

Human errors have been identified as the source of approximately 60% of the incidents and accidents that occur in commercial aviation. It can be assumed that a very large number of human errors occur in aviation operations, even though in most cases the redundancies and diversities built into the design of aircraft systems prevent the errors from leading to serious consequences. In addition, when it is acknowledged that many system failures have their roots in human errors that occur in the design phase, it becomes apparent that the identification and elimination of potential human errors could significantly decrease the risksmore » of aviation operations. This will become even more critical during the design of advanced automation-based aircraft systems as well as next-generation systems for air traffic management. Structured methods to identify and correct potential human errors in aviation operations have been developed and are currently undergoing testing at the Idaho National Engineering and Environmental Laboratory (INEEL).« less

Glycation of antibodies: Modification, methods and potential effects on biological functions.

PubMed

Wei, Bingchuan; Berning, Kelsey; Quan, Cynthia; Zhang, Yonghua Taylor

Glycation is an important protein modification that could potentially affect bioactivity and molecular stability, and glycation of therapeutic proteins such as monoclonal antibodies should be well characterized. Glycated protein could undergo further degradation into advance glycation end (AGE) products. Here, we review the root cause of glycation during the manufacturing, storage and in vivo circulation of therapeutic antibodies, and the current analytical methods used to detect and characterize glycation and AGEs, including boronate affinity chromatography, charge-based methods, liquid chromatography-mass spectrometry and colorimetric assay. The biological effects of therapeutic protein glycation and AGEs, which ranged from no affect to loss of activity, are also discussed.

Ozone dosing alters the biological potential and therapeutic outcomes of plasma rich in growth factors.

PubMed

Anitua, E; Zalduendo, M M; Troya, M; Orive, G

2015-04-01

Until now, ozone has been used in a rather empirical way. This in-vitro study investigates, for the first time, whether different ozone treatments of plasma rich in growth factors (PRGF) alter the biological properties and outcomes of this autologous platelet-rich plasma. Human plasma rich in growth factors was treated with ozone using one of the following protocols: a continuous-flow method; or a syringe method in which constant volumes of ozone and PRGF were mixed. In both cases, ozone was added before, during and after the addition of calcium chloride. Three ozone concentrations, of the therapeutic range 20, 40 and 80 μg/mL, were tested. Fibrin clot properties, growth factor content and the proliferative effect on primary osteoblasts and gingival fibroblasts were evaluated. Ozone treatment of PRGF using the continuous flow protocol impaired formation of the fibrin scaffold, drastically reduced the levels of growth factors and significantly decreased the proliferative potential of PRGF on primary osteoblasts and gingival fibroblasts. In contrast, treatment of PRGF with ozone using the syringe method, before, during and after the coagulation process, did not alter the biological outcomes of the autologous therapy. These findings suggest that ozone dose and the way that ozone combines with PRGF may alter the biological potential and therapeutic outcomes of PRGF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fundamental host range of Leptoypha hospita (Hemiptera: Tingidae), a potential biological control agent of Chinese privet

Treesearch

Yanzhuo Zhang; James L. Hanula; Scott Horn; Cera Jones; S. Kristine Braman; Jianghua Sun

2016-01-01

Chinese privet, Ligustrum sinense Lour., is an invasive shrub within riparian areas of the southeastern United States. Biological control is considered the most suitable management option for Chinese privet. The potential host range of the lace bug, Leptoypha hospita Drake et...

[Clinical treatment adherence of health care workers and students exposed to potentially infectious biological material].

PubMed

Almeida, Maria Cristina Mendes de; Canini, Silvia Rita Marin da Silva; Reis, Renata Karina; Toffano, Silmara Elaine Malaguti; Pereira, Fernanda Maria Vieira; Gir, Elucir

2015-04-01

To assess adherence to clinical appointments by health care workers (HCW) and students who suffered accidents with potentially infectious biological material. A retrospective cross-sectional study that assessed clinical records of accidents involving biological material between 2005 and 2010 in a specialized unit. A total of 461 individuals exposed to biological material were treated, of which 389 (84.4%) were HCWs and 72 (15.6%) students. Of the 461 exposed individuals, 307 (66.6%) attended a follow-up appointment. Individuals who had suffered an accident with a known source patient were 29 times more likely to show up to their scheduled follow-up appointments (OR: 29.98; CI95%: 16.09-55.83). The predictor in both univariate and multivariate analyses for adherence to clinical follow-up appointment was having a known source patient with nonreactive serology for the human immunodeficiency virus and/or hepatitis B and C.

Potential of DNA sequences to identify zoanthids (Cnidaria: Zoantharia).

PubMed

Sinniger, Frederic; Reimer, James D; Pawlowski, Jan

2008-12-01

The order Zoantharia is known for its chaotic taxonomy and difficult morphological identification. One method that potentially could help for examining such troublesome taxa is DNA barcoding, which identifies species using standard molecular markers. The mitochondrial cytochrome oxidase subunit I (COI) has been utilized to great success in groups such as birds and insects; however, its applicability in many other groups is controversial. Recently, some studies have suggested that barcoding is not applicable to anthozoans. Here, we examine the use of COI and mitochondrial 16S ribosomal DNA for zoanthid identification. Despite the absence of a clear barcoding gap, our results show that for most of 54 zoanthid samples, both markers could separate samples to the species, or species group, level, particularly when easily accessible ecological or distributional data were included. Additionally, we have used the short V5 region of mt 16S rDNA to identify eight old (13 to 50 years old) museum samples. We discuss advantages and disadvantages of COI and mt 16S rDNA as barcodes for Zoantharia, and recommend that either one or both of these markers be considered for zoanthid identification in the future.

Evolution Acceptance and Epistemological Beliefs of College Biology Students

ERIC Educational Resources Information Center

Borgerding, Lisa A.; Deniz, Hasan; Anderson, Elizabeth Shevock

2017-01-01

Evolutionary theory is central to biology, and scientifically accurate evolution instruction is promoted within national and state standards documents. Previous literature has identified students' epistemological beliefs as potential predictors of evolution acceptance. The present work seeks to explore more directly how student views of evolution…

The metabolomic approach identifies a biological signature of low-dose chronic exposure to cesium 137.

PubMed

Grison, Stéphane; Martin, Jean-Charles; Grandcolas, Line; Banzet, Nathalie; Blanchardon, Eric; Tourlonias, Elie; Defoort, Catherine; Favé, Gaëlle; Bott, Romain; Dublineau, Isabelle; Gourmelon, Patrick; Souidi, Maâmar

2012-01-01

Reports have described apparent biological effects of (137)Cs (the most persistent dispersed radionuclide) irradiation in people living in Chernobyl-contaminated territory. The sensitive analytical technology described here should now help assess the relation of this contamination to the observed effects. A rat model chronically exposed to (137)Cs through drinking water was developed to identify biomarkers of radiation-induced metabolic disorders, and the biological impact was evaluated by a metabolomic approach that allowed us to detect several hundred metabolites in biofluids and assess their association with disease states. After collection of plasma and urine from contaminated and non-contaminated rats at the end of the 9-months contamination period, analysis with a LC-MS system detected 742 features in urine and 1309 in plasma. Biostatistical discriminant analysis extracted a subset of 26 metabolite signals (2 urinary, 4 plasma non-polar, and 19 plasma polar metabolites) that in combination were able to predict from 68 up to 94% of the contaminated rats, depending on the prediction method used, with a misclassification rate as low as 5.3%. The difference in this metabolic score between the contaminated and non-contaminated rats was highly significant (P = 0.019 after ANOVA cross-validation). In conclusion, our proof-of-principle study demonstrated for the first time the usefulness of a metabolomic approach for addressing biological effects of chronic low-dose contamination. We can conclude that a metabolomic signature discriminated (137)Cs-contaminated from control animals in our model. Further validation is nevertheless required together with full annotation of the metabolic indicators.

(Per)chlorate in Biology on Earth and Beyond.

PubMed

Youngblut, Matthew D; Wang, Ouwei; Barnum, Tyler P; Coates, John D

2016-09-08

Respiration of perchlorate and chlorate [collectively, (per)chlorate] was only recognized in the last 20 years, yet substantial advances have been made in our understanding of the underlying metabolisms. Although it was once considered solely anthropogenic, pervasive natural sources, both terrestrial and extraterrestrial, indicate an ancient (per)chlorate presence across our solar system. These discoveries stimulated interest in (per)chlorate microbiology, and the application of advanced approaches highlights exciting new facets. Forward and reverse genetics revealed new information regarding underlying molecular biology and associated regulatory mechanisms. Structural and functional analysis characterized core enzymes and identified novel reaction sequences. Comparative genomics elucidated evolutionary aspects, and stress analysis identified novel response mechanisms to reactive chlorine species. Finally, systems biology identified unique metabolic versatility and novel mechanisms of (per)chlorate respiration, including symbiosis and a hybrid enzymatic-abiotic metabolism. While many published studies focus on (per)chlorate and their basic metabolism, this review highlights seminal advances made over the last decade and identifies new directions and potential novel applications.

Auditory biological marker of concussion in children

PubMed Central

Kraus, Nina; Thompson, Elaine C.; Krizman, Jennifer; Cook, Katherine; White-Schwoch, Travis; LaBella, Cynthia R.

2016-01-01

Concussions carry devastating potential for cognitive, neurologic, and socio-emotional disease, but no objective test reliably identifies a concussion and its severity. A variety of neurological insults compromise sound processing, particularly in complex listening environments that place high demands on brain processing. The frequency-following response captures the high computational demands of sound processing with extreme granularity and reliably reveals individual differences. We hypothesize that concussions disrupt these auditory processes, and that the frequency-following response indicates concussion occurrence and severity. Specifically, we hypothesize that concussions disrupt the processing of the fundamental frequency, a key acoustic cue for identifying and tracking sounds and talkers, and, consequently, understanding speech in noise. Here we show that children who sustained a concussion exhibit a signature neural profile. They have worse representation of the fundamental frequency, and smaller and more sluggish neural responses. Neurophysiological responses to the fundamental frequency partially recover to control levels as concussion symptoms abate, suggesting a gain in biological processing following partial recovery. Neural processing of sound correctly identifies 90% of concussion cases and clears 95% of control cases, suggesting this approach has practical potential as a scalable biological marker for sports-related concussion and other types of mild traumatic brain injuries. PMID:28005070

Biological soil crusts: Diminutive communities of potential global importance

USGS Publications Warehouse

Ferrenberg, Scott; Tucker, Colin; Reed, Sasha C.

2017-01-01

Biological soil crusts (biocrusts) are widespread, diverse communities of cyanobacteria, fungi, lichens, and mosses living on soil surfaces, primarily in drylands. Biocrusts can locally govern primary production, soil fertility, hydrology, and surface energy balance, with considerable variation in these functions across alternate community states. Further, these communities have been implicated in Earth system functioning via potential influences on global biogeochemistry and climate. Biocrusts are easily destroyed by disturbances and appear to be exceptionally vulnerable to warming temperatures and altered precipitation inputs, signaling possible losses of dryland functions with global change. Despite these concerns, we lack sufficient spatiotemporal data on biocrust function, cover, and community structure to confidently assess their ecological roles across the extensive dryland biome. Here, we present the case for cross-scale research and restoration efforts coupled with remote-sensing and modeling approaches that improve our collective understanding of biocrust responses to global change and the ecological roles of these diminutive communities at global scales.

Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

PubMed Central

Geiselhart, Anja; Lier, Amelie; Walter, Dagmar; Milsom, Michael D.

2012-01-01

Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC). This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients. PMID:22675615

Identifying Pre-Service Teachers' Beliefs about Teaching EFL and Their Potential Changes

ERIC Educational Resources Information Center

Suárez Flórez, Sergio Andrés; Basto Basto, Edwin Arley

2017-01-01

This study aims at identifying pre-service teachers' beliefs about teaching English as a foreign language and tracking their potential changes throughout the teaching practicum. Participants were two pre-service teachers in their fifth year of their Bachelor of Arts in Foreign Languages program in a public university in Colombia. Data were…

CONDITIONAL PROBABILITY ANALYSIS APPROACH FOR IDENTIFYING BIOLOGICAL THRESHOLD OF IMPACT FOR SEDIMENTATION: APPICATION TO FRESHWATER STREAMS IN OREGON COAST RANGE ECOREGION

EPA Science Inventory

A conditional probability analysis (CPA) approach has been developed for identifying biological thresholds of impact for use in the development of geographic-specific water quality criteria for protection of aquatic life. This approach expresses the threshold as the likelihood ...

A systems biology approach identified different regulatory networks targeted by KSHV miR-K12-11 in B cells and endothelial cells.

PubMed

Yang, Yajie; Boss, Isaac W; McIntyre, Lauren M; Renne, Rolf

2014-08-08

Kaposi's sarcoma associated herpes virus (KSHV) is associated with tumors of endothelial and lymphoid origin. During latent infection, KSHV expresses miR-K12-11, an ortholog of the human tumor gene hsa-miR-155. Both gene products are microRNAs (miRNAs), which are important post-transcriptional regulators that contribute to tissue specific gene expression. Advances in target identification technologies and molecular interaction databases have allowed a systems biology approach to unravel the gene regulatory networks (GRNs) triggered by miR-K12-11 in endothelial and lymphoid cells. Understanding the tissue specific function of miR-K12-11 will help to elucidate underlying mechanisms of KSHV pathogenesis. Ectopic expression of miR-K12-11 differentially affected gene expression in BJAB cells of lymphoid origin and TIVE cells of endothelial origin. Direct miRNA targeting accounted for a small fraction of the observed transcriptome changes: only 29 genes were identified as putative direct targets of miR-K12-11 in both cell types. However, a number of commonly affected biological pathways, such as carbohydrate metabolism and interferon response related signaling, were revealed by gene ontology analysis. Integration of transcriptome profiling, bioinformatic algorithms, and databases of protein-protein interactome from the ENCODE project identified different nodes of GRNs utilized by miR-K12-11 in a tissue-specific fashion. These effector genes, including cancer associated transcription factors and signaling proteins, amplified the regulatory potential of a single miRNA, from a small set of putative direct targets to a larger set of genes. This is the first comparative analysis of miRNA-K12-11's effects in endothelial and B cells, from tissues infected with KSHV in vivo. MiR-K12-11 was able to broadly modulate gene expression in both cell types. Using a systems biology approach, we inferred that miR-K12-11 establishes its GRN by both repressing master TFs and influencing

A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells

PubMed Central

Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J.; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

2016-01-01

Abstract The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication

A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

PubMed

Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antczak, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

2016-04-01

The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks

Synthetic biology in space: considering the broad societal and ethical implications

NASA Astrophysics Data System (ADS)

Race, Margaret S.; Moses, Jacob; McKay, Christopher; Venkateswaran, Kasthuri J.

2012-02-01

Although the field of synthetic biology is still in its infancy, there are expectations for great advances in the coming decades, both on Earth and potentially in space. Promising applications for long duration space missions include a variety of biologically engineered products and biologically aided processes and technologies, which will undoubtedly be scrutinized for risks and benefits in the broad context of ethical, legal and social realms. By comparing and contrasting features of Earth-based and space-applied synthetic biology, it is possible to identify the likely similarities and differences, and to identify possible challenges ahead for space applications that will require additional research, both in the short and long terms. Using an analytical framework associated with synthetic biology and new technologies on Earth, this paper analyses the kinds of issues and concerns ahead, and identifies those areas where space applications may require additional examination. In general, while Earth- and space-based synthetic biology share many commonalities, space applications have additional challenges such as those raised by space microbiology and environmental factors, legal complications, planetary protection, lack of decision-making infrastructure(s), long duration human missions, terraforming and the possible discovery of extraterrestrial (ET) life. For synthetic biology, the way forward offers many exciting opportunities, but is not without legitimate concerns - for life, environments and society, both on Earth and beyond.

Obtaining subjects' consent to publish identifying personal information: current practices and identifying potential issues.

PubMed

Yoshida, Akiko; Dowa, Yuri; Murakami, Hiromi; Kosugi, Shinji

2013-11-25

In studies publishing identifying personal information, obtaining consent is regarded as necessary, as it is impossible to ensure complete anonymity. However, current journal practices around specific points to consider when obtaining consent, the contents of consent forms and how consent forms are managed have not yet been fully examined. This study was conducted to identify potential issues surrounding consent to publish identifying personal information. Content analysis was carried out on instructions for authors and consent forms developed by academic journals in four fields (as classified by Journal Citation Reports): medicine general and internal, genetics and heredity, pediatrics, and psychiatry. An online questionnaire survey of editors working for journals that require the submission of consent forms was also conducted. Instructions for authors were reviewed for 491 academic journals (132 for medicine general and internal, 147 for genetics and heredity, 100 for pediatrics, and 112 for psychiatry). Approximately 40% (203: 74 for medicine general and internal, 31 for genetics and heredity, 58 for pediatrics, and 40 for psychiatry) stated that subject consent was necessary. The submission of consent forms was required by 30% (154) of the journals studied, and 10% (50) provided their own consent forms for authors to use. Two journals mentioned that the possible effects of publication on subjects should be considered. Many journal consent forms mentioned the difficulties in ensuring complete anonymity of subjects, but few addressed the study objective, the subjects' right to refuse consent and the withdrawal of consent. The main reason for requiring the submission of consent forms was to confirm that consent had been obtained. Approximately 40% of journals required subject consent to be obtained. However, differences were observed depending on the fields. Specific considerations were not always documented. There is a need to address issues around the study

Obtaining subjects’ consent to publish identifying personal information: current practices and identifying potential issues

PubMed Central

2013-01-01

Background In studies publishing identifying personal information, obtaining consent is regarded as necessary, as it is impossible to ensure complete anonymity. However, current journal practices around specific points to consider when obtaining consent, the contents of consent forms and how consent forms are managed have not yet been fully examined. This study was conducted to identify potential issues surrounding consent to publish identifying personal information. Methods Content analysis was carried out on instructions for authors and consent forms developed by academic journals in four fields (as classified by Journal Citation Reports): medicine general and internal, genetics and heredity, pediatrics, and psychiatry. An online questionnaire survey of editors working for journals that require the submission of consent forms was also conducted. Results Instructions for authors were reviewed for 491 academic journals (132 for medicine general and internal, 147 for genetics and heredity, 100 for pediatrics, and 112 for psychiatry). Approximately 40% (203: 74 for medicine general and internal, 31 for genetics and heredity, 58 for pediatrics, and 40 for psychiatry) stated that subject consent was necessary. The submission of consent forms was required by 30% (154) of the journals studied, and 10% (50) provided their own consent forms for authors to use. Two journals mentioned that the possible effects of publication on subjects should be considered. Many journal consent forms mentioned the difficulties in ensuring complete anonymity of subjects, but few addressed the study objective, the subjects’ right to refuse consent and the withdrawal of consent. The main reason for requiring the submission of consent forms was to confirm that consent had been obtained. Conclusion Approximately 40% of journals required subject consent to be obtained. However, differences were observed depending on the fields. Specific considerations were not always documented. There is a need

Species abundance and potential biological control services in shade vs. sun coffee in Puerto Rico

USGS Publications Warehouse

Borkhataria, Rena R.; Collazo, Jaime A.; Groom, Martha J.

2012-01-01

Birds, lizards and insects were surveyed in three sun and three shade coffee plantations in Puerto Rico to provide a comprehensive comparison of biodiversity between plantations types and to identify potential interrelationships (e.g., biological or natural control services) between members of each taxon and coffee pests. Abundance of avian species, including insectivorous species, was significantly higher in shade coffee. Anolis cristatellus and A. stratulus were significantly more abundant in sun plantations whereas A. gundlachi and A. evermanni were detected more frequently in shade plantations. Insects in the orders Coleoptera, Diptera, Hemiptera, Hymenoptera, Lepidoptera, Neuroptera, and Psocoptera were significantly more abundant in shade coffee, while orthopterans were more abundant in sun. The coffee leaf miner (Leucoptera coffeela) and the flatid planthopper (Petrusa epilepsis) did not differ significantly between plantation types, nor did the abundance of the wasp complex that parasitizes the coffee leaf miner. These findings confirmed that shade plantations harbor a wide array of elements of biodiversity; but sun plantations may also harbor many elements of biodiversity, and in some cases, in higher abundance than in shade plantations.

Workshop Report: Systems Biology for Organotypic Cell Cultures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grego, Sonia; Dougherty, Edward R.; Alexander, Francis Joseph

Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, “organotypic” cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomicmore » data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data.« less

Workshop Report: Systems Biology for Organotypic Cell Cultures

DOE PAGES

Grego, Sonia; Dougherty, Edward R.; Alexander, Francis Joseph; ...

2016-11-14

Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, “organotypic” cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomicmore » data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data.« less

Synthetic biology and biosecurity: challenging the "myths".

PubMed

Jefferson, Catherine; Lentzos, Filippa; Marris, Claire

2014-01-01

Synthetic biology, a field that aims to "make biology easier to engineer," is routinely described as leading to an increase in the "dual-use" threat, i.e., the potential for the same scientific research to be "used" for peaceful purposes or "misused" for warfare or terrorism. Fears have been expressed that the "de-skilling" of biology, combined with online access to the genomic DNA sequences of pathogenic organisms and the reduction in price for DNA synthesis, will make biology increasingly accessible to people operating outside well-equipped professional research laboratories, including people with malevolent intentions. The emergence of do-it-yourself (DIY) biology communities and of the student iGEM competition has come to epitomize this supposed trend toward greater ease of access and the associated potential threat from rogue actors. In this article, we identify five "myths" that permeate discussions about synthetic biology and biosecurity, and argue that they embody misleading assumptions about both synthetic biology and bioterrorism. We demonstrate how these myths are challenged by more realistic understandings of the scientific research currently being conducted in both professional and DIY laboratories, and by an analysis of historical cases of bioterrorism. We show that the importance of tacit knowledge is commonly overlooked in the dominant narrative: the focus is on access to biological materials and digital information, rather than on human practices and institutional dimensions. As a result, public discourse on synthetic biology and biosecurity tends to portray speculative scenarios about the future as realities in the present or the near future, when this is not warranted. We suggest that these "myths" play an important role in defining synthetic biology as a "promissory" field of research and as an "emerging technology" in need of governance.

Proteomic Analysis of Saliva Identifies Potential Biomarkers for Orthodontic Tooth Movement

PubMed Central

Ellias, Mohd Faiz; Zainal Ariffin, Shahrul Hisham; Karsani, Saiful Anuar; Abdul Rahman, Mariati; Senafi, Shahidan; Megat Abdul Wahab, Rohaya

2012-01-01

Orthodontic treatment has been shown to induce inflammation, followed by bone remodelling in the periodontium. These processes trigger the secretion of various proteins and enzymes into the saliva. This study aims to identify salivary proteins that change in expression during orthodontic tooth movement. These differentially expressed proteins can potentially serve as protein biomarkers for the monitoring of orthodontic treatment and tooth movement. Whole saliva from three healthy female subjects were collected before force application using fixed appliance and at 14 days after 0.014′′ Niti wire was applied. Salivary proteins were resolved using two-dimensional gel electrophoresis (2DE) over a pH range of 3–10, and the resulting proteome profiles were compared. Differentially expressed protein spots were then identified by MALDI-TOF/TOF tandem mass spectrometry. Nine proteins were found to be differentially expressed; however, only eight were identified by MALDI-TOF/TOF. Four of these proteins—Protein S100-A9, immunoglobulin J chain, Ig alpha-1 chain C region, and CRISP-3—have known roles in inflammation and bone resorption. PMID:22919344

Pharmacophore modeling and virtual screening to identify potential RET kinase inhibitors.

PubMed

Shih, Kuei-Chung; Shiau, Chung-Wai; Chen, Ting-Shou; Ko, Ching-Huai; Lin, Chih-Lung; Lin, Chun-Yuan; Hwang, Chrong-Shiong; Tang, Chuan-Yi; Chen, Wan-Ru; Huang, Jui-Wen

2011-08-01

Chemical features based 3D pharmacophore model for REarranged during Transfection (RET) tyrosine kinase were developed by using a training set of 26 structurally diverse known RET inhibitors. The best pharmacophore hypothesis, which identified inhibitors with an associated correlation coefficient of 0.90 between their experimental and estimated anti-RET values, contained one hydrogen-bond acceptor, one hydrogen-bond donor, one hydrophobic, and one ring aromatic features. The model was further validated by a testing set, Fischer's randomization test, and goodness of hit (GH) test. We applied this pharmacophore model to screen NCI database for potential RET inhibitors. The hits were docked to RET with GOLD and CDOCKER after filtering by Lipinski's rules. Ultimately, 24 molecules were selected as potential RET inhibitors for further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Time-saving impact of an algorithm to identify potential surgical site infections.

PubMed

Knepper, B C; Young, H; Jenkins, T C; Price, C S

2013-10-01

To develop and validate a partially automated algorithm to identify surgical site infections (SSIs) using commonly available electronic data to reduce manual chart review. Retrospective cohort study of patients undergoing specific surgical procedures over a 4-year period from 2007 through 2010 (algorithm development cohort) or over a 3-month period from January 2011 through March 2011 (algorithm validation cohort). A single academic safety-net hospital in a major metropolitan area. Patients undergoing at least 1 included surgical procedure during the study period. Procedures were identified in the National Healthcare Safety Network; SSIs were identified by manual chart review. Commonly available electronic data, including microbiologic, laboratory, and administrative data, were identified via a clinical data warehouse. Algorithms using combinations of these electronic variables were constructed and assessed for their ability to identify SSIs and reduce chart review. The most efficient algorithm identified in the development cohort combined microbiologic data with postoperative procedure and diagnosis codes. This algorithm resulted in 100% sensitivity and 85% specificity. Time savings from the algorithm was almost 600 person-hours of chart review. The algorithm demonstrated similar sensitivity on application to the validation cohort. A partially automated algorithm to identify potential SSIs was highly sensitive and dramatically reduced the amount of manual chart review required of infection control personnel during SSI surveillance.

Synthetic biology: An emerging research field in China

PubMed Central

Pei, Lei; Schmidt, Markus; Wei, Wei

2011-01-01

Synthetic biology is considered as an emerging research field that will bring new opportunities to biotechnology. There is an expectation that synthetic biology will not only enhance knowledge in basic science, but will also have great potential for practical applications. Synthetic biology is still in an early developmental stage in China. We provide here a review of current Chinese research activities in synthetic biology and its different subfields, such as research on genetic circuits, minimal genomes, chemical synthetic biology, protocells and DNA synthesis, using literature reviews and personal communications with Chinese researchers. To meet the increasing demand for a sustainable development, research on genetic circuits to harness biomass is the most pursed research within Chinese researchers. The environmental concerns are driven force of research on the genetic circuits for bioremediation. The research on minimal genomes is carried on identifying the smallest number of genomes needed for engineering minimal cell factories and research on chemical synthetic biology is focused on artificial proteins and expanded genetic code. The research on protocells is more in combination with the research on molecular-scale motors. The research on DNA synthesis and its commercialisation are also reviewed. As for the perspective on potential future Chinese R&D activities, it will be discussed based on the research capacity and governmental policy. PMID:21729747

Host range of Secusio extensa (Lepidoptera: Arctiidae), and potential for biological control of Senecio madagascariensis (Asteraceae)

Treesearch

M. M. Ramadan; K. T. Murai; T. Johnson

2010-01-01

Secusio extensa (Lepidoptera: Arctiidae) was evaluated as a potential biological control agent for Madagascar fireweed, Senecio madagascariensis (Asteraceae), which has invaded over 400 000 acres of rangeland in the Hawaiian Islands and is toxic to cattle and horses. The moth was introduced from southeastern Madagascar...

40 CFR Table 5 to Subpart Jj of... - List of VHAP of Potential Concern Identified by Industry

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 10 2010-07-01 2010-07-01 false List of VHAP of Potential Concern Identified by Industry 5 Table 5 to Subpart JJ of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION.... 63, Subpt. JJ, Table 5 Table 5 to Subpart JJ of Part 63—List of VHAP of Potential Concern Identified...

Characterization of potential mineralization in Afghanistan: four permissive areas identified using imaging spectroscopy data

USGS Publications Warehouse

King, Trude V.V.; Berger, Byron R.; Johnson, Michaela R.

2014-01-01

As part of the U.S. Geological Survey and Department of Defense Task Force for Business and Stability Operations natural resources revitalization activities in Afghanistan, four permissive areas for mineralization, Bamyan 1, Farah 1, Ghazni 1, and Ghazni 2, have been identified using imaging spectroscopy data. To support economic development, the areas of potential mineralization were selected on the occurrence of selected mineral assemblages mapped using the HyMap™ data (kaolinite, jarosite, hydrated silica, chlorite, epidote, iron-bearing carbonate, buddingtonite, dickite, and alunite) that may be indicative of past mineralization processes in areas with limited or no previous mineral resource studies. Approximately 30 sites were initially determined to be candidates for areas of potential mineralization. Additional criteria and material used to refine the selection and prioritization process included existing geologic maps, Landsat Thematic Mapper data, and published literature. The HyMapTM data were interpreted in the context of the regional geologic and tectonic setting and used the presence of alteration mineral assemblages to identify areas with the potential for undiscovered mineral resources. Further field-sampling, mapping, and supporting geochemical analyses are necessary to fully substantiate and verify the specific deposit types in the four areas of potential mineralization.

Biological characteristics of human-urine-derived stem cells: potential for cell-based therapy in neurology.

PubMed

Guan, Jun-Jie; Niu, Xin; Gong, Fei-Xiang; Hu, Bin; Guo, Shang-Chun; Lou, Yuan-Lei; Zhang, Chang-Qing; Deng, Zhi-Feng; Wang, Yang

2014-07-01

Stem cells in human urine have gained attention in recent years; however, urine-derived stem cells (USCs) are far from being well elucidated. In this study, we compared the biological characteristics of USCs with adipose-derived stem cells (ASCs) and investigated whether USCs could serve as a potential cell source for neural tissue engineering. USCs were isolated from voided urine with a modified culture medium. Through a series of experiments, we examined the growth rate, surface antigens, and differentiation potential of USCs, and compared them with ASCs. USCs showed robust proliferation ability. After serial propagation, USCs retained normal karyotypes. Cell surface antigen expression of USCs was similar to ASCs. With lineage-specific induction factors, USCs could differentiate toward the osteogenic, chondrogenic, adipogenic, and neurogenic lineages. To assess the ability of USCs to survive, differentiate, and migrate, they were seeded onto hydrogel scaffold and transplanted into rat brain. The results showed that USCs were able to survive in the lesion site, migrate to other areas, and express proteins that were associated with neural phenotypes. The results of our study demonstrate that USCs possess similar biological characteristics with ASCs and have multilineage differentiation potential. Moreover USCs can differentiate to neuron-like cells in rat brain. The present study shows that USCs are a promising cell source for tissue engineering and regenerative medicine.

Identifying external nutrient reduction requirements and potential in the hypereutrophic Lake Taihu Basin, China.

PubMed

Peng, Jiao-Ting; Zhu, Xiao-Dong; Sun, Xiang; Song, Xiao-Wei

2018-04-01

Reducing external nutrient loads is the first step for controlling eutrophication. Here, we identified external nutrient reduction requirements and potential of strategies for achieving reductions to remediate a eutrophic water body, Lake Taihu, China. A mass balance approach based on the entire lake was used to identify nutrient reduction requirements; an empirical export coefficient approach was introduced to estimate the nutrient reduction potential of the overall program on integrated regulation of Taihu Lake Basin (hereafter referred to as the "Guideline"). Reduction requirements included external total nitrogen (TN) and total phosphorus (TP) loads, which should be reduced by 41-55 and 25-50%, respectively, to prevent nutrient accumulation in Lake Taihu and to meet the planned water quality targets. In 2010, which is the most seriously polluted calendar year during the 2008-2014 period, the nutrient reduction requirements were estimated to be 36,819 tons of N and 2442 tons of P, and the potential nutrient reduction strategies would reduce approximately 25,821 tons of N and 3024 tons of P. Since there is a net N remaining in the reduction requirements, it should be the focus and deserves more attention in identifying external nutrient reduction strategies. Moreover, abatement measures outlined in the Guideline with high P reduction potential required large monetary investments. Achieving TP reduction requirement using the cost-effective strategy costs about 80.24 million USD. The design of nutrient reduction strategies should be enacted according to regional and sectoral differences and the cost-effectiveness of abatement measures.

What’s the risk? Identifying potential human pathogens within grey-headed flying foxes faeces

PubMed Central

Galbraith, Penelope; Coutts, Scott; Prosser, Toby; Boyce, John; McCarthy, David T.

2018-01-01

Pteropus poliocephalus (grey-headed flying foxes) are recognised vectors for a range of potentially fatal human pathogens. However, to date research has primarily focused on viral disease carriage, overlooking bacterial pathogens, which also represent a significant human disease risk. The current study applied 16S rRNA amplicon sequencing, community analysis and a multi-tiered database OTU picking approach to identify faecal-derived zoonotic bacteria within two colonies of P. poliocephalus from Victoria, Australia. Our data show that sequences associated with Enterobacteriaceae (62.8% ± 24.7%), Pasteurellaceae (19.9% ± 25.7%) and Moraxellaceae (9.4% ± 11.8%) dominate flying fox faeces. Further colony specific differences in bacterial faecal colonisation patterns were also identified. In total, 34 potential pathogens, representing 15 genera, were identified. However, species level definition was only possible for Clostridium perfringens, which likely represents a low infectious risk due to the low proportion observed within the faeces and high infectious dose required for transmission. In contrast, sequences associated with other pathogenic species clusters such as Haemophilus haemolyticus-H. influenzae and Salmonella bongori-S. enterica, were present at high proportions in the faeces, and due to their relatively low infectious doses and modes of transmissions, represent a greater potential human disease risk. These analyses of the microbial community composition of Pteropus poliocephalus have significantly advanced our understanding of the potential bacterial disease risk associated with flying foxes and should direct future epidemiological and quantitative microbial risk assessments to further define the health risks presented by these animals. PMID:29360880

Researchers identify potential therapeutic targets for a rare childhood cancer | Center for Cancer Research

Cancer.gov

CCR researchers have identified the mechanism behind a rare but extremely aggressive childhood cancer called alveolar rhabdomyosarcoma (ARMS) and have pinpointed a potential drug target for its treatment. Learn more...

Surveillance methods for identifying, characterizing, and monitoring tobacco products: potential reduced exposure products as an example

PubMed Central

O’Connor, Richard J.; Cummings, K. Michael; Rees, Vaughan W.; Connolly, Gregory N.; Norton, Kaila J.; Sweanor, David; Parascandola, Mark; Hatsukami, Dorothy K.; Shields, Peter G.

2015-01-01

Tobacco products are widely sold and marketed, yet integrated data systems for identifying, tracking, and characterizing products are lacking. Tobacco manufacturers recently have developed potential reduction exposure products (PREPs) with implied or explicit health claims. Currently, a systematic approach for identifying, defining, and evaluating PREPs sold at the local, state or national levels in the US has not been developed. Identifying, characterizing, and monitoring new tobacco products could be greatly enhanced with a responsive surveillance system. This paper critically reviews available surveillance data sources for identifying and tracking tobacco products, including PREPs, evaluating strengths and weaknesses of potential data sources in light of their reliability and validity. Absent regulations mandating disclosure of product-specific information, it is likely that public health officials will need to rely on a variety of imperfect data sources to help identify, characterize, and monitor tobacco products, including PREPs. PMID:19959680

A high-throughput phenotypic screen identifies clofazimine as a potential treatment for cryptosporidiosis

PubMed Central

Jumani, Rajiv S.; Wright, Timothy M.; Chatterjee, Arnab K.; Huston, Christopher D.; Schultz, Peter G.; McNamara, Case W.

2017-01-01

. Clofazimine has a long history of use and has demonstrated a good safety profile for a disease that requires chronic dosing for a period of time ranging 3–36 months. These results, taken with clofazimine’s status as an FDA-approved drug with over four decades of use for the treatment of leprosy, support the continued investigation of clofazimine both as a new chemical tool for understanding cryptosporidium biology and a potential new treatment of cryptosporidiosis. PMID:28158186

Knowledge Discovery in Biological Databases for Revealing Candidate Genes Linked to Complex Phenotypes.

PubMed

Hassani-Pak, Keywan; Rawlings, Christopher

2017-06-13

Genetics and "omics" studies designed to uncover genotype to phenotype relationships often identify large numbers of potential candidate genes, among which the causal genes are hidden. Scientists generally lack the time and technical expertise to review all relevant information available from the literature, from key model species and from a potentially wide range of related biological databases in a variety of data formats with variable quality and coverage. Computational tools are needed for the integration and evaluation of heterogeneous information in order to prioritise candidate genes and components of interaction networks that, if perturbed through potential interventions, have a positive impact on the biological outcome in the whole organism without producing negative side effects. Here we review several bioinformatics tools and databases that play an important role in biological knowledge discovery and candidate gene prioritization. We conclude with several key challenges that need to be addressed in order to facilitate biological knowledge discovery in the future.

The Spring of Systems Biology-Driven Breeding.

PubMed

Lavarenne, Jérémy; Guyomarc'h, Soazig; Sallaud, Christophe; Gantet, Pascal; Lucas, Mikaël

2018-05-12

Genetics and molecular biology have contributed to the development of rationalized plant breeding programs. Recent developments in both high-throughput experimental analyses of biological systems and in silico data processing offer the possibility to address the whole gene regulatory network (GRN) controlling a given trait. GRN models can be applied to identify topological features helping to shortlist potential candidate genes for breeding purposes. Time-series data sets can be used to support dynamic modelling of the network. This will enable a deeper comprehension of network behaviour and the identification of the few elements to be genetically rewired to push the system towards a modified phenotype of interest. This paves the way to design more efficient, systems biology-based breeding strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Potential of Biological Agents in Decontamination of Agricultural Soil

PubMed Central

Javaid, Muhammad Kashif; Ashiq, Mehrban; Tahir, Muhammad

2016-01-01

Pesticides are widely used for the control of weeds, diseases, and pests of cultivated plants all over the world, mainly since the period after the Second World War. The use of pesticides is very extensive to control harm of pests all over the globe. Persistent nature of most of the synthetic pesticides causes serious environmental concerns. Decontamination of these hazardous chemicals is very essential. This review paper elaborates the potential of various biological agents in decontamination of agricultural soils. The agricultural crop fields are contaminated by the periodic applications of pesticides. Biodegradation is an ecofriendly, cost-effective, highly efficient approach compared to the physical and chemical methods which are expensive as well as unfriendly towards environment. Biodegradation is sensitive to the concentration levels of hydrogen peroxide and nitrogen along with microbial community, temperature, and pH changes. Experimental work for optimum conditions at lab scale can provide very fruitful results about specific bacterial, fungal strains. This study revealed an upper hand of bioremediation over physicochemical approaches. Further studies should be carried out to understand mechanisms of biotransformation. PMID:27293964

Potential of Biological Agents in Decontamination of Agricultural Soil.

PubMed

Javaid, Muhammad Kashif; Ashiq, Mehrban; Tahir, Muhammad

2016-01-01

Pesticides are widely used for the control of weeds, diseases, and pests of cultivated plants all over the world, mainly since the period after the Second World War. The use of pesticides is very extensive to control harm of pests all over the globe. Persistent nature of most of the synthetic pesticides causes serious environmental concerns. Decontamination of these hazardous chemicals is very essential. This review paper elaborates the potential of various biological agents in decontamination of agricultural soils. The agricultural crop fields are contaminated by the periodic applications of pesticides. Biodegradation is an ecofriendly, cost-effective, highly efficient approach compared to the physical and chemical methods which are expensive as well as unfriendly towards environment. Biodegradation is sensitive to the concentration levels of hydrogen peroxide and nitrogen along with microbial community, temperature, and pH changes. Experimental work for optimum conditions at lab scale can provide very fruitful results about specific bacterial, fungal strains. This study revealed an upper hand of bioremediation over physicochemical approaches. Further studies should be carried out to understand mechanisms of biotransformation.

Genes2WordCloud: a quick way to identify biological themes from gene lists and free text.

PubMed

Baroukh, Caroline; Jenkins, Sherry L; Dannenfelser, Ruth; Ma'ayan, Avi

2011-10-13

Word-clouds recently emerged on the web as a solution for quickly summarizing text by maximizing the display of most relevant terms about a specific topic in the minimum amount of space. As biologists are faced with the daunting amount of new research data commonly presented in textual formats, word-clouds can be used to summarize and represent biological and/or biomedical content for various applications. Genes2WordCloud is a web application that enables users to quickly identify biological themes from gene lists and research relevant text by constructing and displaying word-clouds. It provides users with several different options and ideas for the sources that can be used to generate a word-cloud. Different options for rendering and coloring the word-clouds give users the flexibility to quickly generate customized word-clouds of their choice. Genes2WordCloud is a word-cloud generator and a word-cloud viewer that is based on WordCram implemented using Java, Processing, AJAX, mySQL, and PHP. Text is fetched from several sources and then processed to extract the most relevant terms with their computed weights based on word frequencies. Genes2WordCloud is freely available for use online; it is open source software and is available for installation on any web-site along with supporting documentation at http://www.maayanlab.net/G2W. Genes2WordCloud provides a useful way to summarize and visualize large amounts of textual biological data or to find biological themes from several different sources. The open source availability of the software enables users to implement customized word-clouds on their own web-sites and desktop applications.

Biological Networks for Cancer Candidate Biomarkers Discovery

PubMed Central

Yan, Wenying; Xue, Wenjin; Chen, Jiajia; Hu, Guang

2016-01-01

Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field. PMID:27625573

Fungal phytotoxins with potential herbicidal activity: chemical and biological characterization.

PubMed

Cimmino, Alessio; Masi, Marco; Evidente, Marco; Superchi, Stefano; Evidente, Antonio

2015-12-19

Covering: 2007 to 2015 Fungal phytotoxins are secondary metabolites playing an important role in the induction of disease symptoms interfering with host plant physiological processes. Although fungal pathogens represent a heavy constraint for agrarian production and for forest and environmental heritage, they can also represent an ecofriendly alternative to manage weeds. Indeed, the phytotoxins produced by weed pathogenic fungi are an efficient tool to design natural, safe bioherbicides. Their use could avoid that of synthetic pesticides causing resistance in the host plants and the long term impact of residues in agricultural products with a risk to human and animal health. The isolation and structural and biological characterization of phytotoxins produced by pathogenic fungi for weeds, including parasitic plants, are described. Structure activity relationships and mode of action studies for some phytotoxins are also reported to elucidate the herbicide potential of these promising fungal metabolites.

Evaluation of Antioxidant Potential of “Maltese Mushroom” (Cynomorium coccineum) by Means of Multiple Chemical and Biological Assays

PubMed Central

Zucca, Paolo; Rosa, Antonella; Tuberoso, Carlo I. G.; Piras, Alessandra; Rinaldi, Andrea C.; Sanjust, Enrico; Dessì, Maria A.; Rescigno, Antonio

2013-01-01

Cynomorium coccineum is an edible, non-photosynthetic plant widespread along the coasts of the Mediterranean Sea. The medicinal properties of Maltese mushroom—one of the oldest vernacular names used to identify this species—have been kept in high regard since ancient times to the present day. We evaluated the antioxidant potential of fresh specimens of C. coccineum picked in Sardinia, Italy. Both aqueous and methanolic extracts were tested by using multiple assay systems (DPPH, FRAP, TEAC, ORAC-PYR). Total phenolics and flavonoids were also determined. Gallic acid and cyanidin 3-O-glucoside were identified as the main constituents and measured. Both extracts showed antioxidant capacities; ORAC-PYR assay gave the highest antioxidant value in both cases. The methanolic extract was further investigated with in vitro biological models of lipid oxidation; it showed a significant activity in preventing cholesterol degradation and exerted protection against Cu2+-mediated degradation of the liposomal unsaturated fatty acids. Results of the present study demonstrate that the extracts of C. coccineum show a significant total antioxidant power and also exert an in vitro protective effect in different bio-assays of oxidative stress. Therefore, Maltese mushroom can be considered a valuable source of antioxidants and phytochemicals useful in the preparation of nutraceuticals and functional foods. PMID:23344249

The potential roles of biological soil crusts in dryland hydrologic cycles

USGS Publications Warehouse

Belnap, J.

2006-01-01

Biological soil crusts (BSCs) are the dominant living cover in many drylands of the world. They possess many features that can influence different aspects of local hydrologic cycles, including soil porosity, absorptivity, roughness, aggregate stability, texture, pore formation, and water retention. The influence of biological soil crusts on these factors depends on their internal and external structure, which varies with climate, soil, and disturbance history. This paper presents the different types of biological soil crusts, discusses how crust type likely influences various aspects of the hydrologic cycle, and reviews what is known and not known about the influence of biological crusts on sediment production and water infiltration versus runoff in various drylands around the world. Most studies examining the effect of biological soil crusts on local hydrology are done by comparing undisturbed sites with those recently disturbed by the researchers. Unfortunately, this greatly complicates interpretation of the results. Applied disturbances alter many soil features such as soil texture, roughness, aggregate stability, physical crusting, porosity, and bulk density in ways that would not necessarily be the same if crusts were not naturally present. Combined, these studies show little agreement on how biological crusts affect water infiltration or runoff. However, when studies are separated by biological crust type and utilize naturally occurring differences among these types, results indicate that biological crusts in hyperarid regions reduce infiltration and increase runoff, have mixed effects in and regions, and increase infiltration and reduce runoff in semiarid cool and cold drylands. However, more studies are needed before broad generalizations can be made on how biological crusts affect infiltration and runoff. We especially need studies that control for sub-surface soil features such as bulk density, micro- and macropores, and biological crust structure. Unlike

The potential roles of biological soil crusts in dryland hydrologic cycles

NASA Astrophysics Data System (ADS)

Belnap, Jayne

2006-10-01

Biological soil crusts (BSCs) are the dominant living cover in many drylands of the world. They possess many features that can influence different aspects of local hydrologic cycles, including soil porosity, absorptivity, roughness, aggregate stability, texture, pore formation, and water retention. The influence of biological soil crusts on these factors depends on their internal and external structure, which varies with climate, soil, and disturbance history. This paper presents the different types of biological soil crusts, discusses how crust type likely influences various aspects of the hydrologic cycle, and reviews what is known and not known about the influence of biological crusts on sediment production and water infiltration versus runoff in various drylands around the world. Most studies examining the effect of biological soil crusts on local hydrology are done by comparing undisturbed sites with those recently disturbed by the researchers. Unfortunately, this greatly complicates interpretation of the results. Applied disturbances alter many soil features such as soil texture, roughness, aggregate stability, physical crusting, porosity, and bulk density in ways that would not necessarily be the same if crusts were not naturally present. Combined, these studies show little agreement on how biological crusts affect water infiltration or runoff. However, when studies are separated by biological crust type and utilize naturally occurring differences among these types, results indicate that biological crusts in hyperarid regions reduce infiltration and increase runoff, have mixed effects in arid regions, and increase infiltration and reduce runoff in semiarid cool and cold drylands. However, more studies are needed before broad generalizations can be made on how biological crusts affect infiltration and runoff. We especially need studies that control for sub-surface soil features such as bulk density, micro- and macropores, and biological crust structure

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms

PubMed Central

Esplin, M Sean; Manuck, Tracy A.; Varner, Michael W.; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John

2015-01-01

Objective We sought to employ an innovative tool based on common biological pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB), in order to enhance investigators' ability to identify to highlight common mechanisms and underlying genetic factors responsible for SPTB. Study Design A secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks gestation. Each woman was assessed for the presence of underlying SPTB etiologies. A hierarchical cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis using VEGAS software. Results 1028 women with SPTB were assigned phenotypes. Hierarchical clustering of the phenotypes revealed five major clusters. Cluster 1 (N=445) was characterized by maternal stress, cluster 2 (N=294) by premature membrane rupture, cluster 3 (N=120) by familial factors, and cluster 4 (N=63) by maternal comorbidities. Cluster 5 (N=106) was multifactorial, characterized by infection (INF), decidual hemorrhage (DH) and placental dysfunction (PD). These three phenotypes were highly correlated by Chi-square analysis [PD and DH (p<2.2e-6); PD and INF (p=6.2e-10); INF and DH (p=0.0036)]. Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarchal clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors underlying SPTB. PMID:26070700

Identifying Potential Ventilator Auto-Triggering Among Organ Procurement Organization Referrals.

PubMed

Henry, Nicholas R; Russian, Christopher J; Nespral, Joseph

2016-06-01

Ventilator auto-trigger is the delivery of an assisted mechanical ventilated breath over the set ventilator frequency in the absence of a spontaneous inspiratory effort and can be caused by inappropriate ventilator trigger sensitivity. Ventilator auto-trigger can be misinterpreted as a spontaneous breath and has the potential to delay or prevent brain death testing and confuse health-care professionals and/or patient families. To determine the frequency of organ donor referrals from 1 Organ Procurement Organization (OPO) that could benefit from an algorithm designed to assist organ recovery coordinators to identify and correct ventilator auto-triggering. This retrospective analysis evaluated documentation of organ donor referrals from 1 OPO in central Texas during the 2013 calendar year that resulted in the withdrawal of care by the patient's family and the recovery of organs. The frequency of referrals that presented with absent brain stem reflexes except for additional respirations over the set ventilator rate was determined to assess for the need of the proposed algorithm. Documentation of 672 organ procurement organization referrals was evaluated. Documentation from 42 referrals that resulted in the withdrawal of care and 21 referrals that resulted in the recovery of organs were identified with absent brain stem reflexes except for spontaneous respirations on the mechanical ventilator. As a result, an algorithm designed to identify and correct ventilator auto-trigger could have been used 63 times during the 2013 calendar year. © 2016, NATCO.

Insects as test systems for assessing the potential role of microgravity in biological development and evolution

NASA Astrophysics Data System (ADS)

Vernós, I.; Carratalá, M.; González-Jurado, J.; Valverde, J. R.; Calleja, M.; Domingo, A.; Vinós, J.; Cervera, M.; Marco, R.

Gravity and radiation are undoubtedly the two major environmental factors altered in space. Gravity is a weak force, which creates a permanent potential field acting on the mass of biological systems and their cellular components, strongly reduced in space flights. Developmental systems, particularly at very early stages, provide the larger cellular compartments known, where the effects of alterations in the size of the gravity vector on living organisms can be more effectively tested. The insects, one of the more highly evolved classes of animals in which early development occurs in a syncytial embryo, are systems particularly well suited to test these effects and the specific developmental mechanisms affected. Furthermore, they share some basic features such as small size, short life cycles, relatively high radio-resistance, etc. and show a diversity of developmental strategies and tempos advantageous in experiments of this type in space. Drosophila melanogaster, the current biological paradigm to study development, with so much genetic and evolutionary background available, is clearly the reference organism for these studies. The current evidence on the effects of the physical parameters altered in space flights on insect development indicate a surprising correlation between effects seen on the fast developing and relatively small Drosophila embryo and the more slowly developing and large Carausius morosus system. In relation to the issue of the importance of developmental and environmental constraints in biological evolution, still the missing link in current evolutionary thinking, insects and space facilities for long-term experiments could provide useful experimental settings where to critically assess how development and evolution may be interconnected. Finally, it has to be pointed out that since there are experimental data indicating a possible synergism between microgravity and space radiation, possible effects of space radiation should be taken into

Insects as test systems for assessing the potential role of microgravity in biological development and evolution.

PubMed

Vernós, I; Carratalá, M; González-Jurado, J; Valverde, J R; Calleja, M; Domingo, A; Vinós, J; Cervera, M; Marco, R

1989-01-01

Gravity and radiation are undoubtedly the two major environmental factors altered in space. Gravity is a weak force, which creates a permanent potential field acting on the mass of biological systems and their cellular components, strongly reduced in space flights. Developmental systems, particularly at very early stages, provide the larger cellular compartments known, where the effects of alterations in the size of the gravity vector on living organisms can be more effectively tested. The insects, one of the more highly evolved classes of animals in which early development occurs in a syncytial embryo, are systems particularly well suited to test these effects and the specific developmental mechanisms affected. Furthermore, they share some basic features such as small size, short life cycles, relatively high radio-resistance, etc. and show a diversity of developmental strategies and tempos advantageous in experiments of this type in space. Drosophila melanogaster, the current biological paradigm to study development, with so much genetic and evolutionary background available, is clearly the reference organism for these studies. The current evidence on the effects of the physical parameters altered in space flights on insect development indicate a surprising correlation between effects seen on the fast developing and relatively small Drosophila embryo and the more slowly developing and large Carausius morosus system. In relation to the issue of the importance of developmental and environmental constraints in biological evolution, still the missing link in current evolutionary thinking, insects and space facilities for long-term experiments could provide useful experimental settings where to critically assess how development and evolution may be interconnected. Finally, it has to be pointed out that since there are experimental data indicating a possible synergism between microgravity and space radiation, possible effects of space radiation should be taken into

Identifying and exploiting genes that potentiate the evolution of antibiotic resistance.

PubMed

Gifford, Danna R; Furió, Victoria; Papkou, Andrei; Vogwill, Tom; Oliver, Antonio; MacLean, R Craig

2018-06-01

There is an urgent need to develop novel approaches for predicting and preventing the evolution of antibiotic resistance. Here, we show that the ability to evolve de novo resistance to a clinically important β-lactam antibiotic, ceftazidime, varies drastically across the genus Pseudomonas. This variation arises because strains possessing the ampR global transcriptional regulator evolve resistance at a high rate. This does not arise because of mutations in ampR. Instead, this regulator potentiates evolution by allowing mutations in conserved peptidoglycan biosynthesis genes to induce high levels of β-lactamase expression. Crucially, blocking this evolutionary pathway by co-administering ceftazidime with the β-lactamase inhibitor avibactam can be used to eliminate pathogenic P. aeruginosa populations before they can evolve resistance. In summary, our study shows that identifying potentiator genes that act as evolutionary catalysts can be used to both predict and prevent the evolution of antibiotic resistance.

Effects of an Educational Experience Incorporating an Inventory of Factors Potentially Influencing Student Acceptance of Biological Evolution

NASA Astrophysics Data System (ADS)

Wiles, Jason R.; Alters, Brian

2011-12-01

This investigation provides an extensive review of scientific, religious, and otherwise non-scientific factors that may influence student acceptance of biological evolution. We also measure the extent to which students' levels of acceptance changed following an educational experience designed to address an inclusive inventory of factors identified as potentially affecting student acceptance of evolution (n = 81, pre-test/post-test) n = 37, one-year longitudinal). Acceptance of evolution was measured using the Measure of Acceptance of the Theory of Evolution (MATE) instrument among participants enrolled in a secondary-level academic programme during the summer prior to their final year of high school and as they transitioned to the post-secondary level. Student acceptance of evolution was measured to be significantly higher than initial levels both immediately following and over one year after the educational experience. Results reported herein carry implications for future quantitative and qualitative research as well as for cross-disciplinary instruction plans related to evolutionary science and non-scientific factors which may influence student understanding of evolution.

The acclimation of Chlorella to high-level nitrite for potential application in biological NOx removal from industrial flue gases.

PubMed

Li, Tianpei; Xu, Gang; Rong, Junfeng; Chen, Hui; He, Chenliu; Giordano, Mario; Wang, Qiang

2016-05-20

Nitrogen oxides (NOx) are the components of fossil flue gas that give rise to the greatest environmental concerns. This study evaluated the ability of the green algae Chlorella to acclimate to high level of NOx and the potential utilization of Chlorella strains in biological NOx removal (DeNOx) from industrial flue gases. Fifteen Chlorella strains were subject to high-level of nitrite (HN, 176.5 mmolL(-1) nitrite) to simulate exposure to high NOx. These strains were subsequently divided into four groups with respect to their ability to tolerate nitrite (excellent, good, fair, and poor). One strain from each group was selected to evaluate their photosynthetic response to HN condition, and the nitrite adaptability of the four Chlorella strains were further identified by using chlorophyll fluorescence. The outcome of our experiments shows that, although high concentrations of nitrite overall negatively affect growth and photosynthesis of Chlorella strains, the degree of nitrite tolerance is a strain-specific feature. Some Chlorella strains have an appreciably higher ability to acclimate to high-level of nitrite. Acclimation is achieved through a three-step process of restrict, acclimate, and thriving. Notably, Chlorella sp. C2 was found to have a high tolerance and to rapidly acclimate to high concentrations of nitrite; it is therefore a promising candidate for microalgae-based biological NOx removal. Copyright © 2016 Elsevier GmbH. All rights reserved.

Synthetic Biology and Biosecurity: Challenging the “Myths”

PubMed Central

Jefferson, Catherine; Lentzos, Filippa; Marris, Claire

2014-01-01

Synthetic biology, a field that aims to “make biology easier to engineer,” is routinely described as leading to an increase in the “dual-use” threat, i.e., the potential for the same scientific research to be “used” for peaceful purposes or “misused” for warfare or terrorism. Fears have been expressed that the “de-skilling” of biology, combined with online access to the genomic DNA sequences of pathogenic organisms and the reduction in price for DNA synthesis, will make biology increasingly accessible to people operating outside well-equipped professional research laboratories, including people with malevolent intentions. The emergence of do-it-yourself (DIY) biology communities and of the student iGEM competition has come to epitomize this supposed trend toward greater ease of access and the associated potential threat from rogue actors. In this article, we identify five “myths” that permeate discussions about synthetic biology and biosecurity, and argue that they embody misleading assumptions about both synthetic biology and bioterrorism. We demonstrate how these myths are challenged by more realistic understandings of the scientific research currently being conducted in both professional and DIY laboratories, and by an analysis of historical cases of bioterrorism. We show that the importance of tacit knowledge is commonly overlooked in the dominant narrative: the focus is on access to biological materials and digital information, rather than on human practices and institutional dimensions. As a result, public discourse on synthetic biology and biosecurity tends to portray speculative scenarios about the future as realities in the present or the near future, when this is not warranted. We suggest that these “myths” play an important role in defining synthetic biology as a “promissory” field of research and as an “emerging technology” in need of governance. PMID:25191649

Newer Approaches to Identify Potential Untoward Effects in Functional Foods.

PubMed

Marone, Palma Ann; Birkenbach, Victoria L; Hayes, A Wallace

2016-01-01

Globalization has greatly accelerated the numbers and variety of food and beverage products available worldwide. The exchange among greater numbers of countries, manufacturers, and products in the United States and worldwide has necessitated enhanced quality measures for nutritional products for larger populations increasingly reliant on functionality. These functional foods, those that provide benefit beyond basic nutrition, are increasingly being used for their potential to alleviate food insufficiency while enhancing quality and longevity of life. In the United States alone, a steady import increase of greater than 15% per year or 24 million shipments, over 70% products of which are food related, is regulated under the Food and Drug Administration (FDA). This unparalleled growth has resulted in the need for faster, cheaper, and better safety and efficacy screening methods in the form of harmonized guidelines and recommendations for product standardization. In an effort to meet this need, the in vitro toxicology testing market has similarly grown with an anticipatory 15% increase between 2010 and 2015 of US$1.3 to US$2.7 billion. Although traditionally occupying a small fraction of the market behind pharmaceuticals and cosmetic/household products, the scope of functional food testing, including additives/supplements, ingredients, residues, contact/processing, and contaminants, is potentially expansive. Similarly, as functional food testing has progressed, so has the need to identify potential adverse factors that threaten the safety and quality of these products. © The Author(s) 2015.

Hydrology or biology? Modeling simplistic physical constraints on lake carbon biogeochemistry to identify when and where biology is likely to matter

NASA Astrophysics Data System (ADS)

Jones, S.; Zwart, J. A.; Solomon, C.; Kelly, P. T.

2017-12-01

Current efforts to scale lake carbon biogeochemistry rely heavily on empirical observations and rarely consider physical or biological inter-lake heterogeneity that is likely to regulate terrestrial dissolved organic carbon (tDOC) decomposition in lakes. This may in part result from a traditional focus of lake ecologists on in-lake biological processes OR physical-chemical pattern across lake regions, rather than on process AND pattern across scales. To explore the relative importance of local biological processes and physical processes driven by lake hydrologic setting, we created a simple, analytical model of tDOC decomposition in lakes that focuses on the regulating roles of lake size and catchment hydrologic export. Our simplistic model can generally recreate patterns consistent with both local- and regional-scale patterns in tDOC concentration and decomposition. We also see that variation in lake hydrologic setting, including the importance of evaporation as a hydrologic export, generates significant, emergent variation in tDOC decomposition at a given hydrologic residence time, and creates patterns that have been historically attributed to variation in tDOC quality. Comparing predictions of this `biologically null model' to field observations and more biologically complex models could indicate when and where biology is likely to matter most.

Genes2WordCloud: a quick way to identify biological themes from gene lists and free text

PubMed Central

2011-01-01

Background Word-clouds recently emerged on the web as a solution for quickly summarizing text by maximizing the display of most relevant terms about a specific topic in the minimum amount of space. As biologists are faced with the daunting amount of new research data commonly presented in textual formats, word-clouds can be used to summarize and represent biological and/or biomedical content for various applications. Results Genes2WordCloud is a web application that enables users to quickly identify biological themes from gene lists and research relevant text by constructing and displaying word-clouds. It provides users with several different options and ideas for the sources that can be used to generate a word-cloud. Different options for rendering and coloring the word-clouds give users the flexibility to quickly generate customized word-clouds of their choice. Methods Genes2WordCloud is a word-cloud generator and a word-cloud viewer that is based on WordCram implemented using Java, Processing, AJAX, mySQL, and PHP. Text is fetched from several sources and then processed to extract the most relevant terms with their computed weights based on word frequencies. Genes2WordCloud is freely available for use online; it is open source software and is available for installation on any web-site along with supporting documentation at http://www.maayanlab.net/G2W. Conclusions Genes2WordCloud provides a useful way to summarize and visualize large amounts of textual biological data or to find biological themes from several different sources. The open source availability of the software enables users to implement customized word-clouds on their own web-sites and desktop applications. PMID:21995939

Detecting Biological Warfare Agents

PubMed Central

Song, Linan; Ahn, Soohyoun

2005-01-01

We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array. PMID:16318712

Utility of biological sensor tags in animal conservation.

PubMed

Wilson, A D M; Wikelski, M; Wilson, R P; Cooke, S J

2015-08-01

Electronic tags (both biotelemetry and biologging platforms) have informed conservation and resource management policy and practice by providing vital information on the spatial ecology of animals and their environments. However, the extent of the contribution of biological sensors (within electronic tags) that measure an animal's state (e.g., heart rate, body temperature, and details of locomotion and energetics) is less clear. A literature review revealed that, despite a growing number of commercially available state sensor tags and enormous application potential for such devices in animal biology, there are relatively few examples of their application to conservation. Existing applications fell under 4 main themes: quantifying disturbance (e.g., ecotourism, vehicular and aircraft traffic), examining the effects of environmental change (e.g., climate change), understanding the consequences of habitat use and selection, and estimating energy expenditure. We also identified several other ways in which sensor tags could benefit conservation, such as determining the potential efficacy of management interventions. With increasing sensor diversity of commercially available platforms, less invasive attachment techniques, smaller device sizes, and more researchers embracing such technology, we suggest that biological sensor tags be considered a part of the necessary toolbox for conservation. This approach can measure (in real time) the state of free-ranging animals and thus provide managers with objective, timely, relevant, and accurate data to inform policy and decision making. © 2015 Society for Conservation Biology.

77 FR 41406 - Evaluation of In Vitro Tests for Identifying Eye Injury Hazard Potential of Chemicals and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Evaluation of In Vitro Tests for Identifying Eye Injury...-animal testing strategies proposed for identifying eye injury hazard potential of chemicals and products... Panel and submission of data from substances tested in in vitro tests for identifying eye injury hazard...

Identifying potential recommendation domains for conservation agriculture in Ethiopia, Kenya, and Malawi.

PubMed

Tesfaye, Kindie; Jaleta, Moti; Jena, Pradyot; Mutenje, Munyaradzi

2015-02-01

Conservation agriculture (CA) is being promoted as an option for reducing soil degradation, conserving water, enhancing crop productivity, and maintaining yield stability. However, CA is a knowledge- and technology-intensive practice, and may not be feasible or may not perform better than conventional agriculture under all conditions and farming systems. Using high resolution (≈1 km(2)) biophysical and socioeconomic geospatial data, this study identified potential recommendation domains (RDs) for CA in Ethiopia, Kenya, and Malawi. The biophysical variables used were soil texture, surface slope, and rainfall while the socioeconomic variables were market access and human and livestock population densities. Based on feasibility and comparative performance of CA over conventional agriculture, the biophysical and socioeconomic factors were first used to classify cultivated areas into three biophysical and three socioeconomic potential domains, respectively. Combinations of biophysical and socioeconomic domains were then used to develop potential RDs for CA based on adoption potential within the cultivated areas. About 39, 12, and 5% of the cultivated areas showed high biophysical and socioeconomic potential while 50, 39, and 21% of the cultivated areas showed high biophysical and medium socioeconomic potential for CA in Malawi, Kenya, and Ethiopia, respectively. The results indicate considerable acreages of land with high CA adoption potential in the mixed crop-livestock systems of the studied countries. However, there are large differences among countries depending on biophysical and socio-economic conditions. The information generated in this study could be used for targeting CA and prioritizing CA-related agricultural research and investment priorities in the three countries.

Identifying Potential Recommendation Domains for Conservation Agriculture in Ethiopia, Kenya, and Malawi

NASA Astrophysics Data System (ADS)

Tesfaye, Kindie; Jaleta, Moti; Jena, Pradyot; Mutenje, Munyaradzi

2015-02-01

Conservation agriculture (CA) is being promoted as an option for reducing soil degradation, conserving water, enhancing crop productivity, and maintaining yield stability. However, CA is a knowledge- and technology-intensive practice, and may not be feasible or may not perform better than conventional agriculture under all conditions and farming systems. Using high resolution (≈1 km2) biophysical and socioeconomic geospatial data, this study identified potential recommendation domains (RDs) for CA in Ethiopia, Kenya, and Malawi. The biophysical variables used were soil texture, surface slope, and rainfall while the socioeconomic variables were market access and human and livestock population densities. Based on feasibility and comparative performance of CA over conventional agriculture, the biophysical and socioeconomic factors were first used to classify cultivated areas into three biophysical and three socioeconomic potential domains, respectively. Combinations of biophysical and socioeconomic domains were then used to develop potential RDs for CA based on adoption potential within the cultivated areas. About 39, 12, and 5 % of the cultivated areas showed high biophysical and socioeconomic potential while 50, 39, and 21 % of the cultivated areas showed high biophysical and medium socioeconomic potential for CA in Malawi, Kenya, and Ethiopia, respectively. The results indicate considerable acreages of land with high CA adoption potential in the mixed crop-livestock systems of the studied countries. However, there are large differences among countries depending on biophysical and socio-economic conditions. The information generated in this study could be used for targeting CA and prioritizing CA-related agricultural research and investment priorities in the three countries.

Systems to identify potentially inappropriate prescribing in people with advanced dementia: a systematic review.

PubMed

Disalvo, Domenica; Luckett, Tim; Agar, Meera; Bennett, Alexandra; Davidson, Patricia Mary

2016-05-31

Systems for identifying potentially inappropriate medications in older adults are not immediately transferrable to advanced dementia, where the management goal is palliation. The aim of the systematic review was to identify and synthesise published systems and make recommendations for identifying potentially inappropriate prescribing in advanced dementia. Studies were included if published in a peer-reviewed English language journal and concerned with identifying the appropriateness or otherwise of medications in advanced dementia or dementia and palliative care. The quality of each study was rated using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. Synthesis was narrative due to heterogeneity among designs and measures. Medline (OVID), CINAHL, the Cochrane Database of Systematic Reviews (2005 - August 2014) and AMED were searched in October 2014. Reference lists of relevant reviews and included articles were searched manually. Eight studies were included, all of which were scored a high quality using the STROBE checklist. Five studies used the same system developed by the Palliative Excellence in Alzheimer Care Efforts (PEACE) Program. One study used number of medications as an index, and two studies surveyed health professionals' opinions on appropriateness of specific medications in different clinical scenarios. Future research is needed to develop and validate systems with clinical utility for improving safety and quality of prescribing in advanced dementia. Systems should account for individual clinical context and distinguish between deprescribing and initiation of medications.

The State, Potential Distribution, and Biological Implications of Methane in the Martian Crust

NASA Technical Reports Server (NTRS)

Max, Michael D.; Clifford, Stephen M.

2000-01-01

The search for life on Mars has recently focused on its potential survival in deep (>2 km) subpermafrost aquifers where anaerobic bacteria, similar to those found in deep subsurface ecosystems on Earth, may have survived in an environment that has remained stable for billions of years. An anticipated by-product of this biological activity is methane. The detection of large deposits of methane gas and hydrate in the Martian cryosphere, or as emissions from deep fracture zones, would provide persuasive evidence of indigenous life and confirm the presence of a valuable in situ resource for use by future human explorers.

Biology and host range of Tecmessa elegans (Lepidoptera:Notodontidae) a leaf-feeding moth evaluated as a potential biological control agent for Schinus terebinthifolius (Sapindales: Anacardiaceae) in the USA

USDA-ARS?s Scientific Manuscript database

During surveys for natural enemies that could potentially be used as classical biological control agents of Schinus terebinthifolius Raddi (Brazilian pepper) which is invasive in the USA, the caterpillar, Tecmessa elegans Schaus (Lepidoptera: Notodontidae), was recorded feeding on the leaves of the ...

Applications of stem cell biology to oculoplastic surgery.

PubMed

Daniel, Michael G; Wu, Albert Y

2016-09-01

The review examines the utility of stem cell biology in ophthalmology and oculoplastic surgery. The applicability of stem cell biology varies across a range of different subfields within ophthalmology and oculoplastic surgery. Resident stem cells have been identified in the lacrimal gland, corneal limbus, orbital fat, and muscles of the eye, and can potentially be applied for in-vitro cell and organ cultures with the intent of disease modeling and transplants. The discovery of adipocyte-derived stem cells offered a potentially powerful tool for a variety of oculoplastic applications, such as wound healing, skin rejuvenation, and burn therapeutics. Several groups are currently identifying new uses for stem cells in oculoplastic surgery. The need for stem cell treatment spans a wide array of subfields within ophthalmology, ranging from reconstruction of the eyelid to the generation of artificial lacrimal glands and oncological therapeutics. The advent of induced pluripotent stem cells opened the realm of regenerative medicine, making the modeling of patient-specific diseases a possibility. The identification and characterization of endogenous stem cell populations in the eye makes it possible to obtain specific tissues through induced pluripotent stem cells differentiation, permitting their use in transplants for oculoplastic surgery.

Potential of chicken by-products as sources of useful biological resources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lasekan, Adeseye; Abu Bakar, Fatimah, E-mail: fatim@putra.upm.edu.my; Halal Products Research Institute, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor

By-products from different animal sources are currently being utilised for beneficial purposes. Chicken processing plants all over the world generate large amount of solid by-products in form of heads, legs, bones, viscera and feather. These wastes are often processed into livestock feed, fertilizers and pet foods or totally discarded. Inappropriate disposal of these wastes causes environmental pollution, diseases and loss of useful biological resources like protein, enzymes and lipids. Utilisation methods that make use of these biological components for producing value added products rather than the direct use of the actual waste material might be another viable option for dealingmore » with these wastes. This line of thought has consequently led to researches on these wastes as sources of protein hydrolysates, enzymes and polyunsaturated fatty acids. Due to the multi-applications of protein hydrolysates in various branches of science and industry, and the large body of literature reporting the conversion of animal wastes to hydrolysates, a large section of this review was devoted to this subject. Thus, this review reports the known functional and bioactive properties of hydrolysates derived from chicken by-products as well their utilisation as source of peptone in microbiological media. Methods of producing these hydrolysates including their microbiological safety are discussed. Based on the few references available in the literature, the potential of some chicken by-product as sources of proteases and polyunsaturated fatty acids are pointed out along with some other future applications.« less

Identifying the missing proteins in human proteome by biological language model.

PubMed

Dong, Qiwen; Wang, Kai; Liu, Xuan

2016-12-23

With the rapid development of high-throughput sequencing technology, the proteomics research becomes a trendy field in the post genomics era. It is necessary to identify all the native-encoding protein sequences for further function and pathway analysis. Toward that end, the Human Proteome Organization lunched the Human Protein Project in 2011. However many proteins are hard to be detected by experiment methods, which becomes one of the bottleneck in Human Proteome Project. In consideration of the complicatedness of detecting these missing proteins by using wet-experiment approach, here we use bioinformatics method to pre-filter the missing proteins. Since there are analogy between the biological sequences and natural language, the n-gram models from Natural Language Processing field has been used to filter the missing proteins. The dataset used in this study contains 616 missing proteins from the "uncertain" category of the neXtProt database. There are 102 proteins deduced by the n-gram model, which have high probability to be native human proteins. We perform a detail analysis on the predicted structure and function of these missing proteins and also compare the high probability proteins with other mass spectrum datasets. The evaluation shows that the results reported here are in good agreement with those obtained by other well-established databases. The analysis shows that 102 proteins may be native gene-coding proteins and some of the missing proteins are membrane or natively disordered proteins which are hard to be detected by experiment methods.

Plant MetGenMAP: an integrative analysis system for plant systems biology

USDA-ARS?s Scientific Manuscript database

We have developed a web-based system, Plant MetGenMAP, which can identify significantly altered biochemical pathways and highly affected biological processes, predict functional roles of pathway genes, and potential pathway-related regulatory motifs from transcript and metabolite profile datasets. P...

Plant synthetic biology for molecular engineering of signalling and development.

PubMed

Nemhauser, Jennifer L; Torii, Keiko U

2016-03-02

Molecular genetic studies of model plants in the past few decades have identified many key genes and pathways controlling development, metabolism and environmental responses. Recent technological and informatics advances have led to unprecedented volumes of data that may uncover underlying principles of plants as biological systems. The newly emerged discipline of synthetic biology and related molecular engineering approaches is built on this strong foundation. Today, plant regulatory pathways can be reconstituted in heterologous organisms to identify and manipulate parameters influencing signalling outputs. Moreover, regulatory circuits that include receptors, ligands, signal transduction components, epigenetic machinery and molecular motors can be engineered and introduced into plants to create novel traits in a predictive manner. Here, we provide a brief history of plant synthetic biology and significant recent examples of this approach, focusing on how knowledge generated by the reference plant Arabidopsis thaliana has contributed to the rapid rise of this new discipline, and discuss potential future directions.

Synthesis and Characterization of Rhodamine B-ethylenediamine-hyaluronan Acid as Potential Biological Functional Materials

NASA Astrophysics Data System (ADS)

Li, Y. L.; Wang, W. X.; Wang, Y.; Zhang, W. B.; Gong, H. M.; Liu, M. X.

2018-05-01

The purpose of this study is to synthesize and characterize fluorescent polymers, rhodamine B-ethylenediamine-hyaluronan acid (RhB-EA-HA). RhB-EA-HA was successfully synthesized by ester ammonolysis reaction and amidation reaction. Moreover, the structural properties of RhB-EA-HA were characterized by 1H-NMR spectra, UV-vis spectrometry and Fourier transform infrared spectroscopy (FT-IR). RhB-EA-HA can be grafted on the surface of silica nanomaterials, which may be potential biological functional materials for drug delivery system.

Functional screening for anti-CMV biologics identifies a broadly neutralizing epitope of an essential envelope protein.

PubMed

Gardner, Thomas J; Stein, Kathryn R; Duty, J Andrew; Schwarz, Toni M; Noriega, Vanessa M; Kraus, Thomas; Moran, Thomas M; Tortorella, Domenico

2016-12-14

The prototypic β-herpesvirus human cytomegalovirus (CMV) establishes life-long persistence within its human host. The CMV envelope consists of various protein complexes that enable wide viral tropism. More specifically, the glycoprotein complex gH/gL/gO (gH-trimer) is required for infection of all cell types, while the gH/gL/UL128/130/131a (gH-pentamer) complex imparts specificity in infecting epithelial, endothelial and myeloid cells. Here we utilize state-of-the-art robotics and a high-throughput neutralization assay to screen and identify monoclonal antibodies (mAbs) targeting the gH glycoproteins that display broad-spectrum properties to inhibit virus infection and dissemination. Subsequent biochemical characterization reveals that the mAbs bind to gH-trimer and gH-pentamer complexes and identify the antibodies' epitope as an 'antigenic hot spot' critical for virus entry. The mAbs inhibit CMV infection at a post-attachment step by interacting with a highly conserved central alpha helix-rich domain. The platform described here provides the framework for development of effective CMV biologics and vaccine design strategies.

A Psychoevolutionary Approach to Identifying Preferred Nature Scenes With Potential to Provide Restoration From Stress.

PubMed

Thake, Carol L; Bambling, Matthew; Edirippulige, Sisira; Marx, Eric

2017-10-01

Research supports therapeutic use of nature scenes in healthcare settings, particularly to reduce stress. However, limited literature is available to provide a cohesive guide for selecting scenes that may provide optimal therapeutic effect. This study produced and tested a replicable process for selecting nature scenes with therapeutic potential. Psychoevolutionary theory informed the construction of the Importance for Survival Scale (IFSS), and its usefulness for identifying scenes that people generally prefer to view and that hold potential to reduce stress was tested. Relationships between Importance for Survival (IFS), preference, and restoration were tested. General community participants ( N = 20 males, 20 females; M age = 48 years) Q-sorted sets of landscape photographs (preranked by the researcher in terms of IFS using the IFSS) from most to least preferred, and then completed the Short-Version Revised Restoration Scale in response to viewing a selection of the scenes. Results showed significant positive relationships between IFS and each of scene preference (large effect), and restoration potential (medium effect), as well as between scene preference and restoration potential across the levels of IFS (medium effect), and for individual participants and scenes (large effect). IFS was supported as a framework for identifying nature scenes that people will generally prefer to view and that hold potential for restoration from emotional distress; however, greater therapeutic potential may be expected when people can choose which of the scenes they would prefer to view. Evidence for the effectiveness of the IFSS was produced.

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

DOE PAGES

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric; ...

2015-03-30

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less

Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets.

PubMed

Dey-Rao, Rama; Sinha, Animesh A

2017-01-28

Significant gaps remain regarding the pathomechanisms underlying the autoimmune response in vitiligo (VL), where the loss of self-tolerance leads to the targeted killing of melanocytes. Specifically, there is incomplete information regarding alterations in the systemic environment that are relevant to the disease state. We undertook a genome-wide profiling approach to examine gene expression in the peripheral blood of VL patients and healthy controls in the context of our previously published VL-skin gene expression profile. We used several in silico bioinformatics-based analyses to provide new insights into disease mechanisms and suggest novel targets for future therapy. Unsupervised clustering methods of the VL-blood dataset demonstrate a "disease-state"-specific set of co-expressed genes. Ontology enrichment analysis of 99 differentially expressed genes (DEGs) uncovers a down-regulated immune/inflammatory response, B-Cell antigen receptor (BCR) pathways, apoptosis and catabolic processes in VL-blood. There is evidence for both type I and II interferon (IFN) playing a role in VL pathogenesis. We used interactome analysis to identify several key blood associated transcriptional factors (TFs) from within (STAT1, STAT6 and NF-kB), as well as "hidden" (CREB1, MYC, IRF4, IRF1, and TP53) from the dataset that potentially affect disease pathogenesis. The TFs overlap with our reported lesional-skin transcriptional circuitry, underscoring their potential importance to the disease. We also identify a shared VL-blood and -skin transcriptional "hot spot" that maps to chromosome 6, and includes three VL-blood dysregulated genes (PSMB8, PSMB9 and TAP1) described as potential VL-associated genetic susceptibility loci. Finally, we provide bioinformatics-based support for prioritizing dysregulated genes in VL-blood or skin as potential therapeutic targets. We examined the VL-blood transcriptome in context with our (previously published) VL-skin transcriptional profile to address

Factors associated with occupational exposure to biological material among nursing professionals.

PubMed

Negrinho, Nádia Bruna da Silva; Malaguti-Toffano, Silmara Elaine; Reis, Renata Karina; Pereira, Fernanda Maria Vieira; Gir, Elucir

2017-01-01

to identify factors associated with occupational exposure to biological material among nursing professionals. a cross-sectional study was conducted in a high complexity hospital of a city in the state of São Paulo, Brazil. Nursing professionals were interviewed from March to November 2015. All ethical aspects were observed. among the 226 professionals interviewed, 17.3% suffered occupational exposure to potentially contaminated biological material, with 61.5% being percutaneous. Factors such as age (p=0.003), professional experience in nursing (p=0.015), and experience at the institution (p=0.032) were associated with the accidents with biological material. most accidents with biological material among nursing professionals were percutaneous. Age, professional experience, and experience at the institution were considered factors associated with occupational exposure.

The ethical landscape: identifying the right way to think about the ethical and societal aspects of synthetic biology research and products

PubMed Central

Yearley, Steven

2009-01-01

Synthetic biology promises to be highly innovative in its contribution to scientific understanding. But it offers other sorts of innovation too: in the variety of applications that could result and in the wide range of practitioners who could become involved. But directly corresponding to each of these is a kind of regulatory concern. If the entry barriers are low for a form of scientific practice with dramatic implications then the need for regulatory control over access is great since no one wants unlicensed operators releasing experimental organisms. If there are likely to be extensive opportunities for application within the human body and in the open environment (for energy production or novel forms of bioremediation) then the release and safety-testing implications are potentially enormous. Proponents of synthetic biology have been quick to realise that these challenges call for reviews of the societal and ethical aspects of synthetic biology. This paper shows that the template commonly adopted for such reviews draws on bioethics. It goes on to show that this template is far from ideal, both because of limitations in the way that bioethics has been institutionalized and because of key differences between the regulatory demands on synthetic biology and on bioethics. The paper concludes that broader models of societal and ethical review of synthetic biology are urgently required. PMID:19447816

Characterizing Cancer Drug Response and Biological Correlates: A Geometric Network Approach.

PubMed

Pouryahya, Maryam; Oh, Jung Hun; Mathews, James C; Deasy, Joseph O; Tannenbaum, Allen R

2018-04-23

In the present work, we apply a geometric network approach to study common biological features of anticancer drug response. We use for this purpose the panel of 60 human cell lines (NCI-60) provided by the National Cancer Institute. Our study suggests that mathematical tools for network-based analysis can provide novel insights into drug response and cancer biology. We adopted a discrete notion of Ricci curvature to measure, via a link between Ricci curvature and network robustness established by the theory of optimal mass transport, the robustness of biological networks constructed with a pre-treatment gene expression dataset and coupled the results with the GI50 response of the cell lines to the drugs. Based on the resulting drug response ranking, we assessed the impact of genes that are likely associated with individual drug response. For genes identified as important, we performed a gene ontology enrichment analysis using a curated bioinformatics database which resulted in biological processes associated with drug response across cell lines and tissue types which are plausible from the point of view of the biological literature. These results demonstrate the potential of using the mathematical network analysis in assessing drug response and in identifying relevant genomic biomarkers and biological processes for precision medicine.

Nightmares in the general population: identifying potential causal factors.

PubMed

Rek, Stephanie; Sheaves, Bryony; Freeman, Daniel

2017-09-01

Nightmares are inherently distressing, prevent restorative sleep, and are associated with a number of psychiatric problems, but have rarely been the subject of empirical study. Negative affect, linked to stressful events, is generally considered the key trigger of nightmares; hence nightmares have most often been considered in the context of post-traumatic stress disorder (PTSD). However, many individuals with heightened negative affect do not have nightmares. The objective of this study was to identify mechanistically plausible factors, beyond negative affect, that may explain why individuals experience nightmares. 846 participants from the UK general population completed an online survey about nightmare occurrence and severity (pre-occupation, distress, and impairment), negative affect, worry, depersonalisation, hallucinatory experiences, paranoia, alcohol use, sleep duration, physical activity levels, PTSD symptoms, and stressful life events. Associations of nightmares with the putative predictive factors were tested controlling for levels of negative affect. Analyses were also repeated controlling for levels of PTSD and the recent occurrence of stressful life events. Nightmare occurrence, adjusting for negative affect, was associated with higher levels of worry, depersonalisation, hallucinatory experiences, paranoia, and sleep duration (odds ratios 1.25-1.45). Nightmare severity, controlling for negative affect, was associated with higher levels of worry, depersonalisation, hallucinatory experiences, and paranoia (R 2 s: 0.33-0.39). Alcohol use and physical activity levels were not associated with nightmares. The study identifies a number of potential predictors of the occurrence and severity of nightmares. Causal roles require testing in future longitudinal, experimental, and treatment studies.

Predicting biological condition in southern California streams

USGS Publications Warehouse

Brown, Larry R.; May, Jason T.; Rehn, Andrew C.; Ode, Peter R.; Waite, Ian R.; Kennen, Jonathan G.

2012-01-01

As understanding of the complex relations among environmental stressors and biological responses improves, a logical next step is predictive modeling of biological condition at unsampled sites. We developed a boosted regression tree (BRT) model of biological condition, as measured by a benthic macroinvertebrate index of biotic integrity (BIBI), for streams in urbanized Southern Coastal California. We also developed a multiple linear regression (MLR) model as a benchmark for comparison with the BRT model. The BRT model explained 66% of the variance in B-IBI, identifying watershed population density and combined percentage agricultural and urban land cover in the riparian buffer as the most important predictors of B-IBI, but with watershed mean precipitation and watershed density of manmade channels also important. The MLR model explained 48% of the variance in B-IBI and included watershed population density and combined percentage agricultural and urban land cover in the riparian buffer. For a verification data set, the BRT model correctly classified 75% of impaired sites (B-IBI < 40) and 78% of unimpaired sites (B-IBI = 40). For the same verification data set, the MLR model correctly classified 69% of impaired sites and 87% of unimpaired sites. The BRT model should not be used to predict B-IBI for specific sites; however, the model can be useful for general applications such as identifying and prioritizing regions for monitoring, remediation or preservation, stratifying new bioassessments according to anticipated biological condition, or assessing the potential for change in stream biological condition based on anticipated changes in population density and development in stream buffers.

Yeast mitochondria: an overview of mitochondrial biology and the potential of mitochondrial systems biology.

PubMed

Malina, Carl; Larsson, Christer; Nielsen, Jens

2018-08-01

Mitochondria are dynamic organelles of endosymbiotic origin that are essential components of eukaryal cells. They contain their own genetic machinery, have multicopy genomes and like their bacterial ancestors they consist of two membranes. However, the majority of the ancestral genome has been lost or transferred to the nuclear genome of the host, preserving only a core set of genes involved in oxidative phosphorylation. Mitochondria perform numerous biological tasks ranging from bioenergetics to production of protein co-factors, including heme and iron-sulfur clusters. Due to the importance of mitochondria in many cellular processes, mitochondrial dysfunction is implicated in a wide variety of human disorders. Much of our current knowledge on mitochondrial function and dysfunction comes from studies using Saccharomyces cerevisiae. This yeast has good fermenting capacity, rendering tolerance to mutations that inactivate oxidative phosphorylation and complete loss of mitochondrial DNA. Here, we review yeast mitochondrial metabolism and function with focus on S. cerevisiae and its contribution in understanding mitochondrial biology. We further review how systems biology studies, including mathematical modeling, has allowed gaining new insight into mitochondrial function, and argue that this approach may enable us to gain a holistic view on how mitochondrial function interacts with different cellular processes.

Molecular biology of breast cancer stem cells: potential clinical applications.

PubMed

Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

2010-10-01

Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

On the mechanics of growing thin biological membranes

NASA Astrophysics Data System (ADS)

Rausch, Manuel K.; Kuhl, Ellen

2014-02-01

Despite their seemingly delicate appearance, thin biological membranes fulfill various crucial roles in the human body and can sustain substantial mechanical loads. Unlike engineering structures, biological membranes are able to grow and adapt to changes in their mechanical environment. Finite element modeling of biological growth holds the potential to better understand the interplay of membrane form and function and to reliably predict the effects of disease or medical intervention. However, standard continuum elements typically fail to represent thin biological membranes efficiently, accurately, and robustly. Moreover, continuum models are typically cumbersome to generate from surface-based medical imaging data. Here we propose a computational model for finite membrane growth using a classical midsurface representation compatible with standard shell elements. By assuming elastic incompressibility and membrane-only growth, the model a priori satisfies the zero-normal stress condition. To demonstrate its modular nature, we implement the membrane growth model into the general-purpose non-linear finite element package Abaqus/Standard using the concept of user subroutines. To probe efficiently and robustness, we simulate selected benchmark examples of growing biological membranes under different loading conditions. To demonstrate the clinical potential, we simulate the functional adaptation of a heart valve leaflet in ischemic cardiomyopathy. We believe that our novel approach will be widely applicable to simulate the adaptive chronic growth of thin biological structures including skin membranes, mucous membranes, fetal membranes, tympanic membranes, corneoscleral membranes, and heart valve membranes. Ultimately, our model can be used to identify diseased states, predict disease evolution, and guide the design of interventional or pharmaceutic therapies to arrest or revert disease progression.

Identifying Potential Collapse Features Under Highways

DOT National Transportation Integrated Search

2003-01-01

In 1994, subsidence features were identified on Interstate 70 in eastern Ohio. These : features were caused by collapse of old mine workings beneath the highway. An attempt : was made to delineate these features using geophysical methods with no avai...

Use of multi-criteria decision analysis to identify potentially dangerous glacial lakes.

PubMed

Kougkoulos, Ioannis; Cook, Simon J; Jomelli, Vincent; Clarke, Leon; Symeonakis, Elias; Dortch, Jason M; Edwards, Laura A; Merad, Myriam

2018-04-15

Glacial Lake Outburst Floods (GLOFs) represent a significant threat in deglaciating environments, necessitating the development of GLOF hazard and risk assessment procedures. Here, we outline a Multi-Criteria Decision Analysis (MCDA) approach that can be used to rapidly identify potentially dangerous lakes in regions without existing tailored GLOF risk assessments, where a range of glacial lake types exist, and where field data are sparse or non-existent. Our MCDA model (1) is desk-based and uses freely and widely available data inputs and software, and (2) allows the relative risk posed by a range of glacial lake types to be assessed simultaneously within any region. A review of the factors that influence GLOF risk, combined with the strict rules of criteria selection inherent to MCDA, has allowed us to identify 13 exhaustive, non-redundant, and consistent risk criteria. We use our MCDA model to assess the risk of 16 extant glacial lakes and 6 lakes that have already generated GLOFs, and found that our results agree well with previous studies. For the first time in GLOF risk assessment, we employed sensitivity analyses to test the strength of our model results and assumptions, and to identify lakes that are sensitive to the criteria and risk thresholds used. A key benefit of the MCDA method is that sensitivity analyses are readily undertaken. Overall, these sensitivity analyses lend support to our model, although we suggest that further work is required to determine the relative importance of assessment criteria, and the thresholds that determine the level of risk for each criterion. As a case study, the tested method was then applied to 25 potentially dangerous lakes in the Bolivian Andes, where GLOF risk is poorly understood; 3 lakes are found to pose 'medium' or 'high' risk, and require further detailed investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

Behavior of nanoceria in biologically-relevant environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Amit; Das, Soumen; Munusamy, Prabhakaran

2014-09-08

Cerium oxide nanoparticles (CNPs) have gained a considerable attention in biological research due to their anti-oxidant like behaviour and regenerative nature. The current literature on CNPs reports many successful attempts on harnessing the beneficial therapeutic properties in biology. However studies have also shown toxicity effect with some types of CNPs. This review discusses issues associated with the behaviours of CNPs in biological systems and identifies key knowledge gaps. We explore how salient physicochemical properties (size, surface chemistry, surface stabilizers) contribute to the potential positive and negative aspects of nanoceria in biological systems. Based on variations of results reported in themore » literature, important issues need to be addressed. Are we really studying the same particles with slight variations in size and physicochemical properties or do the particles being examined have fundamentally different behaviours? Are the variations observed in the result of differences in the initial properties of the particles or the results of downstream effects that emerge as the particles are prepared for specific studies and they interact with biological or other environmental moieties? How should particles be appropriately prepared for relevant environmental/toxicology/safety studies? It is useful to recognize that nanoparticles encompass some of the same complexities and variability associated with biological components« less

Molecular marker to identify radiolarian species -toward establishment of paleo-environmental proxy-

NASA Astrophysics Data System (ADS)

Ishitani, Y.

2017-12-01

Marine fossilized unicellular plankton are known to have many genetically divergent species (biological species) in the single morphological species and these biological species show the species-specific environments much more precisely than that of morphological species. Among these plankton, Radiolaria are one of the best candidates for time- and environmental-indicators in the modern and past oceans, because radiolarians are the only group which represent entire water column from shallow to deep waters. However, the ecology and evolution of radiolarian were traditionally studied in paleontology and paleoceanography by morphological species. Even Radiolaria has a huge potential for novel proxy of wide and deep environments, there is no criterion to identify the biological species. The motivation for this study is setting the quantitative delimitation to establish the biological species of radiolarians based on molecular data, for leading the future ecological and paleo-environmental study. Identification of the biological species by ribosomal DNA sequences are mainly based on two ways: one is the evolutionary distance of the small subunit (SSU) rDNA, the internal transcribed spacer region of ribosomal DNA (ITS1 and 2), and the large subunit (LSU) rDNA; and the other is the secondary structure of ITS2. In the present study, all four possible genetic markers (SSU, ITS1, ITS2, and LSU rDNA) were amplified from 232 individuals of five radiolarian morphological species and applied to examine the evolutionary distance and secondary structure of rDNA. Comprehensive survey clearly shows that evolutionary distance of ITS1 rDNA and the secondary structure of ITS2 is good to identify the species. Notably, evolutionary distance of ITS1 rDNA is possible to set the common delimitation to identify the biological species, as 0.225 substitution per site. The results show that the ITS1 and ITS 2 rDNA could be the criterion for radiolarian species identification.

Identifying potential collapse features under highways.

DOT National Transportation Integrated Search

2003-03-01

In 1994, subsidence features were identified on Interstate 70 in eastern Ohio. These features were caused by collapse of old mine workings beneath the highway. An attempt was made to delineate these features using geophysical methods with no avail. T...

The neurophysiology of biological motion perception in schizophrenia

PubMed Central

Jahshan, Carol; Wynn, Jonathan K; Mathis, Kristopher I; Green, Michael F

2015-01-01

Introduction The ability to recognize human biological motion is a fundamental aspect of social cognition that is impaired in people with schizophrenia. However, little is known about the neural substrates of impaired biological motion perception in schizophrenia. In the current study, we assessed event-related potentials (ERPs) to human and nonhuman movement in schizophrenia. Methods Twenty-four subjects with schizophrenia and 18 healthy controls completed a biological motion task while their electroencephalography (EEG) was simultaneously recorded. Subjects watched clips of point-light animations containing 100%, 85%, or 70% biological motion, and were asked to decide whether the clip resembled human or nonhuman movement. Three ERPs were examined: P1, N1, and the late positive potential (LPP). Results Behaviorally, schizophrenia subjects identified significantly fewer stimuli as human movement compared to healthy controls in the 100% and 85% conditions. At the neural level, P1 was reduced in the schizophrenia group but did not differ among conditions in either group. There were no group differences in N1 but both groups had the largest N1 in the 70% condition. There was a condition × group interaction for the LPP: Healthy controls had a larger LPP to 100% versus 85% and 70% biological motion; there was no difference among conditions in schizophrenia subjects. Conclusions Consistent with previous findings, schizophrenia subjects were impaired in their ability to recognize biological motion. The EEG results showed that biological motion did not influence the earliest stage of visual processing (P1). Although schizophrenia subjects showed the same pattern of N1 results relative to healthy controls, they were impaired at a later stage (LPP), reflecting a dysfunction in the identification of human form in biological versus nonbiological motion stimuli. PMID:25722951

ICP-MS multielemental determination of metals potentially released from dental implants and articular prostheses in human biological fluids.

PubMed

Sarmiento-González, Alejandro; Marchante-Gayón, Juan Manuel; Tejerina-Lobo, José María; Paz-Jiménez, José; Sanz-Medel, Alfredo

2005-06-01

A sector field high-resolution (HR)-ICP-MS and an octapole reaction system (ORS)-ICP-MS have been compared for the simultaneous determination of traces of metals (Ti, V, Cr, Co, Ni, and Mo) released from dental implants and articular prostheses in human biological fluids. Optimum sample treatments were evaluated to minimize matrix effects in urine and whole blood. Urine samples were diluted tenfold with ultrapure water, whereas whole blood samples were digested with high-purity nitric acid and hydrogen peroxide and finally diluted tenfold with ultrapure water. In both matrices, internal standardization (Ga and Y) was employed to avoid potential matrix interferences and ICP-MS signal drift. Spectral interferences arising from the plasma gases or the major components of urine and whole blood were identified by (HR)-ICP-MS at 3,000 resolving power. The capabilities of (HR)-ICP-MS and (ORS)-ICP-MS for the removal of such spectral interferences were evaluated and compared. Results indicate that polyatomic interferences, which hamper the determination of such metallic elements in these biological samples, could be overcome by using a resolving power of 3,000. Using (ORS)-ICP-MS, all those elements could be quantified except Ti and V (due to the polyatomic ions 31P16O and 35Cl16O, respectively). The accuracy of the proposed methodologies by (HR)- and (ORS)-ICP-MS was checked against two reference materials. Good agreement between the given values and the concentrations obtained for all the analytes under scrutiny was found except for Ti and V when analyzed by (ORS)-ICP-MS.

Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms.

PubMed

Esplin, M Sean; Manuck, Tracy A; Varner, Michael W; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M; Ilekis, John

2015-09-01

We sought to use an innovative tool that is based on common biologic pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB) to enhance investigators' ability to identify and to highlight common mechanisms and underlying genetic factors that are responsible for SPTB. We performed a secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks' gestation. Each woman was assessed for the presence of underlying SPTB causes. A hierarchic cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis with the use of VEGAS software. One thousand twenty-eight women with SPTB were assigned phenotypes. Hierarchic clustering of the phenotypes revealed 5 major clusters. Cluster 1 (n = 445) was characterized by maternal stress; cluster 2 (n = 294) was characterized by premature membrane rupture; cluster 3 (n = 120) was characterized by familial factors, and cluster 4 (n = 63) was characterized by maternal comorbidities. Cluster 5 (n = 106) was multifactorial and characterized by infection (INF), decidual hemorrhage (DH), and placental dysfunction (PD). These 3 phenotypes were correlated highly by χ(2) analysis (PD and DH, P < 2.2e-6; PD and INF, P = 6.2e-10; INF and DH, (P = .0036). Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. We identified 5 major clusters of SPTB based on a phenotype tool and hierarch clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors that were underlying SPTB. Copyright © 2015 Elsevier Inc. All rights reserved.

Potential for enhancement of aerobic biological removal of recalcitrant organic matter in bleached pulp mill effluents.

PubMed

Mounteer, A H; Souza, L C; Silva, C M

2007-02-01

Increasingly stringent effluent quality limits for bleached kraft pulp mills pose a great challenge to mill wastewater system managers since these limits can require levels of chemical oxygen demand (COD) removal efficiency rarely reported for biological treatment of these types of effluents. The present study was therefore undertaken to better understand the nature of recalcitrant COD in bleached kraft pulp effluents that persists through the biological treatment system. Bleaching effluents from a Brazilian eucalypt bleached kraft pulp mill were collected and treated in a bench-scale sequencing batch reactor. Organic matter in raw and treated effluents was characterized before and after separation into low and high molecular mass fractions. Biological treatment removed 71% of the COD, with 83% removal of the low molecular mass COD but only 36% removal of the high molecular mass COD. Microorganisms capable of degrading the recalcitrant COD were isolated from enrichment cultures of the original activated sludge fed on fractions of the bleaching effluent that presented low biodegradabilities. Use of a microbial consortium composed of ten of these isolates to treat the biologically treated effluent removed a further 12% of the effluent COD, all from the high molecular mass fraction. Results of this research indicate that microorganisms with potential for degrading recalcitrant COD are present in activated sludge, but that these are not metabolically active during normal activated sludge treatment of mill effluents. The use of biological selectors in the treatment system to promote growth of such microorganisms may enhance removal of recalcitrant organic matter.

Using high frequency consumption data to identify demand response potential for solar energy integration

NASA Astrophysics Data System (ADS)

Jin, L.; Borgeson, S.; Fredman, D.; Hans, L.; Spurlock, A.; Todd, A.

2015-12-01

California's renewable portfolio standard (2012) requires the state to get 33% of its electricity from renewable sources by 2020. Increased share of variable renewable sources such as solar and wind in the California electricity system may require more grid flexibility to insure reliable power services. Such grid flexibility can be potentially provided by changes in end use electricity consumptions in response to grid conditions (demand-response). In the solar case, residential consumption in the late afternoon can be used as reserve capacity to balance the drop in solar generation. This study presents our initial attempt to identify, from a behavior perspective, residential demand response potentials in relation to solar ramp events using a data-driven approach. Based on hourly residential energy consumption data, we derive representative daily load shapes focusing on discretionary consumption with an innovative clustering analysis technique. We aggregate the representative load shapes into behavior groups in terms of the timing and rhythm of energy use in the context of solar ramp events. Households of different behavior groups that are active during hours with high solar ramp rates are identified for capturing demand response potential. Insights into the nature and predictability of response to demand-response programs are provided.

Biological potential of oxo-vanadium salicylediene amino-acid complexes as cytotoxic, antimicrobial, antioxidant and DNA interaction.

PubMed

Adam, Mohamed Shaker S; Elsawy, Hany

2018-05-04

New series of oxo-vanadium N-salicyledieneamino acid Schiff base complexes are synthesized and characterized. They are synthesized from the reaction of sodium salicylaldehyde-5-sulfonate, some amino acids, alanine (VOHL1), leucine (VOHL2) or glycine (VOHL3) in an aqueous media, and leucine (VOHLpy1) or tryptophan (VOHLpy2) in pyridine with vanadyl acetylacetonate. The complexes are characterized by EA, TGA, IR, UV-Visible and mass spectra, conductivity and magnetic measurements. The biological activity of the VO-complexes shows that VOHL1, VOHL2 and VOHL3 exhibit anti-proliferative effect and may be used as anticancer drugs. VO-complexes manifest high toxicity, except VOHL2 is less toxic, and could be applied for the human being. VOHL1, VOHL2 and VOHL3 display remarkable SOD like potential and act as high inhibiting reagents. VOHLpy1 and VOHLpy2 show low inhibiting potentials. VO-complexes have good anti-oxidant effect, in which VOHL3 affords the best antioxidant activity. The interaction between VO-complexes and DNA is studied spectrophotometrically and by gel electrophoresis. Binding constants and spectrophotometric parameters indicate a strong interaction between VO-complexes and DNA. VO-complexes have respectable anti-bacterial and antifungal activities, where VOHL3 shows the maximum potential. DFT calculations of VOHL1 and VOHL3 were discussed in the light of their biological activity, which are convenient with the obtained results. Copyright © 2018 Elsevier B.V. All rights reserved.

Biology and host range of Heterapoderopsis bicallosicollis; a potential biological control agent for Chinese tallow Triadica sebifera

USDA-ARS?s Scientific Manuscript database

Chinese tallow, Triadica sebifera, is an invasive weed that infests natural and agricultural areas of the southeastern USA. A candidate for biological control of Chinese tallow has been studied under quarantine conditions. The biology and host range of a primitive leaf feeding beetle, Heterapoderops...

Identifying ultrasensitive HGF dose-response functions in a 3D mammalian system for synthetic morphogenesis.

PubMed

Senthivel, Vivek Raj; Sturrock, Marc; Piedrafita, Gabriel; Isalan, Mark

2016-12-16

Nonlinear responses to signals are widespread natural phenomena that affect various cellular processes. Nonlinearity can be a desirable characteristic for engineering living organisms because it can lead to more switch-like responses, similar to those underlying the wiring in electronics. Steeper functions are described as ultrasensitive, and can be applied in synthetic biology by using various techniques including receptor decoys, multiple co-operative binding sites, and sequential positive feedbacks. Here, we explore the inherent non-linearity of a biological signaling system to identify functions that can potentially be exploited using cell genome engineering. For this, we performed genome-wide transcription profiling to identify genes with ultrasensitive response functions to Hepatocyte Growth Factor (HGF). We identified 3,527 genes that react to increasing concentrations of HGF, in Madin-Darby canine kidney (MDCK) cells, grown as cysts in 3D collagen cell culture. By fitting a generic Hill function to the dose-responses of these genes we obtained a measure of the ultrasensitivity of HGF-responsive genes, identifying a subset with higher apparent Hill coefficients (e.g. MMP1, TIMP1, SNORD75, SNORD86 and ERRFI1). The regulatory regions of these genes are potential candidates for future engineering of synthetic mammalian gene circuits requiring nonlinear responses to HGF signalling.

Isoindoline-1,3-dione derivatives targeting cholinesterases: design, synthesis and biological evaluation of potential anti-Alzheimer's agents.

PubMed

Guzior, Natalia; Bajda, Marek; Rakoczy, Jurand; Brus, Boris; Gobec, Stanislav; Malawska, Barbara

2015-04-01

Alzheimer's disease is a fatal neurodegenerative disorder with a complex etiology. Because the available therapy brings limited benefits, the effective treatment for Alzheimer's disease remains the unmet challenge. Our aim was to develop a new series of donepezil-based compounds endowed with inhibitory properties against cholinesterases and β-amyloid aggregation. We designed the target compounds as dual binding site acetylcholinesterase inhibitors with N-benzylamine moiety interacting with the catalytic site of the enzyme and an isoindoline-1,3-dione fragment interacting with the peripheral anionic site of the enzyme. The results of pharmacological evaluation lead us to identify a compound 3b as the most potent and selective human acetylcholinesterase inhibitor (hAChE IC50=0.361μM). Kinetic studies revealed that 3b inhibited acetylcholinesterase in non-competitive mode. The result of the parallel artificial membrane permeability assay for the blood-brain barrier indicated that the compound 3b would be able to cross the blood-brain barrier and reach its biological targets in the central nervous system. The selected compound 3b represents a potential lead structure for further development of anti-Alzheimer's agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interactive learning and action: realizing the promise of synthetic biology for global health.

PubMed

Betten, A Wieke; Roelofsen, Anneloes; Broerse, Jacqueline E W

2013-09-01

The emerging field of synthetic biology has the potential to improve global health. For example, synthetic biology could contribute to efforts at vaccine development in a context in which vaccines and immunization have been identified by the international community as being crucial to international development efforts and, in particular, the millennium development goals. However, past experience with innovations shows that realizing a technology's potential can be difficult and complex. To achieve better societal embedding of synthetic biology and to make sure it reaches its potential, science and technology development should be made more inclusive and interactive. Responsible research and innovation is based on the premise that a broad range of stakeholders with different views, needs and ideas should have a voice in the technological development and deployment process. The interactive learning and action (ILA) approach has been developed as a methodology to bring societal stakeholders into a science and technology development process. This paper proposes an ILA in five phases for an international effort, with national case studies, to develop socially robust applications of synthetic biology for global health, based on the example of vaccine development. The design is based on results of a recently initiated ILA project on synthetic biology; results from other interactive initiatives described in the literature; and examples of possible applications of synthetic biology for global health that are currently being developed.

Identifying candidate drivers of drug response in heterogeneous cancer by mining high throughput genomics data.

PubMed

Nabavi, Sheida

2016-08-15

With advances in technologies, huge amounts of multiple types of high-throughput genomics data are available. These data have tremendous potential to identify new and clinically valuable biomarkers to guide the diagnosis, assessment of prognosis, and treatment of complex diseases, such as cancer. Integrating, analyzing, and interpreting big and noisy genomics data to obtain biologically meaningful results, however, remains highly challenging. Mining genomics datasets by utilizing advanced computational methods can help to address these issues. To facilitate the identification of a short list of biologically meaningful genes as candidate drivers of anti-cancer drug resistance from an enormous amount of heterogeneous data, we employed statistical machine-learning techniques and integrated genomics datasets. We developed a computational method that integrates gene expression, somatic mutation, and copy number aberration data of sensitive and resistant tumors. In this method, an integrative method based on module network analysis is applied to identify potential driver genes. This is followed by cross-validation and a comparison of the results of sensitive and resistance groups to obtain the final list of candidate biomarkers. We applied this method to the ovarian cancer data from the cancer genome atlas. The final result contains biologically relevant genes, such as COL11A1, which has been reported as a cis-platinum resistant biomarker for epithelial ovarian carcinoma in several recent studies. The described method yields a short list of aberrant genes that also control the expression of their co-regulated genes. The results suggest that the unbiased data driven computational method can identify biologically relevant candidate biomarkers. It can be utilized in a wide range of applications that compare two conditions with highly heterogeneous datasets.

Onset dynamics of action potentials in rat neocortical neurons and identified snail neurons: quantification of the difference.

PubMed

Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

2008-04-09

The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics.

Onset Dynamics of Action Potentials in Rat Neocortical Neurons and Identified Snail Neurons: Quantification of the Difference

PubMed Central

Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

2008-01-01

The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the difference between the fast, step-like onset of APs in rat neocortical neurons and the gradual, exponential-like AP onset in identified snail neurons. The quantitative measure of the AP onset dynamics, provided by the method, allows us to perform quantitative analyses of factors influencing the dynamics. PMID:18398478

Significant Deregulated Pathways in Diabetes Type II Complications Identified through Expression Based Network Biology

NASA Astrophysics Data System (ADS)

Ukil, Sanchaita; Sinha, Meenakshee; Varshney, Lavneesh; Agrawal, Shipra

Type 2 Diabetes is a complex multifactorial disease, which alters several signaling cascades giving rise to serious complications. It is one of the major risk factors for cardiovascular diseases. The present research work describes an integrated functional network biology approach to identify pathways that get transcriptionally altered and lead to complex complications thereby amplifying the phenotypic effect of the impaired disease state. We have identified two sub-network modules, which could be activated under abnormal circumstances in diabetes. Present work describes key proteins such as P85A and SRC serving as important nodes to mediate alternate signaling routes during diseased condition. P85A has been shown to be an important link between stress responsive MAPK and CVD markers involved in fibrosis. MAPK8 has been shown to interact with P85A and further activate CTGF through VEGF signaling. We have traced a novel and unique route correlating inflammation and fibrosis by considering P85A as a key mediator of signals. The next sub-network module shows SRC as a junction for various signaling processes, which results in interaction between NF-kB and beta catenin to cause cell death. The powerful interaction between these important genes in response to transcriptionally altered lipid metabolism and impaired inflammatory response via SRC causes apoptosis of cells. The crosstalk between inflammation, lipid homeostasis and stress, and their serious effects downstream have been explained in the present analyses.

LGscore: A method to identify disease-related genes using biological literature and Google data.

PubMed

Kim, Jeongwoo; Kim, Hyunjin; Yoon, Youngmi; Park, Sanghyun

2015-04-01

Since the genome project in 1990s, a number of studies associated with genes have been conducted and researchers have confirmed that genes are involved in disease. For this reason, the identification of the relationships between diseases and genes is important in biology. We propose a method called LGscore, which identifies disease-related genes using Google data and literature data. To implement this method, first, we construct a disease-related gene network using text-mining results. We then extract gene-gene interactions based on co-occurrences in abstract data obtained from PubMed, and calculate the weights of edges in the gene network by means of Z-scoring. The weights contain two values: the frequency and the Google search results. The frequency value is extracted from literature data, and the Google search result is obtained using Google. We assign a score to each gene through a network analysis. We assume that genes with a large number of links and numerous Google search results and frequency values are more likely to be involved in disease. For validation, we investigated the top 20 inferred genes for five different diseases using answer sets. The answer sets comprised six databases that contain information on disease-gene relationships. We identified a significant number of disease-related genes as well as candidate genes for Alzheimer's disease, diabetes, colon cancer, lung cancer, and prostate cancer. Our method was up to 40% more accurate than existing methods. Copyright © 2015 Elsevier Inc. All rights reserved.

Predicting essential genes for identifying potential drug targets in Aspergillus fumigatus.

PubMed

Lu, Yao; Deng, Jingyuan; Rhodes, Judith C; Lu, Hui; Lu, Long Jason

2014-06-01

Aspergillus fumigatus (Af) is a ubiquitous and opportunistic pathogen capable of causing acute, invasive pulmonary disease in susceptible hosts. Despite current therapeutic options, mortality associated with invasive Af infections remains unacceptably high, increasing 357% since 1980. Therefore, there is an urgent need for the development of novel therapeutic strategies, including more efficacious drugs acting on new targets. Thus, as noted in a recent review, "the identification of essential genes in fungi represents a crucial step in the development of new antifungal drugs". Expanding the target space by rapidly identifying new essential genes has thus been described as "the most important task of genomics-based target validation". In previous research, we were the first to show that essential gene annotation can be reliably transferred between distantly related four Prokaryotic species. In this study, we extend our machine learning approach to the much more complex Eukaryotic fungal species. A compendium of essential genes is predicted in Af by transferring known essential gene annotations from another filamentous fungus Neurospora crassa. This approach predicts essential genes by integrating diverse types of intrinsic and context-dependent genomic features encoded in microbial genomes. The predicted essential datasets contained 1674 genes. We validated our results by comparing our predictions with known essential genes in Af, comparing our predictions with those predicted by homology mapping, and conducting conditional expressed alleles. We applied several layers of filters and selected a set of potential drug targets from the predicted essential genes. Finally, we have conducted wet lab knockout experiments to verify our predictions, which further validates the accuracy and wide applicability of the machine learning approach. The approach presented here significantly extended our ability to predict essential genes beyond orthologs and made it possible to

Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

NASA Technical Reports Server (NTRS)

Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

1995-01-01

A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

Identification of Bacteria and Determination of Biological Indicators

NASA Technical Reports Server (NTRS)

Venkateswaran, Kasthuri; La Duc, Myron T.; Vaishampayan, Parag A.

2009-01-01

The ultimate goal of planetary protection research is to develop superior strategies for inactivating resistance bearing micro-organisms like Rummeli - bacillus stabekisii. By first identifying the particular physiologic pathway and/or structural component of the cell/spore that affords it such elevated tolerance, eradication regimes can then be designed to target these resistance-conferring moieties without jeopardizing the structural integrity of spacecraft hardware. Furthermore, hospitals and government agencies frequently use biological indicators to ensure the efficacy of a wide range of sterilization processes. The spores of Rummelibacillus stabekisii, which are far more resistant to many of such perturbations, could likely serve as a more significant biological indicator for potential survival than those being used currently.

Incorporating zebrafish omics into chemical biology and toxicology.

PubMed

Sukardi, Hendrian; Ung, Choong Yong; Gong, Zhiyuan; Lam, Siew Hong

2010-03-01

In this communication, we describe the general aspects of omics approaches for analyses of transcriptome, proteome, and metabolome, and how they can be strategically incorporated into chemical screening and perturbation studies using the zebrafish system. Pharmacological efficacy and selectivity of chemicals can be evaluated based on chemical-induced phenotypic effects; however, phenotypic observation has limitations in identifying mechanistic action of chemicals. We suggest adapting gene-expression-based high-throughput screening as a complementary strategy to zebrafish-phenotype-based screening for mechanistic insights about the mode of action and toxicity of a chemical, large-scale predictive applications and comparative analysis of chemical-induced omics signatures, which are useful to identify conserved biological responses, signaling pathways, and biomarkers. The potential mechanistic, predictive, and comparative applications of omics approaches can be implemented in the zebrafish system. Examples of these using the omics approaches in zebrafish, including data of ours and others, are presented and discussed. Omics also facilitates the translatability of zebrafish studies across species through comparison of conserved chemical-induced responses. This review is intended to update interested readers with the current omics approaches that have been applied in chemical studies on zebrafish and their potential in enhancing discovery in chemical biology.

Applications of stem cell biology to oculoplastic surgery

PubMed Central

Daniel, Michael G.; Wu, Albert Y.

2016-01-01

Purpose of review This review examines the utility of stem cell biology in ophthalmology and oculoplastic surgery. Recent findings The applicability of stem cell biology varies across a range of different subfields within ophthalmology and oculoplastic surgery. Resident stem cells have been identified in the lacrimal gland, corneal limbus, orbital fat, and muscles of the eye, and can potentially be applied for in vitro cell and organ cultures with the intent of disease modeling and transplants. The discovery of adipocyte derived stem cells (ADSCs) offered a potentially powerful tool for a variety of oculoplastic applications, such as wound healing, skin rejuvenation, and burn therapeutics. Several groups are currently identifying new uses for stem cells in oculoplastic surgery. Summary The need for stem cell treatment spans a wide array of subfields within ophthalmology, ranging from reconstruction of the eyelid to the generation of artificial lacrimal glands and oncological therapeutics. The advent of induced pluripotent stem cells (iPSCs) opened the realm of regenerative medicine, making the modeling of patient-specific diseases a possibility. The identification and characterization of endogenous stem cell populations in the eye makes it possible to obtain specific tissues through iPSC differentiation, permitting their use in transplants for oculoplastic surgery. PMID:27206262

Osteosarcoma Genetics and Epigenetics: Emerging Biology and Candidate Therapies

PubMed Central

Morrow, James J.; Khanna, Chand

2016-01-01

Osteosarcoma is the most common primary malignancy of bone, typically presenting in the first or second decade of life. Unfortunately, clinical outcomes for osteosarcoma patients have not substantially improved in over 30 years. This stagnation in therapeutic advances is perhaps explained by the genetic, epigenetic, and biological complexities of this rare tumor. In this review we provide a general background on the biology of osteosarcoma and the clinical status quo. We go on to enumerate the genetic and epigenetic defects identified in osteosarcoma. Finally, we discuss ongoing large-scale studies in the field and potential new therapies that are currently under investigation. PMID:26349415

Identifying Potential Regions of Copy Number Variation for Bipolar Disorder

PubMed Central

Chen, Yi-Hsuan; Lu, Ru-Band; Hung, Hung; Kuo, Po-Hsiu

2014-01-01

Bipolar disorder is a complex psychiatric disorder with high heritability, but its genetic determinants are still largely unknown. Copy number variation (CNV) is one of the sources to explain part of the heritability. However, it is a challenge to estimate discrete values of the copy numbers using continuous signals calling from a set of markers, and to simultaneously perform association testing between CNVs and phenotypic outcomes. The goal of the present study is to perform a series of data filtering and analysis procedures using a DNA pooling strategy to identify potential CNV regions that are related to bipolar disorder. A total of 200 normal controls and 200 clinically diagnosed bipolar patients were recruited in this study, and were randomly divided into eight control and eight case pools. Genome-wide genotyping was employed using Illumina Human Omni1-Quad array with approximately one million markers for CNV calling. We aimed at setting a series of criteria to filter out the signal noise of marker data and to reduce the chance of false-positive findings for CNV regions. We first defined CNV regions for each pool. Potential CNV regions were reported based on the different patterns of CNV status between cases and controls. Genes that were mapped into the potential CNV regions were examined with association testing, Gene Ontology enrichment analysis, and checked with existing literature for their associations with bipolar disorder. We reported several CNV regions that are related to bipolar disorder. Two CNV regions on chromosome 11 and 22 showed significant signal differences between cases and controls (p < 0.05). Another five CNV regions on chromosome 6, 9, and 19 were overlapped with results in previous CNV studies. Experimental validation of two CNV regions lent some support to our reported findings. Further experimental and replication studies could be designed for these selected regions. PMID:27605030

Cellular signaling identifiability analysis: a case study.

PubMed

Roper, Ryan T; Pia Saccomani, Maria; Vicini, Paolo

2010-05-21

Two primary purposes for mathematical modeling in cell biology are (1) simulation for making predictions of experimental outcomes and (2) parameter estimation for drawing inferences from experimental data about unobserved aspects of biological systems. While the former purpose has become common in the biological sciences, the latter is less common, particularly when studying cellular and subcellular phenomena such as signaling-the focus of the current study. Data are difficult to obtain at this level. Therefore, even models of only modest complexity can contain parameters for which the available data are insufficient for estimation. In the present study, we use a set of published cellular signaling models to address issues related to global parameter identifiability. That is, we address the following question: assuming known time courses for some model variables, which parameters is it theoretically impossible to estimate, even with continuous, noise-free data? Following an introduction to this problem and its relevance, we perform a full identifiability analysis on a set of cellular signaling models using DAISY (Differential Algebra for the Identifiability of SYstems). We use our analysis to bring to light important issues related to parameter identifiability in ordinary differential equation (ODE) models. We contend that this is, as of yet, an under-appreciated issue in biological modeling and, more particularly, cell biology. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

An integrated in vitro and in vivo high throughput screen identifies treatment leads for ependymoma

PubMed Central

Atkinson, Jennifer M.; Shelat, Anang A.; Carcaboso, Angel Montero; Kranenburg, Tanya A.; Arnold, Alexander; Boulos, Nidal; Wright, Karen; Johnson, Robert A.; Poppleton, Helen; Mohankumar, Kumarasamypet M.; Feau, Clementine; Phoenix, Timothy; Gibson, Paul; Zhu, Liqin; Tong, Yiai; Eden, Chris; Ellison, David W.; Priebe, Waldemar; Koul, Dimpy; Yung, W. K. Alfred; Gajjar, Amar; Stewart, Clinton F.; Guy, R. Kip; Gilbertson, Richard J.

2011-01-01

Summary Using a mouse model of ependymoma—a chemoresistant brain tumor—we combined multi-cell high-throughput screening (HTS), kinome-wide binding assays, and in vivo efficacy studies, to identify potential treatments with predicted toxicity against neural stem cells (NSC). We identified kinases within the insulin signaling pathway and centrosome cycle as regulators of ependymoma cell proliferation, and their corresponding inhibitors as potential therapies. FDA approved drugs not currently used to treat ependymoma were also identified that posses selective toxicity against ependymoma cells relative to normal NSCs both in vitro and in vivo e.g., 5-fluoruracil. Our comprehensive approach advances understanding of the biology and treatment of ependymoma including the discovery of several treatment leads for immediate clinical translation. PMID:21907928

Fungus-mediated biological synthesis of gold nanoparticles: potential in detection of liver cancer

PubMed Central

Chauhan, Arun; Zubair, Swaleha; Tufail, Saba; Sherwani, Asif; Sajid, Mohammad; Raman, Suri C; Azam, Amir; Owais, Mohammad

2011-01-01

Background Nanomaterials are considered to be the pre-eminent component of the rapidly advancing field of nanotechnology. However, developments in the biologically inspired synthesis of nanoparticles are still in their infancy and consequently attracting the attention of material scientists throughout the world. Keeping in mind the fact that microorganism-assisted synthesis of nanoparticles is a safe and economically viable prospect, in the current study we report Candida albicans-mediated biological synthesis of gold nanoparticles. Methods and results Transmission electron microscopy, atomic force microscopy, and various spectrophotometric analyses were performed to characterize the gold nanoparticles. The morphology of the synthesized gold particles depended on the abundance of C. albicans cytosolic extract. Transmission electron microscopy, nanophox particle analysis, and atomic force microscopy revealed the size of spherical gold nanoparticles to be in the range of 20–40 nm and nonspherical gold particles were found to be 60–80 nm. We also evaluated the potential of biogenic gold nanoparticles to probe liver cancer cells by conjugating them with liver cancer cell surface-specific antibodies. The antibody-conjugated gold particles were found to bind specifically to the surface antigens of the cancer cells. Conclusion The antibody-conjugated gold particles synthesized in this study could successfully differentiate normal cell populations from cancerous cells. PMID:22072868

On the mechanics of growing thin biological membranes

PubMed Central

Rausch, Manuel K.; Kuhl, Ellen

2013-01-01

Despite their seemingly delicate appearance, thin biological membranes fulfill various crucial roles in the human body and can sustain substantial mechanical loads. Unlike engineering structures, biological membranes are able to grow and adapt to changes in their mechanical environment. Finite element modeling of biological growth holds the potential to better understand the interplay of membrane form and function and to reliably predict the effects of disease or medical intervention. However, standard continuum elements typically fail to represent thin biological membranes efficiently, accurately, and robustly. Moreover, continuum models are typically cumbersome to generate from surface-based medical imaging data. Here we propose a computational model for finite membrane growth using a classical midsurface representation compatible with standard shell elements. By assuming elastic incompressibility and membrane-only growth, the model a priori satisfies the zero-normal stress condition. To demonstrate its modular nature, we implement the membrane growth model into the general-purpose non-linear finite element package Abaqus/Standard using the concept of user subroutines. To probe efficiently and robustness, we simulate selected benchmark examples of growing biological membranes under different loading conditions. To demonstrate the clinical potential, we simulate the functional adaptation of a heart valve leaflet in ischemic cardiomyopathy. We believe that our novel approach will be widely applicable to simulate the adaptive chronic growth of thin biological structures including skin membranes, mucous membranes, fetal membranes, tympanic membranes, corneoscleral membranes, and heart valve membranes. Ultimately, our model can be used to identify diseased states, predict disease evolution, and guide the design of interventional or pharmaceutic therapies to arrest or revert disease progression. PMID:24563551

Deciphering the biological effects of acupuncture treatment modulating multiple metabolism pathways.

PubMed

Zhang, Aihua; Yan, Guangli; Sun, Hui; Cheng, Weiping; Meng, Xiangcai; Liu, Li; Xie, Ning; Wang, Xijun

2016-02-16

Acupuncture is an alternative therapy that is widely used to treat various diseases. However, detailed biological interpretation of the acupuncture stimulations is limited. We here used metabolomics and proteomics technology, thereby identifying the serum small molecular metabolites into the effect and mechanism pathways of standardized acupuncture treatments at 'Zusanli' acupoint which was the most often used acupoint in previous reports. Comprehensive overview of serum metabolic profiles during acupuncture stimulation was investigated. Thirty-four differential metabolites were identified in serum metabolome and associated with ten metabolism pathways. Importantly, we have found that high impact glycerophospholipid metabolism, fatty acid metabolism, ether lipid metabolism were acutely perturbed by acupuncture stimulation. As such, these alterations may be useful to clarify the biological mechanism of acupuncture stimulation. A series of differentially expressed proteins were identified and such effects of acupuncture stimulation were found to play a role in transport, enzymatic activity, signaling pathway or receptor interaction. Pathway analysis further revealed that most of these proteins were found to play a pivotal role in the regulation of multiple metabolism pathways. It demonstrated that the metabolomics coupled with proteomics as a powerful approach for potential applications in understanding the biological effects of acupuncture stimulation.

Using Helicopter Electromagnetic Surveys to Identify Potential Hazards at Mine Waste Impoundments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammack, R.W.

2008-01-01

In July 2003, helicopter electromagnetic surveys were conducted at 14 coal waste impoundments in southern West Virginia. The purpose of the surveys was to detect conditions that could lead to impoundment failure either by structural failure of the embankment or by the flooding of adjacent or underlying mine works. Specifically, the surveys attempted to: 1) identify saturated zones within the mine waste, 2) delineate filtrate flow paths through the embankment or into adjacent strata and receiving streams, and 3) identify flooded mine workings underlying or adjacent to the waste impoundment. Data from the helicopter surveys were processed to generate conductivity/depthmore » images. Conductivity/depth images were then spatially linked to georeferenced air photos or topographic maps for interpretation. Conductivity/depth images were found to provide a snapshot of the hydrologic conditions that exist within the impoundment. This information can be used to predict potential areas of failure within the embankment because of its ability to image the phreatic zone. Also, the electromagnetic survey can identify areas of unconsolidated slurry in the decant basin and beneath the embankment. Although shallow, flooded mineworks beneath the impoundment were identified by this survey, it cannot be assumed that electromagnetic surveys can detect all underlying mines. A preliminary evaluation of the data implies that helicopter electromagnetic surveys can provide a better understanding of the phreatic zone than the piezometer arrays that are typically used.« less

The molecular biology of WHO grade I astrocytomas.

PubMed

Marko, Nicholas F; Weil, Robert J

2012-12-01

World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

Biological risk factors for suicidal behaviors: a meta-analysis

PubMed Central

Chang, B P; Franklin, J C; Ribeiro, J D; Fox, K R; Bentley, K H; Kleiman, E M; Nock, M K

2016-01-01

Prior studies have proposed a wide range of potential biological risk factors for future suicidal behaviors. Although strong evidence exists for biological correlates of suicidal behaviors, it remains unclear if these correlates are also risk factors for suicidal behaviors. We performed a meta-analysis to integrate the existing literature on biological risk factors for suicidal behaviors and to determine their statistical significance. We conducted a systematic search of PubMed, PsycInfo and Google Scholar for studies that used a biological factor to predict either suicide attempt or death by suicide. Inclusion criteria included studies with at least one longitudinal analysis using a biological factor to predict either of these outcomes in any population through 2015. From an initial screen of 2541 studies we identified 94 cases. Random effects models were used for both meta-analyses and meta-regression. The combined effect of biological factors produced statistically significant but relatively weak prediction of suicide attempts (weighted mean odds ratio (wOR)=1.41; CI: 1.09–1.81) and suicide death (wOR=1.28; CI: 1.13–1.45). After accounting for publication bias, prediction was nonsignificant for both suicide attempts and suicide death. Only two factors remained significant after accounting for publication bias—cytokines (wOR=2.87; CI: 1.40–5.93) and low levels of fish oil nutrients (wOR=1.09; CI: 1.01–1.19). Our meta-analysis revealed that currently known biological factors are weak predictors of future suicidal behaviors. This conclusion should be interpreted within the context of the limitations of the existing literature, including long follow-up intervals and a lack of tests of interactions with other risk factors. Future studies addressing these limitations may more effectively test for potential biological risk factors. PMID:27622931

The potential of pathogens as biological control of parthenium weed (Parthenium hysterophorus L.) in Ethiopia.

PubMed

Taye, T; Gossmann, M; Einhorn, G; Büttner, C; Metz, R; Abate, D

2002-01-01

P. hsyterophorus is an exotic invasive annual weed now causing severe infestation in Ethiopia. Studies on diagnosis, incidence and distribution of pathogens associated with parthenium weed in Ethiopia were carried out from 1998-2002. Several fungal isolates were obtained from seed and other parts of parthenium plants. Among them were putative pathogenic fungal species of the genus Helminthosporium, Phoma, Curvularia, Chaetomium, Alternaria, and Fusarium. However, pathogenecity test of the isolates obtained showed no or non-specific symptoms. It was concluded that these pathogens could be opportunistic with insignificant potential for biological control of parthenium. Two most important diseases associated with parthenium were a rust disease, caused by Puccinia abrupta var. partheniicola, and a phyllody disease, caused by a phytoplasma of fababean phyllody (PBP) phytoplasma group. The rust was commonly found in cool mid altitude (1500-2500 m) areas while phyllody was observed in low to mid altitude regions (900-2500 m) of Ethiopia, with a disease incidence up to 100% and 75%, respectively, in some locations. Study of the individual effects of the rust and phyllody diseases under field conditions showed a reduction on weed morphological parameters (plant height, leaf area, and dry matter yield). Parthenium seed production was reduced by 42% and 85% due to rust and phyllody, respectively. Phyllody and rust diseases of parthenium showed significant potential for classical biological control of parthenium after further confirmation of insect vectors that transmit phyllody and host range of phyllody disease to the related economic plants in Ethiopia.

7 CFR 170.6 - How are potential market participants identified for the USDA Farmers Market?

Code of Federal Regulations, 2013 CFR

2013-01-01

... the USDA Farmers Market? 170.6 Section 170.6 Agriculture Regulations of the Department of Agriculture... AGRICULTURE (CONTINUED) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market participants identified for the USDA Farmers Market...

7 CFR 170.6 - How are potential market participants identified for the USDA Farmers Market?

Code of Federal Regulations, 2011 CFR

2011-01-01

... the USDA Farmers Market? 170.6 Section 170.6 Agriculture Regulations of the Department of Agriculture... AGRICULTURE (CONTINUED) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market participants identified for the USDA Farmers Market...

7 CFR 170.6 - How are potential market participants identified for the USDA Farmers Market?

Code of Federal Regulations, 2012 CFR

2012-01-01

... the USDA Farmers Market? 170.6 Section 170.6 Agriculture Regulations of the Department of Agriculture... AGRICULTURE (CONTINUED) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market participants identified for the USDA Farmers Market...

7 CFR 170.6 - How are potential market participants identified for the USDA Farmers Market?

Code of Federal Regulations, 2014 CFR

2014-01-01

... the USDA Farmers Market? 170.6 Section 170.6 Agriculture Regulations of the Department of Agriculture... AGRICULTURE (CONTINUED) MISCELLANEOUS MARKETING PRACTICES UNDER THE AGRICULTURAL MARKETING ACT OF 1946 USDA FARMERS MARKET § 170.6 How are potential market participants identified for the USDA Farmers Market...

Fostering synergy between cell biology and systems biology.

PubMed

Eddy, James A; Funk, Cory C; Price, Nathan D

2015-08-01

In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

The Relative Importance of Spatial Versus Temporal Structure in the Perception of Biological Motion: An Event-Related Potential Study

ERIC Educational Resources Information Center

Hirai, Masahiro; Hiraki, Kazuo

2006-01-01

We investigated how the spatiotemporal structure of animations of biological motion (BM) affects brain activity. We measured event-related potentials (ERPs) during the perception of BM under four conditions: normal spatial and temporal structure; scrambled spatial and normal temporal structure; normal spatial and scrambled temporal structure; and…

The interaction between biology and the management of aquatic macrophytes

USGS Publications Warehouse

Nichols, S.A.

1991-01-01

'Management' refers to controlling nuisance aquatic species and to restoring or restructing aquatic plant communities. Producing stable, diverse, aquatic plant communities containing a high percentage of desirable species is a primary management goal. There are a variety of techniques including harvesting, herbicides, water-level fluctuation, sediment alteration, nutrient limitation, light alteration, and biological controls which can be used for managing macrophytes. These techniques are briefly reviewed along with discussions of biological considerations important to the efficacy of the technique and the environmental impacts of the technique. There is a growing interest in restoring and restructing aquatic plant communities. Techniques for community restoration are discussed as are emerging management technologies using growth regulators and bioengineering. New management technologies will probably be limited by costs and environmental impacts. In the near future, better macrophyte management will come through better planning and more effective use of present technology. The challenge is to make current planning and management techniques more effective through increased biological inputs. The potential for biological input ranges from subcellular biology to species biology, to community and ecosystem biology. Some information needs are identified. ?? 1991.

Proteomics and metabolomics in ageing research: from biomarkers to systems biology

PubMed Central

Hoffman, Jessica M.; Lyu, Yang; Pletcher, Scott D.; Promislow, Daniel E.L.

2017-01-01

Age is the single greatest risk factor for a wide range of diseases, and as the mean age of human populations grows steadily older, the impact of this risk factor grows as well. Laboratory studies on the basic biology of ageing have shed light on numerous genetic pathways that have strong effects on lifespan. However, we still do not know the degree to which the pathways that affect ageing in the lab also influence variation in rates of ageing and age-related disease in human populations. Similarly, despite considerable effort, we have yet to identify reliable and reproducible ‘biomarkers’, which are predictors of one’s biological as opposed to chronological age. One challenge lies in the enormous mechanistic distance between genotype and downstream ageing phenotypes. Here, we consider the power of studying ‘endophenotypes’ in the context of ageing. Endophenotypes are the various molecular domains that exist at intermediate levels of organization between the genotype and phenotype. We focus our attention specifically on proteins and metabolites. Proteomic and metabolomic profiling has the potential to help identify the underlying causal mechanisms that link genotype to phenotype. We present a brief review of proteomics and metabolomics in ageing research with a focus on the potential of a systems biology and network-centric perspective in geroscience. While network analyses to study ageing utilizing proteomics and metabolomics are in their infancy, they may be the powerful model needed to discover underlying biological processes that influence natural variation in ageing, age-related disease, and longevity. PMID:28698311

Kidney disease models: tools to identify mechanisms and potential therapeutic targets

PubMed Central

Bao, Yin-Wu; Yuan, Yuan; Chen, Jiang-Hua; Lin, Wei-Qiang

2018-01-01

Acute kidney injury (AKI) and chronic kidney disease (CKD) are worldwide public health problems affecting millions of people and have rapidly increased in prevalence in recent years. Due to the multiple causes of renal failure, many animal models have been developed to advance our understanding of human nephropathy. Among these experimental models, rodents have been extensively used to enable mechanistic understanding of kidney disease induction and progression, as well as to identify potential targets for therapy. In this review, we discuss AKI models induced by surgical operation and drugs or toxins, as well as a variety of CKD models (mainly genetically modified mouse models). Results from recent and ongoing clinical trials and conceptual advances derived from animal models are also explored. PMID:29515089

Positioning Genomics in Biology Education: Content Mapping of Undergraduate Biology Textbooks†

PubMed Central

Wernick, Naomi L. B.; Ndung’u, Eric; Haughton, Dominique; Ledley, Fred D.

2014-01-01

Biological thought increasingly recognizes the centrality of the genome in constituting and regulating processes ranging from cellular systems to ecology and evolution. In this paper, we ask whether genomics is similarly positioned as a core concept in the instructional sequence for undergraduate biology. Using quantitative methods, we analyzed the order in which core biological concepts were introduced in textbooks for first-year general and human biology. Statistical analysis was performed using self-organizing map algorithms and conventional methods to identify clusters of terms and their relative position in the books. General biology textbooks for both majors and nonmajors introduced genome-related content after text related to cell biology and biological chemistry, but before content describing higher-order biological processes. However, human biology textbooks most often introduced genomic content near the end of the books. These results suggest that genomics is not yet positioned as a core concept in commonly used textbooks for first-year biology and raises questions about whether such textbooks, or courses based on the outline of these textbooks, provide an appropriate foundation for understanding contemporary biological science. PMID:25574293

Positioning genomics in biology education: content mapping of undergraduate biology textbooks.

PubMed

Wernick, Naomi L B; Ndung'u, Eric; Haughton, Dominique; Ledley, Fred D

2014-12-01

Biological thought increasingly recognizes the centrality of the genome in constituting and regulating processes ranging from cellular systems to ecology and evolution. In this paper, we ask whether genomics is similarly positioned as a core concept in the instructional sequence for undergraduate biology. Using quantitative methods, we analyzed the order in which core biological concepts were introduced in textbooks for first-year general and human biology. Statistical analysis was performed using self-organizing map algorithms and conventional methods to identify clusters of terms and their relative position in the books. General biology textbooks for both majors and nonmajors introduced genome-related content after text related to cell biology and biological chemistry, but before content describing higher-order biological processes. However, human biology textbooks most often introduced genomic content near the end of the books. These results suggest that genomics is not yet positioned as a core concept in commonly used textbooks for first-year biology and raises questions about whether such textbooks, or courses based on the outline of these textbooks, provide an appropriate foundation for understanding contemporary biological science.

Long Non-coding RNAs and Their Biological Roles in Plants

PubMed Central

Liu, Xue; Hao, Lili; Li, Dayong; Zhu, Lihuang; Hu, Songnian

2015-01-01

With the development of genomics and bioinformatics, especially the extensive applications of high-throughput sequencing technology, more transcriptional units with little or no protein-coding potential have been discovered. Such RNA molecules are called non-protein-coding RNAs (npcRNAs or ncRNAs). Among them, long npcRNAs or ncRNAs (lnpcRNAs or lncRNAs) represent diverse classes of transcripts longer than 200 nucleotides. In recent years, the lncRNAs have been considered as important regulators in many essential biological processes. In plants, although a large number of lncRNA transcripts have been predicted and identified in few species, our current knowledge of their biological functions is still limited. Here, we have summarized recent studies on their identification, characteristics, classification, bioinformatics, resources, and current exploration of their biological functions in plants. PMID:25936895

Nanoparticle-based biologic mimetics

PubMed Central

Cliffel, David E.; Turner, Brian N.; Huffman, Brian J.

2009-01-01

Centered on solid chemistry foundations, biology and materials science have reached a crossroad where bottom-up designs of new biologically important nanomaterials are a reality. The topics discussed here present the interdisciplinary field of creating biological mimics. Specifically, this discussion focuses on mimics that are developed using various types of metal nanoparticles (particularly gold) through facile synthetic methods. These methods conjugate biologically relevant molecules, e.g., small molecules, peptides, proteins, and carbohydrates, in conformationally favorable orientations on the particle surface. These new products provide stable, safe, and effective substitutes for working with potentially hazardous biologicals for applications such as drug targeting, immunological studies, biosensor development, and biocatalysis. Many standard bioanalytical techniques can be used to characterize and validate the efficacy of these new materials, including quartz crystal microbalance (QCM), surface plasmon resonance (SPR), and enzyme-linked immunosorbent assay (ELISA). Metal nanoparticle–based biomimetics continue to be developed as potential replacements for the native biomolecule in applications of immunoassays and catalysis. PMID:20049778

Biological Characterization of an Improved Pyrrole-Based Colchicine Site Agent Identified through Structure-Based Design

PubMed Central

Rohena, Cristina C.; Telang, Nakul S.; Da, Chenxiao; Risinger, April L.; Sikorski, James A.; Kellogg, Glen E.; Gupton, John T.

2016-01-01

A refined model of the colchicine site on tubulin was used to design an improved analog of the pyrrole parent compound, JG-03-14. The optimized compound, NT-7-16, was evaluated in biological assays that confirm that it has potent activities as a new colchicine site microtubule depolymerizer. NT-7-16 exhibits antiproliferative and cytotoxic activities against multiple cancer cell lines, with IC50 values of 10–16 nM, and it is able to overcome drug resistance mediated by the expression of P-glycoprotein and the βIII isotype of tubulin. NT-7-16 initiated the concentration-dependent loss of cellular microtubules and caused the formation of abnormal mitotic spindles, leading to mitotic accumulation. The direct interaction of NT-7-16 with purified tubulin was confirmed, and it was more potent than combretastatin A-4 in these assays. Binding studies verified that NT-7-16 binds to tubulin within the colchicine site. The antitumor effects of NT-7-16 were evaluated in an MDA-MB-435 xenograft model and it had excellent activity at concentrations that were not toxic. A second compound, NT-9-21, which contains dichloro moieties in place of the 3,5-dibromo substituents of NT-7-16, had a poorer fit within the colchicine site as predicted by modeling and the Hydropathic INTeractions score. Biological evaluations showed that NT-9-21 has 10-fold lower potency than NT-7-16, confirming the modeling predictions. These studies highlight the value of the refined colchicine-site model and identify a new pyrrole-based colchicine-site agent with potent in vitro activities and promising in vivo antitumor actions. PMID:26655304

Incorporating Biological Mass Spectrometry into Undergraduate Teaching Labs, Part 1: Identifying Proteins Based on Molecular Mass

ERIC Educational Resources Information Center

Arnquist, Isaac J.; Beussman, Douglas J.

2007-01-01

Biological mass spectrometry is an important analytical technique in drug discovery, proteomics, and research at the biology-chemistry interface. Currently, few hands-on opportunities exist for undergraduate students to learn about this technique. With the 2002 Nobel Prize being awarded, in part, for the development of biological mass…

Identifying novel drug indications through automated reasoning.

PubMed

Tari, Luis; Vo, Nguyen; Liang, Shanshan; Patel, Jagruti; Baral, Chitta; Cai, James

2012-01-01

With the large amount of pharmacological and biological knowledge available in literature, finding novel drug indications for existing drugs using in silico approaches has become increasingly feasible. Typical literature-based approaches generate new hypotheses in the form of protein-protein interactions networks by means of linking concepts based on their cooccurrences within abstracts. However, this kind of approaches tends to generate too many hypotheses, and identifying new drug indications from large networks can be a time-consuming process. In this work, we developed a method that acquires the necessary facts from literature and knowledge bases, and identifies new drug indications through automated reasoning. This is achieved by encoding the molecular effects caused by drug-target interactions and links to various diseases and drug mechanism as domain knowledge in AnsProlog, a declarative language that is useful for automated reasoning, including reasoning with incomplete information. Unlike other literature-based approaches, our approach is more fine-grained, especially in identifying indirect relationships for drug indications. To evaluate the capability of our approach in inferring novel drug indications, we applied our method to 943 drugs from DrugBank and asked if any of these drugs have potential anti-cancer activities based on information on their targets and molecular interaction types alone. A total of 507 drugs were found to have the potential to be used for cancer treatments. Among the potential anti-cancer drugs, 67 out of 81 drugs (a recall of 82.7%) are indeed known cancer drugs. In addition, 144 out of 289 drugs (a recall of 49.8%) are non-cancer drugs that are currently tested in clinical trials for cancer treatments. These results suggest that our method is able to infer drug indications (original or alternative) based on their molecular targets and interactions alone and has the potential to discover novel drug indications for existing drugs.

Gene expression profile of mouse prostate tumors reveals dysregulations in major biological processes and identifies potential murine targets for preclinical development of human prostate cancer therapy.

PubMed

Haram, Kerstyn M; Peltier, Heidi J; Lu, Bin; Bhasin, Manoj; Otu, Hasan H; Choy, Bob; Regan, Meredith; Libermann, Towia A; Latham, Gary J; Sanda, Martin G; Arredouani, Mohamed S

2008-10-01

Translation of preclinical studies into effective human cancer therapy is hampered by the lack of defined molecular expression patterns in mouse models that correspond to the human counterpart. We sought to generate an open source TRAMP mouse microarray dataset and to use this array to identify differentially expressed genes from human prostate cancer (PCa) that have concordant expression in TRAMP tumors, and thereby represent lead targets for preclinical therapy development. We performed microarrays on total RNA extracted and amplified from eight TRAMP tumors and nine normal prostates. A subset of differentially expressed genes was validated by QRT-PCR. Differentially expressed TRAMP genes were analyzed for concordant expression in publicly available human prostate array datasets and a subset of resulting genes was analyzed by QRT-PCR. Cross-referencing differentially expressed TRAMP genes to public human prostate array datasets revealed 66 genes with concordant expression in mouse and human PCa; 56 between metastases and normal and 10 between primary tumor and normal tissues. Of these 10 genes, two, Sox4 and Tubb2a, were validated by QRT-PCR. Our analysis also revealed various dysregulations in major biologic pathways in the TRAMP prostates. We report a TRAMP microarray dataset of which a gene subset was validated by QRT-PCR with expression patterns consistent with previous gene-specific TRAMP studies. Concordance analysis between TRAMP and human PCa associated genes supports the utility of the model and suggests several novel molecular targets for preclinical therapy.

An inexpensive, temporally-integrated system for monitoring occurrence and biological effects of contaminants in the field

EPA Science Inventory

Assessing potential biological impacts of complex mixtures of contaminants in aquatic environments is an ongoing challenge for ecotoxicologists. Instrumental analysis of site waters alone can identify contaminants but provides only limited insights as to possible adverse effects...

Importance of biological systems in industrial waste treatment potential application to the space station

NASA Technical Reports Server (NTRS)

Revis, Nathaniel; Holdsworth, George

1990-01-01

In addition to having applications for waste management issues on planet Earth, microbial systems have application in reducing waste volumes aboard spacecraft. A candidate for such an application is the space station. Many of the planned experiments generate aqueous waste. To recycle air and water the contaminants from previous experiments must be removed before the air and water can be used for other experiments. This can be achieved using microorganisms in a bioreactor. Potential bioreactors (inorganics, organics, and etchants) are discussed. Current technologies that may be applied to waste treatment are described. Examples of how biological systems may be used in treating waste on the space station.

A living foundry for Synthetic Biological Materials: A synthetic biology roadmap to new advanced materials.

PubMed

Le Feuvre, Rosalind A; Scrutton, Nigel S

2018-06-01

Society is on the cusp of harnessing recent advances in synthetic biology to discover new bio-based products and routes to their affordable and sustainable manufacture. This is no more evident than in the discovery and manufacture of Synthetic Biological Materials , where synthetic biology has the capacity to usher in a new Materials from Biology era that will revolutionise the discovery and manufacture of innovative synthetic biological materials. These will encompass novel, smart, functionalised and hybrid materials for diverse applications whose discovery and routes to bio-production will be stimulated by the fusion of new technologies positioned across physical, digital and biological spheres. This article, which developed from an international workshop held in Manchester, United Kingdom, in 2017 [1], sets out to identify opportunities in the new materials from biology era. It considers requirements, early understanding and foresight of the challenges faced in delivering a Discovery to Manufacturing Pipeline for synthetic biological materials using synthetic biology approaches. This challenge spans the complete production cycle from intelligent and predictive design, fabrication, evaluation and production of synthetic biological materials to new ways of bringing these products to market. Pathway opportunities are identified that will help foster expertise sharing and infrastructure development to accelerate the delivery of a new generation of synthetic biological materials and the leveraging of existing investments in synthetic biology and advanced materials research to achieve this goal.

Exploring the MACH Model’s Potential as a Metacognitive Tool to Help Undergraduate Students Monitor Their Explanations of Biological Mechanisms

PubMed Central

Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

2016-01-01

When undergraduate biology students learn to explain biological mechanisms, they face many challenges and may overestimate their understanding of living systems. Previously, we developed the MACH model of four components used by expert biologists to explain mechanisms: Methods, Analogies, Context, and How. This study explores the implementation of the model in an undergraduate biology classroom as an educational tool to address some of the known challenges. To find out how well students’ written explanations represent components of the MACH model before and after they were taught about it and why students think the MACH model was useful, we conducted an exploratory multiple case study with four interview participants. We characterize how two students explained biological mechanisms before and after a teaching intervention that used the MACH components. Inductive analysis of written explanations and interviews showed that MACH acted as an effective metacognitive tool for all four students by helping them to monitor their understanding, communicate explanations, and identify explanatory gaps. Further research, though, is needed to more fully substantiate the general usefulness of MACH for promoting students’ metacognition about their understanding of biological mechanisms. PMID:27252295

Probing the Potential of Neutron Imaging for Biomedical and Biological Applications

NASA Astrophysics Data System (ADS)

Watkin, K. L.; Bilheux, H. Z.; Ankner, J. F.

Neutron imaging of biological specimens began soon after the discovery of the neutron by Chadwick in 1932. The first samples included tumors in tissues, internal organs in rats, and bones. These studies mainly employed thermal neutrons and were often compared with X-ray images of the same or equivalent samples. Although neutron scattering is widely used in biological studies, neutron imaging has yet to be exploited to its full capability in this area. This chapter summarizes past and current research efforts to apply neutron radiography to the study of biological specimens, in the expectation that clinical and medical research, as well as forensic science, may benefit from it.

The Health Informatics Trial Enhancement Project (HITE): Using routinely collected primary care data to identify potential participants for a depression trial

PubMed Central

2010-01-01

Background Recruitment to clinical trials can be challenging. We identified anonymous potential participants to an existing pragmatic randomised controlled depression trial to assess the feasibility of using routinely collected data to identify potential trial participants. We discuss the strengths and limitations of this approach, assess its potential value, report challenges and ethical issues encountered. Methods Swansea University's Health Information Research Unit's Secure Anonymised Information Linkage (SAIL) database of routinely collected health records was interrogated, using Structured Query Language (SQL). Read codes were used to create an algorithm of inclusion/exclusion criteria with which to identify suitable anonymous participants. Two independent clinicians rated the eligibility of the potential participants' identified. Inter-rater reliability was assessed using the kappa statistic and inter-class correlation. Results The study population (N = 37263) comprised all adults registered at five general practices in Swansea UK. Using the algorithm 867 anonymous potential participants were identified. The sensitivity and specificity results > 0.9 suggested a high degree of accuracy from the algorithm. The inter-rater reliability results indicated strong agreement between the confirming raters. The Intra Class Correlation Coefficient (Cronbach's Alpha) > 0.9, suggested excellent agreement and Kappa coefficient > 0.8; almost perfect agreement. Conclusions This proof of concept study showed that routinely collected primary care data can be used to identify potential participants for a pragmatic randomised controlled trial of folate augmentation of antidepressant therapy for the treatment of depression. Further work will be needed to assess generalisability to other conditions and settings and the inclusion of this approach to support Electronic Enhanced Recruitment (EER). PMID:20398303

Frontiers of optofluidics in synthetic biology.

PubMed

Tan, Cheemeng; Lo, Shih-Jie; LeDuc, Philip R; Cheng, Chao-Min

2012-10-07

The development of optofluidic-based technology has ushered in a new era of lab-on-a-chip functionality, including miniaturization of biomedical devices, enhanced sensitivity for molecular detection, and multiplexing of optical measurements. While having great potential, optofluidic devices have only begun to be exploited in many biotechnological applications. Here, we highlight the potential of integrating optofluidic devices with synthetic biological systems, which is a field focusing on creating novel cellular systems by engineering synthetic gene and protein networks. First, we review the development of synthetic biology at different length scales, ranging from single-molecule, single-cell, to cellular population. We emphasize light-sensitive synthetic biological systems that would be relevant for the integration with optofluidic devices. Next, we propose several areas for potential applications of optofluidics in synthetic biology. The integration of optofluidics and synthetic biology would have a broad impact on point-of-care diagnostics and biotechnology.

Identifying and Inactivating Bacterial Spores

NASA Technical Reports Server (NTRS)

Newcombe, David; Dekas, Anne; Venkateswaran, Kasthuri

2009-01-01

Problems associated with, and new strategies for, inactivating resistant organisms like Bacillus canaveralius (found at Kennedy Space Center during a survey of three NASA cleanrooms) have been defined. Identifying the particular component of the spore that allows its heightened resistance can guide the development of sterilization procedures that are targeted to the specific molecules responsible for resistance, while avoiding using unduly harsh methods that jeopardize equipment. The key element of spore resistance is a multilayered protein shell that encases the spore called the spore coat. The coat of the best-studied spore-forming microbe, B. subtilis, consists of at least 45 proteins, most of which are poorly characterized. Several protective roles for the coat are well characterized including resistance to desiccation, large toxic molecules, ortho-phthalaldehyde, and ultraviolet (UV) radiation. One important long-term specific goal is an improved sterilization procedure that will enable NASA to meet planetary protection requirements without a terminal heat sterilization step. This would support the implementation of planetary protection policies for life-detection missions. Typically, hospitals and government agencies use biological indicators to ensure the quality control of sterilization processes. The spores of B. canaveralius that are more resistant to osmotic stress would serve as a better biological indicator for potential survival than those in use currently.

Identifying, studying and making good use of macromolecular crystals

PubMed Central

Calero, Guillermo; Cohen, Aina E.; Luft, Joseph R.; Newman, Janet; Snell, Edward H.

2014-01-01

Structural biology has contributed tremendous knowledge to the understanding of life on the molecular scale. The Protein Data Bank, a depository of this structural knowledge, currently contains over 100 000 protein structures, with the majority stemming from X-ray crystallography. As the name might suggest, crystallography requires crystals. As detectors become more sensitive and X-ray sources more intense, the notion of a crystal is gradually changing from one large enough to embellish expensive jewellery to objects that have external dimensions of the order of the wavelength of visible light. Identifying these crystals is a prerequisite to their study. This paper discusses developments in identifying these crystals during crystallization screening and distinguishing them from other potential outcomes. The practical aspects of ensuring that once a crystal is identified it can then be positioned in the X-ray beam for data collection are also addressed. PMID:25084371

National variety trials identify clones with high potential

USDA-ARS?s Scientific Manuscript database

Quality potato varieties are the backbone of a strong potato industry. Variety trials have been used to identify promising new varieties for well over a century. Trials are repeated and information collected over many years in order to confidently identify lines that may be well suited for productio...

Omen: identifying potential spear-phishing targets before the email is sent.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wendt, Jeremy Daniel.

2013-07-01

We present the results of a two year project focused on a common social engineering attack method called "spear phishing". In a spear phishing attack, the user receives an email with information specifically focused on the user. This email contains either a malware-laced attachment or a link to download the malware that has been disguised as a useful program. Spear phishing attacks have been one of the most effective avenues for attackers to gain initial entry into a target network. This project focused on a proactive approach to spear phishing. To create an effective, user-specific spear phishing email, the attackermore » must research the intended recipient. We believe that much of the information used by the attacker is provided by the target organization's own external website. Thus when researching potential targets, the attacker leaves signs of his research in the webserver's logs. We created tools and visualizations to improve cybersecurity analysts' abilities to quickly understand a visitor's visit patterns and interests. Given these suspicious visitors and log-parsing tools, analysts can more quickly identify truly suspicious visitors, search for potential spear-phishing targeted users, and improve security around those users before the spear phishing email is sent.« less

Toward University Modeling Instruction—Biology: Adapting Curricular Frameworks from Physics to Biology

PubMed Central

Manthey, Seth; Brewe, Eric

2013-01-01

University Modeling Instruction (UMI) is an approach to curriculum and pedagogy that focuses instruction on engaging students in building, validating, and deploying scientific models. Modeling Instruction has been successfully implemented in both high school and university physics courses. Studies within the physics education research (PER) community have identified UMI's positive impacts on learning gains, equity, attitudinal shifts, and self-efficacy. While the success of this pedagogical approach has been recognized within the physics community, the use of models and modeling practices is still being developed for biology. Drawing from the existing research on UMI in physics, we describe the theoretical foundations of UMI and how UMI can be adapted to include an emphasis on models and modeling for undergraduate introductory biology courses. In particular, we discuss our ongoing work to develop a framework for the first semester of a two-semester introductory biology course sequence by identifying the essential basic models for an introductory biology course sequence. PMID:23737628

Toward university modeling instruction--biology: adapting curricular frameworks from physics to biology.

PubMed

Manthey, Seth; Brewe, Eric

2013-06-01

University Modeling Instruction (UMI) is an approach to curriculum and pedagogy that focuses instruction on engaging students in building, validating, and deploying scientific models. Modeling Instruction has been successfully implemented in both high school and university physics courses. Studies within the physics education research (PER) community have identified UMI's positive impacts on learning gains, equity, attitudinal shifts, and self-efficacy. While the success of this pedagogical approach has been recognized within the physics community, the use of models and modeling practices is still being developed for biology. Drawing from the existing research on UMI in physics, we describe the theoretical foundations of UMI and how UMI can be adapted to include an emphasis on models and modeling for undergraduate introductory biology courses. In particular, we discuss our ongoing work to develop a framework for the first semester of a two-semester introductory biology course sequence by identifying the essential basic models for an introductory biology course sequence.

Marine molecular biology: an emerging field of biological sciences.

PubMed

Thakur, Narsinh L; Jain, Roopesh; Natalio, Filipe; Hamer, Bojan; Thakur, Archana N; Müller, Werner E G

2008-01-01

An appreciation of the potential applications of molecular biology is of growing importance in many areas of life sciences, including marine biology. During the past two decades, the development of sophisticated molecular technologies and instruments for biomedical research has resulted in significant advances in the biological sciences. However, the value of molecular techniques for addressing problems in marine biology has only recently begun to be cherished. It has been proven that the exploitation of molecular biological techniques will allow difficult research questions about marine organisms and ocean processes to be addressed. Marine molecular biology is a discipline, which strives to define and solve the problems regarding the sustainable exploration of marine life for human health and welfare, through the cooperation between scientists working in marine biology, molecular biology, microbiology and chemistry disciplines. Several success stories of the applications of molecular techniques in the field of marine biology are guiding further research in this area. In this review different molecular techniques are discussed, which have application in marine microbiology, marine invertebrate biology, marine ecology, marine natural products, material sciences, fisheries, conservation and bio-invasion etc. In summary, if marine biologists and molecular biologists continue to work towards strong partnership during the next decade and recognize intellectual and technological advantages and benefits of such partnership, an exciting new frontier of marine molecular biology will emerge in the future.

Biological effects of space radiation and development of effective countermeasures

NASA Astrophysics Data System (ADS)

Kennedy, Ann R.

2014-04-01

As part of a program to assess the adverse biological effects expected from astronauts' exposure to space radiation, numerous different biological effects relating to astronauts' health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronauts' vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation.

TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, I.

2016-06-15

Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews ofmore » some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.« less

Application of near infrared reflectance (NIR) spectroscopy to identify potential PSE meat.

PubMed

Li, Xiao; Feng, Fang; Gao, Runze; Wang, Lu; Qian, Ye; Li, Chunbao; Zhou, Guanghong

2016-07-01

Pale, soft and exudative (PSE) meat is a quality problem that causes a large economic loss to the pork industry. In the present work, near infrared (NIR) quantification and identification methods were used to investigate the feasibility of differentiating potential PSE meat from normal meat. NIR quantification models were developed to estimate meat pH and colour attributes (L*, a*, b*). Promising results were reported for prediction of muscle pH (R(2) CV  = 70.10%, RPDCV = 1.83) and L* (R(2) CV  = 77.18%, RPDCV = 1.91), but it is still hard to promote to practical application at this level. The Factorisation Method applied to NIR spectra could differentiate potential PSE meat from normal meat at 3 h post-mortem. Correlation analysis showed significant relationship between NIR data and LF-NMR T2 components that were indicative of water distribution and mobility in muscle. PSE meat had unconventionally faster energy metabolism than normal meat, which caused greater water mobility. NIR spectra coupled with the Factorisation Method could be a promising technology to identify potential PSE meat. The difference in the intensity of H2 O absorbance peaks between PSE and normal meat might be the basis of this identification method. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

An Australasian model license reassessment procedure for identifying potentially unsafe drivers.

PubMed

Fildes, Brian N; Charlton, Judith; Pronk, Nicola; Langford, Jim; Oxley, Jennie; Koppel, Sjaanie

2008-08-01

Most licensing jurisdictions in Australia currently employ age-based assessment programs as a means to manage older driver safety, yet available evidence suggests that these programs have no safety benefits. This paper describes a community referral-based model license re assessment procedure for identifying and assessing potentially unsafe drivers. While the model was primarily developed for assessing older driver fitness to drive, it could be applicable to other forms of driver impairment associated with increased crash risk. It includes a three-tier process of assessment, involving the use of validated and relevant assessment instruments. A case is argued that this process is a more systematic, transparent and effective process for managing older driver safety and thus more likely to be widely acceptable to the target community and licensing authorities than age-based practices.

The potential for biologically catalyzed anaerobic methane oxidation on ancient Mars.

PubMed

Marlow, Jeffrey J; Larowe, Douglas E; Ehlmann, Bethany L; Amend, Jan P; Orphan, Victoria J

2014-04-01

This study examines the potential for the biologically mediated anaerobic oxidation of methane (AOM) coupled to sulfate reduction on ancient Mars. Seven distinct fluids representative of putative martian groundwater were used to calculate Gibbs energy values in the presence of dissolved methane under a range of atmospheric CO2 partial pressures. In all scenarios, AOM is exergonic, ranging from -31 to -135 kJ/mol CH4. A reaction transport model was constructed to examine how environmentally relevant parameters such as advection velocity, reactant concentrations, and biomass production rate affect the spatial and temporal dependences of AOM reaction rates. Two geologically supported models for ancient martian AOM are presented: a sulfate-rich groundwater with methane produced from serpentinization by-products, and acid-sulfate fluids with methane from basalt alteration. The simulations presented in this study indicate that AOM could have been a feasible metabolism on ancient Mars, and fossil or isotopic evidence of this metabolic pathway may persist beneath the surface and in surface exposures of eroded ancient terrains.

Rapid, Potentially Automatable, Method Extract Biomarkers for HPLC/ESI/MS/MS to Detect and Identify BW Agents

DTIC Science & Technology

1997-11-01

status can sometimes be reflected in the infectious potential or drug resistance of those pathogens. For example, in Mycobacterium tuberculosis ... Mycobacterium tuberculosis , its antibiotic resistance and prediction of pathogenicity amongst Mycobacterium spp. based on signature lipid biomarkers ...TITLE AND SUBTITLE Rapid, Potentially Automatable, Method Extract Biomarkers for HPLC/ESI/MS/MS to Detect and Identify BW Agents 5a. CONTRACT NUMBER 5b

An inexpensive, temporally-integrated system for monitoring occurrence and biological effects of aquatic contaminants in the field

EPA Science Inventory

Assessment of potential ecological risks of complex contaminant mixtures in the environment requires integrated chemical and biological approaches. Instrumental analysis of environmental samples alone can identify contaminants, but provides only limited insights as to possible a...

Chlorella zofingiensis as an Alternative Microalgal Producer of Astaxanthin: Biology and Industrial Potential

PubMed Central

Liu, Jin; Sun, Zheng; Gerken, Henri; Liu, Zheng; Jiang, Yue; Chen, Feng

2014-01-01

Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione), a high-value ketocarotenoid with a broad range of applications in food, feed, nutraceutical, and pharmaceutical industries, has been gaining great attention from science and the public in recent years. The green microalgae Haematococcus pluvialis and Chlorella zofingiensis represent the most promising producers of natural astaxanthin. Although H. pluvialis possesses the highest intracellular astaxanthin content and is now believed to be a good producer of astaxanthin, it has intrinsic shortcomings such as slow growth rate, low biomass yield, and a high light requirement. In contrast, C. zofingiensis grows fast phototrophically, heterotrophically and mixtrophically, is easy to be cultured and scaled up both indoors and outdoors, and can achieve ultrahigh cell densities. These robust biotechnological traits provide C. zofingiensis with high potential to be a better organism than H. pluvialis for mass astaxanthin production. This review aims to provide an overview of the biology and industrial potential of C. zofingiensis as an alternative astaxanthin producer. The path forward for further expansion of the astaxanthin production from C. zofingiensis with respect to both challenges and opportunities is also discussed. PMID:24918452

Host Specificity of Epiplema albida: A Potential Biological Control Agent for Sri Lankan Privet in the Mascarene Islands

PubMed Central

Shaw, Richard H.

2017-01-01

Epiplema albida (Hampson) (Lepidoptera: Uraniidae, Epipleminae) from Sri Lanka, was studied to assess its safety for use as a biological control agent for Sri Lankan privet, Ligustrum robustum subsp. walkeri (Oleaceae) in La Réunion and other Mascarene Islands. Larval no-choice feeding tests using newly hatched larvae, larval development tests, and multiple choice oviposition tests were used. Adult females of E. albida are shown to have highly selective oviposition behaviour and the species is physiologically restricted to very few hosts for feeding and development. The risk to key test plants in La Réunion is minimal, so this species can be considered for use as a biological control agent there, but would need further evaluation for potential use elsewhere. PMID:28788086

Biologics in pediatric psoriasis - efficacy and safety.

PubMed

Dogra, Sunil; Mahajan, Rahul

2018-01-01

Childhood psoriasis is a special situation that is a management challenge for the treating dermatologist. As is the situation with traditional systemic agents, which are commonly used in managing severe psoriasis in children, the biologics are being increasingly used in the recalcitrant disease despite limited data on long term safety. Areas covered: We performed an extensive literature search to collect evidence-based data on the use of biologics in pediatric psoriasis. The relevant literature published from 2000 to September 2017 was obtained from PubMed, using the MeSH words 'biologics', 'biologic response modifiers' and 'treatment of pediatric/childhood psoriasis'. All clinical trials, randomized double-blind or single-blind controlled trials, open-label studies, retrospective studies, reviews, case reports and letters concerning the use of biologics in pediatric psoriasis were screened. Articles covering the use of biologics in pediatric psoriasis were screened and reference lists in the selected articles were scrutinized to identify other relevant articles that had not been found in the initial search. Articles without relevant information about biologics in general (e.g. its mechanism of action, pharmacokinetics and adverse effects) and its use in psoriasis in particular were excluded. We screened 427 articles and finally selected 41 relevant articles. Expert opinion: The available literature on the use of biologics such as anti-tumor necrosis factor (TNF)-α agents, and anti-IL-12/23 agents like ustekinumab suggests that these are effective and safe in managing severe pediatric psoriasis although there is an urgent need to generate more safety data. Dermatologists must be careful about the potential adverse effects of the biologics before administering them to children with psoriasis. It is likely that with rapidly evolving scenario of biologics in psoriasis, these will prove to be very useful molecules particularly in managing severe and recalcitrant

Biological aspects of chondrosarcoma: Leaps and hurdles.

PubMed

Mery, Benoîte; Espenel, Sophie; Guy, Jean-Baptiste; Rancoule, Chloé; Vallard, Alexis; Aloy, Marie-Thérèse; Rodriguez-Lafrasse, Claire; Magné, Nicolas

2018-06-01

Chondrosarcomas are characterized by their chemo- and radioresistance leading to a therapeutic surgical approach which remains the only available treatment with a 10-year survival between 30% and 80% depending on the grade. Non-surgical treatments are under investigation and rely on an accurate biological understanding of drug resistance mechanisms. Novel targeted therapy which represents a new relevant therapeutic approach will open new treatment options by targeting several pathways responsible for processes of proliferation and invasion. Survival pathways such as PI3K, AKT, mTOR and VEGF have been shown to be involved in proliferation of chondrosarcoma cells and antiapoptotic proteins may also play a relevant role. Other proteins such as p53 or COX2 have been identified as potential new targets. This review provides an insight into the biological substantial treatment challenges of CHS and focuses on improving our understanding of CH biology through an overview of major signaling pathways that could represent targets for new therapeutic approaches. Copyright © 2018 Elsevier B.V. All rights reserved.

Identifiability Results for Several Classes of Linear Compartment Models.

PubMed

Meshkat, Nicolette; Sullivant, Seth; Eisenberg, Marisa

2015-08-01

Identifiability concerns finding which unknown parameters of a model can be estimated, uniquely or otherwise, from given input-output data. If some subset of the parameters of a model cannot be determined given input-output data, then we say the model is unidentifiable. In this work, we study linear compartment models, which are a class of biological models commonly used in pharmacokinetics, physiology, and ecology. In past work, we used commutative algebra and graph theory to identify a class of linear compartment models that we call identifiable cycle models, which are unidentifiable but have the simplest possible identifiable functions (so-called monomial cycles). Here we show how to modify identifiable cycle models by adding inputs, adding outputs, or removing leaks, in such a way that we obtain an identifiable model. We also prove a constructive result on how to combine identifiable models, each corresponding to strongly connected graphs, into a larger identifiable model. We apply these theoretical results to several real-world biological models from physiology, cell biology, and ecology.

Invertebrate-Based Water Quality Impairments and Associated Stressors Identified through the US Clean Water Act

NASA Astrophysics Data System (ADS)

Govenor, Heather; Krometis, Leigh Anne H.; Hession, W. Cully

2017-10-01

Macroinvertebrate community assessment is used in most US states to evaluate stream health under the Clean Water Act. While water quality assessment and impairment determinations are reported to the US Environmental Protection Agency, there is no national summary of biological assessment findings. The objective of this work was to determine the national extent of invertebrate-based impairments and to identify pollutants primarily responsible for those impairments. Evaluation of state data in the US Environmental Protection Agency's Assessment and Total Maximum Daily Load Tracking and Implementation System database revealed considerable differences in reporting approaches and terminologies including differences in if and how states report specific biological assessment findings. Only 15% of waters impaired for aquatic life could be identified as having impairments determined by biological assessments (e.g., invertebrates, fish, periphyton); approximately one-third of these were associated with macroinvertebrate bioassessment. Nearly 650 invertebrate-impaired waters were identified nationwide, and sediment was the most common pollutant in bedded (63%) and suspended (9%) forms. This finding is not unexpected, given previous work on the negative impacts of sediment on aquatic life, and highlights the need to more specifically identify the mechanisms driving sediment impairments in order to design effective remediation plans. It also reinforces the importance of efforts to derive sediment-specific biological indices and numerical sediment quality guidelines. Standardization of state reporting approaches and terminology would significantly increase the potential application of water quality assessment data, reveal national trends, and encourage sharing of best practices to facilitate the attainment of water quality goals.

Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination.

PubMed

Kurashige, Junji; Hasegawa, Takanori; Niida, Atsushi; Sugimachi, Keishi; Deng, Niantao; Mima, Kosuke; Uchi, Ryutaro; Sawada, Genta; Takahashi, Yusuke; Eguchi, Hidetoshi; Inomata, Masashi; Kitano, Seigo; Fukagawa, Takeo; Sasako, Mitsuru; Sasaki, Hiroki; Sasaki, Shin; Mori, Masaki; Yanagihara, Kazuyoshi; Baba, Hideo; Miyano, Satoru; Tan, Patrick; Mimori, Koshi

2016-03-03

Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination.

Exploration of potential biomarkers and related biological pathways for PCB exposure in maternal and cord serum: A pilot birth cohort study in Chiba, Japan.

PubMed

Eguchi, Akifumi; Sakurai, Kenichi; Watanabe, Masahiro; Mori, Chisato

2017-05-01

Polychlorinated biphenyls (PCBs) have been associated with adverse human reproductive and fetal developmental measures or outcomes because of their endocrine-disrupting effects; however, the biological mechanisms of adverse effects of PCB exposure in humans are not currently well established. In this study, we aimed to identify the biological pathways and potential biomarkers of PCB exposure in maternal and umbilical cord serum using a hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) metabolomics platform. The median concentration of total PCBs in maternal (n=93) and cord serum (n=93) were 350 and 70pgg -1 wet wt, respectively. PCB levels in maternal and fetal serum from the Chiba Study of Mother and Children's Health (C-MACH) cohort are comparable to those of earlier cohort studies conducted in Japan, the USA, and European countries. We used the random forest model with the metabolome profile to predict exposure levels of PCB (first quartile [Q1] and fourth quartile [Q4]) for pregnant women and fetuses. In the prediction model for classification of Q1 versus Q4 (area-under-curve [AUC]: pregnant women=0.812 and fetuses=0.919), citraconic acid level in maternal serum and ethanolamine, p-hydroxybenzoate, and purine levels in cord serum had >0.70 AUC values. These candidate biomarkers and metabolite included in composited models were related to glutathione and amino acid metabolism in maternal serum and the amino acid metabolism and ubiquinone and other terpenoid-quinone biosynthesis in cord serum (FDR <0.10), indicating disruption of metabolic pathways by PCB exposure in pregnant women and fetuses. These results showed that metabolome analysis might be useful to explore potential biomarkers and related biological pathways for PCB exposure. Thus, more detailed studies are needed to verify sensitivity of the biomarkers and clarify the biochemical changes resulting from PCB exposure. Copyright © 2017 The Authors. Published by Elsevier Ltd

IDENTIFICATION OF BIOLOGICALLY RELEVANT GENES USING A DATABASE OF RAT LIVER AND KIDNEY BASELINE GENE EXPRESSION

EPA Science Inventory

Microarray data from independent labs and studies can be compared to potentially identify toxicologically and biologically relevant genes. The Baseline Animal Database working group of HESI was formed to assess baseline gene expression from microarray data derived from control or...

A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.

PubMed

Zang, Yong; Lee, J Jack

2017-01-15

We propose a robust two-stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet-multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three-dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose-efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose-toxicity and dose-efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Women are underrepresented in computational biology: An analysis of the scholarly literature in biology, computer science and computational biology.

PubMed

Bonham, Kevin S; Stefan, Melanie I

2017-10-01

While women are generally underrepresented in STEM fields, there are noticeable differences between fields. For instance, the gender ratio in biology is more balanced than in computer science. We were interested in how this difference is reflected in the interdisciplinary field of computational/quantitative biology. To this end, we examined the proportion of female authors in publications from the PubMed and arXiv databases. There are fewer female authors on research papers in computational biology, as compared to biology in general. This is true across authorship position, year, and journal impact factor. A comparison with arXiv shows that quantitative biology papers have a higher ratio of female authors than computer science papers, placing computational biology in between its two parent fields in terms of gender representation. Both in biology and in computational biology, a female last author increases the probability of other authors on the paper being female, pointing to a potential role of female PIs in influencing the gender balance.

Women are underrepresented in computational biology: An analysis of the scholarly literature in biology, computer science and computational biology

PubMed Central

2017-01-01

While women are generally underrepresented in STEM fields, there are noticeable differences between fields. For instance, the gender ratio in biology is more balanced than in computer science. We were interested in how this difference is reflected in the interdisciplinary field of computational/quantitative biology. To this end, we examined the proportion of female authors in publications from the PubMed and arXiv databases. There are fewer female authors on research papers in computational biology, as compared to biology in general. This is true across authorship position, year, and journal impact factor. A comparison with arXiv shows that quantitative biology papers have a higher ratio of female authors than computer science papers, placing computational biology in between its two parent fields in terms of gender representation. Both in biology and in computational biology, a female last author increases the probability of other authors on the paper being female, pointing to a potential role of female PIs in influencing the gender balance. PMID:29023441

[Cybernetics and biology].

PubMed

Vasil'ev, G F

2013-01-01

Owing to methodical disadvantages, the theory of control still lacks the potential for the analysis of biological systems. To get the full benefit of the method in addition to the algorithmic model of control (as of today the only used model in the theory of control) a parametric model of control is offered to employ. The reasoning for it is explained. The approach suggested provides the possibility to use all potential of the modern theory of control for the analysis of biological systems. The cybernetic approach is shown taking a system of the rise of glucose concentration in blood as an example.

The biology of small, introduced populations, with special reference to biological control

PubMed Central

Fauvergue, Xavier; Vercken, Elodie; Malausa, Thibaut; Hufbauer, Ruth A

2012-01-01

Populations are introduced into novel environments in different contexts, one being the biological control of pests. Despite intense efforts, less than half introduced biological control agents establish. Among the possible approaches to improve biological control, one is to better understand the processes that underpin introductions and contribute to ecological and evolutionary success. In this perspective, we first review the demographic and genetic processes at play in small populations, be they stochastic or deterministic. We discuss the theoretical outcomes of these different processes with respect to individual fitness, population growth rate, and establishment probability. Predicted outcomes differ subtly in some cases, but enough so that the evaluating results of introductions have the potential to reveal which processes play important roles in introduced populations. Second, we attempt to link the theory we have discussed with empirical data from biological control introductions. A main result is that there are few available data, but we nonetheless report on an increasing number of well-designed, theory-driven, experimental approaches. Combining demography and genetics from both theoretical and empirical perspectives highlights novel and exciting avenues for research on the biology of small, introduced populations, and great potential for improving both our understanding and practice of biological control. PMID:22949919

An inexpensive, temporally-integrated system for monitoring occurrence and biological effects of contaminants in the field (Poster)

EPA Science Inventory

Assessing potential biological impacts of complex mixtures of contaminants in aquatic environments is an ongoing challenge for ecotoxicologists. Instrumental analysis of site waters alone can identify contaminants but provides only limited insights as to possible adverse effects...

SiC nanoparticles as potential carriers for biologically active substances

NASA Astrophysics Data System (ADS)

Guevara-Lora, Ibeth; Czosnek, Cezary; Smycz, Aleksandra; Janik, Jerzy F.; Kozik, Andrzej

2009-01-01

Silicon carbide SiC thanks to its many advantageous properties has found numerous applications in diverse areas of technology. In this regard, its nanosized forms often with novel properties have been the subject of intense research in recent years. The aim of this study was to investigate the binding of biologically active substances onto SiC nanopowders as a new approach to biomolecule immobilization in terms of their prospective applications in medicine or for biochemical detection. The SiC nanoparticles were prepared by a two-stage aerosol-assisted synthesis from neat hexamethyldisiloxane. The binding of several proteins (bovine serum albumin, high molecular weight kininogen, immunoglobulin G) on SiC particle surfaces was demonstrated at the levels of 1-2 nanograms per mg of SiC. These values were found to significantly increase after suitable chemical modifications of nanoparticle surfaces (by carbodiimide or 3-aminopropyltrietoxysilane treatment). The study of SiC biocompatibility showed a lack of cytotoxicity against macrophages-like cells below the concentration of 1 mg nanoparticles per mL. In summary, we demonstrated the successful immobilization of the selected substances on the SiC nanoparticles. These results including the cytotoxicity study make nano-SiC highly attractive for potential applications in medicine, biotechnology or molecular detection.

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology.

PubMed

Neumann, Heinz; Neumann-Staubitz, Petra

2010-06-01

Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology.

Identifying associations between pig pathologies using a multi-dimensional machine learning methodology.

PubMed

Sanchez-Vazquez, Manuel J; Nielen, Mirjam; Edwards, Sandra A; Gunn, George J; Lewis, Fraser I

2012-08-31

Abattoir detected pathologies are of crucial importance to both pig production and food safety. Usually, more than one pathology coexist in a pig herd although it often remains unknown how these different pathologies interrelate to each other. Identification of the associations between different pathologies may facilitate an improved understanding of their underlying biological linkage, and support the veterinarians in encouraging control strategies aimed at reducing the prevalence of not just one, but two or more conditions simultaneously. Multi-dimensional machine learning methodology was used to identify associations between ten typical pathologies in 6485 batches of slaughtered finishing pigs, assisting the comprehension of their biological association. Pathologies potentially associated with septicaemia (e.g. pericarditis, peritonitis) appear interrelated, suggesting on-going bacterial challenges by pathogens such as Haemophilus parasuis and Streptococcus suis. Furthermore, hepatic scarring appears interrelated with both milk spot livers (Ascaris suum) and bacteria-related pathologies, suggesting a potential multi-pathogen nature for this pathology. The application of novel multi-dimensional machine learning methodology provided new insights into how typical pig pathologies are potentially interrelated at batch level. The methodology presented is a powerful exploratory tool to generate hypotheses, applicable to a wide range of studies in veterinary research.

Biological Antioxidant Potential Negatively Correlates With Carotid Artery Intima-Media Thickness.

PubMed

Yagi, Hideki; Sumino, Hiroyuki; Yoshida, Kensuke; Aoki, Tomoyuki; Tsunekawa, Katsuhiko; Araki, Osamu; Kimura, Takao; Nara, Makoto; Nakajima, Katsuyuki; Murakami, Masami

2016-01-01

Oxidative stress is a crucial factor in the pathogenesis and development of cardiovascular disease. Recently, simplified methods for the detection of reactive oxygen species (ROS) using the derivatives of reactive oxygen metabolites (d-ROMs) test as an index of ROS products and the biological antioxidant potential (BAP) test as an index of antioxidant potential have been utilized. These methods are easy to perform, quick, inexpensive since they use small equipment, and provide reliable results compared with established oxidative stress and antioxidant markers. Because oxidative stress has been shown to represent the balance of production of ROS and antioxidant capacity, it is more appropriate to evaluate ROS and antioxidant capacity simultaneously. However, no study has examined the associations among d-ROMs, BAP values, and carotid artery intima-media thickness (IMT) concurrently. Therefore, we studied the associations among d-ROMs, BAP values, and the carotid artery IMT. Carotid artery IMT, blood pressure (BP), fasting circulating d-ROMs, BAP, glucose metabolism, lipid, and C-reactive protein levels were measured in 95 subjects (age: 49.5 ± 13.8 years; men: 41; women: 54), including 42 healthy subjects and 53 patients with hypertension, dyslipidemia, and diabetes mellitus who were not on medication. The results of multiple regression analysis revealed that dependent carotid artery IMT determinants remained significantly associated with age, systolic BP, total cholesterol, and BAP, whereas dependent BAP determinants remained significantly associated with body mass index and carotid artery IMT. BAP was strongly correlated with carotid artery IMT in our cohort. Our results suggest that BAP may be a useful risk marker for carotid atherosclerosis.

Comparative secretome analysis of Colletotrichum falcatum identifies a cerato-platanin protein (EPL1) as a potential pathogen-associated molecular pattern (PAMP) inducing systemic resistance in sugarcane.

PubMed

Ashwin, N M R; Barnabas, Leonard; Ramesh Sundar, Amalraj; Malathi, Palaniyandi; Viswanathan, Rasappa; Masi, Antonio; Agrawal, Ganesh Kumar; Rakwal, Randeep

2017-10-03

Colletotrichum falcatum, an intriguing hemibiotrophic fungal pathogen causes red rot, a devastating disease of sugarcane. Repeated in vitro subculturing of C. falcatum under dark condition alters morphology and reduces virulence of the culture. Hitherto, no information is available on this phenomenon at molecular level. In this study, the in vitro secretome of C. falcatum cultured under light and dark conditions was analyzed using 2-DE coupled with MALDI TOF/TOF MS. Comparative analysis identified nine differentially abundant proteins. Among them, seven proteins were less abundant in the dark-cultured C. falcatum, wherein only two protein species of a cerato-platanin protein called EPL1 (eliciting plant response-like protein) were found to be highly abundant. Transcriptional expression of candidate high abundant proteins was profiled during host-pathogen interaction using qRT-PCR. Comprehensively, this comparative secretome analysis identified five putative effectors, two pathogenicity-related proteins and one pathogen-associated molecular pattern (PAMP) of C. falcatum. Functional characterization of three distinct domains of the PAMP (EPL1) showed that the major cerato-platanin domain (EPL1∆N1-92) is exclusively essential for inducing defense and hypersensitive response (HR) in sugarcane and tobacco, respectively. Further, priming with EPL1∆N1-92 protein induced systemic resistance and significantly suppressed the red rot severity in sugarcane. Being the first secretomic investigation of C. falcatum, this study has identified five potential effectors, two pathogenicity-related proteins and a PAMP. Although many reports have highlighted the influence of light on pathogenicity, this study has established a direct link between light and expression of effectors, for the first time. This study has presented the influence of a novel N-terminal domain of EPL1 in physical and biological properties and established the functional role of major cerato-platanin domain of

Maize Benefits the Predatory Beetle, Propylea japonica (Thunberg), to Provide Potential to Enhance Biological Control for Aphids in Cotton

PubMed Central

Ouyang, Fang; Men, Xingyuan; Yang, Bing; Su, Jianwei; Zhang, Yongsheng; Zhao, Zihua; Ge, Feng

2012-01-01

Background Biological control provided by natural enemies play an important role in integrated pest management. Generalist insect predators provide an important biological service in the regulation of agricultural insect pests. Our goal is to understand the explicit process of oviposition preference, habitat selection and feeding behavior of predators in farmland ecosystem consisting of multiple crops, which is central to devising and delivering an integrated pest management program. Methodology The hypotheses was that maize can serve as habitat for natural enemies and benefits predators to provide potential to enhance biological control for pest insects in cotton. This explicit process of a predatory beetle, Propylea japonica, in agricultural ecosystem composed of cotton and maize were examined by field investigation and stable carbon isotope analysis during 2008–2010. Principal Finding Field investigation showed that P. japonica adults will search host plants for high prey abundance before laying eggs, indicating indirectly that P. japonica adults prefer to inhabit maize plants and travel to cotton plants to actively prey on aphids. The δ13C values of adult P. japonica in a dietary shift experiment found that individual beetles were shifting from a C3- to a C4-based diet of aphids reared on maize or cotton, respectively, and began to reflect the isotope ratio of their new C4 resources within one week. Approximately 80–100% of the diet of P. japonica adults in maize originated from a C3-based resource in June, July and August, while approximately 80% of the diet originated from a C4-based resource in September. Conclusion/Significance Results suggest that maize can serve as a habitat or refuge source for the predatory beetle, P. japonica, and benefits predators to provide potential to enhance biological control for insect pests in cotton. PMID:22984499

Ecological perspectives on synthetic biology: insights from microbial population biology

PubMed Central

Escalante, Ana E.; Rebolleda-Gómez, María; Benítez, Mariana; Travisano, Michael

2015-01-01

The metabolic capabilities of microbes are the basis for many major biotechnological advances, exploiting microbial diversity by selection or engineering of single strains. However, there are limits to the advances that can be achieved with single strains, and attention has turned toward the metabolic potential of consortia and the field of synthetic ecology. The main challenge for the synthetic ecology is that consortia are frequently unstable, largely because evolution by constituent members affects their interactions, which are the basis of collective metabolic functionality. Current practices in modeling consortia largely consider interactions as fixed circuits of chemical reactions, which greatly increases their tractability. This simplification comes at the cost of essential biological realism, stripping out the ecological context in which the metabolic actions occur and the potential for evolutionary change. In other words, evolutionary stability is not engineered into the system. This realization highlights the necessity to better identify the key components that influence the stable coexistence of microorganisms. Inclusion of ecological and evolutionary principles, in addition to biophysical variables and stoichiometric modeling of metabolism, is critical for microbial consortia design. This review aims to bring ecological and evolutionary concepts to the discussion on the stability of microbial consortia. In particular, we focus on the combined effect of spatial structure (connectivity of molecules and cells within the system) and ecological interactions (reciprocal and non-reciprocal) on the persistence of microbial consortia. We discuss exemplary cases to illustrate these ideas from published studies in evolutionary biology and biotechnology. We conclude by making clear the relevance of incorporating evolutionary and ecological principles to the design of microbial consortia, as a way of achieving evolutionarily stable and sustainable systems. PMID

Proteomics and metabolomics in ageing research: from biomarkers to systems biology.

PubMed

Hoffman, Jessica M; Lyu, Yang; Pletcher, Scott D; Promislow, Daniel E L

2017-07-15

Age is the single greatest risk factor for a wide range of diseases, and as the mean age of human populations grows steadily older, the impact of this risk factor grows as well. Laboratory studies on the basic biology of ageing have shed light on numerous genetic pathways that have strong effects on lifespan. However, we still do not know the degree to which the pathways that affect ageing in the lab also influence variation in rates of ageing and age-related disease in human populations. Similarly, despite considerable effort, we have yet to identify reliable and reproducible 'biomarkers', which are predictors of one's biological as opposed to chronological age. One challenge lies in the enormous mechanistic distance between genotype and downstream ageing phenotypes. Here, we consider the power of studying 'endophenotypes' in the context of ageing. Endophenotypes are the various molecular domains that exist at intermediate levels of organization between the genotype and phenotype. We focus our attention specifically on proteins and metabolites. Proteomic and metabolomic profiling has the potential to help identify the underlying causal mechanisms that link genotype to phenotype. We present a brief review of proteomics and metabolomics in ageing research with a focus on the potential of a systems biology and network-centric perspective in geroscience. While network analyses to study ageing utilizing proteomics and metabolomics are in their infancy, they may be the powerful model needed to discover underlying biological processes that influence natural variation in ageing, age-related disease, and longevity. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

A semantic web ontology for small molecules and their biological targets.

PubMed

Choi, Jooyoung; Davis, Melissa J; Newman, Andrew F; Ragan, Mark A

2010-05-24

A wide range of data on sequences, structures, pathways, and networks of genes and gene products is available for hypothesis testing and discovery in biological and biomedical research. However, data describing the physical, chemical, and biological properties of small molecules have not been well-integrated with these resources. Semantically rich representations of chemical data, combined with Semantic Web technologies, have the potential to enable the integration of small molecule and biomolecular data resources, expanding the scope and power of biomedical and pharmacological research. We employed the Semantic Web technologies Resource Description Framework (RDF) and Web Ontology Language (OWL) to generate a Small Molecule Ontology (SMO) that represents concepts and provides unique identifiers for biologically relevant properties of small molecules and their interactions with biomolecules, such as proteins. We instanced SMO using data from three public data sources, i.e., DrugBank, PubChem and UniProt, and converted to RDF triples. Evaluation of SMO by use of predetermined competency questions implemented as SPARQL queries demonstrated that data from chemical and biomolecular data sources were effectively represented and that useful knowledge can be extracted. These results illustrate the potential of Semantic Web technologies in chemical, biological, and pharmacological research and in drug discovery.

Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology(1.).

PubMed

Robarts, Daniel W H; Wolfe, Andrea D

2014-07-01

In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance.

Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

PubMed Central

Robarts, Daniel W. H.; Wolfe, Andrea D.

2014-01-01

In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

Biological Evaluation of Endophytic Fungus Chaetomium sp. NF15 of Justicia adhatoda L.: A Potential Candidate for Drug Discovery

PubMed Central

Fatima, Nighat; Mukhtar, Usman; Ihsan-Ul-Haq; Ahmed Qazi, Muneer; Jadoon, Muniba; Ahmed, Safia

2016-01-01

Background The endophytes of medicinal plants, such as Justicia adhatoda L., represent a promising and largely underexplored domain that is considered as a repository of biologically active compounds. Objectives The aim of present study was isolation, identification, and biological evaluation of endophytic fungi associated with the J. adhatoda L. plant for the production of antimicrobial, antioxidant, and cytotoxic compounds Materials and Methods Endophytic fungi associated with the J. adhatoda L. plant were isolated from healthy plant parts and taxonomically characterized through morphological, microscopic, and 18S rDNA sequencing methods. The screening for bioactive metabolite production was achieved using ethyl acetate extracts, followed by the optimization of different parameters for maximum production of bioactive metabolites. Crude and partially purified extracts were used to determine the antimicrobial, antioxidant, and cytotoxic potential Results Out of six endophytic fungal isolates, Chaetomium sp. NF15 showed the most promising biological activity and was selected for detailed study. The crude ethyl acetate extract of NF15 isolate after cultivation under optimized culture conditions showed promising antimicrobial activity, with significant inhibition of the clinical isolates of Staphylococcus aureus (87%, n=42), Pseudomonas aeruginosa (> 85%, n = 41), and Candida albicans (62%, n = 24). Conclusions The present study confirms the notion of selecting endophytic fungi of medicinal plant Justicia for the bioassay-guided isolation of its bioactive compounds, and demonstrates that endophytic fungus Chaetomium sp. NF15 could be a potential source of bioactive metabolites PMID:27635208

Biological invasions, climate change and genomics

PubMed Central

Chown, Steven L; Hodgins, Kathryn A; Griffin, Philippa C; Oakeshott, John G; Byrne, Margaret; Hoffmann, Ary A

2015-01-01

The rate of biological invasions is expected to increase as the effects of climate change on biological communities become widespread. Climate change enhances habitat disturbance which facilitates the establishment of invasive species, which in turn provides opportunities for hybridization and introgression. These effects influence local biodiversity that can be tracked through genetic and genomic approaches. Metabarcoding and metagenomic approaches provide a way of monitoring some types of communities under climate change for the appearance of invasives. Introgression and hybridization can be followed by the analysis of entire genomes so that rapidly changing areas of the genome are identified and instances of genetic pollution monitored. Genomic markers enable accurate tracking of invasive species’ geographic origin well beyond what was previously possible. New genomic tools are promoting fresh insights into classic questions about invading organisms under climate change, such as the role of genetic variation, local adaptation and climate pre-adaptation in successful invasions. These tools are providing managers with often more effective means to identify potential threats, improve surveillance and assess impacts on communities. We provide a framework for the application of genomic techniques within a management context and also indicate some important limitations in what can be achieved. PMID:25667601

Hormesis as a biological hypothesis.

PubMed Central

Calabrese, E J; Baldwin, L A

1998-01-01

A comprehensive effort was undertaken to identify articles demonstrating chemical hormesis. Nearly 4000 potentially relevant articles were retrieved from preliminary computer database searches by using various key word descriptors and extensive cross-referencing. A priori evaluation criteria were established including study design features (e.g., number of doses, dose range), statistical analysis, and reproducibility of results. Evidence of chemical hormesis was judged to have occurred in approximately 350 of the 4000 studies evaluated. Chemical hormesis was observed in a wide range of taxonomic groups and involved agents representing highly diverse chemical classes, many of potential environmental relevance. Numerous biological end points were assessed; growth responses were the most prevalent, followed by metabolic effects, longevity, reproductive responses, and survival. Hormetic responses were generally observed to be of limited magnitude. The average low-dose maximum stimulation was approximately 50% greater than controls. The hormetic dose-response range was generally limited to about one order of magnitude, with the upper end of the hormetic curve approaching the estimated no observable effect level for the particular end point. Based on the evaluation criteria, high to moderate evidence of hormesis was observed in studies comprised of > 6 doses; with > 3 doses in the hormetic zone. The present analysis suggests that chemical hormesis is a reproducible and relatively common biological phenomenon. A quantitative scheme is presented for future application to the database. PMID:9539030

Whole-Genome Sequence of Pseudomonas graminis Strain UASWS1507, a Potential Biological Control Agent and Biofertilizer Isolated in Switzerland.

PubMed

Crovadore, Julien; Calmin, Gautier; Chablais, Romain; Cochard, Bastien; Schulz, Torsten; Lefort, François

2016-10-06

We report here the whole-genome shotgun sequence of the strain UASWS1507 of the species Pseudomonas graminis, isolated in Switzerland from an apple tree. This is the first genome registered for this species, which is considered as a potential and valuable resource of biological control agents and biofertilizers for agriculture. Copyright © 2016 Crovadore et al.

Student perception of relevance of biology content to everyday life: A study in higher education biology courses

NASA Astrophysics Data System (ADS)

Himschoot, Agnes Rose

The purpose of this mixed method case study was to examine the effects of methods of instruction on students' perception of relevance in higher education non-biology majors' courses. Nearly ninety percent of all students in a liberal arts college are required to take a general biology course. It is proposed that for many of those students, this is the last science course they will take for life. General biology courses are suspected of discouraging student interest in biology with large enrollment, didactic instruction, covering a huge amount of content in one semester, and are charged with promoting student disengagement with biology by the end of the course. Previous research has been aimed at increasing student motivation and interest in biology as measured by surveys and test results. Various methods of instruction have been tested and show evidence of improved learning gains. This study focused on students' perception of relevance of biology content to everyday life and the methods of instruction that increase it. A quantitative survey was administered to assess perception of relevance pre and post instruction over three topics typically taught in a general biology course. A second quantitative survey of student experiences during instruction was administered to identify methods of instruction used in the course lecture and lab. While perception of relevance dropped in the study, qualitative focus groups provided insight into the surprising results by identifying topics that are more relevant than the ones chosen for the study, conveying the affects of the instructor's personal and instructional skills on student engagement, explanation of how active engagement during instruction promotes understanding of relevance, the roll of laboratory in promoting students' understanding of relevance as well as identifying external factors that affect student engagement. The study also investigated the extent to which gender affected changes in students' perception of

Deciphering the Structural Requirements of Nucleoside Bisubstrate Analogues for Inhibition of MbtA in Mycobacterium tuberculosis: A FB-QSAR Study and Combinatorial Library Generation for Identifying Potential Hits.

PubMed

Maganti, Lakshmi; Das, Sanjit Kumar; Mascarenhas, Nahren Manuel; Ghoshal, Nanda

2011-10-01

The re-emergence of tuberculosis infections, which are resistant to conventional drug therapy, has steadily risen in the last decade. Inhibitors of aryl acid adenylating enzyme known as MbtA, involved in siderophore biosynthesis in Mycobacterium tuberculosis, are being explored as potential antitubercular agents. The ability to identify fragments that interact with a biological target is a key step in fragment based drug design (FBDD). To expand the boundaries of quantitative structure activity relationship (QSAR) paradigm, we have proposed a Fragment Based QSAR methodology, referred here in as FB-QSAR, for deciphering the structural requirements of a series of nucleoside bisubstrate analogs for inhibition of MbtA, a key enzyme involved in siderophore biosynthetic pathway. For the development of FB-QSAR models, statistical techniques such as stepwise multiple linear regression (SMLR), genetic function approximation (GFA) and GFAspline were used. The predictive ability of the generated models was validated using different statistical metrics, and similarity-based coverage estimation was carried out to define applicability boundaries. To aid the creation of novel antituberculosis compounds, a bioisosteric database was enumerated using the combichem approach endorsed mining in a lead-like chemical space. The generated library was screened using an integrated in-silico approach and potential hits identified. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vitro biological evaluation of glyburide as potential inhibitor of collagenases.

PubMed

Bodiga, Vijaya Lakshmi; Eda, Sasidhar Reddy; Chavali, Saishashank; Revur, Nagasaisreelekha Nagavalli; Zhang, Anita; Thokala, Sandhya; Bodiga, Sreedhar

2014-09-01

In tissues with upregulated MMP activity, MMP inhibition remains one of the key strategies. Potential inhibitors of MMPs have been tested for almost 30 years, but none have reached clinical utility due to bioavailability issues and adverse effects. This study utilized the approach of drug repurposing for exploring glyburide as a potential inhibitor against collagenases. In silico molecular docking studies were carried out to probe the interactions of glyburide with the active site Zn. Collagenase enzyme activity measurements and zymography analyses using conditioned medium from lung fibroblasts, rheumatoid synovial fibroblasts, and osteoblasts were carried out to confirm the inhibitory activity. Glyburide binds and interacts with the catalytic Zn residues of the collagenases, as evidenced by in silico molecular docking studies. Fluorescence enzyme activity measurements reveal that glyburide inhibits peptide substrate cleavage by all three collagenases in a dose-dependent manner. Collagen zymography studies validated inhibition of these collagenases by glyburide. These results identify glyburide as a potential inhibitor of collagenases and provide an insight into the mechanism of action of this small molecule. Thus, glyburide may offer additional advantages in diabetics, in controlling MMP activation and collagen degradation and could aid in the treatment of diseases with aberrant MMP activity. Copyright © 2014 Elsevier B.V. All rights reserved.

After the Greeting: Realizing the Potential of Physical Models in Cell Biology.

PubMed

Paluch, Ewa K

2015-12-01

Biophysics is increasingly taking center stage in cell biology as the tools for precise quantifications of cellular behaviors expand. Interdisciplinary approaches, combining quantitative physical modeling with cell biology, are of growing interest to journal editors, funding agencies, and hiring committees. However, despite an ever-increasing emphasis on the importance of interdisciplinary research, the student trained in biology may still be at a loss as to what it actually means. I discuss here some considerations on how to achieve meaningful and high-quality interdisciplinary work. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis, Biological Evaluation and Molecular Docking of New Benzenesulfonylhydrazone as Potential anti-Trypanosoma cruzi Agents.

PubMed

Elizondo-Jimenez, Silvia; Moreno-Herrera, Antonio; Reyes-Olivares, Rogelio; Dorantes-Gonzalez, Edith; Nogueda-Torres, Benjamín; Oliveira, Eduardo A Gamosa de; Romeiro, Nelilma C; Lima, Lidia M; Palos, Isidro; Rivera, Gildardo

2017-01-01

Chagas disease is a public health problem caused by Trypanosoma cruzi. Cruzain is a pharmacological target for designing a new drug against this parasite. Hydrazone and Nacylhydrazone derivatives have been traditionally associated as potential Cruzain inhibitors. Additionally, benzenesulfonyl derivatives show trypanocidal activity. Therefore, in this study, the combination of both structures has been taken into account for drug design. Seven benzenesulfonylhydrazone (BS-H) and seven N-propionyl benzenesulfonylhydrazone (BS-NAH) derivatives were synthetized and elucidated by infrared spectroscopy, nuclear magnetic resonance, and elemental analysis. All compounds were evaluated biologically in vitro against two strains of Trypanosoma cruzi (NINOA and INC-5), which are endemic in Mexico, and compared with the reference drugs nifurtimox and benznidazole. In order to gain insight into the putative molecular origin of the trypanocidal properties of these derivatives, docking studies were carried out with Cruzain. Compounds 4 and 6 (BS-H) and 10, 12-14 (BS-NAH) showed the best biological activity against NINOA and INC-5 strains, respectively. Compound 13 was the most potent trypanocidal compound showing a LC50 of 0.06 µM against INC-5 strain. However, compound 4 showed the best activity against both strains (LC50 <30 µM). Theoretical binding modes obtained suggested covalent binding that could explain their biological activity. Benzenesulfonyl and N-propionyl benzenesulfonyl hydrazone derivatives are good options for developing new trypanocidal agents. Particularly, compound 4 could be considered a lead compound. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness.

PubMed

Willems, Sara M; Wright, Daniel J; Day, Felix R; Trajanoska, Katerina; Joshi, Peter K; Morris, John A; Matteini, Amy M; Garton, Fleur C; Grarup, Niels; Oskolkov, Nikolay; Thalamuthu, Anbupalam; Mangino, Massimo; Liu, Jun; Demirkan, Ayse; Lek, Monkol; Xu, Liwen; Wang, Guan; Oldmeadow, Christopher; Gaulton, Kyle J; Lotta, Luca A; Miyamoto-Mikami, Eri; Rivas, Manuel A; White, Tom; Loh, Po-Ru; Aadahl, Mette; Amin, Najaf; Attia, John R; Austin, Krista; Benyamin, Beben; Brage, Søren; Cheng, Yu-Ching; Cięszczyk, Paweł; Derave, Wim; Eriksson, Karl-Fredrik; Eynon, Nir; Linneberg, Allan; Lucia, Alejandro; Massidda, Myosotis; Mitchell, Braxton D; Miyachi, Motohiko; Murakami, Haruka; Padmanabhan, Sandosh; Pandey, Ashutosh; Papadimitriou, Ioannis; Rajpal, Deepak K; Sale, Craig; Schnurr, Theresia M; Sessa, Francesco; Shrine, Nick; Tobin, Martin D; Varley, Ian; Wain, Louise V; Wray, Naomi R; Lindgren, Cecilia M; MacArthur, Daniel G; Waterworth, Dawn M; McCarthy, Mark I; Pedersen, Oluf; Khaw, Kay-Tee; Kiel, Douglas P; Pitsiladis, Yannis; Fuku, Noriyuki; Franks, Paul W; North, Kathryn N; van Duijn, Cornelia M; Mather, Karen A; Hansen, Torben; Hansson, Ola; Spector, Tim; Murabito, Joanne M; Richards, J Brent; Rivadeneira, Fernando; Langenberg, Claudia; Perry, John R B; Wareham, Nick J; Scott, Robert A

2017-07-12

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10 -8 ) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

Potentially preventable infant and child deaths identified at autopsy; findings and implications.

PubMed

Bamber, Andrew R; Mifsud, William; Wolfe, Ingrid; Cass, Hilary; Pryce, Jeremy; Malone, Marian; Sebire, Neil J

2015-09-01

The purpose of the study was to determine the proportion of pediatric deaths investigated by HM Coronial autopsy which were potentially preventable deaths due to treatable natural disease, and what implications such findings may have for health policies to reduce their occurrence. A retrospective study of 1779 autopsies of individuals between 7 days and 14 years of age requested by HM Coroner, taking place in one specialist pediatric autopsy center, was undertaken. Cases were included if they involved a definite natural disease process in which appropriate recognition and treatment was likely to have affected their outcome. Strict criteria were used and cases were excluded where the individual had any longstanding condition which might have predisposed them to, or altered the recognition of, acute illness, or its response to therapy. Almost 8% (134/1779) of the study group were potentially preventable deaths as a result of natural disease, the majority occurring in children younger than 2 years of age. Most individuals reported between 1 and 7 days of symptoms before their death, and the majority had sought medical advice during this period, including from general practitioners within working hours, and hospital emergency departments. Of those who had sought medical attention, around one-third had done so more than once (28%, 15/53). Sepsis and pneumonia accounted for the majority of deaths (46 and 34% respectively), with all infections (sepsis, pneumonia and meningitis) accounting for 110/134 (82%). Around 10% of pediatric deaths referred to HM Coroner are potentially preventable, being the result of treatable natural acute illnesses. In many cases medical advice had been sought during the final illness. The results highlight how a review of autopsy data can identify significant findings with the potential to reduce mortality, and the importance of centralized investigation and reporting of pediatric deaths.

Systems Biology-an interdisciplinary approach.

PubMed

Friboulet, Alain; Thomas, Daniel

2005-06-15

System-level approaches in biology are not new but foundations of "Systems Biology" are achieved only now at the beginning of the 21st century [Kitano, H., 2001. Foundations of Systems Biology. MIT Press, Cambridge, MA]. The renewed interest for a system-level approach is linked to the progress in collecting experimental data and to the limits of the "reductionist" approach. System-level understanding of native biological and pathological systems is needed to provide potential therapeutic targets. Examples of interdisciplinary approach in Systems Biology are described in U.S., Japan and Europe. Robustness in biology, metabolic engineering and idiotypic networks are discussed in the framework of Systems Biology.

Synthetic biology: navigating the challenges ahead.

PubMed

Bhutkar, Arjun

2005-01-01

The emerging field of synthetic biology is broadly defined as the area of intersection of biology and engineering that focuses on the modification or creation of novel biological systems that do not have a counterpart in nature. Potential applications of this technology range from creating systems for environmental cleanup tasks, for medical diagnosis and treatment, to economical generation of hydrogen fuel. This technology is in tis nascent state and there are a number of concerns surrounding its potential applications and the nature of research being performed. With the potential to create hitherto unknown "living organisms", it raises a number of challenges along different dimensions. This article reviews the current state of the technology and analyzes synthetic biology using different lenses: patentability, ethics, and regulation. It proposes a classification system for the products of synthetic biology and provides recommendations in each of the above areas (patentability, ethics, and regulation) in the context of this classification system. These recommendations include an improved framework for patentability testing, ethical principles to guide work in this area, a controlled approval process, and reference frameworks for regulation.

Student Teachers' Conceptions of Teaching Biology

ERIC Educational Resources Information Center

Subramaniam, Karthigeyan

2014-01-01

The purpose of this qualitative study was to investigate prospective biology teachers' conceptions of teaching biology and identify how these conceptions revealed their strategies for helping their future students' learning of biology. The study utilized drawings, narratives and interviews to investigate the nature of the prospective biology…

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.

PubMed

Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian'an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tõnu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

2012-09-01

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

Using matrix population models to inform biological control management of the wheat stem sawfly, Cephus cinctus

USDA-ARS?s Scientific Manuscript database

Demographic models are a powerful means of identifying vulnerable life stages of pest species and assessing the potential effectiveness of various management approaches in reducing pest population growth and spread. In a biological control context, such models can be used to focus foreign explorati...

A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

2016-05-01

Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure.

PubMed

Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

2016-05-17

Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

Using Osteoclast Differentiation as a Model for Gene Discovery in an Undergraduate Cell Biology Laboratory

ERIC Educational Resources Information Center

Birnbaum, Mark J.; Picco, Jenna; Clements, Meghan; Witwicka, Hanna; Yang, Meiheng; Hoey, Margaret T.; Odgren, Paul R.

2010-01-01

A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory…

Modified Primers for the Identification of Nonpathogenic Fusarium oxysporum Isolates That Have Biological Control Potential against Fusarium Wilt of Cucumber in Taiwan

PubMed Central

Wang, Chaojen; Lin, Yisheng; Lin, Yinghong; Chung, Wenhsin

2013-01-01

Previous investigations demonstrated that Fusarium oxysporum (Fo), which is not pathogenic to cucumbers, could serve as a biological control agent for managing Fusarium wilt of cucumber caused by Fo f. sp. cucumerinum (Foc) in Taiwan. However, thus far it has not been possible to separate the populations of pathogenic Fo from the nonpathogenic isolates that have biological control potential through their morphological characteristics. Although these two populations can be distinguished from one another using a bioassay, the work is laborious and time-consuming. In this study, a fragment of the intergenic spacer (IGS) region of ribosomal DNA from an Fo biological control agent, Fo366, was PCR-amplified with published general primers, FIGS11/FIGS12 and sequenced. A new primer, NPIGS-R, which was designed based on the IGS sequence, was paired with the FIGS11 primer. These primers were then evaluated for their specificity to amplify DNA from nonpathogenic Fo isolates that have biological control potential. The results showed that the modified primer pair, FIGS11/NPIGS-R, amplified a 500-bp DNA fragment from five of seven nonpathogenic Fo isolates. These five Fo isolates delayed symptom development of cucumber Fusarium wilt in greenhouse bioassay tests. Seventy-seven Fo isolates were obtained from the soil and plant tissues and then subjected to amplification using the modified primer pair; six samples showed positive amplification. These six isolates did not cause symptoms on cucumber seedlings when grown in peat moss infested with the isolates and delayed disease development when the same plants were subsequently inoculated with a virulent isolate of Foc. Therefore, the modified primer pair may prove useful for the identification of Fo isolates that are nonpathogenic to cucumber which can potentially act as biocontrol agents for Fusarium wilt of cucumber. PMID:23762289

Positive selection moments identify potential functional residues in human olfactory receptors

NASA Technical Reports Server (NTRS)

Singer, M. S.; Weisinger-Lewin, Y.; Lancet, D.; Shepherd, G. M.

1996-01-01

Correlated mutation analysis and molecular models of olfactory receptors have provided evidence that residues in the transmembrane domains form a binding pocket for odor ligands. As an independent test of these results, we have calculated positive selection moments for the alpha-helical sixth transmembrane domain (TM6) of human olfactory receptors. The moments can be used to identify residues that have been preferentially affected by positive selection and are thus likely to interact with odor ligands. The results suggest that residue 622, which is commonly a serine or threonine, could form critical H-bonds. In some receptors a dual-serine subsite, formed by residues 622 and 625, could bind hydroxyl determinants on odor ligands. The potential importance of these residues is further supported by site-directed mutagenesis in the beta-adrenergic receptor. The findings should be of practical value for future physiological studies, binding assays, and site-directed mutagenesis.

Draft sequencing and comparative genomics of Xylella fastidiosa strains reveal novel biological insights.

PubMed

Bhattacharyya, Anamitra; Stilwagen, Stephanie; Reznik, Gary; Feil, Helene; Feil, William S; Anderson, Iain; Bernal, Axel; D'Souza, Mark; Ivanova, Natalia; Kapatral, Vinayak; Larsen, Niels; Los, Tamara; Lykidis, Athanasios; Selkov, Eugene; Walunas, Theresa L; Purcell, Alexander; Edwards, Rob A; Hawkins, Trevor; Haselkorn, Robert; Overbeek, Ross; Kyrpides, Nikos C; Predki, Paul F

2002-10-01

Draft sequencing is a rapid and efficient method for determining the near-complete sequence of microbial genomes. Here we report a comparative analysis of one complete and two draft genome sequences of the phytopathogenic bacterium, Xylella fastidiosa, which causes serious disease in plants, including citrus, almond, and oleander. We present highlights of an in silico analysis based on a comparison of reconstructions of core biological subsystems. Cellular pathway reconstructions have been used to identify a small number of genes, which are likely to reside within the draft genomes but are not captured in the draft assembly. These represented only a small fraction of all genes and were predominantly large and small ribosomal subunit protein components. By using this approach, some of the inherent limitations of draft sequence can be significantly reduced. Despite the incomplete nature of the draft genomes, it is possible to identify several phage-related genes, which appear to be absent from the draft genomes and not the result of insufficient sequence sampling. This region may therefore identify potential host-specific functions. Based on this first functional reconstruction of a phytopathogenic microbe, we spotlight an unusual respiration machinery as a potential target for biological control. We also predicted and developed a new defined growth medium for Xylella.

Investigating the potential of biological control against Phytophthora ramorum

Treesearch

Timothy L. Widmer

2008-01-01

Phytophthora ramorum is a unique organism in many ways, having a broad host range and both soilborne and aerial infection stages. This makes mplementing effective control measures very complex. The use of biological control has been demonstrated against various Phytophthora spp. in general, but not specifically against P...

Advances in imaging secondary ion mass spectrometry for biological samples

DOE PAGES

Boxer, Steven G.; Kraft, Mary L.; Weber, Peter K.

2008-12-16

Imaging mass spectrometry combines the power of mass spectrometry to identify complex molecules based on mass with sample imaging. Recent advances in secondary ion mass spectrometry have improved sensitivity and spatial resolution, so that these methods have the potential to bridge between high-resolution structures obtained by X-ray crystallography and cyro-electron microscopy and ultrastructure visualized by conventional light microscopy. Following background information on the method and instrumentation, we address the key issue of sample preparation. Because mass spectrometry is performed in high vacuum, it is essential to preserve the lateral organization of the sample while removing bulk water, and this hasmore » been a major barrier for applications to biological systems. Furthermore, recent applications of imaging mass spectrometry to cell biology, microbial communities, and biosynthetic pathways are summarized briefly, and studies of biological membrane organization are described in greater depth.« less

Long non-coding RNAs and their biological roles in plants.

PubMed

Liu, Xue; Hao, Lili; Li, Dayong; Zhu, Lihuang; Hu, Songnian

2015-06-01

With the development of genomics and bioinformatics, especially the extensive applications of high-throughput sequencing technology, more transcriptional units with little or no protein-coding potential have been discovered. Such RNA molecules are called non-protein-coding RNAs (npcRNAs or ncRNAs). Among them, long npcRNAs or ncRNAs (lnpcRNAs or lncRNAs) represent diverse classes of transcripts longer than 200 nucleotides. In recent years, the lncRNAs have been considered as important regulators in many essential biological processes. In plants, although a large number of lncRNA transcripts have been predicted and identified in few species, our current knowledge of their biological functions is still limited. Here, we have summarized recent studies on their identification, characteristics, classification, bioinformatics, resources, and current exploration of their biological functions in plants. Copyright © 2015 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

Serum biological antioxidant potential predicts the prognosis of hemodialysis patients.

PubMed

Ishii, Tomoko; Ohtake, Takayasu; Okamoto, Koji; Mochida, Yasuhiro; Ishioka, Kunihiro; Oka, Machiko; Maesato, Kyoko; Ikee, Ryota; Moriya, Hidekazu; Hidaka, Sumi; Doi, Kent; Noiri, Eisei; Fujita, Toshiro; Kobayashi, Shuzo

2011-01-01

It is well known that oxidative stress is enhanced in patients with end-stage renal disease. However, little is known about the relationship between serum antioxidant capacity and clinical outcome in hemodialysis (HD) patients. We examined the relationship between serum biomarkers of oxidative stress and clinical outcomes including all-cause mortality, hospitalization rate and incidence of cardiovascular events in HD patients. As biomarkers of oxidative stress, we measured serum levels of coenzyme Q10 (CoQ10) and biological antioxidant potential (BAP). 108 patients were observed for 30 months as the follow-up periods. The survival group (n = 83) showed significantly higher BAP values compared with those in death groups (n = 25; p < 0.05). When serum BAP levels were divided into two groups by their median value, the group with higher BAP values had a better survival rate than that with lower BAP values on the Kaplan-Meier survival analysis (p = 0.05). Although serum levels of CoQ10 did not show any association with clinical outcomes, lower BAP was selected as an independent risk factor for all-cause mortality as well as the absence of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers therapy by age-adjusted Cox regression analysis. This study indicated that BAP could predict the prognosis of HD patients. Copyright © 2010 S. Karger AG, Basel.

A Study Assessing the Potential of Negative Effects in Interdisciplinary Math–Biology Instruction

PubMed Central

Madlung, Andreas; Bremer, Martina; Himelblau, Edward; Tullis, Alexa

2011-01-01

There is increasing enthusiasm for teaching approaches that combine mathematics and biology. The call for integrating more quantitative work in biology education has led to new teaching tools that improve quantitative skills. Little is known, however, about whether increasing interdisciplinary work can lead to adverse effects, such as the development of broader but shallower skills or the possibility that math anxiety causes some students to disengage in the classroom, or, paradoxically, to focus so much on the mathematics that they lose sight of its application for the biological concepts in the center of the unit at hand. We have developed and assessed an integrative learning module and found disciplinary learning gains to be equally strong in first-year students who actively engaged in embedded quantitative calculations as in those students who were merely presented with quantitative data in the context of interpreting biological and biostatistical results. When presented to advanced biology students, our quantitative learning tool increased test performance significantly. We conclude from our study that the addition of mathematical calculations to the first year and advanced biology curricula did not hinder overall student learning, and may increase disciplinary learning and data interpretation skills in advanced students. PMID:21364099

Identifying and quantifying interactions in a laboratory swarm

NASA Astrophysics Data System (ADS)

Puckett, James; Kelley, Douglas; Ouellette, Nicholas

2013-03-01

Emergent collective behavior, such as in flocks of birds or swarms of bees, is exhibited throughout the animal kingdom. Many models have been developed to describe swarming and flocking behavior using systems of self-propelled particles obeying simple rules or interacting via various potentials. However, due to experimental difficulties and constraints, little empirical data exists for characterizing the exact form of the biological interactions. We study laboratory swarms of flying Chironomus riparius midges, using stereoimaging and particle tracking techniques to record three-dimensional trajectories for all the individuals in the swarm. We describe methods to identify and quantify interactions by examining these trajectories, and report results on interaction magnitude, frequency, and mutuality.

Where Synthetic Biology Meets ET

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.

2016-01-01

Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

Synthesis of novel Schiff's bases of highly potential biological activities and their structure investigation.

PubMed

Zayed, Ehab M; Zayed, M A

2015-05-15

Novel bisaldehyde-hydrazide Schiff's bases AS1 (2,2'-(ethane-1,2-diylbis(oxy))dibenzaldehyde terephthalohydrazide) and AS2 (N',N'″-(((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(methanylylidene))di(benzohydrazide)) were prepared as new macrocyclic compounds via condensation reactions. AS1 had been prepared by condensation between (2,2'-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and terephthalohydrazide in a ratio1:1. AS2 had been obtained by condensation between (2,2'-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and benzohydrazide in ratio 1:2. The structures of AS1 and AS2 were characterized by elemental analysis (EA), mass (MS), FT-IR and (1)H-NMR spectra, and thermal analyses (TG, DTG). The activation thermodynamic parameters such as ΔE(∗), ΔH(∗), ΔS(∗) and ΔG(∗) were calculated from the TG curves using Coats-Redfern method. It is important to investigate their molecular structures to know the active groups and weak bonds responsible for their biological activities. Consequently in the present work, the obtained thermal (TA) and mass (MS) practical results are confirmed by semi-empirical MO-calculations (MOCS) using PM3 procedure. Their biological activities had been tested in vitro against Escherichia coli, Proteus vulgaris, Bacillus subtilis and Staphylococcus aurous bacteria in order to assess their anti-microbial potential. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis of novel Schiff's bases of highly potential biological activities and their structure investigation

NASA Astrophysics Data System (ADS)

Zayed, Ehab M.; Zayed, M. A.

2015-05-01

Novel bisaldehyde-hydrazide Schiff's bases AS1 (2,2‧-(ethane-1,2-diylbis(oxy))dibenzaldehyde terephthalohydrazide) and AS2 (N‧,N‧″-(((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(methanylylidene))di(benzohydrazide)) were prepared as new macrocyclic compounds via condensation reactions. AS1 had been prepared by condensation between (2,2‧-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and terephthalohydrazide in a ratio1:1. AS2 had been obtained by condensation between (2,2‧-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and benzohydrazide in ratio 1:2. The structures of AS1 and AS2 were characterized by elemental analysis (EA), mass (MS), FT-IR and 1H-NMR spectra, and thermal analyses (TG, DTG). The activation thermodynamic parameters such as ΔE∗, ΔH∗, ΔS∗ and ΔG∗ were calculated from the TG curves using Coats-Redfern method. It is important to investigate their molecular structures to know the active groups and weak bonds responsible for their biological activities. Consequently in the present work, the obtained thermal (TA) and mass (MS) practical results are confirmed by semi-empirical MO-calculations (MOCS) using PM3 procedure. Their biological activities had been tested in vitro against Escherichia coli, Proteus vulgaris, Bacillus subtilis and Staphylococcus aurous bacteria in order to assess their anti-microbial potential.

Biological Effects of Space Radiation and Development of Effective Countermeasures

PubMed Central

Kennedy, Ann R.

2014-01-01

As part of a program to assess the adverse biological effects expected from astronaut exposure to space radiation, numerous different biological effects relating to astronaut health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronaut vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation. PMID:25258703

Identifying sources of tick blood meals using unidentified tandem mass spectral libraries.

PubMed

Önder, Özlem; Shao, Wenguang; Kemps, Brian D; Lam, Henry; Brisson, Dustin

2013-01-01

Rapid and reliable identification of the vertebrate species on which a disease vector previously parasitized is imperative to study ecological factors that affect pathogen distribution and can aid the development of public health programs. Here we describe a proteome profiling technique designed to identify the source of blood meals of haematophagous arthropods. This method employs direct spectral matching and thus does not require a priori knowledge of any genetic or protein sequence information. Using this technology, we detect remnants of blood in blacklegged ticks (Ixodes scapularis) and correctly determine the vertebrate species from which the blood was derived, even 6 months after the tick had fed. This biological fingerprinting methodology is sensitive, fast, cost-effective and can potentially be adapted for other biological and medical applications when existing genome-based methods are impractical or ineffective.

Terahertz spectral unmixing based method for identifying gastric cancer

NASA Astrophysics Data System (ADS)

Cao, Yuqi; Huang, Pingjie; Li, Xian; Ge, Weiting; Hou, Dibo; Zhang, Guangxin

2018-02-01

At present, many researchers are exploring biological tissue inspection using terahertz time-domain spectroscopy (THz-TDS) techniques. In this study, based on a modified hard modeling factor analysis method, terahertz spectral unmixing was applied to investigate the relationships between the absorption spectra in THz-TDS and certain biomarkers of gastric cancer in order to systematically identify gastric cancer. A probability distribution and box plot were used to extract the distinctive peaks that indicate carcinogenesis, and the corresponding weight distributions were used to discriminate the tissue types. The results of this work indicate that terahertz techniques have the potential to detect different levels of cancer, including benign tumors and polyps.

Low-gravity Orbiting Research Laboratory Environment Potential Impact on Space Biology Research

NASA Technical Reports Server (NTRS)

Jules, Kenol

2006-01-01

One of the major objectives of any orbital space research platform is to provide a quiescent low gravity, preferably a zero gravity environment, to perform fundamental as well as applied research. However, small disturbances exist onboard any low earth orbital research platform. The impact of these disturbances must be taken into account by space research scientists during their research planning, design and data analysis in order to avoid confounding factors in their science results. The reduced gravity environment of an orbiting research platform in low earth orbit is a complex phenomenon. Many factors, among others, such as experiment operations, equipment operation, life support systems and crew activity (if it is a crewed platform), aerodynamic drag, gravity gradient, rotational effects as well as the vehicle structural resonance frequencies (structural modes) contribute to form the overall reduced gravity environment in which space research is performed. The contribution of these small disturbances or accelerations is precisely why the environment is NOT a zero gravity environment, but a reduced acceleration environment. This paper does not discuss other factors such as radiation, electromagnetic interference, thermal and pressure gradient changes, acoustic and CO2 build-up to name a few that affect the space research environment as well, but it focuses solely on the magnitude of the acceleration level found on orbiting research laboratory used by research scientists to conduct space research. For ease of analysis this paper divides the frequency spectrum relevant to most of the space research disciplines into three regimes: a) quasi-steady, b) vibratory and c) transient. The International Space Station is used as an example to illustrate the point. The paper discusses the impact of these three regimes on space biology research and results from space flown experiments are used to illustrate the potential negative impact of these disturbances (accelerations

Non-covalent interactions across organic and biological subsets of chemical space: Physics-based potentials parametrized from machine learning

NASA Astrophysics Data System (ADS)

Bereau, Tristan; DiStasio, Robert A.; Tkatchenko, Alexandre; von Lilienfeld, O. Anatole

2018-06-01

Classical intermolecular potentials typically require an extensive parametrization procedure for any new compound considered. To do away with prior parametrization, we propose a combination of physics-based potentials with machine learning (ML), coined IPML, which is transferable across small neutral organic and biologically relevant molecules. ML models provide on-the-fly predictions for environment-dependent local atomic properties: electrostatic multipole coefficients (significant error reduction compared to previously reported), the population and decay rate of valence atomic densities, and polarizabilities across conformations and chemical compositions of H, C, N, and O atoms. These parameters enable accurate calculations of intermolecular contributions—electrostatics, charge penetration, repulsion, induction/polarization, and many-body dispersion. Unlike other potentials, this model is transferable in its ability to handle new molecules and conformations without explicit prior parametrization: All local atomic properties are predicted from ML, leaving only eight global parameters—optimized once and for all across compounds. We validate IPML on various gas-phase dimers at and away from equilibrium separation, where we obtain mean absolute errors between 0.4 and 0.7 kcal/mol for several chemically and conformationally diverse datasets representative of non-covalent interactions in biologically relevant molecules. We further focus on hydrogen-bonded complexes—essential but challenging due to their directional nature—where datasets of DNA base pairs and amino acids yield an extremely encouraging 1.4 kcal/mol error. Finally, and as a first look, we consider IPML for denser systems: water clusters, supramolecular host-guest complexes, and the benzene crystal.

Lycopene metabolism and its biological significance12345

PubMed Central

2012-01-01

The beneficial effects of a high intake of tomatoes and tomato products on the risk of certain chronic diseases have been presented in many epidemiologic studies, with the suggestion that lycopene (a major carotenoid in tomatoes) is a micronutrient with important health benefits. Within the past few years, we have gained greater knowledge of the metabolism of lycopene and the biological effects of lycopene derivatives. In particular, the characterization and study of β-carotene 9′,10′-oxygenase has shown that this enzyme can catalyze the excentric cleavage of both provitamin and non–provitamin A carotenoids to form apo-10′-carotenoids, including apo-10′-lycopenoids from lycopene. This raised an important question of whether the effect of lycopene on various cellular functions and signaling pathways is a result of the direct actions of intact lycopene or its derivatives. Several reports, including our own, support the notion that the biological activities of lycopene can be mediated by apo-10′-lycopenoids. More research is clearly needed to identify and characterize additional lycopene metabolites and their biological activities, which will potentially provide invaluable insights into the mechanisms underlying the effects of lycopene in humans. PMID:23053559

Metabolomic profiling to identify potential serum biomarkers for schizophrenia and risperidone action.

PubMed

Xuan, Jiekun; Pan, Guihua; Qiu, Yunping; Yang, Lun; Su, Mingming; Liu, Yumin; Chen, Jian; Feng, Guoyin; Fang, Yiru; Jia, Wei; Xing, Qinghe; He, Lin

2011-12-02

Despite recent advances in understanding the pathophysiology of schizophrenia and the mechanisms of antipsychotic drug action, the development of biomarkers for diagnosis and therapeutic monitoring in schizophrenia remains challenging. Metabolomics provides a powerful approach to discover diagnostic and therapeutic biomarkers by analyzing global changes in an individual's metabolic profile in response to pathophysiological stimuli or drug intervention. In this study, we performed gas chromatography-mass spectrometry based metabolomic profiling in serum of unmedicated schizophrenic patients before and after an 8-week risperidone monotherapy, to detect potential biomarkers associated with schizophrenia and risperidone treatment. Twenty-two marker metabolites contributing to the complete separation of schizophrenic patients from matched healthy controls were identified, with citrate, palmitic acid, myo-inositol, and allantoin exhibiting the best combined classification performance. Twenty marker metabolites contributing to the complete separation between posttreatment and pretreatment patients were identified, with myo-inositol, uric acid, and tryptophan showing the maximum combined classification performance. Metabolic pathways including energy metabolism, antioxidant defense systems, neurotransmitter metabolism, fatty acid biosynthesis, and phospholipid metabolism were found to be disturbed in schizophrenic patients and partially normalized following risperidone therapy. Further study of these metabolites may facilitate the development of noninvasive biomarkers and more efficient therapeutic strategies for schizophrenia.

Identifying cooperative transcriptional regulations using protein–protein interactions

PubMed Central

Nagamine, Nobuyoshi; Kawada, Yuji; Sakakibara, Yasubumi

2005-01-01

Cooperative transcriptional activations among multiple transcription factors (TFs) are important to understand the mechanisms of complex transcriptional regulations in eukaryotes. Previous studies have attempted to find cooperative TFs based on gene expression data with gene expression profiles as a measure of similarity of gene regulations. In this paper, we use protein–protein interaction data to infer synergistic binding of cooperative TFs. Our fundamental idea is based on the assumption that genes contributing to a similar biological process are regulated under the same control mechanism. First, the protein–protein interaction networks are used to calculate the similarity of biological processes among genes. Second, we integrate this similarity and the chromatin immuno-precipitation data to identify cooperative TFs. Our computational experiments in yeast show that predictions made by our method have successfully identified eight pairs of cooperative TFs that have literature evidences but could not be identified by the previous method. Further, 12 new possible pairs have been inferred and we have examined the biological relevances for them. However, since a typical problem using protein–protein interaction data is that many false-positive data are contained, we propose a method combining various biological data to increase the prediction accuracy. PMID:16126847

Designing synthetic biology.

PubMed

Agapakis, Christina M

2014-03-21

Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology.

A Diagnostic Assessment for Introductory Molecular and Cell Biology

PubMed Central

Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.

2010-01-01

We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed for use as a pre- and posttest to measure student learning gains. To develop the assessment, we first worked with faculty to create a set of learning goals that targeted important concepts in the field and seemed likely to be emphasized by most instructors teaching these subjects. We interviewed students using open-ended questions to identify commonly held misconceptions, formulated multiple-choice questions that included these ideas as distracters, and reinterviewed students to establish validity of the instrument. The assessment was then evaluated by 25 biology experts and modified based on their suggestions. The complete revised assessment was administered to more than 1300 students at three institutions. Analysis of statistical parameters including item difficulty, item discrimination, and reliability provides evidence that the IMCA is a valid and reliable instrument with several potential uses in gauging student learning of key concepts in molecular and cell biology. PMID:21123692

Causal network analysis of head and neck keloid tissue identifies potential master regulators.

PubMed

Garcia-Rodriguez, Laura; Jones, Lamont; Chen, Kang Mei; Datta, Indrani; Divine, George; Worsham, Maria J

2016-10-01

To generate novel insights and hypotheses in keloid development from potential master regulators. Prospective cohort. Six fresh keloid and six normal skin samples from 12 anonymous donors were used in a prospective cohort study. Genome-wide profiling was done previously on the cohort using the Infinium HumanMethylation450 BeadChip (Illumina, San Diego, CA). The 190 statistically significant CpG islands between keloid and normal tissue mapped to 152 genes (P < .05). The top 10 statistically significant genes (VAMP5, ACTR3C, GALNT3, KCNAB2, LRRC61, SCML4, SYNGR1, TNS1, PLEKHG5, PPP1R13-α, false discovery rate <.015) were uploaded into the Ingenuity Pathway Analysis software's Causal Network Analysis (QIAGEN, Redwood City, CA). To reflect expected gene expression direction in the context of methylation changes, the inverse of the methylation ratio from keloid versus normal tissue was used for the analysis. Causal Network Analysis identified disease-specific master regulator molecules based on downstream differentially expressed keloid-specific genes and expected directionality of expression (hypermethylated vs. hypomethylated). Causal Network Analysis software identified four hierarchical networks that included four master regulators (pyroxamide, tributyrin, PRKG2, and PENK) and 19 intermediate regulators. Causal Network Analysis of differentiated methylated gene data of keloid versus normal skin demonstrated four causal networks with four master regulators. These hierarchical networks suggest potential driver roles for their downstream keloid gene targets in the pathogenesis of the keloid phenotype, likely triggered due to perturbation/injury to normal tissue. NA Laryngoscope, 126:E319-E324, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

PubMed Central

Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian’an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O’Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tönu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

2012-01-01

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

Integrating virtual screening and biochemical experimental approach to identify potential anti-cancer agents from drug databank.

PubMed

Deka, Suman Jyoti; Roy, Ashalata; Manna, Debasis; Trivedi, Vishal

2018-06-01

Chemical libraries constitute a reservoir of pharmacophoric molecules to identify potent anti-cancer agents. Virtual screening of heterocyclic compound library in conjugation with the agonist-competition assay, toxicity-carcinogenicity analysis, and string-based structural searches enabled us to identify several drugs as potential anti-cancer agents targeting protein kinase C (PKC) as a target. Molecular modeling study indicates that Cinnarizine fits well within the PKC C2 domain and exhibits extensive interaction with the protein residues. Molecular dynamics simulation of PKC-Cinnarizine complex at different temperatures (300, 325, 350, 375, and 400[Formula: see text]K) confirms that Cinnarizine fits nicely into the C2 domain and forms a stable complex. The drug Cinnarizine was found to bind PKC with a dissociation constant Kd of [Formula: see text]M. The breast cancer cells stimulated with Cinnarizine causes translocation of PKC-[Formula: see text] to the plasma membrane as revealed by immunoblotting and immunofluorescence studies. Cinnarizine also dose dependently reduced the viability of MDAMB-231 and MCF-7 breast cancer cells with an IC[Formula: see text] of [Formula: see text] and [Formula: see text]g/mL, respectively. It is due to the disturbance of cell cycle of breast cancer cells with reduction of S-phase and accumulation of cells in G1-phase. It disturbs mitochondrial membrane potentials to release cytochrome C into the cytosol and activates caspase-3 to induce apoptosis in cancer cells. The cell death was due to induction of apoptosis involving mitochondrial pathway. Hence, the current study has assigned an additional role to Cinnarizine as an activator of PKC and potentials of the approach to identify new molecules for anti-cancer therapy. Thus, in silico screening along with biochemical experimentation is a robust approach to assign additional roles to the drugs present in the databank for anti-cancer therapy.

Using gene chips to identify organ-specific, smooth muscle responses to experimental diabetes: potential applications to urological diseases.

PubMed

Hipp, Jason D; Davies, Kelvin P; Tar, Moses; Valcic, Mira; Knoll, Abraham; Melman, Arnold; Christ, George J

2007-02-01

To identify early diabetes-related alterations in gene expression in bladder and erectile tissue that would provide novel diagnostic and therapeutic treatment targets to prevent, delay or ameliorate the ensuing bladder and erectile dysfunction. The RG-U34A rat GeneChip (Affymetrix Inc., Sunnyvale, CA, USA) oligonucleotide microarray (containing approximately 8799 genes) was used to evaluate gene expression in corporal and male bladder tissue excised from rats 1 week after confirmation of a diabetic state, but before demonstrable changes in organ function in vivo. A conservative analytical approach was used to detect alterations in gene expression, and gene ontology (GO) classifications were used to identify biological themes/pathways involved in the aetiology of the organ dysfunction. In all, 320 and 313 genes were differentially expressed in bladder and corporal tissue, respectively. GO analysis in bladder tissue showed prominent increases in biological pathways involved in cell proliferation, metabolism, actin cytoskeleton and myosin, as well as decreases in cell motility, and regulation of muscle contraction. GO analysis in corpora showed increases in pathways related to ion channel transport and ion channel activity, while there were decreases in collagen I and actin genes. The changes in gene expression in these initial experiments are consistent with the pathophysiological characteristics of the bladder and erectile dysfunction seen later in the diabetic disease process. Thus, the observed changes in gene expression might be harbingers or biomarkers of impending organ dysfunction, and could provide useful diagnostic and therapeutic targets for a variety of progressive urological diseases/conditions (i.e. lower urinary tract symptoms related to benign prostatic hyperplasia, erectile dysfunction, etc.).

Ability of Slovakian Pupils to Identify Birds

ERIC Educational Resources Information Center

Prokop, Pavol; Rodak, Rastislav

2009-01-01

A pupil's ability to identify common organisms is necessary for acquiring further knowledge of biology. We investigated how pupils were able to identify 25 bird species following their song, growth habits, or both features presented simultaneously. Just about 19% of birds were successfully identified by song, about 39% by growth habit, and 45% of…

Assessing urban potential flooding risk and identifying effective risk-reduction measures.

PubMed

Cherqui, Frédéric; Belmeziti, Ali; Granger, Damien; Sourdril, Antoine; Le Gauffre, Pascal

2015-05-01

Flood protection is one of the traditional functions of any drainage system, and it remains a major issue in many cities because of economic and health impact. Heavy rain flooding has been well studied and existing simulation software can be used to predict and improve level of protection. However, simulating minor flooding remains highly complex, due to the numerous possible causes related to operational deficiencies or negligent behaviour. According to the literature, causes of blockages vary widely from one case to another: it is impossible to provide utility managers with effective recommendations on how to improve the level of protection. It is therefore vital to analyse each context in order to define an appropriate strategy. Here we propose a method to represent and assess the flooding risk, using GIS and data gathered during operation and maintenance. Our method also identifies potential management responses. The approach proposed aims to provide decision makers with clear and comprehensible information. Our method has been successfully applied to the Urban Community of Bordeaux (France) on 4895 interventions related to flooding recorded during the 2009-2011 period. Results have shown the relative importance of different issues, such as human behaviour (grease, etc.) or operational deficiencies (roots, etc.), and lead to identify corrective and proactive. This study also confirms that blockages are not always directly due to the network itself and its deterioration. Many causes depend on environmental and operating conditions on the network and often require collaboration between municipal departments in charge of roads, green spaces, etc. Copyright © 2015 Elsevier B.V. All rights reserved.

Structure Based Virtual Screening Studies to Identify Novel Potential Compounds for GPR142 and Their Relative Dynamic Analysis for Study of Type 2 Diabetes

NASA Astrophysics Data System (ADS)

Kaushik, Aman C.; Kumar, Sanjay; Wei, Dong Q.; Sahi, Shakti

2018-02-01

GPR142 (G protein receptor 142) is a novel orphan GPCR (G protein coupled receptor) belonging to ‘Class A’ of GPCR family and expressed in beta cells of pancreas. In this study, we reported the structure based virtual screening to identify the hit compounds which can be developed as leads for potential agonists. The results were validated through induced fit docking, pharmacophore modeling and system biology approaches. Since, there is no solved crystal structure of GPR142, we attempted to predict the 3D structure followed by validation and then identification of active site using threading and ab initio methods. Also, structure based virtual screening was performed against a total of 1171519 compounds from different libraries and only top 20 best hit compounds were screened and analyzed. Moreover, the biochemical pathway of GPR142 complex with screened compound2 was also designed and compared with experimental data. Interestingly, compound2 showed an increase in insulin production via Gq mediated signaling pathway suggesting the possible role of novel GPR142 agonists in therapy against type 2 diabetes.

Sense-antisense (complementary) peptide interactions and the proteomic code; potential opportunities in biology and pharmaceutical science.

PubMed

Miller, Andrew D

2015-02-01

A sense peptide can be defined as a peptide whose sequence is coded by the nucleotide sequence (read 5' → 3') of the sense (positive) strand of DNA. Conversely, an antisense (complementary) peptide is coded by the corresponding nucleotide sequence (read 5' → 3') of the antisense (negative) strand of DNA. Research has been accumulating steadily to suggest that sense peptides are capable of specific interactions with their corresponding antisense peptides. Unfortunately, although more and more examples of specific sense-antisense peptide interactions are emerging, the very idea of such interactions does not conform to standard biology dogma and so there remains a sizeable challenge to lift this concept from being perceived as a peripheral phenomenon if not worse, into becoming part of the scientific mainstream. Specific interactions have now been exploited for the inhibition of number of widely different protein-protein and protein-receptor interactions in vitro and in vivo. Further, antisense peptides have also been used to induce the production of antibodies targeted to specific receptors or else the production of anti-idiotypic antibodies targeted against auto-antibodies. Such illustrations of utility would seem to suggest that observed sense-antisense peptide interactions are not just the consequence of a sequence of coincidental 'lucky-hits'. Indeed, at the very least, one might conclude that sense-antisense peptide interactions represent a potentially new and different source of leads for drug discovery. But could there be more to come from studies in this area? Studies on the potential mechanism of sense-antisense peptide interactions suggest that interactions may be driven by amino acid residue interactions specified from the genetic code. If so, such specified amino acid residue interactions could form the basis for an even wider amino acid residue interaction code (proteomic code) that links gene sequences to actual protein structure and function, even

Comparative transcriptome analysis of shoot and root tissue of Bacopa monnieri identifies potential genes related to triterpenoid saponin biosynthesis.

PubMed

Jeena, Gajendra Singh; Fatima, Shahnoor; Tripathi, Pragya; Upadhyay, Swati; Shukla, Rakesh Kumar

2017-06-28

Bacopa monnieri commonly known as Brahmi is utilized in Ayurveda to improve memory and many other human health benefits. Bacosides enriched standardized extract of Bacopa monnieri is being marketed as a memory enhancing agent. In spite of its well known pharmacological properties it is not much studied in terms of transcripts involved in biosynthetic pathway and its regulation that controls the secondary metabolic pathway in this plant. The aim of this study was to identify the potential transcripts and provide a framework of identified transcripts involved in bacosides production through transcriptome assembly. We performed comparative transcriptome analysis of shoot and root tissue of Bacopa monnieri in two independent biological replicate and obtained 22.48 million and 22.0 million high quality processed reads in shoot and root respectively. After de novo assembly and quantitative assessment total 26,412 genes got annotated in root and 18,500 genes annotated in shoot sample. Quality of raw reads was determined by using SeqQC-V2.2. Assembled sequences were annotated using BLASTX against public database such as NR or UniProt. Searching against the KEGG pathway database indicated that 37,918 unigenes from root and 35,130 unigenes from shoot were mapped to 133 KEGG pathways. Based on the DGE data we found that most of the transcript related to CYP450s and UDP-glucosyltransferases were specifically upregulated in shoot tissue as compared to root tissue. Finally, we have selected 43 transcripts related to secondary metabolism including transcription factor families which are differentially expressed in shoot and root tissues were validated by qRT-PCR and their expression level were monitored after MeJA treatment and wounding for 1, 3 and 5 h. This study not only represents the first de novo transcriptome analysis of Bacopa monnieri but also provides information about the identification, expression and differential tissues specific distribution of transcripts related

Identifying Chemical Groups for Biomonitoring

PubMed Central

Krowech, Gail; Hoover, Sara; Plummer, Laurel; Sandy, Martha; Zeise, Lauren; Solomon, Gina

2016-01-01

Summary: Regulatory agencies face daunting challenges identifying emerging chemical hazards because of the large number of chemicals in commerce and limited data on exposure and toxicology. Evaluating one chemical at a time is inefficient and can lead to replacement with uncharacterized chemicals or chemicals with structural features already linked to toxicity. The Office of Environmental Health Hazard Assessment (OEHHA) has developed a process for constructing and assessing chemical groups for potential biomonitoring in California. We screen for chemicals with significant exposure potential and propose possible chemical groups, based on structure and function. To support formal consideration of these groups by Biomonitoring California’s Scientific Guidance Panel, we conduct a detailed review of exposure and toxicity data and examine the likelihood of detection in biological samples. To date, 12 chemical groups have been constructed and added to the pool of chemicals that can be selected for Biomonitoring California studies, including p,p´-bisphenols, brominated and chlorinated organic compounds used as flame retardants, non-halogenated aromatic phosphates, and synthetic polycyclic musks. Evaluating chemical groups, rather than individual chemicals, is an efficient way to respond to shifts in chemical use and the emergence of new chemicals. This strategy can enable earlier identification of important chemicals for monitoring and intervention. PMID:27905275

Evaluation of denitrification potential of rotating biological contactors for treatment of municipal wastewater.

PubMed

Hanhan, O; Orhon, D; Krauth, Kh; Günder, B

2005-01-01

In this study the effect of retention time and rotation speed in the denitrification process in two full-scale rotating biological contactors (RBC) which were operated parallel and fed with municipal wastewater is evaluated. Each rotating biological contactor was covered to prevent oxygen input. The discs were 40% submerged. On the axle of one of the rotating biological contactors lamellas were placed (RBC1). During the experiments the nitrate removal performance of the rotating biological contactor with lamellas was observed to be less than the other (RBC2) since the lamellas caused oxygen diffusion through their movement. The highest nitrate removal observed was 2.06 g/m2.d achieved by a contact time of 28.84 minutes and a recycle flow of 1 l/s. The rotation speed during this set had the constant value of 0.8 min(-1). Nitrate removal efficiency on RBC1 was decreasing with increasing rotation speed. On the rotating biological contactor without lamellas no effect on denitrification could be determined within a speed range from 0.67 to 2.1 min-1. If operated in proper conditions denitrification on RBC is a very suitable alternative for nitrogen removal that can easily fulfil the nutrient limitations in coastal areas due to the rotating biological contactors economical benefits and uncomplicated handling.

The multiscale backbone of the human phenotype network based on biological pathways.

PubMed

Darabos, Christian; White, Marquitta J; Graham, Britney E; Leung, Derek N; Williams, Scott M; Moore, Jason H

2014-01-25

Networks are commonly used to represent and analyze large and complex systems of interacting elements. In systems biology, human disease networks show interactions between disorders sharing common genetic background. We built pathway-based human phenotype network (PHPN) of over 800 physical attributes, diseases, and behavioral traits; based on about 2,300 genes and 1,200 biological pathways. Using GWAS phenotype-to-genes associations, and pathway data from Reactome, we connect human traits based on the common patterns of human biological pathways, detecting more pleiotropic effects, and expanding previous studies from a gene-centric approach to that of shared cell-processes. The resulting network has a heavily right-skewed degree distribution, placing it in the scale-free region of the network topologies spectrum. We extract the multi-scale information backbone of the PHPN based on the local densities of the network and discarding weak connection. Using a standard community detection algorithm, we construct phenotype modules of similar traits without applying expert biological knowledge. These modules can be assimilated to the disease classes. However, we are able to classify phenotypes according to shared biology, and not arbitrary disease classes. We present examples of expected clinical connections identified by PHPN as proof of principle. We unveil a previously uncharacterized connection between phenotype modules and discuss potential mechanistic connections that are obvious only in retrospect. The PHPN shows tremendous potential to become a useful tool both in the unveiling of the diseases' common biology, and in the elaboration of diagnosis and treatments.

Microbial Biogeochemistry of Seafloor Fluid Flow on Earth and Implications for Biological Potential on Enceladus

NASA Astrophysics Data System (ADS)

Huber, J. A.

2017-12-01

The interaction between liquid water and the rocky seafloor provides high potential for release of chemical energy, thus seafloor fluid flow is viewed an essential driver of subseafloor microbial life in Earth's oceans. Given predictions that Enceladus hosts a global-scale ocean underlain by a rocky seafloor, and new data suggesting on-going hydrothermal activity on Enceladus based on detection of hydrogen by Cassini, it is timely to investigate those subseafloor Earth analogs that may be informative when developing future missions to and interpreting mission data from Enceladus. Over the last 35 years, the breadth of seafloor fluid flow regimes that have been discovered and studied on Earth has expanded to include a wide spectrum of geological settings, geochemical characteristics, and microorganisms, including environments that were not previously known to exist, e.g. hydrogen-rich mafic systems, ridge-flank oxic systems, etc. This presentation will provide an overview of the latest and most exciting findings on the microbial biogeochemistry of seafloor fluid flow in Earth's oceans and place these findings in the context of biological potential for Enceladus.

Drug-Induced Acute Myocardial Infarction: Identifying ‘Prime Suspects’ from Electronic Healthcare Records-Based Surveillance System

PubMed Central

Coloma, Preciosa M.; Schuemie, Martijn J.; Trifirò, Gianluca; Furlong, Laura; van Mulligen, Erik; Bauer-Mehren, Anna; Avillach, Paul; Kors, Jan; Sanz, Ferran; Mestres, Jordi; Oliveira, José Luis; Boyer, Scott; Helgee, Ernst Ahlberg; Molokhia, Mariam; Matthews, Justin; Prieto-Merino, David; Gini, Rosa; Herings, Ron; Mazzaglia, Giampiero; Picelli, Gino; Scotti, Lorenza; Pedersen, Lars; van der Lei, Johan; Sturkenboom, Miriam

2013-01-01

Background Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in ‘real-world’ settings. Objective To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI) from a large international healthcare data network. Methods Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996–2010. Primary care physicians’ medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible. Results Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs (‘prime suspects’): azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate. Limitations Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. Conclusion A strategy to identify potentially drug-induced AMI from electronic healthcare data has

Agroterrorism, Biological Crimes, and Biological Warfare Targeting Animal Agriculture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, Terry M.; Logan-Henfrey, Linda; Weller, Richard E.

2000-04-12

There is a rising level of concern that agriculture might be targeted for economic sabotage by terrorists. Knowledge gathered about the Soviet Union biological weapons program and Iraq following the Gulf War, confirmed that animals and agricultural crops were targets of bioweapon development. These revelations are particularly disturbing in light of the fact that both countries are States Parties to the Biological and Toxin Weapons Convention that entered into force in 1975. The potential for misusing biotechnology to create more virulent pathogens and the lack of international means to detect unethical uses of new technologies to create destructive bioweapons ismore » of increasing concern. Disease outbreaks, whether naturally occurring or intentionally, involving agricultural pathogens that destroy livestock and crops would have a profound impact on a country's infrastructure, economy and export markets. This chapter deals with the history of agroterrorism, biological crimes and biological warfare directed toward animal agriculture, specifically, horses, cattle, swine, sheep, goats, and poultry.« less

Mostly Plants. Individualized Biology Activities on: I. Investigating Bread Mold; II. Transpiration; III. Botany Project; IV. Collecting/Preserving/Identifying Leaves; [and] V. Student Science Laboratory Write-Ups.

ERIC Educational Resources Information Center

Gibson, Paul R.

Individualized biology activities for secondary students are presented in this teaching guide. The guide is divided into five sections: (1) investigating bread mold; (2) investigating transpiration; (3) completing a botany project; (4) collecting, preserving, and identifying leaves; and (5) writing up science laboratory investigations. The…