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Sample records for biology identifies alteration

  1. Expression-based network biology identifies alteration in key regulatory pathways of type 2 diabetes and associated risk/complications.

    Science.gov (United States)

    Sengupta, Urmi; Ukil, Sanchaita; Dimitrova, Nevenka; Agrawal, Shipra

    2009-01-01

    Type 2 diabetes mellitus (T2D) is a multifactorial and genetically heterogeneous disease which leads to impaired glucose homeostasis and insulin resistance. The advanced form of disease causes acute cardiovascular, renal, neurological and microvascular complications. Thus there is a constant need to discover new and efficient treatment against the disease by seeking to uncover various novel alternate signalling mechanisms that can lead to diabetes and its associated complications. The present study allows detection of molecular targets by unravelling their role in altered biological pathways during diabetes and its associated risk factors and complications. We have used an integrated functional networks concept by merging co-expression network and interaction network to detect the transcriptionally altered pathways and regulations involved in the disease. Our analysis reports four novel significant networks which could lead to the development of diabetes and other associated dysfunctions. (a) The first network illustrates the up regulation of TGFBRII facilitating oxidative stress and causing the expression of early transcription genes via MAPK pathway leading to cardiovascular and kidney related complications. (b) The second network demonstrates novel interactions between GAPDH and inflammatory and proliferation candidate genes i.e., SUMO4 and EGFR indicating a new link between obesity and diabetes. (c) The third network portrays unique interactions PTPN1 with EGFR and CAV1 which could lead to an impaired vascular function in diabetic nephropathy condition. (d) Lastly, from our fourth network we have inferred that the interaction of beta-catenin with CDH5 and TGFBR1 through Smad molecules could contribute to endothelial dysfunction. A probability of emergence of kidney complication might be suggested in T2D condition. An experimental investigation on this aspect may further provide more decisive observation in drug target identification and better understanding of

  2. Expression-based network biology identifies alteration in key regulatory pathways of type 2 diabetes and associated risk/complications.

    Directory of Open Access Journals (Sweden)

    Urmi Sengupta

    Full Text Available Type 2 diabetes mellitus (T2D is a multifactorial and genetically heterogeneous disease which leads to impaired glucose homeostasis and insulin resistance. The advanced form of disease causes acute cardiovascular, renal, neurological and microvascular complications. Thus there is a constant need to discover new and efficient treatment against the disease by seeking to uncover various novel alternate signalling mechanisms that can lead to diabetes and its associated complications. The present study allows detection of molecular targets by unravelling their role in altered biological pathways during diabetes and its associated risk factors and complications. We have used an integrated functional networks concept by merging co-expression network and interaction network to detect the transcriptionally altered pathways and regulations involved in the disease. Our analysis reports four novel significant networks which could lead to the development of diabetes and other associated dysfunctions. (a The first network illustrates the up regulation of TGFBRII facilitating oxidative stress and causing the expression of early transcription genes via MAPK pathway leading to cardiovascular and kidney related complications. (b The second network demonstrates novel interactions between GAPDH and inflammatory and proliferation candidate genes i.e., SUMO4 and EGFR indicating a new link between obesity and diabetes. (c The third network portrays unique interactions PTPN1 with EGFR and CAV1 which could lead to an impaired vascular function in diabetic nephropathy condition. (d Lastly, from our fourth network we have inferred that the interaction of beta-catenin with CDH5 and TGFBR1 through Smad molecules could contribute to endothelial dysfunction. A probability of emergence of kidney complication might be suggested in T2D condition. An experimental investigation on this aspect may further provide more decisive observation in drug target identification and better

  3. Advances in the translational genomics of neuroblastoma: From improving risk stratification and revealing novel biology to identifying actionable genomic alterations.

    Science.gov (United States)

    Bosse, Kristopher R; Maris, John M

    2016-01-01

    Neuroblastoma is an embryonal malignancy that commonly affects young children and is remarkably heterogenous in its malignant potential. Recently, the genetic basis of neuroblastoma has come into focus and not only has catalyzed a more comprehensive understanding of neuroblastoma tumorigenesis but also has revealed novel oncogenic vulnerabilities that are being therapeutically leveraged. Neuroblastoma is a model pediatric solid tumor in its use of recurrent genomic alterations, such as high-level MYCN (v-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog) amplification, for risk stratification. Given the relative paucity of recurrent, activating, somatic point mutations or gene fusions in primary neuroblastoma tumors studied at initial diagnosis, innovative treatment approaches beyond small molecules targeting mutated or dysregulated kinases will be required moving forward to achieve noticeable improvements in overall patient survival. However, the clonally acquired, oncogenic aberrations in relapsed neuroblastomas are currently being defined and may offer an opportunity to improve patient outcomes with molecularly targeted therapy directed toward aberrantly regulated pathways in relapsed disease. This review summarizes the current state of knowledge about neuroblastoma genetics and genomics, highlighting the improved prognostication and potential therapeutic opportunities that have arisen from recent advances in understanding germline predisposition, recurrent segmental chromosomal alterations, somatic point mutations and translocations, and clonal evolution in relapsed neuroblastoma.

  4. Wham: Identifying Structural Variants of Biological Consequence.

    Science.gov (United States)

    Kronenberg, Zev N; Osborne, Edward J; Cone, Kelsey R; Kennedy, Brett J; Domyan, Eric T; Shapiro, Michael D; Elde, Nels C; Yandell, Mark

    2015-12-01

    Existing methods for identifying structural variants (SVs) from short read datasets are inaccurate. This complicates disease-gene identification and efforts to understand the consequences of genetic variation. In response, we have created Wham (Whole-genome Alignment Metrics) to provide a single, integrated framework for both structural variant calling and association testing, thereby bypassing many of the difficulties that currently frustrate attempts to employ SVs in association testing. Here we describe Wham, benchmark it against three other widely used SV identification tools-Lumpy, Delly and SoftSearch-and demonstrate Wham's ability to identify and associate SVs with phenotypes using data from humans, domestic pigeons, and vaccinia virus. Wham and all associated software are covered under the MIT License and can be freely downloaded from github (https://github.com/zeeev/wham), with documentation on a wiki (http://zeeev.github.io/wham/). For community support please post questions to https://www.biostars.org/.

  5. Wham: Identifying Structural Variants of Biological Consequence.

    Directory of Open Access Journals (Sweden)

    Zev N Kronenberg

    2015-12-01

    Full Text Available Existing methods for identifying structural variants (SVs from short read datasets are inaccurate. This complicates disease-gene identification and efforts to understand the consequences of genetic variation. In response, we have created Wham (Whole-genome Alignment Metrics to provide a single, integrated framework for both structural variant calling and association testing, thereby bypassing many of the difficulties that currently frustrate attempts to employ SVs in association testing. Here we describe Wham, benchmark it against three other widely used SV identification tools-Lumpy, Delly and SoftSearch-and demonstrate Wham's ability to identify and associate SVs with phenotypes using data from humans, domestic pigeons, and vaccinia virus. Wham and all associated software are covered under the MIT License and can be freely downloaded from github (https://github.com/zeeev/wham, with documentation on a wiki (http://zeeev.github.io/wham/. For community support please post questions to https://www.biostars.org/.

  6. Structural health monitoring (vibration) as a tool for identifying structural alterations of the lumbar spine

    DEFF Research Database (Denmark)

    Kawchuk, Gregory N; Hartvigsen, Jan; Edgecombe, Tiffany;

    2016-01-01

    Structural health monitoring (SHM) is an engineering technique used to identify mechanical abnormalities not readily apparent through other means. Recently, SHM has been adapted for use in biological systems, but its invasive nature limits its clinical application. As such, the purpose of this...... project was to determine if a non-invasive form of SHM could identify structural alterations in the spines of living human subjects. Lumbar spines of 10 twin pairs were visualized by magnetic resonance imaging then assessed by a blinded radiologist to determine whether twin pairs were structurally...

  7. Biological invasion by Myrica faya alters ecosystem development in Hawaii

    Science.gov (United States)

    Vitousek, Peter M.; Walker, Lawrence R.; Whiteaker, Louis D.; Mueller-Dombois, Dieter; Matson, Pamela A.

    1987-01-01

    The exotic nitrogen-fixing tree Myrica faya invades young volcanic sites where the growth of native plants is limited by a lack of nitrogen. Myrica quadruples the amount of nitrogen entering certain sites and increases the overall biological availability of nitrogen, thereby altering the nature of ecosystem development after volcanic eruptions.

  8. Chromatic alteration on marble surfaces analysed by molecular biology tools

    Directory of Open Access Journals (Sweden)

    Franco Palla

    2007-07-01

    Full Text Available The patina represents a superficial natural alteration of the constituting matter of the work of art. It emerges from the natural and usual stabilization process that the materials of the surface undergo because of the interaction with outdoor agents characterizing the surrounding environment. Besides, it is not linked to an obvious phenomenon of degradation that can be noticed through the change in the original colour of the matter. This is what we intend when we talk about biological patina usually generated by macro and/or micro-organic colonization (fungi, bacteria, alga which contributes to surface bio-deterioration and thus lead to the formation of orange, red or even brown and dark pigmented areas. The presence of chromatic alterations (rose-coloured areas, as a consequence of bacterial colonization, was most particularly pointed out in different sites, such as in the marble slabs on the facades of both the Cathedral of Siena (Duomo di Siena and the Certosa of Pavia. The present study shows an example of chromatic alteration of the surface of marble works due to bacterial colonization.

  9. TAGCNA: a method to identify significant consensus events of copy number alterations in cancer.

    Science.gov (United States)

    Yuan, Xiguo; Zhang, Junying; Yang, Liying; Zhang, Shengli; Chen, Baodi; Geng, Yaojun; Wang, Yue

    2012-01-01

    Somatic copy number alteration (CNA) is a common phenomenon in cancer genome. Distinguishing significant consensus events (SCEs) from random background CNAs in a set of subjects has been proven to be a valuable tool to study cancer. In order to identify SCEs with an acceptable type I error rate, better computational approaches should be developed based on reasonable statistics and null distributions. In this article, we propose a new approach named TAGCNA for identifying SCEs in somatic CNAs that may encompass cancer driver genes. TAGCNA employs a peel-off permutation scheme to generate a reasonable null distribution based on a prior step of selecting tag CNA markers from the genome being considered. We demonstrate the statistical power of TAGCNA on simulated ground truth data, and validate its applicability using two publicly available cancer datasets: lung and prostate adenocarcinoma. TAGCNA identifies SCEs that are known to be involved with proto-oncogenes (e.g. EGFR, CDK4) and tumor suppressor genes (e.g. CDKN2A, CDKN2B), and provides many additional SCEs with potential biological relevance in these data. TAGCNA can be used to analyze the significance of CNAs in various cancers. It is implemented in R and is freely available at http://tagcna.sourceforge.net/. PMID:22815924

  10. TAGCNA: a method to identify significant consensus events of copy number alterations in cancer.

    Directory of Open Access Journals (Sweden)

    Xiguo Yuan

    Full Text Available Somatic copy number alteration (CNA is a common phenomenon in cancer genome. Distinguishing significant consensus events (SCEs from random background CNAs in a set of subjects has been proven to be a valuable tool to study cancer. In order to identify SCEs with an acceptable type I error rate, better computational approaches should be developed based on reasonable statistics and null distributions. In this article, we propose a new approach named TAGCNA for identifying SCEs in somatic CNAs that may encompass cancer driver genes. TAGCNA employs a peel-off permutation scheme to generate a reasonable null distribution based on a prior step of selecting tag CNA markers from the genome being considered. We demonstrate the statistical power of TAGCNA on simulated ground truth data, and validate its applicability using two publicly available cancer datasets: lung and prostate adenocarcinoma. TAGCNA identifies SCEs that are known to be involved with proto-oncogenes (e.g. EGFR, CDK4 and tumor suppressor genes (e.g. CDKN2A, CDKN2B, and provides many additional SCEs with potential biological relevance in these data. TAGCNA can be used to analyze the significance of CNAs in various cancers. It is implemented in R and is freely available at http://tagcna.sourceforge.net/.

  11. Integrative biology approach identifies cytokine targeting strategies for psoriasis.

    Science.gov (United States)

    Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O

    2014-02-12

    Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.

  12. Identifying features in biological sequences: Sixth workshop report

    Energy Technology Data Exchange (ETDEWEB)

    Burks, C. [Los Alamos National Lab., NM (United States); Myers, E. [Univ. of Arizona (United States); Pearson, W.R. [Univ. of Virginia (United States)

    1995-12-31

    This report covers the sixth of an annual series of workshops held at the Aspen Center for Physics concentrating particularly on the identification of features in DNA sequence, and more broadly on related topics in computational molecular biology. The workshop series originally focused primarily on discussion of current needs and future strategies for identifying and predicting the presence of complex functional units on sequenced, but otherwise uncharacterized, genomic DNA. We addressed the need for computationally-based, automatic tools for synthesizing available data about individual consensus sequences and local compositional patterns into the composite objects (e.g., genes) that are -- as composite entities -- the true object of interest when scanning DNA sequences. The workshop was structured to promote sustained informal contact and exchange of expertise between molecular biologists, computer scientists, and mathematicians.

  13. Six Siderophore-Producing Microorganisms Identified in Biological Soil Crusts

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  15. Alteration of biological samples in speciation analysis of metalloproteins.

    Science.gov (United States)

    Wolf, Christian; Wenda, Nadine; Richter, Andrea; Kyriakopoulos, Antonios

    2007-10-01

    For investigations of metalloproteins by speciation analysis, the integrity of the protein-metal complexes before and during separation is crucial. Knowledge about potential alterations of the samples is thus essential to avoid misinterpretations of the analytical results. Chromatographic element profiles of different cytosolic samples from animal tissues were measured repeatedly to estimate the sample stability. The dependence of the signals on the dwell time of the sample in an autosampling device at 4 degrees C for a period of 10 h was observed. Alterations in the element content of different metal-containing fractions were quantified by means of recovery values. Some metalloprotein fractions (e.g. approximately 27-kDa arsenic, approximately 27-kDa iron and different zinc fractions) were stable or only minor alterations were observed and for their investigation an autosampling device is therefore suitable. However, most of the other metalloprotein fractions, especially nickel-containing proteins, showed major alterations: these samples should therefore be analysed immediately after preparation or directly after thawing.

  16. Identifying and Visualizing Macromolecular Flexibility in Structural Biology.

    Science.gov (United States)

    Palamini, Martina; Canciani, Anselmo; Forneris, Federico

    2016-01-01

    Structural biology comprises a variety of tools to obtain atomic resolution data for the investigation of macromolecules. Conventional structural methodologies including crystallography, NMR and electron microscopy often do not provide sufficient details concerning flexibility and dynamics, even though these aspects are critical for the physiological functions of the systems under investigation. However, the increasing complexity of the molecules studied by structural biology (including large macromolecular assemblies, integral membrane proteins, intrinsically disordered systems, and folding intermediates) continuously demands in-depth analyses of the roles of flexibility and conformational specificity involved in interactions with ligands and inhibitors. The intrinsic difficulties in capturing often subtle but critical molecular motions in biological systems have restrained the investigation of flexible molecules into a small niche of structural biology. Introduction of massive technological developments over the recent years, which include time-resolved studies, solution X-ray scattering, and new detectors for cryo-electron microscopy, have pushed the limits of structural investigation of flexible systems far beyond traditional approaches of NMR analysis. By integrating these modern methods with powerful biophysical and computational approaches such as generation of ensembles of molecular models and selective particle picking in electron microscopy, more feasible investigations of dynamic systems are now possible. Using some prominent examples from recent literature, we review how current structural biology methods can contribute useful data to accurately visualize flexibility in macromolecular structures and understand its important roles in regulation of biological processes.

  17. Topics in space gerontology: Effects of altered gravity and the problem of biological age

    Science.gov (United States)

    Economos, A. C.

    1982-01-01

    The use of altered gravity experimentation as a gerontological research tool is examined and a rationale for a systems approach to the adaptation to spaceflight is presented. The dependence of adaptation capacity on biological age is also discussed.

  18. Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

    OpenAIRE

    Lee, Kuei-Fang; Weng, Julia Tzu-Ya; Hsu, Paul Wei-Che; Chi, Yu-Hsiang; Chen, Ching-Kai; Liu, Ingrid Y.; CHEN, YI-CHENG; Wu, Lawrence Shih-Hsin

    2014-01-01

    Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from...

  19. Structural health monitoring (vibration) as a tool for identifying structural alterations of the lumbar spine

    DEFF Research Database (Denmark)

    Kawchuk, Gregory N; Hartvigsen, Jan; Edgecombe, Tiffany;

    2016-01-01

    Structural health monitoring (SHM) is an engineering technique used to identify mechanical abnormalities not readily apparent through other means. Recently, SHM has been adapted for use in biological systems, but its invasive nature limits its clinical application. As such, the purpose...

  20. Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Kuei-Fang Lee

    2014-01-01

    Full Text Available Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.

  1. Structural health monitoring (vibration) as a tool for identifying structural alterations of the lumbar spine: a twin control study.

    Science.gov (United States)

    Kawchuk, Gregory N; Hartvigsen, Jan; Edgecombe, Tiffany; Prasad, Narasimha; van Dieen, Jaap H

    2016-01-01

    Structural health monitoring (SHM) is an engineering technique used to identify mechanical abnormalities not readily apparent through other means. Recently, SHM has been adapted for use in biological systems, but its invasive nature limits its clinical application. As such, the purpose of this project was to determine if a non-invasive form of SHM could identify structural alterations in the spines of living human subjects. Lumbar spines of 10 twin pairs were visualized by magnetic resonance imaging then assessed by a blinded radiologist to determine whether twin pairs were structurally concordant or discordant. Vibration was then applied to each subject's spine and the resulting response recorded from sensors overlying lumbar spinous processes. The peak frequency, area under the curve and the root mean square were computed from the frequency response function of each sensor. Statistical analysis demonstrated that in twins whose structural appearance was discordant, peak frequency was significantly different between twin pairs while in concordant twins, no outcomes were significantly different. From these results, we conclude that structural changes within the spine can alter its vibration response. As such, further investigation of SHM to identify spinal abnormalities in larger human populations is warranted. PMID:26964507

  2. The Alteration of Lipid Metabolism in Burkitt Lymphoma Identifies a Novel Marker: Adipophilin

    OpenAIRE

    Ambrosio, Maria R.; Piccaluga, Pier P.; Maurilio Ponzoni; Rocca, Bruno J; Valeria Malagnino; Monica Onorati; Giulia De Falco; Valeria Calbi; Martin Ogwang; Naresh, Kikkeri N.; Pileri, Stefano A.; Claudio Doglioni; Lorenzo Leoncini; Stefano Lazzi

    2012-01-01

    BACKGROUND: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. METHODS AND RESULTS: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymp...

  3. Identifying and relating biological concepts in the Catalogue of Life

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    Jones Andrew C

    2011-10-01

    Full Text Available Abstract Background In this paper we describe our experience of adding globally unique identifiers to the Species 2000 and ITIS Catalogue of Life, an on-line index of organisms which is intended, ultimately, to cover all the world's known species. The scientific species names held in the Catalogue are names that already play an extensive role as terms in the organisation of information about living organisms in bioinformatics and other domains, but the effectiveness of their use is hindered by variation in individuals' opinions and understanding of these terms; indeed, in some cases more than one name will have been used to refer to the same organism. This means that it is desirable to be able to give unique labels to each of these differing concepts within the catalogue and to be able to determine which concepts are being used in other systems, in order that they can be associated with the concepts in the catalogue. Not only is this needed, but it is also necessary to know the relationships between alternative concepts that scientists might have employed, as these determine what can be inferred when data associated with related concepts is being processed. A further complication is that the catalogue itself is evolving as scientific opinion changes due to an increasing understanding of life. Results We describe how we are using Life Science Identifiers (LSIDs as globally unique identifiers in the Catalogue of Life, explaining how the mapping to species concepts is performed, how concepts are associated with specific editions of the catalogue, and how the Taxon Concept Schema has been adopted in order to express information about concepts and their relationships. We explore the implications of using globally unique identifiers in order to refer to abstract concepts such as species, which incorporate at least a measure of subjectivity in their definition, in contrast with the more traditional use of such identifiers to refer to more tangible

  4. Identifying biological pathway interrupting toxins using multi-tree ensembles

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    Gergo Barta

    2016-08-01

    Full Text Available The pharmaceutical industry constantly seeks new ways to improve current methods that scientists use to evaluate environmental chemicals and develop new medicines. Various automated steps are involved in the process as testing hundreds of thousands of chemicals manually would be infeasible. Our research effort and the Toxicology in the 21st Century Data Challenge focused on cost-effective automation of toxicological testing, a chemical substance screening process looking for possible toxic effects caused by interrupting biological pathways. The computational models we propose in this paper successfully combine various publicly available substance fingerprinting tools with advanced machine learning techniques. In our paper, we explore the significance and utility of assorted feature selection methods as the structural analyzers generate a plethora of features for each substance. Machine learning models were carefully selected and evaluated based on their capability to cope with the high-dimensional high-variety data with multi-tree ensemble methods coming out on top. Techniques like Random forests and Extra trees combine numerous simple tree models and proved to produce reliable predictions on toxic activity while being nearly non-parametric and insensitive to dimensionality extremes. The Tox21 Data Challenge contest offered a great platform to compare a wide range of solutions in a controlled and orderly manner. The results clearly demonstrate that the generic approach presented in this paper is comparable to advanced deep learning and domain-specific solutions. Even surpassing the competition in some nuclear receptor signaling and stress pathway assays and achieving an accuracy of up to 94 percent.

  5. Genome wide association mapping in Arabidopsis thaliana identifies novel genes involved in linking allyl glucosinolate to altered biomass and defense

    Directory of Open Access Journals (Sweden)

    Marta Francisco

    2016-07-01

    Full Text Available A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL, may provide direct feedback regulation, linking defense metabolism outputs to the growth and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 µM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis.

  6. RNA-Seq identifies key reproductive gene expression alterations in response to cadmium exposure.

    Science.gov (United States)

    Hu, Hanyang; Lu, Xing; Cen, Xiang; Chen, Xiaohua; Li, Feng; Zhong, Shan

    2014-01-01

    Cadmium is a common toxicant that is detrimental to many tissues. Although a number of transcriptional signatures have been revealed in different tissues after cadmium treatment, the genes involved in the cadmium caused male reproductive toxicity, and the underlying molecular mechanism remains unclear. Here we observed that the mice treated with different amount of cadmium in their rodent chow for six months exhibited reduced serum testosterone. We then performed RNA-seq to comprehensively investigate the mice testicular transcriptome to further elucidate the mechanism. Our results showed that hundreds of genes expression altered significantly in response to cadmium treatment. In particular, we found several transcriptional signatures closely related to the biological processes of regulation of hormone, gamete generation, and sexual reproduction, respectively. The expression of several testosterone synthetic key enzyme genes, such as Star, Cyp11a1, and Cyp17a1, were inhibited by the cadmium exposure. For better understanding of the cadmium-mediated transcriptional regulatory mechanism of the genes, we computationally analyzed the transcription factors binding sites and the mircoRNAs targets of the differentially expressed genes. Our findings suggest that the reproductive toxicity by cadmium exposure is implicated in multiple layers of deregulation of several biological processes and transcriptional regulation in mice. PMID:24982889

  7. RNA-Seq Identifies Key Reproductive Gene Expression Alterations in Response to Cadmium Exposure

    Directory of Open Access Journals (Sweden)

    Hanyang Hu

    2014-01-01

    Full Text Available Cadmium is a common toxicant that is detrimental to many tissues. Although a number of transcriptional signatures have been revealed in different tissues after cadmium treatment, the genes involved in the cadmium caused male reproductive toxicity, and the underlying molecular mechanism remains unclear. Here we observed that the mice treated with different amount of cadmium in their rodent chow for six months exhibited reduced serum testosterone. We then performed RNA-seq to comprehensively investigate the mice testicular transcriptome to further elucidate the mechanism. Our results showed that hundreds of genes expression altered significantly in response to cadmium treatment. In particular, we found several transcriptional signatures closely related to the biological processes of regulation of hormone, gamete generation, and sexual reproduction, respectively. The expression of several testosterone synthetic key enzyme genes, such as Star, Cyp11a1, and Cyp17a1, were inhibited by the cadmium exposure. For better understanding of the cadmium-mediated transcriptional regulatory mechanism of the genes, we computationally analyzed the transcription factors binding sites and the mircoRNAs targets of the differentially expressed genes. Our findings suggest that the reproductive toxicity by cadmium exposure is implicated in multiple layers of deregulation of several biological processes and transcriptional regulation in mice.

  8. Biological Alteration of Basaltic Glass With Altered Composition and Oxidation States

    Science.gov (United States)

    Bailey, B. E.; Staudigel, H.; Templeton, A.; Tebo, B. M.; Ryerson, F.; Plank, T.; Schroder, C.; Klingelhoefer, G.

    2004-12-01

    The ocean crust is an extreme and oligotrophic environment and yet recent studies have shown that reactions between oceanic crust and seawater are capable of supporting microbial life. We are specifically targeting volcanic glass as a source of energy and nutrients necessary to support endolithic microbial communities. A significant amount of chemical energy is available from the process of iron oxidation and our goal is to determine the ability of microorganisms to use Fe(II) as an energy source as well as liberate other essential nutrients from the host rock. In addition, microbes may oxidize Mn or use phosphate from glass. To explore the dependency of microbial life on these nutrients and energy sources, we produce basaltic glasses with varying Fe oxidation states and relative abundance of iron, manganese and phosphate and introduce them to microbial isolates and consortia both in the laboratory and in deep-ocean environments. The natural exposure experiments occur in a variety of settings including hydrothermal vents and cold deep seawater (Loihi Seamount), brines (Mediterranean), and basaltic flows at spreading ridges (EPR), when possible on submarine lava flows of recent and known age. Upon collection of the exposure experiments, we compare basalt colonizing microbial communities on our synthetic glasses with the in situ glass communities through a large culturing effort and molecular (t-RFLP) studies. So far we have produced a number of enrichment cultures and isolated several iron-oxidizing and manganese-oxidizing bacteria that were used to inoculate glasses in the laboratory. Laboratory experiments concentrate on biofilm formation and dissolution of the colonized glasses. Continued collection of exposure experiments on a yearly time-scale provides valuable information regarding spatial and temporal variations in microbial community diversity and structure. We have also analyzed the authigenic reaction products of seafloor, microbially mediated alteration

  9. Microbial community changes in biological phosphate-removal systems on altering sludge phosphorus content

    NARCIS (Netherlands)

    Liu, WT; Linning, KD; Nakamura, K; Mino, T; Matsuo, T; Forney, LJ

    2000-01-01

    Biomarkers (respiratory quinones and cellular fatty acids) and denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA genes were used to characterize the microbial community structure of lab-scale enhanced biological phosphate-removal (EBPR) systems in response to altering sludge p

  10. Genome wide transcriptome analysis of dendritic cells identifies genes with altered expression in psoriasis.

    Directory of Open Access Journals (Sweden)

    Kata Filkor

    Full Text Available Activation of dendritic cells by different pathogens induces the secretion of proinflammatory mediators resulting in local inflammation. Importantly, innate immunity must be properly controlled, as its continuous activation leads to the development of chronic inflammatory diseases such as psoriasis. Lipopolysaccharide (LPS or peptidoglycan (PGN induced tolerance, a phenomenon of transient unresponsiveness of cells to repeated or prolonged stimulation, proved valuable model for the study of chronic inflammation. Thus, the aim of this study was the identification of the transcriptional diversity of primary human immature dendritic cells (iDCs upon PGN induced tolerance. Using SAGE-Seq approach, a tag-based transcriptome sequencing method, we investigated gene expression changes of primary human iDCs upon stimulation or restimulation with Staphylococcus aureus derived PGN, a widely used TLR2 ligand. Based on the expression pattern of the altered genes, we identified non-tolerizeable and tolerizeable genes. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (Kegg analysis showed marked enrichment of immune-, cell cycle- and apoptosis related genes. In parallel to the marked induction of proinflammatory mediators, negative feedback regulators of innate immunity, such as TNFAIP3, TNFAIP8, Tyro3 and Mer are markedly downregulated in tolerant cells. We also demonstrate, that the expression pattern of TNFAIP3 and TNFAIP8 is altered in both lesional, and non-lesional skin of psoriatic patients. Finally, we show that pretreatment of immature dendritic cells with anti-TNF-α inhibits the expression of IL-6 and CCL1 in tolerant iDCs and partially releases the suppression of TNFAIP8. Our findings suggest that after PGN stimulation/restimulation the host cell utilizes different mechanisms in order to maintain critical balance between inflammation and tolerance. Importantly, the transcriptome sequencing of stimulated/restimulated iDCs identified

  11. Novel Somatic Copy Number Alteration Identified for Cervical Cancer in the Mexican American Population

    Directory of Open Access Journals (Sweden)

    Alireza Torabi

    2016-08-01

    Full Text Available Cervical cancer affects millions of Americans, but the rate for cervical cancer in the Mexican American is approximately twice that for non-Mexican Americans. The etiologies of cervical cancer are still not fully understood. A number of somatic mutations, including several copy number alterations (CNAs, have been identified in the pathogenesis of cervical carcinomas in non-Mexican Americans. Thus, the purpose of this study was to investigate CNAs in association with cervical cancer in the Mexican American population. We conducted a pilot study of genome-wide CNA analysis using 2.5 million markers in four diagnostic groups: reference (n = 125, low grade dysplasia (cervical intraepithelial neoplasia (CIN-I, n = 4, high grade dysplasia (CIN-II and -III, n = 5 and invasive carcinoma (squamous cell carcinoma (SCC, n = 5 followed by data analyses using Partek. We observed a statistically-significant difference of CNA burden between case and reference groups of different sizes (>100 kb, 10–100 kb and 1–10 kb of CNAs that included deletions and amplifications, e.g., a statistically-significant difference of >100 kb deletions was observed between the reference (6.6% and pre-cancer and cancer (91.3% groups. Recurrent aberrations of 98 CNA regions were also identified in cases only. However, none of the CNAs have an impact on cancer progression. A total of 32 CNA regions identified contained tumor suppressor genes and oncogenes. Moreover, the pathway analysis revealed endometrial cancer and estrogen signaling pathways associated with this cancer (p < 0.05 using Kyoto Encyclopedia of Genes and Genomes (KEGG. This is the first report of CNAs identified for cervical cancer in the U.S. Latino population using high density markers. We are aware of the small sample size in the study. Thus, additional studies with a larger sample are needed to confirm the current findings.

  12. Comparative analysis of methods for identifying recurrent copy number alterations in cancer.

    Directory of Open Access Journals (Sweden)

    Xiguo Yuan

    Full Text Available Recurrent copy number alterations (CNAs play an important role in cancer genesis. While a number of computational methods have been proposed for identifying such CNAs, their relative merits remain largely unknown in practice since very few efforts have been focused on comparative analysis of the methods. To facilitate studies of recurrent CNA identification in cancer genome, it is imperative to conduct a comprehensive comparison of performance and limitations among existing methods. In this paper, six representative methods proposed in the latest six years are compared. These include one-stage and two-stage approaches, working with raw intensity ratio data and discretized data respectively. They are based on various techniques such as kernel regression, correlation matrix diagonal segmentation, semi-parametric permutation and cyclic permutation schemes. We explore multiple criteria including type I error rate, detection power, Receiver Operating Characteristics (ROC curve and the area under curve (AUC, and computational complexity, to evaluate performance of the methods under multiple simulation scenarios. We also characterize their abilities on applications to two real datasets obtained from cancers with lung adenocarcinoma and glioblastoma. This comparison study reveals general characteristics of the existing methods for identifying recurrent CNAs, and further provides new insights into their strengths and weaknesses. It is believed helpful to accelerate the development of novel and improved methods.

  13. Targeted alteration of real and imaginary refractive index of biological cells by histological staining

    OpenAIRE

    Cherkezyan, Lusik; Subramanian, Hariharan; Stoyneva, Valentina; Rogers, Jeremy D.; Yang, Seungmoo; Damania, Dhwanil; Taflove, Allen; Backman, Vadim

    2012-01-01

    Various staining techniques are commonly used in biomedical research to investigate cellular morphology. By inducing absorption of light, staining dyes change the intracellular refractive index due to the Kramers-Kronig relationship. We present a method for creating 2-D maps of real and imaginary refractive indices of stained biological cells using their thickness and absorptance. We validate our technique on dyed polystyrene microspheres and quantify the alteration in refractive index of sta...

  14. Convergence of mutation and epigenetic alterations identifies common genes in cancer that predict for poor prognosis.

    Directory of Open Access Journals (Sweden)

    Timothy A Chan

    2008-05-01

    Full Text Available BACKGROUND: The identification and characterization of tumor suppressor genes has enhanced our understanding of the biology of cancer and enabled the development of new diagnostic and therapeutic modalities. Whereas in past decades, a handful of tumor suppressors have been slowly identified using techniques such as linkage analysis, large-scale sequencing of the cancer genome has enabled the rapid identification of a large number of genes that are mutated in cancer. However, determining which of these many genes play key roles in cancer development has proven challenging. Specifically, recent sequencing of human breast and colon cancers has revealed a large number of somatic gene mutations, but virtually all are heterozygous, occur at low frequency, and are tumor-type specific. We hypothesize that key tumor suppressor genes in cancer may be subject to mutation or hypermethylation. METHODS AND FINDINGS: Here, we show that combined genetic and epigenetic analysis of these genes reveals many with a higher putative tumor suppressor status than would otherwise be appreciated. At least 36 of the 189 genes newly recognized to be mutated are targets of promoter CpG island hypermethylation, often in both colon and breast cancer cell lines. Analyses of primary tumors show that 18 of these genes are hypermethylated strictly in primary cancers and often with an incidence that is much higher than for the mutations and which is not restricted to a single tumor-type. In the identical breast cancer cell lines in which the mutations were identified, hypermethylation is usually, but not always, mutually exclusive from genetic changes for a given tumor, and there is a high incidence of concomitant loss of expression. Sixteen out of 18 (89% of these genes map to loci deleted in human cancers. Lastly, and most importantly, the reduced expression of a subset of these genes strongly correlates with poor clinical outcome. CONCLUSIONS: Using an unbiased genome

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

    Science.gov (United States)

    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...

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

    Directory of Open Access Journals (Sweden)

    Lu Xinghua

    2006-02-01

    Full Text Available Abstract 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.

  17. Upper airway alterations/abnormalities in a case series of obstructive sleep apnea patients identified with cone-beam CT

    Energy Technology Data Exchange (ETDEWEB)

    Shigeta, Y.; Shintaku, W.H.; Clark, G.T. [Orofacial Pain/Oral Medicine Center, Div. of Diagnostic Sciences, School of Dentistry, Univ. of Southern California, Los Angeles, CA (United States); Enciso, R. [Div. of Craniofacial Sciences and Therapeutics, School of Dentistry, Univ. of Southern California, Los Angeles, CA (United States); Ogawa, T. [Dept. of Fixed Prosthodontic Dentistry, Tsurumi Univ., School of Dental Medicine, Tsurumi (Japan)

    2007-06-15

    There are many factors that influence the configuration of the upper airway and may contribute to the development of obstructive sleep apnea (OSA). This paper presents a series of 12 consecutive OSA cases where various upper airway alteration/abnormalities were identified using 3D anatomic reconstructions generated from cone-beam CT (CBCT) images. Some cases exhibited more than one type of abnormality and below we describe each of the six types identified with CBCT in this case series. (orig.)

  18. Hypertension is associated with marked alterations in sphingolipid biology: a potential role for ceramide.

    Directory of Open Access Journals (Sweden)

    Léon J A Spijkers

    Full Text Available BACKGROUND: Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. METHODS AND FINDINGS: In isolated carotid arteries from spontaneously hypertensive rats (SHR and normotensive Wistar-Kyoto (WKY rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4±0.4 and SMase: 2.1±0.1 mN/mm; n = 10, that were virtually absent in WKY vessels (DMS: 0.0±0.0 and SMase: 0.6±0.1 mN/mm; n = 9, p<0.05. Imaging mass spectrometry and immunohistochemistry indicated that these contractions were most likely mediated by ceramide and dependent on iPLA(2, cyclooxygenase-1 and thromboxane synthase. Expression levels of these enzymes were higher in SHR vessels. In concurrence, infusion of dimethylsphingosine caused a marked rise in blood pressure in anesthetized SHR (42±4%; n = 7, but not in WKY (-12±10%; n = 6. Lipidomics analysis by mass spectrometry, revealed elevated levels of ceramide in arterial tissue of SHR compared to WKY (691±42 vs. 419±27 pmol, n = 3-5 respectively, p<0.05. These pronounced alterations in SHR sphingolipid biology are also reflected in increased plasma ceramide levels (513±19 pmol WKY vs. 645±25 pmol SHR, n = 6-12, p<0.05. Interestingly, we observed similar increases in ceramide levels (correlating with hypertension grade in plasma from humans with essential hypertension (185±8 pmol vs. 252±23 pmol; n = 18 normotensive vs. n = 19 hypertensive patients, p<0.05. CONCLUSIONS: Hypertension is associated with marked alterations in vascular

  19. Model Order and Identifiability of Non-Linear Biological Systems in Stable Oscillation.

    Science.gov (United States)

    Wigren, Torbjörn

    2015-01-01

    The paper presents a theoretical result that clarifies when it is at all possible to determine the nonlinear dynamic equations of a biological system in stable oscillation, from measured data. As it turns out the minimal order needed for this is dependent on the minimal dimension in which the stable orbit of the system does not intersect itself. This is illustrated with a simulated fourth order Hodgkin-Huxley spiking neuron model, which is identified using a non-linear second order differential equation model. The simulated result illustrates that the underlying higher order model of the spiking neuron cannot be uniquely determined given only the periodic measured data. The result of the paper is of general validity when the dynamics of biological systems in stable oscillation is identified, and illustrates the need to carefully address non-linear identifiability aspects when validating models based on periodic data.

  20. Simple Empirical Model for Identifying Rheological Properties of Soft Biological Tissues

    CERN Document Server

    Kobayashi, Yo; Miyashita, Tomoyuki; Fujie, Masakatsu G

    2015-01-01

    Understanding the rheological properties of soft biological tissue is a key issue for mechanical systems used in the healthcare field. We propose a simple empirical model using Fractional Dynamics and Exponential Nonlinearity (FDEN) to identify the rheological properties of soft biological tissue. The model is derived from detailed material measurements using samples isolated from porcine liver. We conducted dynamic viscoelastic and creep tests on liver samples using a rheometer. The experimental results indicated that biological tissue has specific properties: i) power law increases in storage elastic modulus and loss elastic modulus with the same slope; ii) power law gain decrease and constant phase delay in the frequency domain over two decades; iii) log-log scale linearity between time and strain relationships under constant force; and iv) linear and log scale linearity between strain and stress relationships. Our simple FDEN model uses only three dependent parameters and represents the specific propertie...

  1. Structural identifiability of systems biology models: a critical comparison of methods.

    Directory of Open Access Journals (Sweden)

    Oana-Teodora Chis

    Full Text Available Analysing the properties of a biological system through in silico experimentation requires a satisfactory mathematical representation of the system including accurate values of the model parameters. Fortunately, modern experimental techniques allow obtaining time-series data of appropriate quality which may then be used to estimate unknown parameters. However, in many cases, a subset of those parameters may not be uniquely estimated, independently of the experimental data available or the numerical techniques used for estimation. This lack of identifiability is related to the structure of the model, i.e. the system dynamics plus the observation function. Despite the interest in knowing a priori whether there is any chance of uniquely estimating all model unknown parameters, the structural identifiability analysis for general non-linear dynamic models is still an open question. There is no method amenable to every model, thus at some point we have to face the selection of one of the possibilities. This work presents a critical comparison of the currently available techniques. To this end, we perform the structural identifiability analysis of a collection of biological models. The results reveal that the generating series approach, in combination with identifiability tableaus, offers the most advantageous compromise among range of applicability, computational complexity and information provided.

  2. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    International Nuclear Information System (INIS)

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis

  3. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    Energy Technology Data Exchange (ETDEWEB)

    Fukunaga, Satoki [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Kakehashi, Anna [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Gi, Min [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2015-08-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis.

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

    Science.gov (United States)

    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.

  5. DTAF dye concentrations commonly used to measure microscale deformations in biological tissues alter tissue mechanics.

    Directory of Open Access Journals (Sweden)

    Spencer E Szczesny

    Full Text Available Identification of the deformation mechanisms and specific components underlying the mechanical function of biological tissues requires mechanical testing at multiple levels within the tissue hierarchical structure. Dichlorotriazinylaminofluorescein (DTAF is a fluorescent dye that is used to visualize microscale deformations of the extracellular matrix in soft collagenous tissues. However, the DTAF concentrations commonly employed in previous multiscale experiments (≥2000 µg/ml may alter tissue mechanics. The objective of this study was to determine whether DTAF affects tendon fascicle mechanics and if a concentration threshold exists below which any observed effects are negligible. This information is valuable for guiding the continued use of this fluorescent dye in future experiments and for interpreting the results of previous work. Incremental strain testing demonstrated that high DTAF concentrations (≥100 µg/ml increase the quasi-static modulus and yield strength of rat tail tendon fascicles while reducing their viscoelastic behavior. Subsequent multiscale testing and modeling suggests that these effects are due to a stiffening of the collagen fibrils and strengthening of the interfibrillar matrix. Despite these changes in tissue behavior, the fundamental deformation mechanisms underlying fascicle mechanics appear to remain intact, which suggests that conclusions from previous multiscale investigations of strain transfer are still valid. The effects of lower DTAF concentrations (≤10 µg/ml on tendon mechanics were substantially smaller and potentially negligible; nevertheless, no concentration was found that did not at least slightly alter the tissue behavior. Therefore, future studies should either reduce DTAF concentrations as much as possible or use other dyes/techniques for measuring microscale deformations.

  6. Altered lipid metabolism in the aging kidney identified by three layered omic analysis.

    Science.gov (United States)

    Braun, Fabian; Rinschen, Markus M; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Hoeijmakers, Jan H J; Schumacher, Björn; Dollé, Martijn E T; Müller, Roman-Ulrich; Benzing, Thomas; Schermer, Bernhard; Kurschat, Christine E

    2016-03-01

    Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease. PMID:26886165

  7. Comparing the biological coherence of network clusters identified by different detection algorithms

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Protein-protein interaction networks serve to carry out basic molecular activity in the cell. Detecting the modular structures from the protein-protein interaction network is important for understanding the organization, function and dynamics of a biological system. In order to identify functional neighborhoods based on network topology, many network cluster identification algorithms have been developed. However, each algorithm might dissect a network from a different aspect and may provide different insight on the network partition. In order to objectively evaluate the performance of four commonly used cluster detection algorithms: molecular complex detection (MCODE), NetworkBlast, shortest-distance clustering (SDC) and Girvan-Newman (G-N) algorithm, we compared the biological coherence of the network clusters found by these algorithms through a uniform evaluation framework. Each algorithm was utilized to find network clusters in two different protein-protein interaction networks with various parameters. Comparison of the resulting network clusters indicates that clusters found by MCODE and SDC are of higher biological coherence than those by NetworkBlast and G-N algorithm.

  8. A systems biological approach to identify key transcription factors and their genomic neighborhoods in human sarcomas

    Institute of Scientific and Technical Information of China (English)

    Antti Ylip(a)(a); Olli Yli-Harja; Wei Zhang; Matti Nykter

    2011-01-01

    Identification of genetic signatures is the main objective for many computational oncology studies. The signature usually consists of numerous genes that are differentially expressed between two clinically distinct groups of samples, such as tumor subtypes. Prospectively, many signatures have been found to generalize poorly to other datasets and, thus, have rarely been accepted into clinical use. Recognizing the limited success of traditionally generated signatures, we developed a systems biology-based framework for robust identification of key transcription factors and their genomic regulatory neighborhoods. Application of the framework to study the differences between gastrointestinal stromal tumor (GIST) and leiomyosarcoma (LMS) resulted in the identification of nine transcription factors (SRF, NKX2-5, CCDC6, LEF1, VDR, ZNF250, TRIM63, MAF, and MYC). Functional annotations of the obtained neighborhoods identified the biological processes which the key transcription factors regulate differently between the tumor types. Analyzing the differences in the expression patterns using our approach resulted in a more robust genetic signature and more biological insight into the diseases compared to a traditional genetic signature.

  9. Messina: a novel analysis tool to identify biologically relevant molecules in disease.

    Directory of Open Access Journals (Sweden)

    Mark Pinese

    Full Text Available BACKGROUND: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can identify those genes that only sometimes show aberrant expression in cancer. We demonstrate with simulated data that Messina is highly sensitive and specific when used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporary analysis techniques. We illustrate Messina by using it to detect the aberrant expression of a gene that may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE: Messina allows the detection of genes with profiles typical of markers of molecular subtype, and complements existing methods to assist the identification of such markers. Messina is applicable to any global expression profiling data, and to allow its easy application has been packaged into a freely-available stand-alone software package.

  10. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Demontis, Ditte; Castro Dias Cuyabano, Beatriz;

    2016-01-01

    Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited...... power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from...... genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT...

  11. Identifying biological pathways in the MRI findings of people with low back pain

    DEFF Research Database (Denmark)

    Jensen, Rikke Krüger; Jensen, Tue Secher; Kjær, Per;

    Title Identifying biological pathways in the MRI findings of people with low back pain Authors and affiliations Rikke K Jensen1, Tue Secher Jensen1, Per Kjaer1,2, Peter Kent1 1Research Department, Spine Centre of Southern Denmark, Hospital Lillebaelt, Institute of Regional Health Services Research...... Investigations into the association between lumbar MRI findings and low back pain (LBP) are complicated by multiple MRI findings being present at the same time. Findings such as lumbar intervertebral disc protrusions or endplate changes almost always co-exist with other degenerative disc findings...... such as the reduction of disc height and signal intensity. Despite this, the majority of previous research has focused solely on the associations between single imaging findings and pain or other clinical outcomes. Only recently have researchers started to engage with this complexity of MRI findings. An initial...

  12. Correlation analyses of clinical and molecular findings identify candidate biological pathways in systemic juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Ling Xuefeng B

    2012-10-01

    Full Text Available Abstract Background Clinicians have long appreciated the distinct phenotype of systemic juvenile idiopathic arthritis (SJIA compared to polyarticular juvenile idiopathic arthritis (POLY. We hypothesized that gene expression profiles of peripheral blood mononuclear cells (PBMC from children with each disease would reveal distinct biological pathways when analyzed for significant associations with elevations in two markers of JIA activity, erythrocyte sedimentation rate (ESR and number of affected joints (joint count, JC. Methods PBMC RNA from SJIA and POLY patients was profiled by kinetic PCR to analyze expression of 181 genes, selected for relevance to immune response pathways. Pearson correlation and Student's t-test analyses were performed to identify transcripts significantly associated with clinical parameters (ESR and JC in SJIA or POLY samples. These transcripts were used to find related biological pathways. Results Combining Pearson and t-test analyses, we found 91 ESR-related and 92 JC-related genes in SJIA. For POLY, 20 ESR-related and 0 JC-related genes were found. Using Ingenuity Systems Pathways Analysis, we identified SJIA ESR-related and JC-related pathways. The two sets of pathways are strongly correlated. In contrast, there is a weaker correlation between SJIA and POLY ESR-related pathways. Notably, distinct biological processes were found to correlate with JC in samples from the earlier systemic plus arthritic phase (SAF of SJIA compared to samples from the later arthritis-predominant phase (AF. Within the SJIA SAF group, IL-10 expression was related to JC, whereas lack of IL-4 appeared to characterize the chronic arthritis (AF subgroup. Conclusions The strong correlation between pathways implicated in elevations of both ESR and JC in SJIA argues that the systemic and arthritic components of the disease are related mechanistically. Inflammatory pathways in SJIA are distinct from those in POLY course JIA, consistent with

  13. Faculty of 1000: a way of identifying what are currently considered the most interesting research articles in biology

    OpenAIRE

    Velterop, Johannes JM; Weedon, David

    2002-01-01

    Faculty of 1000 is a new reviewing, evaluation and rating system of primary scientific papers in the area of biology, produced by Biology Reports Limited and published by BioMed Central Limited (www.biomedcentral.com). Both companies are part of The Current Science Group. The service will identify the current most interesting and most important research papers in biology, picked by a group of over 1000 leading international researchers from any journal, and provide reasons why these articles ...

  14. On alterations in the refractive index and scattering properties of biological tissue caused by histological processing

    Science.gov (United States)

    Aung, Htet; DeAngelo, Bianca; Soldano, John; Kostyk, Piotr; Rodriguez, Braulio; Xu, M.

    2013-02-01

    Clinical tissue processing such as formalin fixing, paraffin-embedding and histological staining alters significantly the optical properties of the tissue. We document the alterations in the optical properties of prostate cancer tissue specimens in the 500nm to 700nm spectral range caused by histological processing with quantitative differential interference contrast (qDIC) microscopy. A simple model to explain these alterations is presented at the end.

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

    Directory of Open Access Journals (Sweden)

    Susan J Cunningham

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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…

  18. Hon-yaku: a biology-driven Bayesian methodology for identifying translation initiation sites in prokaryotes

    Directory of Open Access Journals (Sweden)

    de Hoon Michiel JL

    2007-02-01

    Full Text Available Abstract Background Computational prediction methods are currently used to identify genes in prokaryote genomes. However, identification of the correct translation initiation sites remains a difficult task. Accurate translation initiation sites (TISs are important not only for the annotation of unknown proteins but also for the prediction of operons, promoters, and small non-coding RNA genes, as this typically makes use of the intergenic distance. A further problem is that most existing methods are optimized for Escherichia coli data sets; applying these methods to newly sequenced bacterial genomes may not result in an equivalent level of accuracy. Results Based on a biological representation of the translation process, we applied Bayesian statistics to create a score function for predicting translation initiation sites. In contrast to existing programs, our combination of methods uses supervised learning to optimally use the set of known translation initiation sites. We combined the Ribosome Binding Site (RBS sequence, the distance between the translation initiation site and the RBS sequence, the base composition of the start codon, the nucleotide composition (A-rich sequences following start codons, and the expected distribution of the protein length in a Bayesian scoring function. To further increase the prediction accuracy, we also took into account the operon orientation. The outcome of the procedure achieved a prediction accuracy of 93.2% in 858 E. coli genes from the EcoGene data set and 92.7% accuracy in a data set of 1243 Bacillus subtilis 'non-y' genes. We confirmed the performance in the GC-rich Gamma-Proteobacteria Herminiimonas arsenicoxydans, Pseudomonas aeruginosa, and Burkholderia pseudomallei K96243. Conclusion Hon-yaku, being based on a careful choice of elements important in translation, improved the prediction accuracy in B. subtilis data sets and other bacteria except for E. coli. We believe that most remaining

  19. A systems biology approach identifies a regulatory network in parotid acinar cell terminal differentiation.

    Directory of Open Access Journals (Sweden)

    Melissa A Metzler

    Full Text Available The transcription factor networks that drive parotid salivary gland progenitor cells to terminally differentiate, remain largely unknown and are vital to understanding the regeneration process.A systems biology approach was taken to measure mRNA and microRNA expression in vivo across acinar cell terminal differentiation in the rat parotid salivary gland. Laser capture microdissection (LCM was used to specifically isolate acinar cell RNA at times spanning the month-long period of parotid differentiation.Clustering of microarray measurements suggests that expression occurs in four stages. mRNA expression patterns suggest a novel role for Pparg which is transiently increased during mid postnatal differentiation in concert with several target gene mRNAs. 79 microRNAs are significantly differentially expressed across time. Profiles of statistically significant changes of mRNA expression, combined with reciprocal correlations of microRNAs and their target mRNAs, suggest a putative network involving Klf4, a differentiation inhibiting transcription factor, which decreases as several targeting microRNAs increase late in differentiation. The network suggests a molecular switch (involving Prdm1, Sox11, Pax5, miR-200a, and miR-30a progressively decreases repression of Xbp1 gene transcription, in concert with decreased translational repression by miR-214. The transcription factor Xbp1 mRNA is initially low, increases progressively, and may be maintained by a positive feedback loop with Atf6. Transfection studies show that Xbp1 activates the Mist1 promoter [corrected]. In addition, Xbp1 and Mist1 each activate the parotid secretory protein (Psp gene, which encodes an abundant salivary protein, and is a marker of terminal differentiation.This study identifies novel expression patterns of Pparg, Klf4, and Sox11 during parotid acinar cell differentiation, as well as numerous differentially expressed microRNAs. Network analysis identifies a novel stemness arm, a

  20. Genome-wide DNA methylation identifies trophoblast invasion-related genes: Claudin-4 and Fucosyltransferase IV control mobility via altering matrix metalloproteinase activity.

    Science.gov (United States)

    Hu, Yuxiang; Blair, John D; Yuen, Ryan K C; Robinson, Wendy P; von Dadelszen, Peter

    2015-05-01

    Previously we showed that extravillous cytotrophoblast (EVT) outgrowth and migration on a collagen gel explant model were affected by exposure to decidual natural killer cells (dNK). This study investigates the molecular causes behind this phenomenon. Genome wide DNA methylation of exposed and unexposed EVT was assessed using the Illumina Infinium HumanMethylation450 BeadChip array (450 K array). We identified 444 differentially methylated CpG loci in dNK-treated EVT compared with medium control (P EVT. Among these genes, CLDN4 (encoding claudin-4) and FUT4 (encoding fucosyltransferase IV) were chosen for follow-up studies because of their biological relevance from research on tumor cells. The results showed that the mRNA and protein expressions of both CLDN4 and FUT4 in dNK-treated EVT were significantly reduced compared with control (P EVT mobility at least partially in association with an alteration of DNA methylation profile. Hypermethylation of CLDN4 and FUT4 reduces protein expression. CLDN4 and FUT4 are representative genes that participate in modulating trophoblast mobility. PMID:25697377

  1. Comprehensive genetic testing identifies targetable genomic alterations in most patients with non-small cell lung cancer, specifically adenocarcinoma, single institute investigation

    Science.gov (United States)

    Won, Brian M.; Patton, Kathryn Alexa; Villaflor, Victoria M.; Hoffman, Philip C.; Hensing, Thomas; Hogarth, D. Kyle; Malik, Renuka; MacMahon, Heber; Mueller, Jeffrey; Simon, Cassie A.; Vigneswaran, Wickii T.; Wigfield, Christopher H.; Ferguson, Mark K.; Husain, Aliya N.; Vokes, Everett E.; Salgia, Ravi

    2016-01-01

    This study reviews extensive genetic analysis in advanced non-small cell lung cancer (NSCLC) patients in order to: describe how targetable mutation genes interrelate with the genes identified as variants of unknown significance; assess the percentage of patients with a potentially targetable genetic alterations; evaluate the percentage of patients who had concurrent alterations, previously considered to be mutually exclusive; and characterize the molecular subset of KRAS. Thoracic Oncology Research Program Databases at the University of Chicago provided patient demographics, pathology, and results of genetic testing. 364 patients including 289 adenocarcinoma underwent genotype testing by various platforms such as FoundationOne, Caris Molecular Intelligence, and Response Genetics Inc. For the entire adenocarcinoma cohort, 25% of patients were African Americans; 90% of KRAS mutations were detected in smokers, including current and former smokers; 46% of EGFR and 61% of ALK alterations were detected in never smokers. 99.4% of patients, whose samples were analyzed by next-generation sequencing (NGS), had genetic alterations identified with an average of 10.8 alterations/tumor throughout different tumor subtypes. However, mutations were not mutually exclusive. NGS in this study identified potentially targetable genetic alterations in the majority of patients tested, detected concurrent alterations and provided information on variants of unknown significance at this time but potentially targetable in the future. PMID:26934441

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

    Science.gov (United States)

    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.

  3. A Method to Identify and Analyze Biological Programs through Automated Reasoning

    Science.gov (United States)

    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

  4. Penetration Capacity, Color Alteration and Biological Response of Two In-office Bleaching Protocols.

    Science.gov (United States)

    Cintra, Luciano Tavares Angelo; Benetti, Francine; Ferreira, Luciana Louzada; Gomes-Filho, João Eduardo; Ervolino, Edilson; Gallinari, Marjorie de Oliveira; Rahal, Vanessa; Briso, André Luiz Fraga

    2016-01-01

    Hydrogen peroxide (H2O2) penetrates into the dental hard tissues causing color alteration but also alterations in pulpal tissues. Hard-tissue penetration, color alteration and the pulp response alterations were evaluated for two in-office bleaching protocols with H2O2. For trans-enamel/dentin penetration and color alteration, discs of bovine teeth were attached to an artificial pulp chamber and bleached according to the groups: BLU (20% H2O2 - 1x50 min, Whiteness HP Blue); MAX (35% H2O2 - 3x15 min, Whiteness HP Maxx); Control (1x50 min, placebo). Trans-enamel/dentin penetration was quantified based on the reaction of H2O2 with leucocrystal violet and the color analyzed by CIELab System. Twenty Wistar rats were divided into two groups (BLU and MAX) and their maxillary right molars were treated according to the same protocols of the in vitro study; the maxillary left molars were used as controls. After 2 days, the animals were killed and their maxillae were examined by light microscopy. The inflammation of pulp tissue was scored according to the inflammatory infiltrate (1, absent; 2, mild; 3, moderate; 4, severe/necrosis). Data were analyzed by statistical tests (α=0.05). MAX showed higher trans-enamel/dentinal penetration of H2O2 (p0.05), and different when compared to Control group (pbleaching protocols using lower concentrations of hydrogen peroxide should be preferred due to their reduced trans-enamel/dentinal penetration since they cause less pulp damage and provide same bleaching efficiency. PMID:27058379

  5. GWAS-identified risk variants for major depressive disorder: Preliminary support for an association with late-life depressive symptoms and brain structural alterations.

    Science.gov (United States)

    Ryan, Joanne; Artero, Sylvaine; Carrière, Isabelle; Maller, Jerome J; Meslin, Chantal; Ritchie, Karen; Ancelin, Marie-Laure

    2016-01-01

    A number of genome-wide association studies (GWAS) have investigated risk factors for major depressive disorder (MDD), however there has been little attempt to replicate these findings in population-based studies of depressive symptoms. Variants within three genes, BICC1, PCLO and GRM7 were selected for replication in our study based on the following criteria: they were identified in a prior MDD GWAS study; a subsequent study found evidence that they influenced depression risk; and there is a solid biological basis for a role in depression. We firstly investigated whether these variants were associated with depressive symptoms in our population-based cohort of 929 elderly (238 with clinical depressive symptoms and 691 controls), and secondly to investigate associations with structural brain alterations. A number of nominally significant associations were identified, but none reached Bonferroni-corrected significance levels. Common SNPs in BICC1 and PCLO were associated with a 50% and 30% decreased risk of depression, respectively. PCLO rs2522833 was also associated with the volume of grey matter (p=1.6×10(-3)), and to a lesser extent with hippocampal volume and white matter lesions. Among depressed individuals rs9870680 (GRM7) was associated with the volume of grey and white matter (p=10(-4) and 8.3×10(-3), respectively). Our results provide some support for the involvement of BICC1 and PCLO in late-life depressive disorders and preliminary evidence that these genetic variants may also influence brain structural volumes. However effect sizes remain modest and associations did not reach corrected significance levels. Further large imaging studies are needed to confirm our findings.

  6. Mass spectrometry-based proteomics as a tool to identify biological matrices in forensic science.

    Science.gov (United States)

    Van Steendam, Katleen; De Ceuleneer, Marlies; Dhaenens, Maarten; Van Hoofstat, David; Deforce, Dieter

    2013-03-01

    In forensic casework analysis, identification of the biological matrix and the species of a forensic trace, preferably without loss of DNA, is of major importance. The biological matrices that can be encountered in a forensic context are blood (human or non-human), saliva, semen, vaginal fluid, and to a lesser extent nasal secretions, feces, and urine. All these matrices were applied on swabs and digested with trypsin in order to obtain peptides. These peptides were injected on a mass spectrometer (ESI Q-TOF) resulting in the detection of several biomarkers that were used to build a decision tree for matrix identification. Saliva and blood were characterized by the presence of alpha-amylase 1 and hemoglobin, respectively. In vaginal fluid, cornulin, cornifin, and/or involucrin were found as biomarkers while semenogelin, prostate-specific antigen, and/or acid phosphatase were characteristic proteins for semen. Uromodulin or AMBP protein imply the presence of urine, while plunc protein is present in nasal secretions. Feces could be determined by the presence of immunoglobulins without hemoglobin. The biomarkers for the most frequently encountered biological matrices (saliva, blood, vaginal fluid, and semen) were validated in blind experiments and on real forensic samples. Additionally, by means of this proteomic approach, species identification was possible. This approach has the advantage that the analysis is performed on the first "washing" step of the chelex DNA extraction, a solution which is normally discarded, and that one single test is sufficient to determine the identity and the species of the biological matrix, while the conventional methods require cascade testing. This technique can be considered as a useful additional tool for biological matrix identification in forensic science and holds the promise of further automation.

  7. Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Zhou Jing

    2011-04-01

    Full Text Available Abstract Background Autosomal dominant polycystic kidney disease (ADPKD is characterized by cyst formation throughout the kidney parenchyma. It is caused by mutations in either of two genes, PKD1 and PKD2. Mice that lack functional Pkd1 (Pkd1-/-, develop rapidly progressive cystic disease during embryogenesis, and serve as a model to study human ADPKD. Genome wide transcriptome reprogramming and the possible roles of micro-RNAs (miRNAs that affect the initiation and progression of cyst formation in the Pkd1-/- have yet to be studied. miRNAs are small, regulatory non-coding RNAs, implicated in a wide spectrum of biological processes. Their expression levels are altered in several diseases including kidney cancer, diabetic nephropathy and PKD. Results We examined the molecular pathways that modulate renal cyst formation and growth in the Pkd1-/- model by performing global gene-expression profiling in embryonic kidneys at days 14.5 and 17.5. Gene Ontology and gene set enrichment analysis were used to identify overrepresented signaling pathways in Pkd1-/- kidneys. We found dysregulation of developmental, metabolic, and signaling pathways (e.g. Wnt, calcium, TGF-β and MAPK in Pkd1-/- kidneys. Using a comparative transcriptomics approach, we determined similarities and differences with human ADPKD: ~50% overlap at the pathway level among the mis-regulated pathways was observed. By using computational approaches (TargetScan, miRanda, microT and miRDB, we then predicted miRNAs that were suggested to target the differentially expressed mRNAs. Differential expressions of 9 candidate miRNAs, miRs-10a, -30a-5p, -96, -126-5p, -182, -200a, -204, -429 and -488, and 16 genes were confirmed by qPCR. In addition, 14 candidate miRNA:mRNA reciprocal interactions were predicted. Several of the highly regulated genes and pathways were predicted as targets of miRNAs. Conclusions We have described global transcriptional reprogramming during the progression of PKD in

  8. A magnetic-dependent protein corona of tailor-made superparamagnetic iron oxides alters their biological behaviors

    Science.gov (United States)

    Liu, Ziyao; Zhan, Xiaohui; Yang, Minggang; Yang, Qi; Xu, Xianghui; Lan, Fang; Wu, Yao; Gu, Zhongwei

    2016-03-01

    In recent years, it is becoming increasingly evident that once nanoparticles come into contact with biological fluids, a protein corona surely forms and critically affects the biological behaviors of nanoparticles. Herein, we investigate whether the formation of protein corona on the surface of superparamagnetic iron oxides (SPIOs) is influenced by static magnetic field. Under static magnetic field, there is no obvious variation in the total amount of protein adsorption, but the proportion of adsorbed proteins significantly changes. Noticeably, certain proteins including apolipoproteins, complement system proteins and acute phase proteins, increase in the protein corona of SPIOs in the magnetic field. More importantly, the magnetic-dependent protein corona of SPIOs enhances the cellular uptake of SPIOs into the normal cell line (3T3 cells) and tumor cell line (HepG2 cells), due to increased adsorption of apolipoprotein. In addition, SPIOs with the magnetic-dependent protein corona cause high cytotoxicity to 3T3 cells and HepG2 cells. This work discloses that superparamagnetism as a key feature of SPIOs affects the composition of protein corona to a large extent, which further alters the biological behaviors of SPIOs.In recent years, it is becoming increasingly evident that once nanoparticles come into contact with biological fluids, a protein corona surely forms and critically affects the biological behaviors of nanoparticles. Herein, we investigate whether the formation of protein corona on the surface of superparamagnetic iron oxides (SPIOs) is influenced by static magnetic field. Under static magnetic field, there is no obvious variation in the total amount of protein adsorption, but the proportion of adsorbed proteins significantly changes. Noticeably, certain proteins including apolipoproteins, complement system proteins and acute phase proteins, increase in the protein corona of SPIOs in the magnetic field. More importantly, the magnetic-dependent protein

  9. Can OCT be sensitive to nanoscale structural alterations in biological tissue?

    OpenAIRE

    Yi, Ji; Radosevich, Andrew J.; Rogers, Jeremy D.; Norris, Sam C.P.; Çapoğlu, İlker R.; Taflove, Allen; Backman, Vadim

    2013-01-01

    Exploration of nanoscale tissue structures is crucial in understanding biological processes. Although novel optical microscopy methods have been developed to probe cellular features beyond the diffraction limit, nanometer-scale quantification remains still inaccessible for in situ tissue. Here we demonstrate that, without actually resolving specific geometrical feature, OCT can be sensitive to tissue structural properties at the nanometer length scale. The statistical mass-density distributio...

  10. Maternal postnatal depression predicts altered offspring biological stress reactivity in adulthood

    OpenAIRE

    Barry, Tom J.; Murray, Lynne; Fearon, R. M. Pasco; Moutsiana, Christina; Cooper, Peter; Goodyer, Ian M.; Herbert, Joe; Halligan, Sarah L.

    2015-01-01

    Summary The offspring of depressed parents have been found to show elevated basal levels of the stress hormone cortisol. Whether heightened cortisol stress reactivity is also present in this group has yet to be clearly demonstrated. We tested whether postnatal maternal depression predicts subsequent increases in offspring biological sensitivity to social stress, as indexed by elevated cortisol reactivity. Participants (mean age 22.4-years) derived from a 22-year prospective longitudinal study...

  11. Systems Biology of cancer: Moving toward the Integrative Study of the metabolic alterations in cancer cells.

    Directory of Open Access Journals (Sweden)

    Claudia Erika Hernández Patiño

    2013-01-01

    Full Text Available One of the main objectives in systems biology is to understand the biological mechanisms that give rise to the phenotype of a microorganism by using high-throughput technologies and genome-scale mathematical modeling. The computational modeling of genome-scale metabolic reconstructions is one systemic and quantitative strategy for characterizing the metabolic phenotype associated with human diseases and potentially for designing drugs with optimal clinical effects. The purpose of this short review is to describe how computational modeling, including the specific case of constraint-based modeling, can be used to explore, characterize and predict the metabolic capacities that distinguish the metabolic phenotype of cancer cell lines. As we show herein, this computational framework is far from a pure theoretical description, and to ensure proper biological interpretation, it is necessary to integrate high-throughput data and generate predictions for later experimental assessment. Hence, genome-scale modeling serves as a platform for the following: 1 the integration of data from high-throughput technologies, 2 the assessment of how metabolic activity is related to phenotype in cancer cell lines and 3 the design of new experiments to evaluate the outcomes of the in silico analysis. By combining the functions described above, we show that computational modeling is a useful methodology to construct an integrative, systemic and quantitative scheme for understanding the metabolic profiles of cancer cell lines, a first step to determine the metabolic mechanism by which cancer cells maintain and support their malignant phenotype in human tissues.

  12. Systems biology of cancer: moving toward the integrative study of the metabolic alterations in cancer cells.

    Science.gov (United States)

    Hernández Patiño, Claudia E; Jaime-Muñoz, Gustavo; Resendis-Antonio, Osbaldo

    2012-01-01

    One of the main objectives in systems biology is to understand the biological mechanisms that give rise to the phenotype of a microorganism by using high-throughput technologies (HTs) and genome-scale mathematical modeling. The computational modeling of genome-scale metabolic reconstructions is one systemic and quantitative strategy for characterizing the metabolic phenotype associated with human diseases and potentially for designing drugs with optimal clinical effects. The purpose of this short review is to describe how computational modeling, including the specific case of constraint-based modeling, can be used to explore, characterize, and predict the metabolic capacities that distinguish the metabolic phenotype of cancer cell lines. As we show herein, this computational framework is far from a pure theoretical description, and to ensure proper biological interpretation, it is necessary to integrate high-throughput data and generate predictions for later experimental assessment. Hence, genome-scale modeling serves as a platform for the following: (1) the integration of data from HTs, (2) the assessment of how metabolic activity is related to phenotype in cancer cell lines, and (3) the design of new experiments to evaluate the outcomes of the in silico analysis. By combining the functions described above, we show that computational modeling is a useful methodology to construct an integrative, systemic, and quantitative scheme for understanding the metabolic profiles of cancer cell lines, a first step to determine the metabolic mechanism by which cancer cells maintain and support their malignant phenotype in human tissues.

  13. Are biological effects of space radiation really altered under the microgravity environment?

    Science.gov (United States)

    Yatagai, Fumio; Ishioka, Noriaki

    2014-10-01

    Two major factors of space environment are space radiation and microgravity. It is generally considered that a high level of ionizing radiation (IR) in space has an influence on living organisms including humans; therefore, the possible alteration of space-radiation influences by the microgravity environment is of great concern. In fact, examination of such a possibility has been extensively conducted since the early days of space experiments, suggesting a possible synergistic effect of radiation and microgravity in some experiments but a negative observation in others. Because these complicated results remain not well understood, we propose a solution to this problem. Gene expression analysis is one of the solutions to the problem. In fact, gene expression may be changed by microgravity, and further modification may be possible through IR. This result could reveal an interactive effect of both factors on the cellular responses, which could in turn reveal whether the human-health abnormalities expected under the microgravity environment can be altered by space radiation. We believe that this is a new aspect in the study of the interactive effect of radiation and microgravity. However, further improvements in space experimental technologies are required for future studies.

  14. A systems biology approach identifies Molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    OpenAIRE

    Nil Turan; Susana Kalko; Anna Stincone; Kim Clarke; Ayesha Sabah; Katherine Howlett; S John Curnow; Rodriguez, Diego A.; Marta Cascante; Laura O'Neill; Stuart Egginton; Josep Roca; Francesco Falciani

    2011-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular an...

  15. Chromosome translocations as biological dosimeter identified by in situ fluorescent hybridization (FISH)

    International Nuclear Information System (INIS)

    Chromosomal aberration analysis in lymphocytes is used for dose assessment by workers overexposed to ionizing radiation. The conventional method is based on the dicentric metaphase chromosomes and/or micronucleus scoring, which gives thoroughly satisfactory results for accidental and recent exposures. Nevertheless, when evaluating acute doses occurring in the past or accidents where the time elapsed between exposure and analysis is unknown, the translocations scoring could be the method to use. This is because translocations retain the cell's reproductive potential so that they persist over time. For a long time the detection of translocations for dosimetric purposes was impractical as a routine method until situ fluorescent hybridization (FISH) techniques appeared. This method arising from molecular biology and applied to biological dosimetry has greatly simplified detection and although it is expensive, requiring special infrastructure, its availability is a sign of the state of development for these techniques in the region. The use of translocations scoring for biological dosimetry, as for the dicentric scoring, requires calibration curves for the different types of ionizing radiation. Therefore, the aim of this work was to prepare a dose-effect curve for Co-60 γ rays by chromosome translocations analysis. The study material was peripheral lymphocytes from a clinically healthy donor, irradiated and cultured in vitro and the detection of translocations in chromosomes 1, 2 and 4. The results showed a dose effect curve linear quadratic, accordingly with other authors

  16. Bergamot (Citrus bergamia Risso fruit extracts and identified components alter expression of interleukin 8 gene in cystic fibrosis bronchial epithelial cell lines

    Directory of Open Access Journals (Sweden)

    Sacchetti Gianni

    2011-04-01

    Full Text Available Abstract Background Cystic fibrosis (CF airway pathology is a fatal, autosomal, recessive genetic disease characterized by extensive lung inflammation. After induction by TNF-α, elevated concentrations of several pro-inflammatory cytokines (i.e. IL-6, IL-1β and chemokines (i.e. IL-8 are released from airway epithelial cells. In order to reduce the excessive inflammatory response in the airways of CF patients, new therapies have been developed and in this respect, medicinal plant extracts have been studied. In this article we have investigated the possible use of bergamot extracts (Citrus bergamia Risso and their identified components to alter the expression of IL-8 associated with the cystic fibrosis airway pathology. Methods The extracts were chemically characterized by 1H-NMR (nuclear magnetic resonance, GC-FID (gas chromatography-flame ionization detector, GC-MS (gas chromatography-mass spectrometry and HPLC (high pressure liquid chromatography. Both bergamot extracts and main detected chemical constituents were assayed for their biological activity measuring (a cytokines and chemokines in culture supernatants released from cystic fibrosis IB3-1 cells treated with TNF-α by Bio-Plex cytokine assay; (b accumulation of IL-8 mRNA by real-time PCR. Results The extracts obtained from bergamot (Citrus bergamia Risso epicarps contain components displaying an inhibitory activity on IL-8. Particularly, the most active molecules were bergapten and citropten. These effects have been confirmed by analyzing mRNA levels and protein release in the CF cellular models IB3-1 and CuFi-1 induced with TNF-α or exposed to heat-inactivated Pseudomonas aeruginosa. Conclusions These obtained results clearly indicate that bergapten and citropten are strong inhibitors of IL-8 expression and could be proposed for further studies to verify possible anti-inflammatory properties to reduce lung inflammation in CF patients.

  17. Connecting Genomic Alterations to Cancer Biology with Proteomics: The NCI Clinical Proteomic Tumor Analysis Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, Matthew; Gillette, Michael; Carr, Steven A.; Paulovich, Amanda G.; Smith, Richard D.; Rodland, Karin D.; Townsend, Reid; Kinsinger, Christopher; Mesri, Mehdi; Rodriguez, Henry; Liebler, Daniel

    2013-10-03

    The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium is applying the latest generation of proteomic technologies to genomically annotated tumors from The Cancer Genome Atlas (TCGA) program, a joint initiative of the NCI and the National Human Genome Research Institute. By providing a fully integrated accounting of DNA, RNA, and protein abnormalities in individual tumors, these datasets will illuminate the complex relationship between genomic abnormalities and cancer phenotypes, thus producing biologic insights as well as a wave of novel candidate biomarkers and therapeutic targets amenable to verifi cation using targeted mass spectrometry methods.

  18. Sinking rates of microplastics and potential implications of their alteration by physical, biological, and chemical factors.

    Science.gov (United States)

    Kowalski, Nicole; Reichardt, Aurelia M; Waniek, Joanna J

    2016-08-15

    To follow the pathways of microplastics in aquatic environments, profound knowledge about the behaviour of microplastics is necessary. Therefore, sinking experiments were conducted with diverse polymer particles using fluids with different salinity. Particles ranged from 0.3 and 3.6mm with sinking rates between 6 and 91×10(-3)ms(-1). The sinking velocity was not solely related to particle density, size and fluid density but also to the particles shape leading to considerable deviation from calculated theoretical values. Thus, experimental studies are indispensable to get basic knowledge about the sinking behaviour and to gain representative datasets for model approaches estimating the distribution of microplastics in aquatic systems. The sinking behaviour may be altered considerably by weathering and biofouling demanding further studies with aged and fouled plastic particles. Furthermore, assumptions are made about the influence of sinking fouled microplastics on the marine carbon pump by transferring organic carbon to deeper water depths. PMID:27297594

  19. Cosmetics alter biologically-based factors of beauty: evidence from facial contrast.

    Science.gov (United States)

    Jones, Alex L; Russell, Richard; Ward, Robert

    2015-01-01

    The use of cosmetics by women seems to consistently increase their attractiveness. What factors of attractiveness do cosmetics alter to achieve this? Facial contrast is a known cue to sexual dimorphism and youth, and cosmetics exaggerate sexual dimorphisms in facial contrast. Here, we demonstrate that the luminance contrast pattern of the eyes and eyebrows is consistently sexually dimorphic across a large sample of faces, with females possessing lower brow contrasts than males, and greater eye contrast than males. Red-green and yellow-blue color contrasts were not found to differ consistently between the sexes. We also show that women use cosmetics not only to exaggerate sexual dimorphisms of brow and eye contrasts, but also to increase contrasts that decline with age. These findings refine the notion of facial contrast, and demonstrate how cosmetics can increase attractiveness by manipulating factors of beauty associated with facial contrast. PMID:25725411

  20. Cosmetics alter biologically-based factors of beauty: evidence from facial contrast.

    Science.gov (United States)

    Jones, Alex L; Russell, Richard; Ward, Robert

    2015-02-28

    The use of cosmetics by women seems to consistently increase their attractiveness. What factors of attractiveness do cosmetics alter to achieve this? Facial contrast is a known cue to sexual dimorphism and youth, and cosmetics exaggerate sexual dimorphisms in facial contrast. Here, we demonstrate that the luminance contrast pattern of the eyes and eyebrows is consistently sexually dimorphic across a large sample of faces, with females possessing lower brow contrasts than males, and greater eye contrast than males. Red-green and yellow-blue color contrasts were not found to differ consistently between the sexes. We also show that women use cosmetics not only to exaggerate sexual dimorphisms of brow and eye contrasts, but also to increase contrasts that decline with age. These findings refine the notion of facial contrast, and demonstrate how cosmetics can increase attractiveness by manipulating factors of beauty associated with facial contrast.

  1. Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells.

    Directory of Open Access Journals (Sweden)

    Joanna eŚlusarczyk

    2015-03-01

    Full Text Available Several lines of evidence suggest that the dysregulation of the immune system is an important factor in the development of depression. Microglia are the resident macrophages of the central nervous system and a key player in innate immunity of the brain. We hypothesized that prenatal stress (an animal model of depression as a priming factor could affect microglial cells and might lead to depressive-like disturbances in adult male rat offspring. We investigated the behavioral changes (sucrose preference test, Porsolt test, the expression of C1q and CD40 mRNA and the level of microglia (Iba1 positive in 3 month old control and prenatally stressed male offspring rats. In addition, we characterized the morphological and biochemical parameters of potentially harmful (NO, iNOS, IL-1β, IL-18, IL-6, TNF-α, CCL2, CXCL12, CCR2, CXCR4 and beneficial (IGF-1, BDNF phenotypes in cultures of microglia obtained from the cortices of 1-2 days old control and prenatally stressed pups. The adult prenatally stressed rats showed behavioral (anhedonic- and depression-like disturbances, enhanced expression of microglial activation markers and an increased number of Iba1-immunopositive cells in the hippocampus and frontal cortex. The morphology of glia was altered in cultures from prenatally stressed rats, as demonstrated by immunofluorescence microscopy. Moreover, in these cultures, we observed enhanced expression of CD40 and MHC II and release of pro-inflammatory cytokines, including IL-1β, IL-18, TNF-α and IL-6. Prenatal stress significantly up-regulated levels of the chemokines CCL2, CXCL12 and altered expression of their receptors, CCR2 and CXCR4 while IGF-1 production was suppressed in cultures of microglia from prenatally stressed rats.Our results suggest that prenatal stress may lead to excessive microglia activation and contribute to the behavioral changes observed in depression in adulthood.

  2. A magnetic-dependent protein corona of tailor-made superparamagnetic iron oxides alters their biological behaviors.

    Science.gov (United States)

    Liu, Ziyao; Zhan, Xiaohui; Yang, Minggang; Yang, Qi; Xu, Xianghui; Lan, Fang; Wu, Yao; Gu, Zhongwei

    2016-04-14

    In recent years, it is becoming increasingly evident that once nanoparticles come into contact with biological fluids, a protein corona surely forms and critically affects the biological behaviors of nanoparticles. Herein, we investigate whether the formation of protein corona on the surface of superparamagnetic iron oxides (SPIOs) is influenced by static magnetic field. Under static magnetic field, there is no obvious variation in the total amount of protein adsorption, but the proportion of adsorbed proteins significantly changes. Noticeably, certain proteins including apolipoproteins, complement system proteins and acute phase proteins, increase in the protein corona of SPIOs in the magnetic field. More importantly, the magnetic-dependent protein corona of SPIOs enhances the cellular uptake of SPIOs into the normal cell line (3T3 cells) and tumor cell line (HepG2 cells), due to increased adsorption of apolipoprotein. In addition, SPIOs with the magnetic-dependent protein corona cause high cytotoxicity to 3T3 cells and HepG2 cells. This work discloses that superparamagnetism as a key feature of SPIOs affects the composition of protein corona to a large extent, which further alters the biological behaviors of SPIOs.

  3. Effects of altered temperature and precipitation on desert protozoa associated with biological soil crusts

    Science.gov (United States)

    Darby, B.J.; Housman, D.C.; Zaki, A.M.; Shamout, Y.; Adl, S.M.; Belnap, J.; Neher, D.A.

    2006-01-01

    Biological soil crusts are diverse assemblages of bacteria, cyanobacteria, algae, fungi, lichens, and mosses that cover much of arid land soils. The objective of this study was to quantify protozoa associated with biological soil crusts and test the response of protozoa to increased temperature and precipitation as is predicted by some global climate models. Protozoa were more abundant when associated with cyanobacteria/lichen crusts than with cyanobacteria crusts alone. Amoebae, flagellates, and ciliates originating from the Colorado Plateau desert (cool desert, primarily winter precipitation) declined 50-, 10-, and 100-fold, respectively, when moved in field mesocosms to the Chihuahuan Desert (hot desert, primarily summer rain). However, this was not observed in protozoa collected from the Chihuahuan Desert and moved to the Sonoran desert (hot desert, also summer rain, but warmer than Chihuahuan Desert). Protozoa in culture began to encyst at 37??C. Cysts survived the upper end of daily temperatures (37-55??C), and could be stimulated to excyst if temperatures were reduced to 15??C or lower. Results from this study suggest that cool desert protozoa are influenced negatively by increased summer precipitation during excessive summer temperatures, and that desert protozoa may be adapted to a specific desert's temperature and precipitation regime. ?? 2006 by the International Society of Protistologists.

  4. Frankenstein 2.0.: Identifying and characterising synthetic biology engineers in science fiction films

    OpenAIRE

    Meyer, Angela; Cserer, Amelie; Schmidt, Markus

    2013-01-01

    Synthetic biology (SB) has emerged as one of the newest and promising areas of bio-technology. Issues typically associated to SB, notably in the media, like the idea of artificial life creation and “real” engineering of life also appear in many popular films. Drawing upon the analysis of 48 films, the article discusses how scientists applying technologies that can be related to SB are represented in these movies. It hereby discusses that traditional clichés of scientists in general tend to be...

  5. A stochastic multicellular model identifies biological watermarks from disorders in self-organized patterns of phyllotaxis

    Science.gov (United States)

    Refahi, Yassin; Brunoud, Géraldine; Farcot, Etienne; Jean-Marie, Alain; Pulkkinen, Minna; Vernoux, Teva; Godin, Christophe

    2016-01-01

    Exploration of developmental mechanisms classically relies on analysis of pattern regularities. Whether disorders induced by biological noise may carry information on building principles of developmental systems is an important debated question. Here, we addressed theoretically this question using phyllotaxis, the geometric arrangement of plant aerial organs, as a model system. Phyllotaxis arises from reiterative organogenesis driven by lateral inhibitions at the shoot apex. Motivated by recurrent observations of disorders in phyllotaxis patterns, we revisited in depth the classical deterministic view of phyllotaxis. We developed a stochastic model of primordia initiation at the shoot apex, integrating locality and stochasticity in the patterning system. This stochastic model recapitulates phyllotactic patterns, both regular and irregular, and makes quantitative predictions on the nature of disorders arising from noise. We further show that disorders in phyllotaxis instruct us on the parameters governing phyllotaxis dynamics, thus that disorders can reveal biological watermarks of developmental systems. DOI: http://dx.doi.org/10.7554/eLife.14093.001 PMID:27380805

  6. A systems biology approach to identify intelligence quotient score-related genomic regions, and pathways relevant to potential therapeutic treatments

    OpenAIRE

    Min Zhao; Lei Kong; Hong Qu

    2014-01-01

    Although the intelligence quotient (IQ) is the most popular intelligence test in the world, little is known about the underlying biological mechanisms that lead to the differences in human. To improve our understanding of cognitive processes and identify potential biomarkers, we conducted a comprehensive investigation of 158 IQ-related genes selected from the literature. A genomic distribution analysis demonstrated that IQ-related genes were enriched in seven regions of chromosome 7 and the X...

  7. Biochemical evaluation of a 108-member deglycobleomycin library: viability of a selection strategy for identifying bleomycin analogues with altered properties.

    Science.gov (United States)

    Ma, Qian; Xu, Zhidong; Schroeder, Benjamin R; Sun, Wenyue; Wei, Fang; Hashimoto, Shigeki; Konishi, Kazuhide; Leitheiser, Christopher J; Hecht, Sidney M

    2007-10-17

    The bleomycins (BLMs) are clinically used glycopeptide antitumor antibiotics that have been shown to mediate the sequence-selective oxidative damage of both DNA and RNA. Previously, we described the solid-phase synthesis of a library of 108 unique analogues of deglycoBLM A6, a congener that cleaves DNA analogously to BLM itself. Each member of the library was assayed for its ability to effect single- and double-strand nicking of duplex DNA, sequence-selective DNA cleavage, and RNA cleavage in the presence and absence of a metal ion cofactor. All of the analogues tested were found to mediate concentration-dependent plasmid DNA relaxation to some extent, and a number exhibited double-strand cleavage with an efficiency comparable to or greater than deglycoBLM A6. Further, some analogues having altered linker and metal-binding domains mediated altered sequence-selective cleavage, and a few were found to cleave a tRNA3Lys transcript both in the presence and in the absence of a metal cofactor. The results provide insights into structural elements within BLM that control DNA and RNA cleavage. The present study also permits inferences to be drawn regarding the practicality of a selection strategy for the solid-phase construction and evaluation of large libraries of BLM analogues having altered properties.

  8. A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Nil Turan

    2011-09-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

  9. Biological and economic impact of stream alteration in the Virginia Piedmont

    Science.gov (United States)

    Whelan, James B.

    1981-01-01

    A 31 month (September 1974 - March 1977) study was conducted on warmwater streams located in the Roanoke Creek watershed of the Piedmont Region of Virginia. The purpose of the study was to determine the effects of stream channelization on the aquatic/riparian wildlife resource and agricultural land-use patterns associated with the altered streams. Three streams, which were channelized 3, 6, and 10 years prior to initiation of the study, and teo unaltered streams, were selected as representative streams for the study. Recently channelized streams lacked overstory cover but has an abundance of herbaceous and small woody plany cover, Conversely, control streams had significantly larger percentages of trees over 46 m tall. Plant species diversity, foliage height diversity, and evenness diversity increased as age since channelization increased. No major differences in water quality parameters were found for either channelized or control streams, although channelized streams had greater deposits of sand and lesser amount of rock, rubble, and gravel. These changes in substrate composition did not significantly modify actual stream flow rates. Fish species composition and species diversity among channelized and unchannelized streams were only slightly different, with most of the differences probably attributable to strays from adjacent habitats, However, evenness diversity for fish communities was lower in channelized streams. The benthic population showed greater changes than did the fish populations with an increase in Chironominae tolerant of unstable sand substrates in channelized streams. Evenness diversity of benthic populations was also higher and showed more consistency in the control stream than in channelized streams. Evenness diversity of benthic communities in control stream averaged between 0.5 to 0.6 and was quite consistent; whereas, the average in the two youngest channelized streams was 0.3 to 0.4. These data seem to indicate decreased stability of the

  10. Biological monitoring and selected trends in environmental quality. [Use of National Inventory of Selected Biological Monitoring Programs at ORNL to identify documented environmental trends

    Energy Technology Data Exchange (ETDEWEB)

    Suffern, J.S.; West, D.C.; Kemp, H.T.; Burgess, R.L.

    1976-10-01

    Under a contract with the President's Council on Environmental Quality, the National Inventory of Selected Biological Monitoring Programs at ORNL was used to identify documented environmental trends. Fish population trends were described for the Great Lakes and the Colorado River system. Trends in amphibian populations in the northeast were examined and correlated with acid precipitation. Increases in breeding success among large birds of prey were correlated with reductions in ambient levels of DDT and its residues. Geographic variation in PCB contamination was examined along with differences between aquatic and terrestrial contamination levels. Changes in air quality were documented, and their effects on plant viability were outlined. Trends in the biological effects of environmental deposition of lead were documented. Long-term changes in forest structure in the southeast were presented, and a general reduction in wildlife habitat, associated with land use practices, was documented for several areas in the US.

  11. Can OCT be sensitive to nanoscale structural alterations in biological tissue?

    Science.gov (United States)

    Yi, Ji; Radosevich, Andrew J; Rogers, Jeremy D; Norris, Sam C P; Çapoğlu, İlker R; Taflove, Allen; Backman, Vadim

    2013-04-01

    Exploration of nanoscale tissue structures is crucial in understanding biological processes. Although novel optical microscopy methods have been developed to probe cellular features beyond the diffraction limit, nanometer-scale quantification remains still inaccessible for in situ tissue. Here we demonstrate that, without actually resolving specific geometrical feature, OCT can be sensitive to tissue structural properties at the nanometer length scale. The statistical mass-density distribution in tissue is quantified by its autocorrelation function modeled by the Whittle-Mateŕn functional family. By measuring the wavelength-dependent backscattering coefficient μb(λ) and the scattering coefficient μs, we introduce a technique called inverse spectroscopic OCT (ISOCT) to quantify the mass-density correlation function. We find that the length scale of sensitivity of ISOCT ranges from ~30 to ~450 nm. Although these sub-diffractional length scales are below the spatial resolution of OCT and therefore not resolvable, they are nonetheless detectable. The sub-diffractional sensitivity is validated by 1) numerical simulations; 2) tissue phantom studies; and 3) ex vivo colon tissue measurements cross-validated by scanning electron microscopy (SEM). Finally, the 3D imaging capability of ISOCT is demonstrated with ex vivo rat buccal and human colon samples. PMID:23571994

  12. Classification System for Identifying Women at Risk for Altered Partial Breast Irradiation Recommendations After Breast Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kowalchik, Kristin V. [Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida (United States); Vallow, Laura A., E-mail: vallow.laura@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida (United States); McDonough, Michelle [Department of Radiology, Mayo Clinic, Jacksonville, Florida (United States); Thomas, Colleen S.; Heckman, Michael G. [Section of Biostatistics, Mayo Clinic, Jacksonville, Florida (United States); Peterson, Jennifer L. [Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida (United States); Adkisson, Cameron D. [Department of General Surgery, Mayo Clinic, Jacksonville, Florida (United States); Serago, Christopher [Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida (United States); McLaughlin, Sarah A. [Department of General Surgery, Mayo Clinic, Jacksonville, Florida (United States)

    2013-09-01

    Purpose: To study the utility of preoperative breast MRI for partial breast irradiation (PBI) patient selection, using multivariable analysis of significant risk factors to create a classification rule. Methods and Materials: Between 2002 and 2009, 712 women with newly diagnosed breast cancer underwent preoperative bilateral breast MRI at Mayo Clinic Florida. Of this cohort, 566 were retrospectively deemed eligible for PBI according to the National Surgical Adjuvant Breast and Bowel Project Protocol B-39 inclusion criteria using physical examination, mammogram, and/or ultrasound. Magnetic resonance images were then reviewed to determine their impact on patient eligibility. The patient and tumor characteristics were evaluated to determine risk factors for altered PBI eligibility after MRI and to create a classification rule. Results: Of the 566 patients initially eligible for PBI, 141 (25%) were found ineligible because of pathologically proven MRI findings. Magnetic resonance imaging detected additional ipsilateral breast cancer in 118 (21%). Of these, 62 (11%) had more extensive disease than originally noted before MRI, and 64 (11%) had multicentric disease. Contralateral breast cancer was detected in 28 (5%). Four characteristics were found to be significantly associated with PBI ineligibility after MRI on multivariable analysis: premenopausal status (P=.021), detection by palpation (P<.001), first-degree relative with a history of breast cancer (P=.033), and lobular histology (P=.002). Risk factors were assigned a score of 0-2. The risk of altered PBI eligibility from MRI based on number of risk factors was 0:18%; 1:22%; 2:42%; 3:65%. Conclusions: Preoperative bilateral breast MRI altered the PBI recommendations for 25% of women. Women who may undergo PBI should be considered for breast MRI, especially those with lobular histology or with 2 or more of the following risk factors: premenopausal, detection by palpation, and first-degree relative with a history of

  13. Classification System for Identifying Women at Risk for Altered Partial Breast Irradiation Recommendations After Breast Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Purpose: To study the utility of preoperative breast MRI for partial breast irradiation (PBI) patient selection, using multivariable analysis of significant risk factors to create a classification rule. Methods and Materials: Between 2002 and 2009, 712 women with newly diagnosed breast cancer underwent preoperative bilateral breast MRI at Mayo Clinic Florida. Of this cohort, 566 were retrospectively deemed eligible for PBI according to the National Surgical Adjuvant Breast and Bowel Project Protocol B-39 inclusion criteria using physical examination, mammogram, and/or ultrasound. Magnetic resonance images were then reviewed to determine their impact on patient eligibility. The patient and tumor characteristics were evaluated to determine risk factors for altered PBI eligibility after MRI and to create a classification rule. Results: Of the 566 patients initially eligible for PBI, 141 (25%) were found ineligible because of pathologically proven MRI findings. Magnetic resonance imaging detected additional ipsilateral breast cancer in 118 (21%). Of these, 62 (11%) had more extensive disease than originally noted before MRI, and 64 (11%) had multicentric disease. Contralateral breast cancer was detected in 28 (5%). Four characteristics were found to be significantly associated with PBI ineligibility after MRI on multivariable analysis: premenopausal status (P=.021), detection by palpation (P<.001), first-degree relative with a history of breast cancer (P=.033), and lobular histology (P=.002). Risk factors were assigned a score of 0-2. The risk of altered PBI eligibility from MRI based on number of risk factors was 0:18%; 1:22%; 2:42%; 3:65%. Conclusions: Preoperative bilateral breast MRI altered the PBI recommendations for 25% of women. Women who may undergo PBI should be considered for breast MRI, especially those with lobular histology or with 2 or more of the following risk factors: premenopausal, detection by palpation, and first-degree relative with a history of

  14. Be alert to the alterations in the biological characteristics in heterogeneous vancomycin-intermediate Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    X Zhou

    2012-01-01

    Full Text Available The development of reduced vancomycin susceptibility in Staphylococcus aureus in many cases appears to be associated with characteristic changes. These changes may have pitfall of identifying S. aureus by automated testing methods like Vitek 32. In this study, we retested 24 heterogeneous vancomycin-intermediate Staphylococcus haemolyticus (h-VISH collected in 2008-2010 at the Department of Clinical Microbiology by conventional biochemical tests and polymerase chain reaction (PCR. The heterogeneous vancomycin-intermediate S. aureus (hVISA reversion test and electron microscopic examination were also used. Six isolates of 24 h-VISH possessed nuc, coa, and 16S rRNA genes, and could be reversed into S. aureus. It suggested that biochemical and morphological changes in hVISA and vancomycin-intermediate S. aureus (VISA should be considered, and the detection of S. aureus, especially reduced vancomycin susceptibility isolates, requires more attention and different techniques.

  15. Rapidly detecting disorder in rhythmic biological signals: a spectral entropy measure to identify cardiac arrhythmias

    CERN Document Server

    Staniczenko, Phillip P A; Jones, Nick S

    2008-01-01

    We consider the use of a running measure of power spectrum disorder to distinguish between the normal sinus rhythm of the heart and two forms of cardiac arrhythmia: atrial fibrillation and atrial flutter. This is motivated by characteristic differences in the spectra of beats during the three rhythms. We plot patient data derived from 10-beat windows on a `disorder map' and identify rhythm-defining ranges in the level and variance of spectral entropy values. Employing the spectral entropy within an automatic arrhythmia detection algorithm enables the classification of periods of atrial fibrillation from the time series of patients' beats. When the algorithm is set to identify abnormal rhythms within 6s it agrees with 85.7% of the annotations of professional rhythm assessors; for a response time of 30s this becomes 89.5%, and with 60s it is 90.3%. The algorithm provides a rapid way to detect atrial fibrillation, demonstrating usable response times as low as six seconds. Measures of disorder in the frequency do...

  16. Impact on disease development, genomic location and biological function of copy number alterations in non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Yen-Tsung Huang

    Full Text Available Lung cancer, of which more than 80% is non-small cell, is the leading cause of cancer-related death in the United States. Copy number alterations (CNAs in lung cancer have been shown to be positionally clustered in certain genomic regions. However, it remains unclear whether genes with copy number changes are functionally clustered. Using a dense single nucleotide polymorphism array, we performed genome-wide copy number analyses of a large collection of non-small cell lung tumors (n = 301. We proposed a formal statistical test for CNAs between different groups (e.g., non-involved lung vs. tumors, early vs. late stage tumors. We also customized the gene set enrichment analysis (GSEA algorithm to investigate the overrepresentation of genes with CNAs in predefined biological pathways and gene sets (i.e., functional clustering. We found that CNAs events increase substantially from germline, early stage to late stage tumor. In addition to genomic position, CNAs tend to occur away from the gene locations, especially in germline, non-involved tissue and early stage tumors. Such tendency decreases from germline to early stage and then to late stage tumors, suggesting a relaxation of selection during tumor progression. Furthermore, genes with CNAs in non-small cell lung tumors were enriched in certain gene sets and biological pathways that play crucial roles in oncogenesis and cancer progression, demonstrating the functional aspect of CNAs in the context of biological pathways that were overlooked previously. We conclude that CNAs increase with disease progression and CNAs are both positionally and functionally clustered. The potential functional capabilities acquired via CNAs may be sufficient for normal cells to transform into malignant cells.

  17. Chemicals identified in human biological media: a data base. Third annual report, October 1981

    Energy Technology Data Exchange (ETDEWEB)

    Cone, M.V.; Baldauf, M.F.; Martin, F.M. (comps.)

    1981-12-01

    Data from almost 1600 of the 3800 body-burden documents collected to date have been entered in the data base as of October 1981. The emphasis on including recent literature and significant research documents has resulted in a chronological mix of articles from 1974 to the present. When body-burden articles are identified, data are extracted and entered in the data base by chemical and tissue/body fluid. Each data entry comprises a single record (or line entry) and is assigned a record number. If a particular document deals with more than one chemical and/or tissue, there will be multiple records for that document. For example, a study of 5 chemicals in each of 3 tissues has 15 different records (or 15 line entries) in the data base with 15 record numbers. Record numbers are assigned consecutively throughout the entire data base and appear in the upper left corner of the first column for each record.

  18. Comprehensive genomic profiling of orbital and ocular adnexal lymphomas identifies frequent alterations in MYD88 and chromatin modifiers: new routes to targeted therapies.

    Science.gov (United States)

    Cani, Andi K; Soliman, Moaaz; Hovelson, Daniel H; Liu, Chia-Jen; McDaniel, Andrew S; Haller, Michaela J; Bratley, Jarred V; Rahrig, Samantha E; Li, Qiang; Briceño, César A; Tomlins, Scott A; Rao, Rajesh C

    2016-07-01

    Non-Hodgkin lymphoma of the orbit and ocular adnexa is the most common primary orbital malignancy. Treatments for low- (extra-nodal marginal zone and follicular lymphomas) and high-grade (diffuse large B-cell lymphoma) are associated with local and vision-threatening toxicities. High-grade lymphomas relapse frequently and exhibit poor survival rates. Despite advances in genomic profiling and precision medicine, orbital and ocular adnexal lymphomas remain poorly characterized molecularly. We performed targeted next-generation sequencing (NGS) profiling of 38 formalin-fixed, paraffin-embedded orbital and ocular adnexal lymphomas obtained from a single-center using a panel targeting near-term, clinically relevant genes. Potentially actionable mutations and copy number alterations were prioritized based on gain- and loss-of-function analyses, and catalogued, approved, and investigational therapies. Of 36 informative samples, including marginal zone lymphomas (n=20), follicular lymphomas (n=9), and diffuse large B-cell lymphomas (n=7), 53% harbored a prioritized alteration (median=1, range 0-5/sample). MYD88 was the most frequently altered gene in our cohort, with potentially clinically relevant hotspot gain-of-function mutations identified in 71% of diffuse large B-cell lymphomas and 25% of marginal zone lymphomas. Prioritized alterations in epigenetic modulators were common and included gain-of-function EZH2 and loss-of-function ARID1A mutations (14% of diffuse large B-cell lymphomas and 22% of follicular lymphomas contained alterations in each of these two genes). Single prioritized alterations were also identified in the histone methyltransferases KMT2B (follicular lymphoma) and KMT3B (diffuse large B-cell lymphoma). Loss-of-function mutations and copy number alterations in the tumor suppressors TP53 (diffuse large B-cell and follicular lymphoma), CDKN2A (diffuse large B-cell and marginal zone lymphoma), PTEN (diffuse large B-cell lymphoma), ATM (diffuse large B

  19. Extracting gene expression patterns and identifying co-expressed genes from microarray data reveals biologically responsive processes

    Directory of Open Access Journals (Sweden)

    Paules Richard S

    2007-11-01

    Full Text Available Abstract Background A common observation in the analysis of gene expression data is that many genes display similarity in their expression patterns and therefore appear to be co-regulated. However, the variation associated with microarray data and the complexity of the experimental designs make the acquisition of co-expressed genes a challenge. We developed a novel method for Extracting microarray gene expression Patterns and Identifying co-expressed Genes, designated as EPIG. The approach utilizes the underlying structure of gene expression data to extract patterns and identify co-expressed genes that are responsive to experimental conditions. Results Through evaluation of the correlations among profiles, the magnitude of variation in gene expression profiles, and profile signal-to-noise ratio's, EPIG extracts a set of patterns representing co-expressed genes. The method is shown to work well with a simulated data set and microarray data obtained from time-series studies of dauer recovery and L1 starvation in C. elegans and after ultraviolet (UV or ionizing radiation (IR-induced DNA damage in diploid human fibroblasts. With the simulated data set, EPIG extracted the appropriate number of patterns which were more stable and homogeneous than the set of patterns that were determined using the CLICK or CAST clustering algorithms. However, CLICK performed better than EPIG and CAST with respect to the average correlation between clusters/patterns of the simulated data. With real biological data, EPIG extracted more dauer-specific patterns than CLICK. Furthermore, analysis of the IR/UV data revealed 18 unique patterns and 2661 genes out of approximately 17,000 that were identified as significantly expressed and categorized to the patterns by EPIG. The time-dependent patterns displayed similar and dissimilar responses between IR and UV treatments. Gene Ontology analysis applied to each pattern-related subset of co-expressed genes revealed underlying

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    2016-04-01

    Full Text Available 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

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

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, 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

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

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, 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

  4. Integration of molecular biology tools for identifying promoters and genes abundantly expressed in flowers of Oncidium Gower Ramsey

    Directory of Open Access Journals (Sweden)

    Tung Shu-Yun

    2011-04-01

    Full Text Available Abstract Background Orchids comprise one of the largest families of flowering plants and generate commercially important flowers. However, model plants, such as Arabidopsis thaliana do not contain all plant genes, and agronomic and horticulturally important genera and species must be individually studied. Results Several molecular biology tools were used to isolate flower-specific gene promoters from Oncidium 'Gower Ramsey' (Onc. GR. A cDNA library of reproductive tissues was used to construct a microarray in order to compare gene expression in flowers and leaves. Five genes were highly expressed in flower tissues, and the subcellular locations of the corresponding proteins were identified using lip transient transformation with fluorescent protein-fusion constructs. BAC clones of the 5 genes, together with 7 previously published flower- and reproductive growth-specific genes in Onc. GR, were identified for cloning of their promoter regions. Interestingly, 3 of the 5 novel flower-abundant genes were putative trypsin inhibitor (TI genes (OnTI1, OnTI2 and OnTI3, which were tandemly duplicated in the same BAC clone. Their promoters were identified using transient GUS reporter gene transformation and stable A. thaliana transformation analyses. Conclusions By combining cDNA microarray, BAC library, and bombardment assay techniques, we successfully identified flower-directed orchid genes and promoters.

  5. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

    Science.gov (United States)

    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.

  6. A systems biology and proteomics-based approach identifies SRC and VEGFA as biomarkers in risk factor mediated coronary heart disease.

    Science.gov (United States)

    V, Alexandar; Nayar, Pradeep G; Murugesan, R; S, Shajahan; Krishnan, Jayalakshmi; Ahmed, Shiek S S J

    2016-07-19

    Coronary heart disease (CHD) is the most common cause of death worldwide. The burden of CHD increases with risk factors such as smoking, hypertension, obesity and diabetes. Several studies have demonstrated the association of these classical risk factors with CHD. However, the mechanisms of these associations remain largely unclear due to the complexity of disease pathophysiology and the lack of an integrative approach that fails to provide a definite understanding of molecular linkage. To overcome these problems, we propose a novel systems biology approach that relates causative genes, interactomes and pathways to elucidate the risk factors mediating the molecular mechanisms and biomarkers for feasible diagnosis. The literature was mined to retrieve the causative genes of each risk factor and CHD to construct protein interactomes. The interactomes were examined to identify 298 common molecular signatures. The common signatures were mapped to the tissue network to synthesize a sub-network consisting of 82 proteins. Further, the dissection of the sub-network provides functional modules representing a diverse range of molecular functions, including the AKT/p13k, MAPK and wnt pathways. Also, the prioritization of functional modules identifies SRC, VEGFA and HIF1A as potential candidate markers. Further, we validate these candidates with the existing markers CRP, NOS3 and VCAM1 in the serum of 63 individuals, 33 with CHD and 30 controls, using ELISA. SRC, VEGFA, H1F1A, CRP and NOS3 were significantly altered in patients compared to controls. These results support the utility of these candidate markers for the diagnosis of CHD. Overall, our molecular observations indicate the influence of risk factors in the pathophysiology of CHD and identify serum markers for diagnosis. PMID:27279347

  7. Solar ultraviolet radiation induces biological alterations in human skin in vitro: Relevance of a well-balanced UVA/UVB protection

    Directory of Open Access Journals (Sweden)

    Françoise Bernerd

    2012-01-01

    Full Text Available Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

  8. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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. PMID:27632082

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

    Science.gov (United States)

    Zhao, Junfei; Sheng, Jinsong; Rubin, Donald H.

    2016-01-01

    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. PMID:27632082

  11. Development of biological indices for identifying and evaluating impacts of pollutants on freshwater ecosystems. Final report, June 1975-October 1980

    Energy Technology Data Exchange (ETDEWEB)

    Cairns, J. Jr.; Cherry, D.S.

    1980-09-30

    The ten Research Areas reported included: (1) the development of functional indices for identifying and evaluating impacts of pollutants on Aufwuchs communities, (2) relationship of protozoan colonization rates to the eutrophication process, (3) testing of methods to determine the functioning of zooplankton communities subjected to entrainment stress, (4) the use of the first steps of detritus processing (microbial decomposition) as a technique for assessing pollutional stress on aquatic communities in a river system, (5) relationship of protozoan invasion and extinction rate to the eutrophication process, (6) extension of present early colonization studies to the simultaneous evaluation of natural environmental parameters and power plant effluents and application of the early colonization approach to microbial communities in streams of the New River drainage, (7) testing of single species-community responses of protozoans from selected heavy metals, (8) the effects of selected power plant pollutants on grazer utilization of Aufwuchs, (9) investigation of bioconcentration and bioaccumulation mechanisms of the Asiatic clam (Corbicula fluminea) populations in field artificial streams and laboratory microcosms with reference to physical chemistry and diet alterations, and (10) investigation of the homeostatic regulation in bluegill sunfish following acute hypothermal shock and to other power plant related effluents.

  12. Use of a bovine genome array to identify new biological pathways for beef marbling in Hanwoo (Korean Cattle

    Directory of Open Access Journals (Sweden)

    Lim Da-jeong

    2010-11-01

    Full Text Available Abstract Background Marbling (intramuscular fat is a valuable trait that impacts on meat quality and an important factor determining price of beef in the Korean beef market. Animals that are destined for this high marbling market are fed a high concentrate ration for approximately 30 months in the Korean finishing farms. However, this feeding strategy leads to inefficiencies and excessive fat production. This study aimed to identify candidate genes and pathways associated with intramuscular fat deposition on highly divergent marbling phenotypes in adult Hanwoo cattle. Results Bovine genome array analysis was conducted to detect differentially expressed genes (DEGs in m. longissimus with divergent marbling phenotype (marbling score 2 to 7. Three data-processing methods (MAS5.0, GCRMA and RMA were used to test for differential expression (DE. Statistical analysis identified 21 significant transcripts from at least two data-processing methods (P . All 21 differentially expressed genes were validated by real-time PCR. Results showed a high concordance in the gene expression fold change between the microarrays and the real time PCR data. Gene Ontology (GO and pathway analysis demonstrated that some genes (ADAMTS4, CYP51A and SQLE over expressed in high marbled animals are involved in a protein catabolic process and a cholesterol biosynthesis process. In addition, pathway analysis also revealed that ADAMTS4 is activated by three regulators (IL-17A, TNFα and TGFβ1. QRT-PCR was used to investigate gene expression of these regulators in muscle with divergent intramuscular fat contents. The results demonstrate that ADAMTS4 and TGFβ1 are associated with increasing marbling fat. An ADAMTS4/TGFβ1 pathway seems to be associated with the phenotypic differences between high and low marbled groups. Conclusions Marbling differences are possibly a function of complex signaling pathway interactions between muscle and fat. These results suggest that ADAMTS4

  13. Biological soil crust as a bio-mediator alters hydrological processes in stabilized dune system of the Tengger Desert, China

    Science.gov (United States)

    Li, Xinrong

    2016-04-01

    Biological soil crust (BSC) is a vital component in the stabilized sand dunes with a living cover up to more than 70% of the total, which has been considered as a bio-mediator that directly influences and regulates the sand dune ecosystem processes. However, its influences on soil hydrological processes have been long neglected in Chinese deserts. In this study, BSCs of different successional stages were chose to test their influence on the hydrological processes of stabilized dune, where the groundwater deep exceeds 30m, further to explore why occur the sand-binding vegetation replacement between shrubs and herbs. Our long-term observation (60 years) shows that cyanobacteria crust has been colonized and developed after 3 years since the sand-binding vegetation has been established and dune fixation using planted xerophytic shrubs and made sand barrier (straw-checkerboard) on shifting dune surface, lichen and moss crust occurred after 20 years, and the cover of moss dominated crust could reach 70 % after 50 years. The colonization and development of BSC altered the initial soil water balance of revegetated areas by influencing rainfall infiltration, soil evaporation and dew water entrapment. The results show that BSC obviously reduced the infiltration that occurred during most rainfall events (80%), when rainfall was greater than 5 mm or less than 20 mm. The presence of BSC reduced evaporation of topsoil after small rainfall (facilitated topsoil evaporation when rainfall reached 10 mm. The amount of dew entrapment increases with the succession of BSC. Moreover, the effect of the later successional BSC to dew entrapment, rainfall infiltration and evaporation was more obvious than the early successional BSC on stabilized dunes. In general, BSC reduced the amount of rainfall water that reached deeper soil (0.4-3m), which is where the roots of shrubs are primarily distributed. These changes in the soil moisture pattern induced shifting of sand-binding vegetation from

  14. Biological soil crust as a bio-mediator alters hydrological processes in stabilized dune system of the Tengger Desert, China

    Science.gov (United States)

    Li, Xinrong

    2016-04-01

    Biological soil crust (BSC) is a vital component in the stabilized sand dunes with a living cover up to more than 70% of the total, which has been considered as a bio-mediator that directly influences and regulates the sand dune ecosystem processes. However, its influences on soil hydrological processes have been long neglected in Chinese deserts. In this study, BSCs of different successional stages were chose to test their influence on the hydrological processes of stabilized dune, where the groundwater deep exceeds 30m, further to explore why occur the sand-binding vegetation replacement between shrubs and herbs. Our long-term observation (60 years) shows that cyanobacteria crust has been colonized and developed after 3 years since the sand-binding vegetation has been established and dune fixation using planted xerophytic shrubs and made sand barrier (straw-checkerboard) on shifting dune surface, lichen and moss crust occurred after 20 years, and the cover of moss dominated crust could reach 70 % after 50 years. The colonization and development of BSC altered the initial soil water balance of revegetated areas by influencing rainfall infiltration, soil evaporation and dew water entrapment. The results show that BSC obviously reduced the infiltration that occurred during most rainfall events (80%), when rainfall was greater than 5 mm or less than 20 mm. The presence of BSC reduced evaporation of topsoil after small rainfall (BSC. Moreover, the effect of the later successional BSC to dew entrapment, rainfall infiltration and evaporation was more obvious than the early successional BSC on stabilized dunes. In general, BSC reduced the amount of rainfall water that reached deeper soil (0.4-3m), which is where the roots of shrubs are primarily distributed. These changes in the soil moisture pattern induced shifting of sand-binding vegetation from initial planted xerophytic shrub communities with higher coverage (35%) to complex communities dominated by shallow

  15. Diazotrophy in the Deep: Measuring Rates and Identifying Biological Mediators of N2 fixation in Deep-Sea Sediments

    Science.gov (United States)

    Dekas, A. E.; Fike, D. A.; Chadwick, G.; Connon, S. A.; Orphan, V. J.

    2013-12-01

    Biological N2 fixation (the conversion of N2 to NH3) is the largest natural source of bioavailable nitrogen to the biosphere, and dictates the rate of community productivity in many nitrogen-limited environments. Deep-sea sediments are traditionally not thought to host N2 fixation, however evidence from a metagenomics dataset targeting deep-sea methanotrophic archaea (ANME) suggested their ability to fix N2 (Pernthaler, et al., PNAS 2008). Using stable isotope labeling experiments and FISH-NanoSIMS, a technique which allows the visualization of isotopic composition within phylogenetically identified cells on the nanometer scale, we demonstrated that the ANME are capable of N2 fixation (Dekas et al., Science 2009). In the present work, we use FISH-NanoSIMS and bulk Isotope Ratio Mass Spectrometry (IRMS) to show that the ANME are the most significant source of new nitrogen at a Costa Rican methane seep. This suggests that the ANME may play a significant role in N2 fixation in methane seeps worldwide. We expand our investigation of deep-sea diazotrophy to include diverse habitats, including sulfide- and carbon-rich whalefalls, and observe that N2 fixation is widespread in sediments on the seafloor. Outside of methane seeps, N2 fixation appears to be mediated by a diversity of anaerobic microbes potentially including methanogens and sulfate reducing bacteria. Interestingly, deep-sea N2 fixation often occurs in the presence of high levels of NH4+. Our observations challenge long-held hypotheses about where and when N2 fixation occurs, and suggest a bigger role for N2 fixation on the seafloor - and potentially the deep-biosphere - than previously realized.

  16. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  17. Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants.

    Science.gov (United States)

    Leister, Dario; Kleine, Tatjana

    2016-07-01

    Retrograde signaling can be triggered by changes in organellar gene expression (OGE) induced by inhibitors such as lincomycin (LIN) or mutations that perturb OGE. Thus, an insufficiency of the organelle-targeted prolyl-tRNA synthetase PRORS1 in Arabidopsis thaliana activates retrograde signaling and reduces the expression of nuclear genes for photosynthetic proteins. Recently, we showed that mTERF6, a member of the so-called mitochondrial transcription termination factor (mTERF) family, is involved in the formation of chloroplast (cp) isoleucine-tRNA. To obtain further insights into its functions, co-expression analysis of MTERF6, PRORS1 and two other genes for organellar aminoacyl-tRNA synthetases was conducted. The results suggest a prominent role of mTERF6 in aminoacylation activity, light signaling and seed storage. Analysis of changes in whole-genome transcriptomes in the mterf6-1 mutant showed that levels of nuclear transcripts for cp OGE proteins were particularly affected. Comparison of the mterf6-1 transcriptome with that of prors1-2 showed that reduced aminoacylation of proline (prors1-2) and isoleucine (mterf6-1) tRNAs alters retrograde signaling in similar ways. Database analyses indicate that comparable gene expression changes are provoked by treatment with LIN, norflurazon or high light. A core OGE response module was defined by identifying genes that were differentially expressed under at least four of six conditions relevant to OGE signaling. Based on this module, overexpressors of the Golden2-like transcription factors GLK1 and GLK2 were identified as genomes uncoupled mutants. PMID:26876646

  18. Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants.

    Science.gov (United States)

    Leister, Dario; Kleine, Tatjana

    2016-07-01

    Retrograde signaling can be triggered by changes in organellar gene expression (OGE) induced by inhibitors such as lincomycin (LIN) or mutations that perturb OGE. Thus, an insufficiency of the organelle-targeted prolyl-tRNA synthetase PRORS1 in Arabidopsis thaliana activates retrograde signaling and reduces the expression of nuclear genes for photosynthetic proteins. Recently, we showed that mTERF6, a member of the so-called mitochondrial transcription termination factor (mTERF) family, is involved in the formation of chloroplast (cp) isoleucine-tRNA. To obtain further insights into its functions, co-expression analysis of MTERF6, PRORS1 and two other genes for organellar aminoacyl-tRNA synthetases was conducted. The results suggest a prominent role of mTERF6 in aminoacylation activity, light signaling and seed storage. Analysis of changes in whole-genome transcriptomes in the mterf6-1 mutant showed that levels of nuclear transcripts for cp OGE proteins were particularly affected. Comparison of the mterf6-1 transcriptome with that of prors1-2 showed that reduced aminoacylation of proline (prors1-2) and isoleucine (mterf6-1) tRNAs alters retrograde signaling in similar ways. Database analyses indicate that comparable gene expression changes are provoked by treatment with LIN, norflurazon or high light. A core OGE response module was defined by identifying genes that were differentially expressed under at least four of six conditions relevant to OGE signaling. Based on this module, overexpressors of the Golden2-like transcription factors GLK1 and GLK2 were identified as genomes uncoupled mutants.

  19. Design, Development, and Psychometric Analysis of a General, Organic, and Biological Chemistry Topic Inventory Based on the Identified Main Chemistry Topics Relevant to Nursing Clinical Practice

    Science.gov (United States)

    Brown, Corina E.

    2013-01-01

    This two-stage study focused on the undergraduate nursing course that covers topics in general, organic, and biological (GOB) chemistry. In the first stage, the central objective was to identify the main concepts of GOB chemistry relevant to the clinical practice of nursing. The collection of data was based on open-ended interviews of both nursing…

  20. Biological effect of Acidithiobacillus thiooxidans on some potentially toxic elements during alteration of SON 68 nuclear glass

    Science.gov (United States)

    Bachelet, M.; Crovisier, J. L.; Stille, P.; Vuilleumier, S.; Geoffroy, V.

    2009-04-01

    Although underground nuclear waste repositories are not expected to be favourable places for microbial activity, one should not exclude localized action of extremophilic bacteria on some materials involved in the storage concept. Among endogenous or accidentally introduced acidophiles, some are susceptible to lead to a locally drastic decreased in pH, with potential consequences on materials corrosion. Experiments were performed with Acidithiobacillus thiooxidans on 100-125 m french reference nuclear glass SON68 grains in a mineral medium under static conditions during 60 days at 25degC. Growth medium was periodically renewed and analyzed by ICP-AES and ICP-MS spectrometry for both major, trace and ultra-trace elements. Biofilm formation was evidenced by confocal laser microscopy, staining DNA with ethidium bromide and exopolysaccharides with calcofluor white. Biofilm thickness around material grains exceeded 20 m under the chosen experimental conditions. It can be noticed that while numerous studies on biofilm formation upon interaction between Acidithiobacillus ferrooxidans and materials are found in the literature, evidence for biofilm formation is still scarce for the case of the acidophilic bacterium A. thiooxidans. Presence of biofilm is a key parameter for material alteration at the solid/solution interface in biotic systems. Indeed, various constitutive elements of materials trapped in the polyanionic polymer of biofilm may also influence the alteration process. In particular, biofilm may reduce the alteration rate of materials by forming a protective barrier at their surface (Aouad et al., 2008). In this study, glass alteration rates, determined using strontium as tracer, showed that the progressive formation of a biofilm on the surface of glass has a protective effect against its alteration. Uranium and rare earth elements (REE) are efficiently trapped in the biogenic compartment of the system (exopolysaccharides + bacterial cells). Besides, the ratio

  1. Gene expression profiling identifies microphthalmia-associated transcription factor (MITF and Dickkopf-1 (DKK1 as regulators of microenvironment-driven alterations in melanoma phenotype.

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    Mariusz L Hartman

    Full Text Available BACKGROUND: The diversity of functional phenotypes observed within a tumor does not exclusively result from intratumoral genetic heterogeneity but also from the response of cancer cells to the microenvironment. We have previously demonstrated that the morphological and functional phenotypes of melanoma can be dynamically altered upon external stimuli. FINDINGS: In the present study, transcriptome profiles were generated to explore the molecules governing phenotypes of melanospheres grown in the bFGF(+EGF(+ serum-free cultures and monolayers maintained in the serum-containing medium. Higher expression levels of MITF-dependent genes that are responsible for differentiation, e.g., TYR and MLANA, and stemness-related genes, e.g., ALDH1A1, were detected in melanospheres. These results were supported by the observation that the melanospheres contained more pigmented cells and cells exerting the self-renewal capacity than the monolayers. In addition, the expression of the anti-apoptotic, MITF-dependent genes e.g., BCL2A1 was also higher in the melanospheres. The enhanced activity of MITF in melanospheres, as illustrated by the increased expression of 74 MITF-dependent genes, identified MITF as a central transcriptional regulator in melanospheres. Importantly, several genes including MITF-dependent ones were expressed in melanospheres and original tumors at similar levels. The reduced MITF level in monolayers might be partially explained by suppression of the Wnt/β-catenin pathway, and DKK1, a secreted inhibitor of this pathway, was highly up-regulated in monolayers in comparison to melanospheres and original tumors. Furthermore, the silencing of DKK1 in monolayers increased the percentage of cells with self-renewing capacity. CONCLUSIONS: Our study indicates that melanospheres can be used to unravel the molecular pathways that sustain intratumoral phenotypic heterogeneity. Melanospheres directly derived from tumor specimens more accurately mirrored

  2. The AstroBiology Explorer (ABE) MIDEX Mission: Using Infrared Spectroscopy to Identify Organic Molecules in Space

    Science.gov (United States)

    Sandford, S. A.

    2002-01-01

    The AstroBiology Explorer (ABE) mission is one of four selected for Phase A Concept Study in NASA's current call for MIDEX class missions. ABE is a cooled space telescope equipped with spectrographs covering the 2.5-20 micron spectral range. The ABE mission is devoted to the detection and identification of organic and related molecular species in space. ABE is currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace.

  3. Elevated temperature altered photosynthetic products in wheat seedlings and organic compounds and biological activity in rhizopshere soil under cadmium stress

    Science.gov (United States)

    Jia, Xia; Zhao, Yonghua; Wang, Wenke; He, Yunhua

    2015-09-01

    The objective of this study was to investigate the effects of slightly elevated atmospheric temperature in the spring on photosynthetic products in wheat seedlings and on organic compounds and biological activity in rhizosphere soil under cadmium (Cd) stress. Elevated temperature was associated with increased soluble sugars, reducing sugars, starch, and total sugars, and with decreased amino acids in wheat seedlings under Cd stress. Elevated temperature improved total soluble sugars, free amino acids, soluble phenolic acids, and organic acids in rhizosphere soil under Cd stress. The activity of amylase, phenol oxidase, invertase, β-glucosidase, and L-asparaginase in rhizosphere soil was significantly improved by elevated temperature under Cd stress; while cellulase, neutral phosphatase, and urease activity significantly decreased. Elevated temperature significantly improved bacteria, fungi, actinomycetes, and total microorganisms abundance and fluorescein diacetate activity under Cd stress. In conclusion, slightly elevated atmospheric temperature in the spring improved the carbohydrate levels in wheat seedlings and organic compounds and biological activity in rhizosphere soil under Cd stress in the short term. In addition, elevated atmospheric temperature in the spring stimulated available Cd by affecting pH, DOC, phenolic acids, and organic acids in rhizosphere soil, which resulted in the improvement of the Cd uptake by wheat seedlings.

  4. Identification of Altered Metabolomic Profiles Following a Panchakarma-based Ayurvedic Intervention in Healthy Subjects: The Self-Directed Biological Transformation Initiative (SBTI).

    Science.gov (United States)

    Peterson, Christine Tara; Lucas, Joseph; John-Williams, Lisa St; Thompson, J Will; Moseley, M Arthur; Patel, Sheila; Peterson, Scott N; Porter, Valencia; Schadt, Eric E; Mills, Paul J; Tanzi, Rudolph E; Doraiswamy, P Murali; Chopra, Deepak

    2016-01-01

    The effects of integrative medicine practices such as meditation and Ayurveda on human physiology are not fully understood. The aim of this study was to identify altered metabolomic profiles following an Ayurveda-based intervention. In the experimental group, 65 healthy male and female subjects participated in a 6-day Panchakarma-based Ayurvedic intervention which included herbs, vegetarian diet, meditation, yoga, and massage. A set of 12 plasma phosphatidylcholines decreased (adjusted p metabolomic alterations may reflect a Panchakarma-induced modulation of metabotypes. Panchakarma promoted statistically significant changes in plasma levels of phosphatidylcholines, sphingomyelins and others in just 6 days. Forthcoming studies that integrate metabolomics with genomic, microbiome and physiological parameters may facilitate a broader systems-level understanding and mechanistic insights into these integrative practices that are employed to promote health and well-being. PMID:27611967

  5. Breeding biology and nest-site selection of red-tailed hawks in an altered desert grassland

    Science.gov (United States)

    Hobbs, R.J.; DeStefano, S.; Halvorson, W.L.

    2006-01-01

    Red-tailed Hawks (Buteo jamaicensis) have expanded their range as trees have invaded formerly-open grasslands. Desert grasslands of southern Arizona have been invaded by mesquite trees (Prosopis velutina) since Anglo-American settlement and now support a large population of Red-tailed Hawks. We studied a population of Red-tailed Hawks in an altered desert grassland in southern Arizona. Our objectives were to determine what environmental characteristics influence Red-tailed Hawk habitat selection in mesquite-invaded desert grasslands and to evaluate the habitat quality of these grasslands for Red-tailed Hawks based on nesting density, nest success, and productivity. Red-tailed Hawks had 86% (95% C.I. = 73-99) nest success and 1.82 young per breeding pair (95% C.I. = 1.41-2.23). Nesting density was 0.15 (95% CI = 0.08-0.21) breeding pairs/km2 and the mean nearest-neighbor distance was 1.95 km (95% C.I. = 1.74-2.16). Red-tailed Hawks selected nest-sites with taller nest-trees and greater tree height and cover than were available at random. Mesquite trees in desert grasslands provide abundant potential nesting structures for Red-tailed Hawks. ?? 2006 The Raptor Research Foundation, Inc.

  6. Identifying Variables Responsible for Clustering in Discriminant Analysis of Data from Infrared Microspectroscopy of a Biological Sample

    NARCIS (Netherlands)

    Martin, Francis L.; German, Matthew J.; Wit, Ernst; Fearn, Thomas; Ragavan, Narasimhan; Pollock, Hubert M.

    2007-01-01

    In the biomedical field, infrared (IR) spectroscopic studies can involve the processing of data derived from many samples, divided into classes such as category of tissue (e.g., normal or cancerous) or patient identity. We require reliable methods to identify the class-specific information on which

  7. Use of a bovine genome array to identify new biological pathways for beef marbling in Hanwoo (Korean Cattle)

    OpenAIRE

    Lim Da-jeong; Kim Nam-Kuk; Werf Julius; Gondro Cedric; Lee Seung-Hwan; Park Eung-Woo; Oh Sung-Jong; Gibson John P; Thompson John M

    2010-01-01

    Abstract Background Marbling (intramuscular fat) is a valuable trait that impacts on meat quality and an important factor determining price of beef in the Korean beef market. Animals that are destined for this high marbling market are fed a high concentrate ration for approximately 30 months in the Korean finishing farms. However, this feeding strategy leads to inefficiencies and excessive fat production. This study aimed to identify candidate genes and pathways associated with intramuscular ...

  8. High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses.

    Science.gov (United States)

    Abd El-Rehim, Dalia M; Ball, Graham; Pinder, Sarah E; Rakha, Emad; Paish, Claire; Robertson, John F R; Macmillan, Douglas; Blamey, Roger W; Ellis, Ian O

    2005-09-01

    Recent studies on gene molecular profiling using cDNA microarray in a relatively small series of breast cancer have identified biologically distinct groups with apparent clinical and prognostic relevance. The validation of such new taxonomies should be confirmed on larger series of cases prior to acceptance in clinical practice. The development of tissue microarray (TMA) technology provides methodology for high-throughput concomitant analyses of multiple proteins on large numbers of archival tumour samples. In our study, we have used immunohistochemistry techniques applied to TMA preparations of 1,076 cases of invasive breast cancer to study the combined protein expression profiles of a large panel of well-characterized commercially available biomarkers related to epithelial cell lineage, differentiation, hormone and growth factor receptors and gene products known to be altered in some forms of breast cancer. Using hierarchical clustering methodology, 5 groups with distinct patterns of protein expression were identified. A sixth group of only 4 cases was also identified but deemed too small for further detailed assessment. Further analysis of these clusters was performed using multiple layer perceptron (MLP)-artificial neural network (ANN) with a back propagation algorithm to identify key biomarkers driving the membership of each group. We have identified 2 large groups by their expression of luminal epithelial cell phenotypic characteristics, hormone receptors positivity, absence of basal epithelial phenotype characteristics and lack of c-erbB-2 protein overexpression. Two additional groups were characterized by high c-erbB-2 positivity and negative or weak hormone receptors expression but showed differences in MUC1 and E-cadherin expression. The final group was characterized by strong basal epithelial characteristics, p53 positivity, absent hormone receptors and weak to low luminal epithelial cytokeratin expression. In addition, we have identified significant

  9. Combining Methods to Describe Important Marine Habitats for Top Predators: Application to Identify Biological Hotspots in Tropical Waters.

    Directory of Open Access Journals (Sweden)

    Laurie Thiers

    Full Text Available In tropical waters resources are usually scarce and patchy, and predatory species generally show specific adaptations for foraging. Tropical seabirds often forage in association with sub-surface predators that create feeding opportunities by bringing prey close to the surface, and the birds often aggregate in large multispecific flocks. Here we hypothesize that frigatebirds, a tropical seabird adapted to foraging with low energetic costs, could be a good predictor of the distribution of their associated predatory species, including other seabirds (e.g. boobies, terns and subsurface predators (e.g., dolphins, tunas. To test this hypothesis, we compared distribution patterns of marine predators in the Mozambique Channel based on a long-term dataset of both vessel- and aerial surveys, as well as tracking data of frigatebirds. By developing species distribution models (SDMs, we identified key marine areas for tropical predators in relation to contemporaneous oceanographic features to investigate multi-species spatial overlap areas and identify predator hotspots in the Mozambique Channel. SDMs reasonably matched observed patterns and both static (e.g. bathymetry and dynamic (e.g. Chlorophyll a concentration and sea surface temperature factors were important explaining predator distribution patterns. We found that the distribution of frigatebirds included the distributions of the associated species. The central part of the channel appeared to be the best habitat for the four groups of species considered in this study (frigatebirds, brown terns, boobies and sub-surface predators.

  10. Advanced computational biology methods identify molecular switches for malignancy in an EGF mouse model of liver cancer.

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    Philip Stegmaier

    Full Text Available The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification.

  11. The AstroBiology Explorer (ABE) MIDEX Mission Concept: Using Infrared Spectroscopy to Identify Organic Molecules in Space

    Science.gov (United States)

    Sandford, Scott A.; Ennico, Kimberly; Allamandola, Louis; Bregman, Jesse; Greene, Thomas; Hudgins, Douglas

    2002-01-01

    One of the principal means by which organic compounds are detected and identified in space is by infrared spectroscopy. Past IR telescopic and laboratory studies have shown that much of the carbon in the interstellar medium (ISM) is in complex organic species but the distribution, abundance and evolutionary relationships of these materials are not well understood. The Astrobiology Explorer (ABE) is a MIDEX mission concept designed to conduct IR spectroscopic observations to detect and identify these materials and address outstanding problems in astrobiology, astrochemistry, and astrophysics. ABE's core science program includes observations of planetary nebulae and stellar outflows, protostellar objects, Solar System objects, and galaxies, and lines of sight through dense molecular clouds and the diffuse ISM. ABE is a cryogenically-cooled 60 cm diameter space telescope equipped with 3 cross-dispersed R-2000 spectrometers that share a single common slit. Each spectrometer measures one spectral octave and together cover the entire 2.5-20 micron region simultaneously. The spectrometers use state-of-the-art InSb and Si:As 1024x1024 pixel detectors. ABE would operate in a heliocentric, Earth drift-away orbit and have a core science mission lasting approximately 1.5 years. ABE is currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace and Technologies Corp.

  12. Biological Agents Influencing Physical Process in a Stream: A Case Study in Response to Human-Induced Alteration

    Science.gov (United States)

    Sondossi, H. A.; Bienz, C.

    2013-12-01

    We present a case study of the Upper Williamson River, a major tributary to Upper Klamath Lake (UKL), to demonstrate illustrate the importance of biophysical interactions. The Klamath River is called 'the upside-down river' by some, due to its peculiar longitudinal profile--low-gradient at the headwaters east of the Cascade Range and steeper close to the mouth as it crosses the Cascades. The Upper Williamson River, as with other tributaries of UKL, flows through highly erodible volcanic ash (pumice) deposits of the Mazama eruption ~7,000 years ago, which created Crater Lake. There is little or no gravel in the broad, shallow alluvial valley of the River. We make the case that in this particular setting, the role of biological agents (e.g., riparian vegetation) is even more prominent than in settings with normal silica-derived sediment. Therefore, typical agricultural practices (removal of woody riparian vegetation, livestock grazing and trampling, etc.) cause rapid and severe channel response and therefore habitat degradation. However, when appropriately restored the recovery is also rapid and drastic. This spring-fed stream with few tributaries in the study area conveys relatively stable discharge, and has good water quality particularly in the upper reaches. It historically supported a population of native redband trout (Oncorhynchus mykiss gairdnerii), and the candidate species (for listing under the Endangered Species Act) Oregon spotted frog (Rana pretiosa) and countless other avian species. In the late 20th Century, after decades of heavy grazing and active removal of willows from the floodplain, the River banks were nearly bare and unstable. The channel was wide, shallow, and smooth. Consequently, poor water quality, particularly high temperature rendered the stream extremely poor habitat. With controlled grazing, re-establishment of willow galleries, and addition of large woody debris (LWD) the channel has recovered to a narrower, deeper cross-section, with

  13. Moving from Capstones towards Cornerstones: Successes and challenges in applying systems biology to identify mechanisms of autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Nathan eKopp

    2015-10-01

    Full Text Available The substantial progress in the last few years towards uncovering genetic causes and risk factors for autism spectrum disorders (ASD has opened new experimental avenues for identifying the underlying neurobiological mechanism of the condition. The bounty of genetic findings has led to a variety of data-driven exploratory analyses aimed at deriving new insights about the shared features of these genes. These approaches leverage data from a variety of different sources such as co-expression in transcriptomic studies, protein-protein interaction networks, Gene Ontologies annotations, or multi-level combinations of all of these. Here, we review the recurrent themes emerging from these analyses and highlight some of the challenges going forward. Themes include findings that ASD associated genes discovered by a variety of methods have been shown to contain disproportionate amounts of neurite outgrowth/cytoskeletal, synaptic, and more recently Wnt-related and chromatin modifying genes. Expression studies have highlighted a disproportionate expression of ASD gene sets during mid fetal cortical development, particularly for rare-variants, with multiple analyses highlighting the striatum and cortical projection and interneurons as well. While these explorations have highlighted potentially interesting relationships among these ASD-related genes, there are challenges in how to best transition these insights into empirically testable hypotheses. Nonetheless, defining shared molecular or cellular pathology downstream of the diverse genes associated with autism spectrum disorders could provide the cornerstones needed to build towards broadly applicable therapeutic approaches.

  14. Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology.

    Science.gov (United States)

    Moreno, Marta; Fernández, Virginia; Monllau, Josep M; Borrell, Víctor; Lerin, Carles; de la Iglesia, Núria

    2015-08-11

    Neural stem cells (NSCs) reside in a hypoxic microenvironment within the brain. However, the crucial transcription factors (TFs) that regulate NSC biology under physiologic hypoxia are poorly understood. Here we have performed gene set enrichment analysis (GSEA) of microarray datasets from hypoxic versus normoxic NSCs with the aim of identifying pathways and TFs that are activated under oxygen concentrations mimicking normal brain tissue microenvironment. Integration of TF target (TFT) and pathway enrichment analysis identified the calcium-regulated TF NFATc4 as a major candidate to regulate hypoxic NSC functions. Nfatc4 expression was coordinately upregulated by top hypoxia-activated TFs, while NFATc4 target genes were enriched in hypoxic NSCs. Loss-of-function analyses further revealed that the calcineurin-NFATc4 signaling axis acts as a major regulator of NSC self-renewal and proliferation in vitro and in vivo by promoting the expression of TFs, including Id2, that contribute to the maintenance of the NSC state.

  15. Integrated copy number and expression analysis identifies profiles of whole-arm chromosomal alterations and subgroups with favorable outcome in ovarian clear cell carcinomas.

    Directory of Open Access Journals (Sweden)

    Yuriko Uehara

    Full Text Available Ovarian clear cell carcinoma (CCC is generally associated with chemoresistance and poor clinical outcome, even with early diagnosis; whereas high-grade serous carcinomas (SCs and endometrioid carcinomas (ECs are commonly chemosensitive at advanced stages. Although an integrated genomic analysis of SC has been performed, conclusive views on copy number and expression profiles for CCC are still limited. In this study, we performed single nucleotide polymorphism analysis with 57 epithelial ovarian cancers (31 CCCs, 14 SCs, and 12 ECs and microarray expression analysis with 55 cancers (25 CCCs, 16 SCs, and 14 ECs. We then evaluated PIK3CA mutations and ARID1A expression in CCCs. SNP array analysis classified 13% of CCCs into a cluster with high frequency and focal range of copy number alterations (CNAs, significantly lower than for SCs (93%, P < 0.01 and ECs (50%, P = 0.017. The ratio of whole-arm to all CNAs was higher in CCCs (46.9% than SCs (21.7%; P < 0.0001. SCs with loss of heterozygosity (LOH of BRCA1 (85% also had LOH of NF1 and TP53, and LOH of BRCA2 (62% coexisted with LOH of RB1 and TP53. Microarray analysis classified CCCs into three clusters. One cluster (CCC-2, n = 10 showed more favorable prognosis than the CCC-1 and CCC-3 clusters (P = 0.041. Coexistent alterations of PIK3CA and ARID1A were more common in CCC-1 and CCC-3 (7/11, 64% than in CCC-2 (0/10, 0%; P < 0.01. Being in cluster CCC-2 was an independent favorable prognostic factor in CCC. In conclusion, CCC was characterized by a high ratio of whole-arm CNAs; whereas CNAs in SC were mainly focal, but preferentially caused LOH of well-known tumor suppressor genes. As such, expression profiles might be useful for sub-classification of CCC, and might provide useful information on prognosis.

  16. Identifying the Alteration Patterns of Brain Functional Connectivity in Progressive Mild Cognitive Impairment Patients: A Longitudinal Whole-Brain Voxel-Wise Degree Analysis.

    Science.gov (United States)

    Deng, Yanjia; Liu, Kai; Shi, Lin; Lei, Yi; Liang, Peipeng; Li, Kuncheng; Chu, Winnie C W; Wang For The Alzheimer's Disease Neuroimaging Initiative, Defeng

    2016-01-01

    Patients with mild cognitive impairment (MCI) are at high risk for developing Alzheimer's disease (AD), while some of them may remain stable over decades. The underlying mechanism is still not fully understood. In this study, we aimed to explore the connectivity differences between progressive MCI (PMCI) and stable MCI (SMCI) individuals on a whole-brain scale and on a voxel-wise basis, and we also aimed to reveal the differential dynamic alteration patterns between these two disease subtypes. The resting-state functional magnetic resonance images of PMCI and SMCI patients at baseline and year-one were obtained from the Alzheimer's Disease Neuroimaging Initiative dataset, and the progression was determined based on a 3-year follow-up. A whole-brain voxel-wise degree map that was calculated based on graph-theory was constructed for each subject, and then the cross-sectional and longitudinal analyses on the degree maps were performed between PMCI and SMCI patients. In longitudinal analyses, compared with SMCI group, PMCI group showed decreased long-range degree in the left middle occipital/supramarginal gyrus, while the short-range degree was increased in the left supplementary motor area and middle frontal gyrus and decreased in the right middle temporal pole. A significant longitudinal alteration of decreased short-range degree in the right middle occipital was found in PMCI group. Taken together with previous evidence, our current findings may suggest that PMCI, compared with SMCI, might be a "severe" presentation of disease along the AD continuum, and the rapidly reduced degree in the right middle occipital gyrus may have indicative value for the disease progression. Moreover, the cross-sectional comparison results and corresponding receiver-operator characteristic-curves analyses may indicate that the baseline degree difference is not a good predictor of disease progression in MCI patients. Overall, these findings may provide objective evidence and an indicator

  17. Genomic profiling of papillary renal cell tumours identifies small regions of DNA alterations: a possible role of HNF1B in tumour development

    NARCIS (Netherlands)

    Szponar, A.; Yusenko, M.V.; Kuiper, R.P.; Geurts van Kessel, A.H.M.; Kovacs, G.

    2011-01-01

    AIMS: Papillary renal cell tumours (RCT) are characterized by specific trisomies. The aim of this study was to identify small regions of duplication marking putative tumour genes. METHODS AND RESULTS: Full-tiling path bacterial artificial chromosome (BAC) array hybridization of 20 papillary RCTs con

  18. A Thyroid Hormone Challenge in Hypothyroid Rats Identifies T3 Regulated Genes in the Hypothalamus and in Models with Altered Energy Balance and Glucose Homeostasis

    OpenAIRE

    Herwig, Annika; Campbell, Gill; Mayer, Claus-Dieter; Boelen, Anita; Richard A. Anderson; Alexander W Ross; Mercer, Julian G.; Barrett, Perry

    2014-01-01

    Background: The thyroid hormone triiodothyronine (T3) is known to affect energy balance. Recent evidence points to an action of T3 in the hypothalamus, a key area of the brain involved in energy homeostasis, but the components and mechanisms are far from understood. The aim of this study was to identify components in the hypothalamus that may be involved in the action of T3 on energy balance regulatory mechanisms.

  19. Post-factum detection of radiation treatment of meat and fish by means of DNA alterations identified by gas chromatography-mass spectrometry or pulsed-field gel electrophoresis

    International Nuclear Information System (INIS)

    The doctoral thesis explains methods and experiments for post-factum detection of radiation-induced alterations of DNA. There are various manifestations of such alterations. Ionizing radiation can directly alter the bases and/or sugar component, or can indirectly induce DNA damage by way of forming water radicals. Both mechanisms result in base derivatives, released for some part from the DNA strand, or formed by alterations of the 2-deoxyribose, inducing strand breaks ( single and double strand breaks). The first part of the thesis explains the approach applying GC-MS for detection of radiation-induced base derivatives, using herring sperm DNA as a model DNA. Some typical types of base derivatives were identified (thymine glycol, 5-hydroxycytosine).Some base derivatives were also found in DNA samples derived from poultry meat. These base derivatives are known to be indicators of food processing with ionizing radiation, but surprisingly were also found in non-irradiated controls, although in minor amounts. The second part discusses the identification of strand breaks applying the pused-field gel electrophoresis. This method is capable of producing evidence that irradiation markedly enhances the short-chain DNA molecules as compared to non-irradiated controls. DNA molecules of a size of approx. 2.2 million base pairs are almost completely broken into short-chain fragments. The method reliably detects radiation treatments down to 1500 Gy, even if applied long ago. (orig./MG)

  20. A phenotypic screen in zebrafish identifies a novel small-molecule inducer of ectopic tail formation suggestive of alterations in non-canonical Wnt/PCP signaling.

    Directory of Open Access Journals (Sweden)

    Evelien Gebruers

    Full Text Available Zebrafish have recently emerged as an attractive model for the in vivo bioassay-guided isolation and characterization of pharmacologically active small molecules of natural origin. We carried out a zebrafish-based phenotypic screen of over 3000 plant-derived secondary metabolite extracts with the goal of identifying novel small-molecule modulators of the BMP and Wnt signaling pathways. One of the bioactive plant extracts identified in this screen - Jasminum gilgianum, an Oleaceae species native to Papua New Guinea - induced ectopic tails during zebrafish embryonic development. As ectopic tail formation occurs when BMP or non-canonical Wnt signaling is inhibited during the tail protrusion process, we suspected a constituent of this extract to act as a modulator of these pathways. A bioassay-guided isolation was carried out on the basis of this zebrafish phenotype, identifying para-coumaric acid methyl ester (pCAME as the active compound. We then performed an in-depth phenotypic analysis of pCAME-treated zebrafish embryos, including a tissue-specific marker analysis of the secondary tails. We found pCAME to synergize with the BMP-inhibitors dorsomorphin and LDN-193189 in inducing ectopic tails, and causing convergence-extension defects in compound-treated embryos. These results indicate that pCAME may interfere with non-canonical Wnt signaling. Inhibition of Jnk, a downstream target of Wnt/PCP signaling (via morpholino antisense knockdown and pharmacological inhibition with the kinase inhibitor SP600125 phenocopied pCAME-treated embryos. However, immunoblotting experiments revealed pCAME to not directly inhibit Jnk-mediated phosphorylation of c-Jun, suggesting additional targets of SP600125, and/or other pathways, as possibly being involved in the ectopic tail formation activity of pCAME. Further investigation of pCAME's mechanism of action will help determine this compound's pharmacological utility.

  1. Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: A potential biological unifying mechanism for their corresponding disease profiles

    International Nuclear Information System (INIS)

    Combined exposures to maternal lead (Pb) and prenatal stress (PS) can act synergistically to enhance behavioral and neurochemical toxicity in offspring. Maternal Pb itself causes permanent dysfunction of the body's major stress system, the hypothalamic pituitary adrenal (HPA) axis. The current study sought to determine the potential involvement of altered negative glucocorticoid feedback as a mechanistic basis of the effects in rats of maternal Pb (0, 50 or 150 ppm in drinking water beginning 2 mo prior to breeding), prenatal stress (PS; restraint on gestational days 16-17) and combined maternal Pb + PS in 8 mo old male and female offspring. Corticosterone changes were measured over 24 h following an i.p. injection stress containing vehicle or 100 or 300 μg/kg (females) or 100 or 150 μg/kg (males) dexamethasone (DEX). Both Pb and PS prolonged the time course of corticosterone reduction following vehicle injection stress. Pb effects were non-monotonic, with a greater impact at 50 vs. 150 ppm, particularly in males, where further enhancement occurred with PS. In accord with these findings, the efficacy of DEX in suppressing corticosterone was reduced by Pb and Pb + PS in both genders, with Pb efficacy enhanced by PS in females, over the first 6 h post-administration. A marked prolongation of DEX effects was found in males. Thus, Pb, PS and Pb + PS, sometimes additively, produced hypercortisolism in both genders, followed by hypocortisolism in males, consistent with HPA axis dysfunction. These findings may provide a plausible unifying biological mechanism for the reported links between Pb exposure and stress-associated diseases and disorders mediated via the HPA axis, including obesity, hypertension, diabetes, anxiety, schizophrenia and depression. They also suggest broadening of Pb screening programs to pregnant women in high stress environments

  2. Exome and transcriptome sequencing of Aedes aegypti identifies a locus that confers resistance to Brugia malayi and alters the immune response.

    Science.gov (United States)

    Juneja, Punita; Ariani, Cristina V; Ho, Yung Shwen; Akorli, Jewelna; Palmer, William J; Pain, Arnab; Jiggins, Francis M

    2015-03-01

    Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait. PMID:25815506

  3. Exome and transcriptome sequencing of Aedes aegypti identifies a locus that confers resistance to Brugia malayi and alters the immune response.

    Directory of Open Access Journals (Sweden)

    Punita Juneja

    2015-03-01

    Full Text Available Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.

  4. Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response

    KAUST Repository

    Juneja, Punita

    2015-03-27

    Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.

  5. Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology

    Directory of Open Access Journals (Sweden)

    Marta Moreno

    2015-08-01

    Full Text Available Neural stem cells (NSCs reside in a hypoxic microenvironment within the brain. However, the crucial transcription factors (TFs that regulate NSC biology under physiologic hypoxia are poorly understood. Here we have performed gene set enrichment analysis (GSEA of microarray datasets from hypoxic versus normoxic NSCs with the aim of identifying pathways and TFs that are activated under oxygen concentrations mimicking normal brain tissue microenvironment. Integration of TF target (TFT and pathway enrichment analysis identified the calcium-regulated TF NFATc4 as a major candidate to regulate hypoxic NSC functions. Nfatc4 expression was coordinately upregulated by top hypoxia-activated TFs, while NFATc4 target genes were enriched in hypoxic NSCs. Loss-of-function analyses further revealed that the calcineurin-NFATc4 signaling axis acts as a major regulator of NSC self-renewal and proliferation in vitro and in vivo by promoting the expression of TFs, including Id2, that contribute to the maintenance of the NSC state.

  6. A systems biology approach identifies a R2R3 MYB gene subfamily with distinct and overlapping functions in regulation of aliphatic glucosinolates.

    Directory of Open Access Journals (Sweden)

    Ida Elken Sønderby

    Full Text Available BACKGROUND: Glucosinolates are natural metabolites in the order Brassicales that defend plants against both herbivores and pathogens and can attract specialized insects. Knowledge about the genes controlling glucosinolate regulation is limited. Here, we identify three R2R3 MYB transcription factors regulating aliphatic glucosinolate biosynthesis in Arabidopsis by combining several systems biology tools. METHODOLOGY/PRINCIPAL FINDINGS: MYB28 was identified as a candidate regulator of aliphatic glucosinolates based on its co-localization within a genomic region controlling variation both in aliphatic glucosinolate content (metabolite QTL and in transcript level for genes involved in the biosynthesis of aliphatic glucosinolates (expression QTL, as well as its co-expression with genes in aliphatic glucosinolate biosynthesis. A phylogenetic analysis with the R2R3 motif of MYB28 showed that it and two homologues, MYB29 and MYB76, were members of an Arabidopsis-specific clade that included three characterized regulators of indole glucosinolates. Over-expression of the individual MYB genes showed that they all had the capacity to increase the production of aliphatic glucosinolates in leaves and seeds and induce gene expression of aliphatic biosynthetic genes within leaves. Analysis of leaves and seeds of single knockout mutants showed that mutants of MYB29 and MYB76 have reductions in only short-chained aliphatic glucosinolates whereas a mutant in MYB28 has reductions in both short- and long-chained aliphatic glucosinolates. Furthermore, analysis of a double knockout in MYB28 and MYB29 identified an emergent property of the system since the absence of aliphatic glucosinolates in these plants could not be predicted by the chemotype of the single knockouts. CONCLUSIONS/SIGNIFICANCE: It seems that these cruciferous-specific MYB regulatory genes have evolved both overlapping and specific regulatory capacities. This provides a unique system within which to

  7. Fundamental studies of matrix-assisted laser desorption/ionization, using time-of-flight mass spectrometry to identify biological molecules

    Energy Technology Data Exchange (ETDEWEB)

    Eades, D.; Wruck, D.; Gregg, H.

    1996-11-11

    MALDI MS was developed as a way of getting molecular weight information on small quantities (picomole to femtomole levels) of high-mass, thermally labile macromolecules. While most other analytical MS ionization techniques cause fragmentation, decomposition, or multiple charging, MALDI efficiently places intact macromolecules into the gas phase with little fragmentation or rearrangement. This project had 3 objectives: establish the MALDI capability at LLNL, perform fundamental studies of analyte-matrix interactions, and apply the technique for biochemical research. A retired time-of-flight instrument was adapted for MALDI analyses, relevant parameters influencing the MALDI process were identified for further study (matrix molar absorptivity, sample crystal preparation), and collaborations were established with research groups in the Biology and Biotechnology Research Program at LLNL. In MALDI, the macromolecule of interest is mixed with a high-molar excess (1:100 to 1:10,000) of an organic matrix which readily absorbs energy at the wavelength corresponding to a UV laser. Upon laser irradiation, the matrix absorbs the majority of the energy, causing it to desorb from the surface and gently release the macromolecule into the gas phase with little or no fragmentation. Once in the gas phase, ion-molecule reactions between excited matrix and neutral macromolecules generated ionized analyte species which then can be focused into a MS for detection.

  8. Determination of MBT-waste reactivity - An infrared spectroscopic and multivariate statistical approach to identify and avoid failures of biological tests.

    Science.gov (United States)

    Böhm, K; Smidt, E; Binner, E; Schwanninger, M; Tintner, J; Lechner, P

    2010-04-01

    The Austrian Landfill Ordinance provides limit values regarding the reactivity for the disposal of mechanically biologically treated (MBT) waste before landfilling. The potential reactivity determined by biological tests according to the Austrian Standards (OENORM S 2027 1-2) can be underestimated if the microbial community is affected by environmental conditions. New analytical tools have been developed as an alternative to error-prone and time-consuming biological tests. Fourier Transform Infrared (FT-IR) spectroscopy in association with Partial Least Squares Regression (PLS-R) was used to predict the reactivity parameters respiration activity (RA(4)) and gas generation sum (GS(21)) as well as to detect errors resulting from inhibiting effects on biological tests. For this purpose 250 MBT-waste samples from different Austrian MBT-plants were investigated using FT-IR spectroscopy in the mid (MIR) and near infrared (NIR) area and biological tests. Spectroscopic results were compared with those from biological tests. Arising problems caused by interferences of RA(4) and GS(21) are discussed. It is shown that FT-IR spectroscopy predicts RA(4) and GS(21) reliably to assess stability of MBT-waste materials and to detect errors. PMID:19854633

  9. Re-assessing the last 3,000 years of archaeological and biological sea-level data from Israel and Greece to identify East Mediterranean trends.

    Science.gov (United States)

    Sivan, Dorit; Dean, Silas; Sisma-Ventura, Guy; Bechor, Benny; Evelpidou, Niki; Baika, Kalliopi; Theodoulou, Theotokis A.

    2016-04-01

    The last 3,000 years of relative sea level (RSL) in Israel are derived primarily from archaeological indicators with additional bio-construction indicators (Dendropoma petraeum reefs at the edge of the abrasion platform along the Israeli coast). The current study examines whether sea-level fluctuations (above and mainly below present-day MSL) observed along the coast of Israel can also be observed in other East Mediterranean areas like Greece so that better evaluations can be made of local and regional driving mechanisms. There are three objectives for achieving this goal: 1) Identify new and already published archaeological and biological RSL indicators from this period in Israel and Greece; 2) Assess the reliability of both existing and new indicators using consistent standards to determine which types most accurately indicate ancient RSL and with what degree of uncertainty; 3) Correct the data for isostatic and tectonic effects. The survey collected nearly 140 archaeological indicators from Israel and about 120 from Greece. Of the Israeli indicators, some 120 were deemed reliable enough for reconstructions, whereas in Greece only 40 were, and not all of these from tectonically stable areas. The Israeli data includes 31 dates obtained from Dendropoma reefs in Israel. The higher reliability of the Israeli dataset may stem from a smaller coastline and more focused SL research over the past few decades. In Greece, many measurements were taken before precise surveying methods were available, and published without sufficient metadata. The two regional datasets reveal chronological gaps and disparities: Israel has a strong set of many indicators from the Roman Period (~2000BP) to present, but fewer from 3000-2000BP, while Greek indicators are strongly clustered in the Classical to Hellenistic Periods (2500-2000BP). On-going research is focusing now also on the last Millennial Greek sea levels (mainly the 'Venetian' period). Results however suggest some correspondence

  10. Altered global brain signal in schizophrenia

    Science.gov (United States)

    Yang, Genevieve J.; Murray, John D.; Repovs, Grega; Cole, Michael W.; Savic, Aleksandar; Glasser, Matthew F.; Pittenger, Christopher; Krystal, John H.; Wang, Xiao-Jing; Pearlson, Godfrey D.; Glahn, David C.; Anticevic, Alan

    2014-01-01

    Neuropsychiatric conditions like schizophrenia display a complex neurobiology, which has long been associated with distributed brain dysfunction. However, no investigation has tested whether schizophrenia shows alterations in global brain signal (GS), a signal derived from functional MRI and often discarded as a meaningless baseline in many studies. To evaluate GS alterations associated with schizophrenia, we studied two large chronic patient samples (n = 90, n = 71), comparing them to healthy subjects (n = 220) and patients diagnosed with bipolar disorder (n = 73). We identified and replicated increased cortical power and variance in schizophrenia, an effect predictive of symptoms yet obscured by GS removal. Voxel-wise signal variance was also increased in schizophrenia, independent of GS effects. Both findings were absent in bipolar patients, confirming diagnostic specificity. Biologically informed computational modeling of shared and nonshared signal propagation through the brain suggests that these findings may be explained by altered net strength of overall brain connectivity in schizophrenia. PMID:24799682

  11. 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.

    Science.gov (United States)

    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…

  12. TF-finder: A software package for identifying transcription factors involved in biological processes using microarray data and existing knowledge base

    Directory of Open Access Journals (Sweden)

    Cui Xiaoqi

    2010-08-01

    Full Text Available Abstract Background Identification of transcription factors (TFs involved in a biological process is the first step towards a better understanding of the underlying regulatory mechanisms. However, due to the involvement of a large number of genes and complicated interactions in a gene regulatory network (GRN, identification of the TFs involved in a biology process remains to be very challenging. In reality, the recognition of TFs for a given a biological process can be further complicated by the fact that most eukaryotic genomes encode thousands of TFs, which are organized in gene families of various sizes and in many cases with poor sequence conservation except for small conserved domains. This poses a significant challenge for identification of the exact TFs involved or ranking the importance of a set of TFs to a process of interest. Therefore, new methods for recognizing novel TFs are desperately needed. Although a plethora of methods have been developed to infer regulatory genes using microarray data, it is still rare to find the methods that use existing knowledge base in particular the validated genes known to be involved in a process to bait/guide discovery of novel TFs. Such methods can replace the sometimes-arbitrary process of selection of candidate genes for experimental validation and significantly advance our knowledge and understanding of the regulation of a process. Results We developed an automated software package called TF-finder for recognizing TFs involved in a biological process using microarray data and existing knowledge base. TF-finder contains two components, adaptive sparse canonical correlation analysis (ASCCA and enrichment test, for TF recognition. ASCCA uses positive target genes to bait TFS from gene expression data while enrichment test examines the presence of positive TFs in the outcomes from ASCCA. Using microarray data from salt and water stress experiments, we showed TF-finder is very efficient in recognizing

  13. Dose Addition Models Based on Biologically Relevant Reductions in Fetal Testosterone Accurately Predict Postnatal Reproductive Tract Alterations by a Phthalate Mixture in Rats.

    Science.gov (United States)

    Howdeshell, Kembra L; Rider, Cynthia V; Wilson, Vickie S; Furr, Johnathan R; Lambright, Christy R; Gray, L Earl

    2015-12-01

    Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the current study were 2-fold: (1) to test whether a mixture model of dose addition based on the fetal T production data of individual phthalates would predict the effects of a 5 phthalate mixture on androgen-sensitive postnatal male reproductive tract development, and (2) to determine the biological relevance of the reductions in fetal T to induce abnormal postnatal reproductive tract development using data from the mixture study. We administered a dose range of the mixture (60, 40, 20, 10, and 5% of the top dose used in the previous fetal T production study consisting of 300 mg/kg per chemical of benzyl butyl (BBP), di(n)butyl (DBP), diethyl hexyl phthalate (DEHP), di-isobutyl phthalate (DiBP), and 100 mg dipentyl (DPP) phthalate/kg; the individual phthalates were present in equipotent doses based on their ability to reduce fetal T production) via gavage to Sprague Dawley rat dams on GD8-postnatal day 3. We compared observed mixture responses to predictions of dose addition based on the previously published potencies of the individual phthalates to reduce fetal T production relative to a reference chemical and published postnatal data for the reference chemical (called DAref). In addition, we predicted DA (called DAall) and response addition (RA) based on logistic regression analysis of all 5 individual phthalates when complete data were available. DA ref and DA all accurately predicted the observed mixture effect for 11 of 14 endpoints. Furthermore, reproductive tract malformations were seen in 17-100% of F1 males when fetal T production was reduced by about 25-72%, respectively. PMID:26350170

  14. Development of biological indices for identifying and evaluating impacts of pollutants on freshwater ecosystems. Annual progress report, June 1, 1976--June 1, 1977

    Energy Technology Data Exchange (ETDEWEB)

    Cairns, J. Jr.; Benfield, E.F.; Buikema, A.L. Jr.; Dickson, K.L.; Hendricks, A.C.

    1977-01-01

    The overall objectives of this joint research effort were to devise and evaluate biological methods for determining the functional response of aquatic organisms to perturbations. Structural and functional aspects of autotrophic and heterotrophic attached microbial communities were studied in lotic systems with emphasis on carbon, nitrogen and sulfur. The uptake of carbon, nitrogen and sulfur under controlled and field situations was investigated along with biomass, ATP and chlorophyll measurement. Relationship of protozoan invasion and extinction rates to the eutrophication process were investigated. Protozoan invasion and extinction rates (utilizing artificial substrates) were measured under oligotrophic and eutrophic conditions in numerous lakes and reservoirs. Behavioral responses of zooplankton subjected to cooling water entrainment were examined. Zooplankton were subjected to various conditions that would be encountered during entrainment in order that the responses of the organisms might be ascertained. Detritus processing by macroinvertebrates was studied as a pollutional stress assessment technique.

  15. Accuracy of self-report, biological tests, collateral reports and clinician ratings in identifying substance use disorders among adults with schizophrenia.

    Science.gov (United States)

    Desmarais, Sarah L; Van Dorn, Richard A; Sellers, Brian G; Young, M Scott; Swartz, Marvin S

    2013-09-01

    Identifying substance use disorders among adults with schizophrenia presents unique challenges but is critical to research and practice. This study examined: (a) the accuracy of assessments completed using various approaches in identifying substance use disorders, (b) their ability to discriminate between disorders of abuse and dependence, and (c) the benefits of using multiple indicators to identify substance use disorders. Data are from the Clinical Antipsychotic Trials of Intervention Effectiveness study. The sample comprised 1,460 community-based adults with schizophrenia, 15.8% (n = 230) of whom were positive for a current (past month) drug or alcohol use disorder using the Structured Clinical Interview for DSM-IV Disorders (SCID). Clinician ratings, self-report, collateral reports, and results of hair and urine tests were compared to SCID diagnoses. Congruence with SCID diagnoses was good across approaches and evidence for superiority of one approach over another was limited. No approach discriminated between abuse and dependence. There was limited benefit of using multiple indicators. Findings suggest that the decision regarding the "best" approach for identifying substance use disorders among adults with schizophrenia may be made through consideration of practical issues and assessment purpose, rather than selection of the approach that yields the most accurate diagnostic assessment.

  16. Benefit of STR-based chimerism analysis to identify TA-GVHD as a cause of death: Utility of various biological specimens.

    Science.gov (United States)

    Raina, Anupuma; Chaudhary, Garima; Dogra, Tirath Das; Khandelwal, Deepchand; Balayan, Ajay; Jain, Vandana; Kanga, Uma; Seth, Tulika

    2016-04-01

    Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare condition. It can occur after blood transfusion in immune-compromised and occasionally even in immune-competent patients, and is associated with a mortality rate of >90%. The diagnosis of TA-GVHD is often delayed because of its non-specific clinical features. A case of an immune-competent child who developed TA-GVHD is reported here. DNA profiling (short tandem repeat analysis), a technique that has a wide application in forensic medicine, was performed to detect the presence of donor cells in this patient. The findings suggest that more studies are needed with this tool, and the diagnostic potential of using other multiple biological specimens for DNA profiling such as the hair follicle and buccal swab should be evaluated. This is the first case report where the donor's DNA fingerprinting pattern was substantiated from a patient's hair follicle sample. Chimerism was also present in the blood and buccal swab specimens. PMID:25852093

  17. Development of biological indices for identifying and evaluating impacts of pollutants on freshwater ecosystems. Annual progress report, June 1, 1975--February 28, 1976

    Energy Technology Data Exchange (ETDEWEB)

    Cairns, J. Jr.; Benfield, E.F.; Buikema, A.L. Jr.; Dickson, K.L.; Hendricks, A.C.

    1976-01-01

    The overall objective of this joint research effort was to devise and evaluate biological methods for determining the functional response of aquatic organisms to perturbations. The research effort fell into four general categories: structural and functional aspects of autotrophic and heterotrophic attached microbial communities in lotic systems with emphasis on carbon, nitrogen, and sulfur. The uptake of carbon, nitrogen, and sulfur under controlled and field situations was investigated along with biomass, ATP, and chlorophyll measurement. Relationship of protozoan invasion and extinction rates to the eutrophication process. Protozoan invasion and extinction rates (utilizing artificial substrates) were measured under oligotrophic and eutrophic conditions in numerous lakes and reservoirs. Behavioral responses of zooplankton subjected to cooling water entrainment. Zooplankton were subjected to various conditions that would be encountered during entrainment in order that the responses of the organisms might be ascertained. Detritus processing by macroinvertebrates as a pollutional stress assessment technique. Exposed measured units of detrital material to pollutional stress through time and compared their rates of processing to processing rates of similar units that were not exposed to the stress. (auth)

  18. Soluble metals in the atmosphere and their biological implications. A study to identify important aerosol components by statistical analysis of PIXE data.

    Science.gov (United States)

    Winchester, J W

    1990-01-01

    Multivariate statistical analysis has been applied to time series measurements of aerosol elemental composition from PIXE analysis of filter samples, and principal components have been resolved that represent distinct particle types in an external mixture in the atmosphere. In this study, it is argued that a combination of chemical and statistical analyses of the data may be more powerful in determining chemical species in atmospheric aerosols than studied that employ mainly direct chemical analysis of chemical species in unresolved mixtures of aerosol particle samples. Sulfur is generally associated with mineral dust elements. It is reasoned that the association may represent sulfuric acid coatings on particles that can lead to mineral dissolution and solubilization of significant amounts of aluminum, iron, and other metals. Upon wet or dry deposition to the surface, the fluxes of these metals in biologically-available form may be sufficient to affect primary productivity in the world ocean and cause ecological damage in lakes. As a consequence, the fluxes of biogenic trace gases to the atmosphere may be changed, possibly leading to changes in the tropospheric concentration of ozone. The inputs to lakes of soluble aluminum, which is toxic to fish, may be partly by deposition directly from the atmosphere, thus not limited to leaching of soils by acid deposition. Human inhalation of soluble aluminum and other solubilized mineral metals may account, in part, for the observed geographic pattern of deaths attributed to chronic obstructive pulmonary disease (COPD) that show high rates in cities of the Western US and the southeast region, but low in most of the midwest and northeast.

  19. MICROSATELLITE ALTERATION AND ITS CHARACTERISTICS IN COLORECTAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To determine the role of microsatellite alterations incarcinogenesis of colorectal carcinoma (CRC). Methods: Alterations of 10 microsatellite loci from 5 different chromosomes were detected in 92 colorectal cancers and their paired normal mucosa by PCR, denatured polyacrylamide gel electrophoresis and silver staining. Associations of microsatellite alterations with clinopathologic parameters were statistically clarified.Results: Alterations of microsatellite were classified into microsatellite instability type I, type II and loss of heterozygosity (LOH). The carcinoma with ≥30% loci microsatellite alterations was defined as replication error(RER) positive tumors. Of 92 cases, 14 were RER+. Microsatellite alterations of P53(1) and D18S363 loci (64.29% ) was most commonly identified in the RER+ tumors. RER+ were more commonly seen in poorly differentiated carcinomas and tended to occur in mucoid carcinomas. The type of microsatellite alterations varied in different histological types of CRC. Conclusions: Microsatellite alteration is a common molecular event in CRC. Different microsatellite loci showed various biologic significance. P53(1) and D18S363 should be essentially detected loci that can show the RER status of tumors.

  20. Evidence for Alteration in Chemical and Physical Properties of Water and Modulation of its Biological Functions by Sunlight Transmitted through Color Ranges of the Visible Spectrum-A Novel Study

    Directory of Open Access Journals (Sweden)

    M. Rajeswara Rao

    2005-08-01

    Full Text Available We investigated the changes in the properties of water when exposed to sunlight for 40 days. We hypothesize and prove that solar irradiation to water entraps electromagnetic radiation as potential energy, which becomes kinetic energy in various systems. It is postulated that photochemically-induced energy transfers, associated with individual spectral emission of visible spectrum of solar light, exert diverse influences on biological systems. Bottles of distilled water, individually wrapped in spectral-colored cellophane were exposed to sunlight and compared to an unwrapped bottle to determine chemical and physical changes as well as modifications of biological properties. Each bottle of water was named according to the color of cellophane paper with letter E (stands for exposed as a prefix with (E-violet, E-indigo, E-blue, E-green, E-yellow, E-orange, and Ered. E-control (without wrap was exposed to polychromatic sunlight. This study addresses two main issues viz., the chemical and physical changes in E-water and its effect on biological activities. Chemical and physical composition analysis using inductively coupled plasma atomic emission spectrometry; physical conductance by a Wheatstone Bridge type conductivity meter; osmolarity by a vapor pressure osmometer; and, salt solubility profile of 10% sodium bicarbonate were determined. Furthermore, testing the effect of E-waters on human lymphocyte proliferation, mosquito larvae hatching and seed germination determined the functional role of solar radiation through specific spectrum/s of visible light on various biological processes. We found that water exposed to visible spectral emissions of sunlight had an altered elemental composition, electrical conductance, osmolarity and salt-solubility, as well as differences in bio-modulatory effects. A gradual increase in leaching of Boron from Eviolet to E-red was noted. E-indigo showed maximal increase in electrical conductance and maximal salt

  1. Hierarchical super-structure identified by polarized light microscopy, electron microscopy and nanoindentation: Implications for the limits of biological control over the growth mode of abalone sea shells

    Directory of Open Access Journals (Sweden)

    Schneider Andreas S

    2012-09-01

    Full Text Available Abstract Background Mollusc shells are commonly investigated using high-resolution imaging techniques based on cryo-fixation. Less detailed information is available regarding the light-optical properties. Sea shells of Haliotis pulcherina were embedded for polishing in defined orientations in order to investigate the interface between prismatic calcite and nacreous aragonite by standard materialographic methods. A polished thin section of the interface was prepared with a defined thickness of 60 μm for quantitative birefringence analysis using polarized light and LC-PolScope microscopy. Scanning electron microscopy images were obtained for comparison. In order to study structural-mechanical relationships, nanoindentation experiments were performed. Results Incident light microscopy revealed a super-structure in semi-transparent regions of the polished cross-section under a defined angle. This super-structure is not visible in transmitted birefringence analysis due to the blurred polarization of small nacre platelets and numerous organic interfaces. The relative orientation and homogeneity of calcite prisms was directly identified, some of them with their optical axes exactly normal to the imaging plane. Co-oriented "prism colonies" were identified by polarized light analyses. The nacreous super-structure was also visualized by secondary electron imaging under defined angles. The domains of the super-structure were interpreted to consist of crystallographically aligned platelet stacks. Nanoindentation experiments showed that mechanical properties changed with the same periodicity as the domain size. Conclusions In this study, we have demonstrated that insights into the growth mechanisms of nacre can be obtained by conventional light-optical methods. For example, we observed super-structures formed by co-oriented nacre platelets as previously identified using X-ray Photo-electron Emission Microscopy (X-PEEM [Gilbert et al., Journal of the

  2. Biological alterations resulting from chronic lung irradiation. I. The pulmonary lipid composition, physiology, and pathology after inhalation by beagle dogs of 144Ce-labeled fused clay aerosols

    International Nuclear Information System (INIS)

    Three groups of four beagle dogs inhaled a 144Ce-labeled fused clay aerosol; two additional dogs per group, exposed to a stable cerium-labeled fused clay aerosol, were used as controls. At monthly intervals, one diaphragmatic lobe of each of two dogs exposed to 144Ce and one control animal from each group was lavaged with isotonic saline. The recovered lavage solutions were centrifuged to isolate lung cells (mostly macrophages) and surfactant for lipid analyses. The groups were sacrificed at 2, 4, and 6 mo after exposure, when the lungs of the dogs exposed to 144Ce had average cumulative radiation doses of 23, 36, and 59 krad, respectively. Chronic irradiation of the lung resulted in a progressive radiation pneumonitis which was assessed clinically and pathologically at various intervals. At sacrifice, the lungs were analyzed for 144Ce and the right apical and diaphragmatic lobes were minced and lyophilized and the lipids were extracted. Total lipids from all lung samples were determined gravimetrically and individual compounds were identified, isolated, and quantitated. The quantities of lipid in lung tissue, in pulmonary cells, and in surfactant increased as a function of time and radiation dose. Neutral lipids (sterol esters and triglycerides) accounted for most of the increase. (U.S.)

  3. Integrative radiation systems biology.

    Science.gov (United States)

    Unger, Kristian

    2014-01-01

    Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer" of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology. PMID:24411063

  4. Integrative radiation systems biology

    International Nuclear Information System (INIS)

    Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer” of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology

  5. Altered Bone Biology in Psoriatic Arthritis

    OpenAIRE

    Rahimi, Homaira; Ritchlin, Christopher T.

    2012-01-01

    Psoriatic arthritis (PsA) is characterized by focal bone erosions mediated by osteoclasts at the bone–pannus junction. The bulk of research over the past decade has centered on mechanisms that underlie osteoclastogenesis along with new insights into osteoimmunology; however, recent advances that focus on steps that lead to new bone formation are beginning to emerge. New revelations about bone formation may have direct relevance to PsA given the presence of enthesophytes, syndesmophytes, and b...

  6. Smectite alteration

    International Nuclear Information System (INIS)

    This report contains the proceedings of a second workshop in Washington DC December 8-9, 1983 on the alteration of smectites intended for use as buffer materials in the long-term containment of nuclear wastes. It includes extended summaries of all presentations and a transcript of the detailed scientific discussion. The discussions centered on three main questions: What is the prerequisite for and what is the precise mechanism by which smectite clays may be altered to illite. What are likly sources of potassium with respect to the KBS project. Is it likely that the conversion of smectite to illite will be of importance in the 10 5 to the 10 6 year time frame. The workshop was convened to review considerations and conclusions in connection to these questions and also to broaden the discussion to consider the use of smectite clays as buffer materials for similar applications in different geographical and geological settings. SKBF/KBS technical report 83-03 contains the proceedings from the first workshop on these matters that was held at the State University of New York, Buffalo May 26-27, 1982. (Author)

  7. Biology Myth-Killers

    Science.gov (United States)

    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…

  8. Quest to identify geochemical risk factors associated with chronic kidney disease of unknown etiology (CKDu) in an endemic region of Sri Lanka-a multimedia laboratory analysis of biological, food, and environmental samples.

    Science.gov (United States)

    Levine, Keith E; Redmon, Jennifer Hoponick; Elledge, Myles F; Wanigasuriya, Kamani P; Smith, Kristin; Munoz, Breda; Waduge, Vajira A; Periris-John, Roshini J; Sathiakumar, Nalini; Harrington, James M; Womack, Donna S; Wickremasinghe, Rajitha

    2015-10-01

    fluoride, iron, manganese, sodium, and lead exceeding applicable drinking water standards in some instances. Current literature suggests that the etiology of CKDu is likely multifactorial, with no single biological or hydrogeochemical parameter directly related to disease genesis and progression. This preliminary screening identified that specific constituents may be present above levels of concern, but does not compare results against specific kidney toxicity values or cumulative risk related to a multifactorial disease process. The data collected from this limited investigation are intended to be used in the subsequent study design of a comprehensive and multifactorial etiological study of CKDu risk factors that includes sample collection, individual surveys, and laboratory analyses to more fully evaluate the potential environmental, behavioral, genetic, and lifestyle risk factors associated with CKDu. PMID:27591985

  9. Quest to identify geochemical risk factors associated with chronic kidney disease of unknown etiology (CKDu) in an endemic region of Sri Lanka-a multimedia laboratory analysis of biological, food, and environmental samples.

    Science.gov (United States)

    Levine, Keith E; Redmon, Jennifer Hoponick; Elledge, Myles F; Wanigasuriya, Kamani P; Smith, Kristin; Munoz, Breda; Waduge, Vajira A; Periris-John, Roshini J; Sathiakumar, Nalini; Harrington, James M; Womack, Donna S; Wickremasinghe, Rajitha

    2015-10-01

    fluoride, iron, manganese, sodium, and lead exceeding applicable drinking water standards in some instances. Current literature suggests that the etiology of CKDu is likely multifactorial, with no single biological or hydrogeochemical parameter directly related to disease genesis and progression. This preliminary screening identified that specific constituents may be present above levels of concern, but does not compare results against specific kidney toxicity values or cumulative risk related to a multifactorial disease process. The data collected from this limited investigation are intended to be used in the subsequent study design of a comprehensive and multifactorial etiological study of CKDu risk factors that includes sample collection, individual surveys, and laboratory analyses to more fully evaluate the potential environmental, behavioral, genetic, and lifestyle risk factors associated with CKDu.

  10. Myeloid neoplasm demonstrating a STAT5B-RARA rearrangement and genetic alterations associated with all-trans retinoic acid resistance identified by a custom next-generation sequencing assay.

    Science.gov (United States)

    Kluk, Michael J; Abo, Ryan P; Brown, Ronald D; Kuo, Frank C; Dal Cin, Paola; Pozdnyakova, Olga; Morgan, Elizabeth A; Lindeman, Neal I; DeAngelo, Daniel J; Aster, Jon C

    2015-10-01

    We describe the case of a patient presenting with several weeks of symptoms related to pancytopenia associated with a maturation arrest at the late promyelocyte/early myelocyte stage of granulocyte differentiation. A diagnosis of acute promyelocytic leukemia was considered, but the morphologic features were atypical for this entity and conventional tests for the presence of a PML-RARA fusion gene were negative. Additional analysis using a custom next-generation sequencing assay revealed a rearrangement producing a STAT5B-RARA fusion gene, which was confirmed by reverse transcription polymerase chain reaction (RT-PCR) and supplementary cytogenetic studies, allowing the diagnosis of a morphologically atypical form of acute promyelocytic leukemia to be made. Analysis of the sequencing data permitted characterization of both chromosomal breakpoints and revealed two additional alterations, a small deletion in RARA exon 9 and a RARA R276W substitution, that have been linked to resistance to all-trans retinoic acid. This case highlights how next-generation sequencing can augment currently standard testing to establish diagnoses in difficult cases, and in doing so help guide selection of therapy. PMID:27148563

  11. 市售蕲蛇样品的传统鉴定与分子生物学鉴定特征%Characteristics of Commercial Ancistrodon Acutus Identified by Traditional Method and Molecular Biology

    Institute of Scientific and Technical Information of China (English)

    刘晓青

    2014-01-01

    Objective: To investigate the accuracy of different methods in distinguishing commercial an-cistrodon acutus. Methods: The samples from different companies were identified with traditional method and the method of molecular biology respectively. Results: Altogether 30 kinds of samples from three pharmaceutical com-panies were collected. the results showed that there were 25 kinds of authentic ones and five counterfeit ones, quali-fication rate was 83.3%; DNA of mitochondria were extracted from the samples by the method of molecular biology, specific primers were amplified by PCR method. There were 20 kinds of qualified goods and ten kinds of unqualified ones, qualification rate was 66.67%. Conclusion: Traditional identification method is of low specificity, the method of molecular biology is simple, accurate and rapid, it demonstrates broad prospect to regulate the marketing of an-cistrodon acutus.%目的:探讨不同方法对市售蕲蛇样品真伪特征鉴别结果的准确性。方法:对来自不同销售公司蕲蛇样品分别采用传统鉴别方法和分子生物学方法进行鉴定。结果:采集三个城市医药销售公司共30个蕲蛇样品,传统外观和显微镜方法鉴定30个样品中有25个正品,5个伪品,合格率为83.3%;用分子生物学方法从市售蕲蛇样品中抽提线粒体DNA,采用PCR方法进行特异性引物扩增。30个蕲蛇样品中合格品20个,不合格品10个,合格率为66.67%。结论:传统鉴别方法鉴别市售蕲蛇样品特异性较低,分子生物学方法检测简单、准确、快捷,对规范市售蕲蛇中药材市场具有广阔前景。

  12. Altered cerebrospinal fluid proteins in Smith-Lemli-Opitz syndrome patients.

    Science.gov (United States)

    Cologna, Stephanie M; Shieh, Christine; Toth, Cynthia L; Cougnoux, Antony; Burkert, Kathryn R; Bianconi, Simona E; Wassif, Christopher A; Porter, Forbes D

    2016-08-01

    Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple malformation syndrome with neurocognitive impairment. SLOS arises from mutations in the 7-dehydrocholesterol reductase gene which results in impaired enzymatic conversion of 7-dehydrocholesterol to cholesterol. In the current work, we sought to measure proteins that were altered in the cerebrospinal fluid from SLOS patients compared to pediatric controls. Using a multi-analyte antibody-based assay, we found that 12 proteins are altered in SLOS patients. Validation studies were carried out and the findings from this study suggest alterations in extracellular matrix remodeling and further evidence of oxidative stress within the disease pathophysiology. The results of this study will be used to explore biological pathways altered in SLOS and identifies a set of CSF proteins that can be evaluated as biomarkers in future therapeutic trials. © 2016 Wiley Periodicals, Inc. PMID:27148958

  13. Biological Threats

    Science.gov (United States)

    ... Workplace Plans School Emergency Plans Main Content Biological Threats Biological agents are organisms or toxins that can ... for Disease Control and Prevention . Before a Biological Threat Unlike an explosion, a biological attack may or ...

  14. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T;

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

  15. Wnt Signaling in Cancer Stem Cell Biology.

    Science.gov (United States)

    de Sousa E Melo, Felipe; Vermeulen, Louis

    2016-06-27

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer.

  16. Wnt Signaling in Cancer Stem Cell Biology

    Science.gov (United States)

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  17. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata;

    2015-01-01

    Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gene...... expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles...... for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying...

  18. Biological rhythms and preeclampsia

    Directory of Open Access Journals (Sweden)

    Agnès eDitisheim

    2013-04-01

    Full Text Available The impact of impaired circadian rhythm on health has been widely studied in shift workers and trans-meridian travelers. A part from its correlation with sleep and mood disorders, biological rhythm impairment is a recognized risk factor for cardiovascular diseases and breast cancer.Preeclampsia is a major public health issue, associated with a significant maternal and fetal morbidity and mortality worldwide. While the risks factors for this condition such as obesity, diabetes, pre-existing hypertension have been identified, the underlying mechanism of this multi-factorial disease is yet not fully understood.The disruption of the light/dark cycle in pregnancy has been associated with adverse outcomes. Slightly increased risk for small for gestational age babies, low birth weight babies and preterm deliveries has been reported in shift working women. Whether altered circadian cycle represents a risk factor for preeclampsia or preeclampsia is itself linked with an abnormal circadian cycle is less clear. There are only few reports available, showing conflicting results. In this review, we will discuss recent observations concerning circadian pattern of blood pressure in normotensive and hypertensive pregnancies. We explore the hypothesis that circadian misalignments may represent a risk factor for preeclampsia. Unraveling potential link between circadian clock gene and preeclampsia could offer a novel approach to our understanding of this multi-system disease specific to pregnancy.

  19. Biological Rhythms and Preeclampsia

    Science.gov (United States)

    Ditisheim, Agnès J.; Dibner, Charna; Philippe, Jacques; Pechère-Bertschi, Antoinette

    2013-01-01

    The impact of impaired circadian rhythm on health has been widely studied in shift workers and trans-meridian travelers. A part from its correlation with sleep and mood disorders, biological rhythm impairment is a recognized risk factor for cardiovascular diseases and breast cancer. Preeclampsia is a major public health issue, associated with a significant maternal and fetal morbidity and mortality worldwide. While the risks factors for this condition such as obesity, diabetes, pre-existing hypertension have been identified, the underlying mechanism of this multi-factorial disease is yet not fully understood. The disruption of the light/dark cycle in pregnancy has been associated with adverse outcomes. Slightly increased risk for “small for gestational age” babies, “low birth weight” babies, and preterm deliveries has been reported in shift working women. Whether altered circadian cycle represents a risk factor for preeclampsia or preeclampsia is itself linked with an abnormal circadian cycle is less clear. There are only few reports available, showing conflicting results. In this review, we will discuss recent observations concerning circadian pattern of blood pressure in normotensive and hypertensive pregnancies. We explore the hypothesis that circadian misalignments may represent a risk factor for preeclampsia. Unraveling potential link between circadian clock gene and preeclampsia could offer a novel approach to our understanding of this multi-system disease specific to pregnancy. PMID:23579266

  20. Evidence for Alteration in Chemical and Physical Properties of Water and Modulation of its Biological Functions by Sunlight Transmitted through Color Ranges of the Visible Spectrum-A Novel Study

    OpenAIRE

    M. Rajeswara Rao; Angel, Michael F.; Das, Suman K.; Margot S. Koelle; Don Obenhuber; Reno, William L.; Asit Panja; Hari H. P. Cohly

    2005-01-01

    We investigated the changes in the properties of water when exposed to sunlight for 40 days. We hypothesize and prove that solar irradiation to water entraps electromagnetic radiation as potential energy, which becomes kinetic energy in various systems. It is postulated that photochemically-induced energy transfers, associated with individual spectral emission of visible spectrum of solar light, exert diverse influences on biological systems. Bottles of distilled water, individually wrapped i...

  1. Natural fumarolic alteration of fluorapatite, olivine, and basaltic glass, and implications for habitable environments on Mars.

    Science.gov (United States)

    Hausrath, Elisabeth M; Tschauner, Oliver

    2013-11-01

    Fumaroles represent a very important potential habitat on Mars because they contain water and nutrients. Global deposition of volcanic sulfate aerosols may also have been an important soil-forming process affecting large areas of Mars. Here we identify alteration from the Senator fumarole, northwest Nevada, USA, and in low-temperature environments near the fumarole to help interpret fumarolic and acid vapor alteration of rocks and soils on Mars. We analyzed soil samples and fluorapatite, olivine, and basaltic glass placed at and near the fumarole in in situ mineral alteration experiments designed to measure weathering under natural field conditions. Using synchrotron X-ray diffraction, we clearly observe hydroxyl-carbonate-bearing fluorapatite as a fumarolic alteration product of the original material, fluorapatite. The composition of apatites as well as secondary phosphates has been previously used to infer magmatic conditions as well as fumarolic conditions on Mars. To our knowledge, the observations reported here represent the first documented instance of formation of hydroxyl-carbonate-bearing apatite from fluorapatite in a field experiment. Retreat of olivine surfaces, as well as abundant NH4-containing minerals, was also characteristic of fumarolic alteration. In contrast, alteration in the nearby low-temperature environment resulted in formation of large pits on olivine surfaces, which were clearly distinguishable from the fumarolic alteration. Raman signatures of some fumarolically impacted surfaces are consistent with detection of the biological molecules chlorophyll and scytenomin, potentially useful biosignatures. Observations of altered minerals on Mars may therefore help identify the environment of formation and understand the aqueous history and potential habitability of that planet. PMID:24283927

  2. Semi-Automatic Classification of Skeletal Morphology in Genetically Altered Mice Using Flat-Panel Volume Computed Tomography

    OpenAIRE

    Christian Dullin; Jeannine Missbach-Guentner; Vogel, Wolfgang F.; Eckhardt Grabbe; Frauke Alves

    2007-01-01

    Rapid progress in exploring the human and mouse genome has resulted in the generation of a multitude of mouse models to study gene functions in their biological context. However, effective screening methods that allow rapid noninvasive phenotyping of transgenic and knockout mice are still lacking. To identify murine models with bone alterations in vivo, we used flat-panel volume computed tomography (fpVCT) for high-resolution 3-D imaging and developed an algorithm with a computational intelli...

  3. [Biological etiologies of transsexualism].

    Science.gov (United States)

    Butty, Anne-Virginie; Bianchi-Demicheli, Francesco

    2016-03-16

    Transsexualism or gender dysphoria is a disorder of sexual identity of unknown etiology. At the biological level, one assumes atypical brain development during certain periods of its formation (genesis) notably during embryogenesis, as a result of altered hormonal influence and a particular genetic polymorphism. This article summarizes the research conducted to date in these three areas only, excluding psycho-social and environmental factors. PMID:27149713

  4. Systems biology analysis merging phenotype, metabolomic and genomic data identifies Non-SMC Condensin I Complex, Subunit G (NCAPG) and cellular maintenance processes as major contributors to genetic variability in bovine feed efficiency.

    Science.gov (United States)

    Widmann, Philipp; Reverter, Antonio; Weikard, Rosemarie; Suhre, Karsten; Hammon, Harald M; Albrecht, Elke; Kuehn, Christa

    2015-01-01

    Feed efficiency is a paramount factor for livestock economy. Previous studies had indicated a substantial heritability of several feed efficiency traits. In our study, we investigated the genetic background of residual feed intake, a commonly used parameter of feed efficiency, in a cattle resource population generated from crossing dairy and beef cattle. Starting from a whole genome association analysis, we subsequently performed combined phenotype-metabolome-genome analysis taking a systems biology approach by inferring gene networks based on partial correlation and information theory approaches. Our data about biological processes enriched with genes from the feed efficiency network suggest that genetic variation in feed efficiency is driven by genetic modulation of basic processes relevant to general cellular functions. When looking at the predicted upstream regulators from the feed efficiency network, the Tumor Protein P53 (TP53) and Transforming Growth Factor beta 1 (TGFB1) genes stood out regarding significance of overlap and number of target molecules in the data set. These results further support the hypothesis that TP53 is a major upstream regulator for genetic variation of feed efficiency. Furthermore, our data revealed a significant effect of both, the Non-SMC Condensin I Complex, Subunit G (NCAPG) I442M (rs109570900) and the Growth /differentiation factor 8 (GDF8) Q204X (rs110344317) loci, on residual feed intake and feed conversion. For both loci, the growth promoting allele at the onset of puberty was associated with a negative, but favorable effect on residual feed intake. The elevated energy demand for increased growth triggered by the NCAPG 442M allele is obviously not fully compensated for by an increased efficiency in converting feed into body tissue. As a consequence, the individuals carrying the NCAPG 442M allele had an additional demand for energy uptake that is reflected by the association of the allele with increased daily energy intake as

  5. Thermal, physico-chemical and biological alteration of organic components and genesis of sulfide mineralisation : the La Florida Zn-Pb deposit (Cantabria, Spain); Processus d`alteration thermique, physico-chimique et biologique de constituants organiques et genese d`une mineralisation sulfuree : le gite Zn-Pb de La Florida (Cantabria, Espagne)

    Energy Technology Data Exchange (ETDEWEB)

    Hu, M.A.; Disnar, J.R.; Barbanson, L. [Orleans Univ. (France); Suarez-Ruiz, I. [Carbon Ins., (Spain)

    1998-08-01

    Conditions of mineralisation and related alteration processes of the La Florida Zn-Pb deposit from Cantabria, Spain are summarized. The stratiform ore deposit is composed of sphalerite, galena and barite and is hosted by Cretaceous dolostones. The geochemistry of hydrocarbons and organic compounds associated with the deposit was documented by coupled gas chromatography-mass spectrometry, optical reflectometry and fluorescence. Results indicate the immaturity of the organic compounds in the deposit. The proposed genetic model for the deposit involves migration of hydrothermal fluids that would have carried the metals and the organic matter necessary for in-situ hydrogen sulfide production and mineralisation. Sulfate reduction by bacteria introduced during meteoric water infiltration is believed to have occurred at the expense of allochthonous organic material. 65 refs., 3 tabs., 8 figs.

  6. Biological computation

    CERN Document Server

    Lamm, Ehud

    2011-01-01

    Introduction and Biological BackgroundBiological ComputationThe Influence of Biology on Mathematics-Historical ExamplesBiological IntroductionModels and Simulations Cellular Automata Biological BackgroundThe Game of Life General Definition of Cellular Automata One-Dimensional AutomataExamples of Cellular AutomataComparison with a Continuous Mathematical Model Computational UniversalitySelf-Replication Pseudo Code Evolutionary ComputationEvolutionary Biology and Evolutionary ComputationGenetic AlgorithmsExample ApplicationsAnalysis of the Behavior of Genetic AlgorithmsLamarckian Evolution Genet

  7. Ability of Slovakian Pupils to Identify Birds

    Science.gov (United States)

    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…

  8. Long-term alterations in neural and endocrine processes induced by motherhood in mammals.

    Science.gov (United States)

    Bridges, Robert S

    2016-01-01

    This article is part of a Special Issue "Parental Care". The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female's biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages. PMID:26388065

  9. Prostate cancer stem cell biology

    OpenAIRE

    Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan T.

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of s...

  10. Genetic alterations in pancreatic carcinoma

    Directory of Open Access Journals (Sweden)

    Schmid Roland M

    2003-01-01

    Full Text Available Abstract Cancer of the exocrine pancreas represents the fifth leading cause of cancer death in the Western population with an average survival after diagnosis of 3 to 6 months and a five-year survival rate under 5%. Our understanding of the molecular carcinogenesis has improved in the last few years due to the development of novel molecular biological techniques. Pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. In this article we describe major genetic alterations of pancreatic cancer, mutations in the proto-oncogene K-RAS and the tumor suppressors INK4A, TP53 and DPC4/SMAD4. The accumulation of these genetic changes leads to a profound disturbance in cell cycle regulation and continuous growth. The knowledge of the underlying molecular mechanisms will offer new therapeutic and diagnostic options and hopefully improve the outcome of this aggressive disease.

  11. PathogenIdentify and Biological Characteristics of Verticillium wilt of Sunflower%向日葵黄萎病病原鉴定及其生物学特性研究

    Institute of Scientific and Technical Information of China (English)

    马立功; 张匀华; 孟庆林; 石凤梅; 刘佳; 李易初; 纪武鹏

    2011-01-01

    为更好地研究向日葵黄萎病发病规律及其有效防治方法,对向日葵黄萎病菌的形态和生物学特性进行了研究。结果表明:该病菌在梅干培养基上分生孢子透明无色,孢子梗基部为黑褐色,后期有黑色念珠状菌丝产生,未发现微菌核和厚垣孢子,证实为黄萎轮枝菌(Verticillium albo-atrumReinke et Berthold)。其菌丝生长的最佳条件为PSC,25℃,pH5~6,最适碳氮源为蔗糖和甘氨酸。产孢的最佳条件为PSC,25~30℃,pH8,最适碳氮源为D-木糖和L-组氨酸。孢子萌发的最适温度为25℃,最适pH5.9,偏酸偏碱均可促进萌发,6 h以后孢子即可萌发,12 h萌发率可达80%以上。%In order to better study the law of Verticillium wilt of sunflower and its effective control method,the morphology and biological characteristics of Verticillium albo-atrum of sunflower were studied through cultivation on culture medium PLYA.The results showed that hyaline conidia with conidiophores of dark-brown bases were produced on the medium,and black dormant mycelium appeared later with prolonged time of culturing.Microsclerotia and chlamydospores were not found.It seemed that the mycelium could grow better on PSC medium and the optimum growth conditions of the pathogen were 25℃,pH 5~6,and the optimal carbon and nitrogen sources were sucrose and glycine,respectively.For spore germination of pathogen,the optimum conditions were PSC medium,25℃and pH 8,the suitable carbon and nitrogen sources were D-xylose and L-histidine.The optimal conditions for spore germination were 25℃and pH 5.9,and it could be promoted when the culture medium was partial alkaline acidic or partial base.The spores begin to germinate after 6 hours where it cultured at 25℃ Incubator,and the germination rate would reach above 80% after 12 hours.

  12. Oral alterations among chemical dependents

    Directory of Open Access Journals (Sweden)

    Estela Vanessa COLODEL

    2009-03-01

    Full Text Available Introduction: It has been daily observed a significant increase ofchemical dependent individuals, as well as the lack of depth on thisissue in the dentistry area. Nevertheless many times the dentalclinicians are the first professionals to diagnose possible alterations,which appear due to the consumption of tobacco, alcohol and other illicit drugs. Objectives: To make a literature review of oral alterations and to identify them on a specific group of persons, which are addicted to different types of drugs. Material and methods: The clinical history of the selected individuals was added to the answers of a questionnaire,comprising the data of the present research. Results: Besides other minor soft tissue alterations, a high prevalence of caries and periodontal diseases were found in the studied population. Conclusion: It was concluded that the role of the dental clinician is very important to the health rehabilitation of drug addicts, individuals with physical and mental disorders that need specific oral care, which sometimes is neglected.

  13. Alterations of 5-Hydroxymethylcytosine in Human Cancers

    Directory of Open Access Journals (Sweden)

    Ali Yesilkanal

    2013-06-01

    Full Text Available Prior to 2009, 5-methylcytosine (5-mC was thought to be the only biologically significant cytosine modification in mammalian DNA. With the discovery of the TET enzymes, which convert 5-methylcytosine (5-mC to 5-hydroxymethylcytosine (5-hmC, however, intense interest has emerged in determining the biological function of 5-hmC. Here, we review the techniques used to study 5-hmC and evidence that alterations to 5-hmC physiology play a functional role in the molecular pathogenesis of human cancers.

  14. Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer

    OpenAIRE

    Ming Shi; Shan Wang; Yuanfei Yao; Yiqun Li; Hao Zhang; Fang Han; Huan Nie; Jie Su; Zeyu Wang; Lei Yue; Jingyan Cao; Yu Li

    2014-01-01

    Epigenetic silence in cancer frequently altered signal-transduction pathways during the early stages of tumor development. Recent progress in the field of cancer epigenetics has led to new opportunities for diagnosis and treatment of cancer. We previously demonstrated that novel identified nuclear factor MARVELD1 was widely expressed in human tissues, but down-regulated by promoter methylation in multiple cancers. This study was carried out to determine the biological and clinical significanc...

  15. Is synthetic biology mechanical biology?

    Science.gov (United States)

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  16. Biology Notes.

    Science.gov (United States)

    School Science Review, 1982

    1982-01-01

    Presents procedures, exercises, demonstrations, and information on a variety of biology topics including labeling systems, biological indicators of stream pollution, growth of lichens, reproductive capacity of bulbous buttercups, a straw balance to measure transpiration, interaction of fungi, osmosis, and nitrogen fixation and crop production. (DC)

  17. Biological variables and prognosis of DCIS.

    Science.gov (United States)

    van de Vijver, Marc J

    2005-12-01

    Based on current knowledge, biological factors that have been investigated in ductal carcinoma in situ (DCIS) include histology of these lesions, the impact of margin status on local recurrence, and several genetic alterations. Optimal integration of these factors in guiding optimal therapy is of great importance, since the incidence of DCIS is rising as a result of population-based mammographic screening. Mastectomy will almost always cure patients with DCIS but represents overtreatment for many. Less extensive treatment options should combine an optimal cosmetic result with the same safety for outcome of disease as mastectomy. To guide such optimal treatment, histological classification is not sufficient and additional biological factors are being investigated for their ability to predict outcome for individual patients with DCIS. In this review, the histological classification of DCIS is described and in addition the emerging knowledge on genetic alterations is summarised. For clinical management of DCIS patients, genetic or other biological factors should be identified that can predict the risk of progression of DCIS to invasive breast cancer and distant metastases. At present, insufficient knowledge on prognostic and predictive factors in DCIS is available. Research in this area is hampered by the difficulties in obtaining DCIS tumour tissue, as the tumour cells grow in the lumen of pre-existing ducts and lobules. As the recurrence rates are relatively low and the most relevant clinical endpoint, distant metastases, is indeed very rare, large numbers of patients (hundreds to a few thousand) need to be studied. Integration of translational studies into clinical trials aimed at optimising the treatment of DCIS are required to achieve this goal.

  18. Attention Alters Perceived Attractiveness.

    Science.gov (United States)

    Störmer, Viola S; Alvarez, George A

    2016-04-01

    Can attention alter the impression of a face? Previous studies showed that attention modulates the appearance of lower-level visual features. For instance, attention can make a simple stimulus appear to have higher contrast than it actually does. We tested whether attention can also alter the perception of a higher-order property-namely, facial attractiveness. We asked participants to judge the relative attractiveness of two faces after summoning their attention to one of the faces using a briefly presented visual cue. Across trials, participants judged the attended face to be more attractive than the same face when it was unattended. This effect was not due to decision or response biases, but rather was due to changes in perceptual processing of the faces. These results show that attention alters perceived facial attractiveness, and broadly demonstrate that attention can influence higher-level perception and may affect people's initial impressions of one another. PMID:26966228

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

    Science.gov (United States)

    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.

  20. Sex speeds adaptation by altering the dynamics of molecular evolution.

    Science.gov (United States)

    McDonald, Michael J; Rice, Daniel P; Desai, Michael M

    2016-03-10

    Sex and recombination are pervasive throughout nature despite their substantial costs. Understanding the evolutionary forces that maintain these phenomena is a central challenge in biology. One longstanding hypothesis argues that sex is beneficial because recombination speeds adaptation. Theory has proposed several distinct population genetic mechanisms that could underlie this advantage. For example, sex can promote the fixation of beneficial mutations either by alleviating interference competition (the Fisher-Muller effect) or by separating them from deleterious load (the ruby in the rubbish effect). Previous experiments confirm that sex can increase the rate of adaptation, but these studies did not observe the evolutionary dynamics that drive this effect at the genomic level. Here we present the first, to our knowledge, comparison between the sequence-level dynamics of adaptation in experimental sexual and asexual Saccharomyces cerevisiae populations, which allows us to identify the specific mechanisms by which sex speeds adaptation. We find that sex alters the molecular signatures of evolution by changing the spectrum of mutations that fix, and confirm theoretical predictions that it does so by alleviating clonal interference. We also show that substantially deleterious mutations hitchhike to fixation in adapting asexual populations. In contrast, recombination prevents such mutations from fixing. Our results demonstrate that sex both speeds adaptation and alters its molecular signature by allowing natural selection to more efficiently sort beneficial from deleterious mutations.

  1. Vibrations, Quanta and Biology

    CERN Document Server

    Huelga, S F

    2013-01-01

    Quantum biology is an emerging field of research that concerns itself with the experimental and theoretical exploration of non-trivial quantum phenomena in biological systems. In this tutorial overview we aim to bring out fundamental assumptions and questions in the field, identify basic design principles and develop a key underlying theme -- the dynamics of quantum dynamical networks in the presence of an environment and the fruitful interplay that the two may enter. At the hand of three biological phenomena whose understanding is held to require quantum mechanical processes, namely excitation and charge transfer in photosynthetic complexes, magneto-reception in birds and the olfactory sense, we demonstrate that this underlying theme encompasses them all, thus suggesting its wider relevance as an archetypical framework for quantum biology.

  2. Quantum Biology

    Directory of Open Access Journals (Sweden)

    Alessandro Sergi

    2009-06-01

    Full Text Available A critical assessment of the recent developmentsof molecular biology is presented.The thesis that they do not lead to a conceptualunderstanding of life and biological systems is defended.Maturana and Varela's concept of autopoiesis is briefly sketchedand its logical circularity avoided by postulatingthe existence of underlying living processes,entailing amplification from the microscopic to the macroscopic scale,with increasing complexity in the passage from one scale to the other.Following such a line of thought, the currently accepted model of condensed matter, which is based on electrostatics and short-ranged forces,is criticized. It is suggested that the correct interpretationof quantum dispersion forces (van der Waals, hydrogen bonding, and so onas quantum coherence effects hints at the necessity of includinglong-ranged forces (or mechanisms for them incondensed matter theories of biological processes.Some quantum effects in biology are reviewedand quantum mechanics is acknowledged as conceptually important to biology since withoutit most (if not all of the biological structuresand signalling processes would not even exist. Moreover, it is suggested that long-rangequantum coherent dynamics, including electron polarization,may be invoked to explain signal amplificationprocess in biological systems in general.

  3. Acid Sulfate Alteration on Mars

    Science.gov (United States)

    Ming, D. W.; Morris, R. V.

    2016-01-01

    A variety of mineralogical and geochemical indicators for aqueous alteration on Mars have been identified by a combination of surface and orbital robotic missions, telescopic observations, characterization of Martian meteorites, and laboratory and terrestrial analog studies. Acid sulfate alteration has been identified at all three landing sites visited by NASA rover missions (Spirit, Opportunity, and Curiosity). Spirit landed in Gusev crater in 2004 and discovered Fe-sulfates and materials that have been extensively leached by acid sulfate solutions. Opportunity landing on the plains of Meridiani Planum also in 2004 where the rover encountered large abundances of jarosite and hematite in sedimentary rocks. Curiosity landed in Gale crater in 2012 and has characterized fluvial, deltaic, and lacustrine sediments. Jarosite and hematite were discovered in some of the lacustrine sediments. The high elemental abundance of sulfur in surface materials is obvious evidence that sulfate has played a major role in aqueous processes at all landing sites on Mars. The sulfate-rich outcrop at Meridiani Planum has an SO3 content of up to 25 wt.%. The interiors of rocks and outcrops on the Columbia Hills within Gusev crater have up to 8 wt.% SO3. Soils at both sites generally have between 5 to 14 wt.% SO3, and several soils in Gusev crater contain around 30 wt.% SO3. After normalization of major element compositions to a SO3-free basis, the bulk compositions of these materials are basaltic, with a few exceptions in Gusev crater and in lacustrine mudstones in Gale crater. These observations suggest that materials encountered by the rovers were derived from basaltic precursors by acid sulfate alteration under nearly isochemical conditions (i.e., minimal leaching). There are several cases, however, where acid sulfate alteration minerals (jarosite and hematite) formed in open hydrologic systems, e.g., in Gale crater lacustrine mudstones. Several hypotheses have been suggested for the

  4. Human Metabolic Network: Reconstruction, Simulation, and Applications in Systems Biology

    Science.gov (United States)

    Wu, Ming; Chan, Christina

    2012-01-01

    Metabolism is crucial to cell growth and proliferation. Deficiency or alterations in metabolic functions are known to be involved in many human diseases. Therefore, understanding the human metabolic system is important for the study and treatment of complex diseases. Current reconstructions of the global human metabolic network provide a computational platform to integrate genome-scale information on metabolism. The platform enables a systematic study of the regulation and is applicable to a wide variety of cases, wherein one could rely on in silico perturbations to predict novel targets, interpret systemic effects, and identify alterations in the metabolic states to better understand the genotype-phenotype relationships. In this review, we describe the reconstruction of the human metabolic network, introduce the constraint based modeling approach to analyze metabolic networks, and discuss systems biology applications to study human physiology and pathology. We highlight the challenges and opportunities in network reconstruction and systems modeling of the human metabolic system. PMID:24957377

  5. Hypertension is associated with marked alterations in sphingolipid biology

    DEFF Research Database (Denmark)

    Spijkers, Léon J A; van den Akker, Rob F P; Janssen, Ben J A;

    2011-01-01

    indicated that these contractions were most likely mediated by ceramide and dependent on iPLA(2), cyclooxygenase-1 and thromboxane synthase. Expression levels of these enzymes were higher in SHR vessels. In concurrence, infusion of dimethylsphingosine caused a marked rise in blood pressure in anesthetized...... SHR (42±4%; n = 7), but not in WKY (-12±10%; n = 6). Lipidomics analysis by mass spectrometry, revealed elevated levels of ceramide in arterial tissue of SHR compared to WKY (691±42 vs. 419±27 pmol, n = 3-5 respectively, p... reflected in increased plasma ceramide levels (513±19 pmol WKY vs. 645±25 pmol SHR, n = 6-12, plevels (correlating with hypertension grade) in plasma from humans with essential hypertension (185±8 pmol vs. 252±23 pmol; n = 18 normotensive vs...

  6. Cerebrospinal fluid space alterations in melancholic depression.

    Directory of Open Access Journals (Sweden)

    Esther Via

    Full Text Available Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm ('new segment', as implemented in the software Statistical Parametric Mapping-SPM8, incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the 'new segment' algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the 'unified segmentation' approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the 'unified segmentation' approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches

  7. Quantum Biology

    CERN Document Server

    Sergi, Alessandro

    2009-01-01

    A critical assessment of the recent developments of molecular biology is presented. The thesis that they do not lead to a conceptual understanding of life and biological systems is defended. Maturana and Varela's concept of autopoiesis is briefly sketched and its logical circularity avoided by postulating the existence of underlying {\\it living processes}, entailing amplification from the microscopic to the macroscopic scale, with increasing complexity in the passage from one scale to the other. Following such a line of thought, the currently accepted model of condensed matter, which is based on electrostatics and short-ranged forces, is criticized. It is suggested that the correct interpretation of quantum dispersion forces (van der Waals, hydrogen bonding, and so on) as quantum coherence effects hints at the necessity of including long-ranged forces (or mechanisms for them) in condensed matter theories of biological processes. Some quantum effects in biology are reviewed and quantum mechanics is acknowledge...

  8. MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation

    Science.gov (United States)

    Zhao, Jin; Schnitzler, Gavin R.; Iyer, Lakshmanan K.; Aronovitz, Mark J.; Baur, Wendy E.; Karas, Richard H.

    2016-01-01

    MicroRNA-offset RNAs (moRs) were first identified in simple chordates and subsequently in mouse and human cells by deep sequencing of short RNAs. MoRs are derived from sequences located immediately adjacent to microRNAs (miRs) in the primary miR (pri-miR). Currently moRs are considered to be simply a by-product of miR biosynthesis that lack biological activity. Here we show for the first time that a moR is biologically active. We demonstrate that endogenous or over-expressed moR-21 significantly alters gene expression and inhibits the proliferation of vascular smooth muscle cells (VSMC). In addition, we find that miR-21 and moR-21 may regulate different genes in a given pathway and can oppose each other in regulating certain genes. We report that there is a “seed region” of moR-21 as well as a “seed match region” in the target gene 3’UTR that are indispensable for moR-21-mediated gene down-regulation. We further demonstrate that moR-21-mediated gene repression is Argonaute 2 (Ago2) dependent. Taken together, these findings provide the first evidence that microRNA offset RNA alters gene expression and is biologically active. PMID:27276022

  9. Tipificação de sintomas relacionados à voz e sua produção em professores identificados com ausência de alteração vocal na avaliação fonoaudiológica Typification of symptoms related to voice and its production in teachers identified with absence of vocal alteration in Speech-Language Pathology evaluation

    Directory of Open Access Journals (Sweden)

    Emilse Aparecida Merlin Servilha

    2010-06-01

    Full Text Available OBJETIVO: tipificar os sintomas relacionados à voz e sua produção auto referidos por professoras, cujas vozes foram identificadas como saudáveis na avaliação fonoaudiológica. MÉTODOS: participaram 36 docentes, idade média de 37 anos, solteiras (75% e escolaridade superior (83,33% da rede municipal de ensino de uma cidade do interior do estado de São Paulo. Os docentes responderam a um questionário e referiram a alteração, suas vozes foram gravadas e submetidas à avaliação fonoaudiológica perceptivo-auditiva e posteriormente comparados os dois tipos de avaliação. Procedeu-se a caracterização sócio demográfica, condições ambientais e organizacionais do trabalho dos docentes e seus sintomas tipificados e submetidos à análise estatística descritiva. RESULTADOS: constatou-se a presença de poeira (91,67%, ruído (75% e excesso de trabalho (88,88%, falta de tempo para desenvolver as atividades na escola (88,88% e fiscalização constante do desempenho (33,33%. Quanto à voz, a alteração foi percebida há mais de quatro anos (30,56%, secundária ao seu uso intensivo (94,44% e ao estresse (61,11%, classificada como moderada (66,67%, sendo proeminentes como sintomas auditivos, a rouquidão e o cansaço ao falar, ambos com 69,44% e como sintomas proprioceptivos, o pigarro (63,88% e a garganta seca (61,11%. A comparação entre os sintomas mostra que os proprioceptivos (63,26 % foram mais mencionados do que os auditivos (36,73 %. CONCLUSÃO: os professores trabalham em ambientes adversos à saúde e à voz; a prevalência de sintomas proprioceptivos foi maior que os auditivos, o que pode ter interferido na avaliação perceptual de suas vozes pelas fonoaudiólogas que contaram apenas com a pista auditiva.PURPOSE: to typify the symptoms related to voice and its production self-referred by teachers, whose voices were identified as healthful in the Speech-Language Pathology evaluation. METHODS: 36 teachers took part, with mean

  10. The Virtual Institute for Integrative Biology (VIIB)

    OpenAIRE

    Rivera, Gustavo; González-Nilo, Fernando; Perez-Acle, Tomás; Isea, Raul; Holmes, David S.

    2010-01-01

    The Virtual Institute for Integrative Biology (VIIB) is a Latin American initiative for achieving global collaborative e-Science in the areas of bioinformatics, genome biology, systems biology, metagenomics, medical applications and nanobiotechnolgy. The scientific agenda of VIIB includes: construction of databases for comparative genomics, the AlterORF database for alternate open reading frames discovery in genomes, bioinformatics services and protein simulations for biotechnological and med...

  11. Computational Biology: A Programming Perspective

    DEFF Research Database (Denmark)

    Hartmann, Lars; Jones, Neil; Simonsen, Jakob Grue;

    2011-01-01

    identify some strengths and shortcomings from a programming perspective. To show concretely what one could see as programming in biocomputing, we outline (from recent work) a computation model and a small programming language that are biologically more plausible than existing silicon-inspired models....... Whether or not the model is biologically plausible in an absolute sense, we believe it sets a standard for a biological device that can be both universal and programmable....

  12. Network community structure alterations in adult schizophrenia: identification and localization of alterations.

    Science.gov (United States)

    Lerman-Sinkoff, Dov B; Barch, Deanna M

    2016-01-01

    A growing body of literature suggests functional connectivity alterations in schizophrenia. While findings have been mixed, evidence points towards a complex pattern of hyper-connectivity and hypo-connectivity. This altered connectivity can be represented and analyzed using the mathematical frameworks provided by graph and information theory to represent functional connectivity data as graphs comprised of nodes and edges linking the nodes. One analytic technique in this framework is the determination and analysis of network community structure, which is the grouping of nodes into linked communities or modules. This data-driven technique finds a best-fit structure such that nodes in a given community have greater connectivity with nodes in their community than with nodes in other communities. These community structure representations have been found to recapitulate known neural-systems in healthy individuals, have been used to identify novel functional systems, and have identified and localized community structure alterations in a childhood onset schizophrenia cohort. In the present study, we sought to determine whether community structure alterations were present in an adult onset schizophrenia cohort while stringently controlling for sources of imaging artifacts. Group level average graphs in healthy controls and individuals with schizophrenia exhibited visually similar network community structures and high amounts of normalized mutual information (NMI). However, testing of individual subject community structures identified small but significant alterations in community structure with alterations being driven by changes in node community membership in the somatosensory, auditory, default mode, salience, and subcortical networks.

  13. Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer

    OpenAIRE

    Kim, Michael Paul; Zhang, Yun; Lozano, Guillermina

    2015-01-01

    The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve p53 missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may concomitantly gain novel functions, often with deleterious effects. Here, we rev...

  14. Modeling biological systems with Answer Set Programming

    OpenAIRE

    Thiele, Sven

    2012-01-01

    Biology has made great progress in identifying and measuring the building blocks of life. The availability of high-throughput methods in molecular biology has dramatically accelerated the growth of biological knowledge for various organisms. The advancements in genomic, proteomic and metabolomic technologies allow for constructing complex models of biological systems. An increasing number of biological repositories is available on the web, incorporating thousands of biochemical reactions and ...

  15. Biologic therapies for juvenile arthritis

    OpenAIRE

    Wilkinson, N; Jackson, G.; Gardner-Medwin, J.

    2003-01-01

    A group of therapies with exciting potential has emerged for children and young people with severe juvenile idiopathic arthritis (JIA) uncontrolled by conventional disease modifying drugs. Theoretical understanding from molecular biologic research has identified specific targets within pathophysiological pathways that control rheumatoid arthritis (RA) and JIA. This review identifies the pathways of autoimmunity to begin to show how biologic agents have been produced to replicate, mimic, or bl...

  16. Biological Oceanography

    Science.gov (United States)

    Abbott, M. R.

    1984-01-01

    Within the framework of global biogeochemical cycles and ocean productivity, there are two areas that will be of particular interest to biological oceanography in the 1990s. The first is the mapping in space time of the biomass and productivity of phytoplankton in the world ocean. The second area is the coupling of biological and physical processes as it affects the distribution and growth rate of phytoplankton biomass. Certainly other areas will be of interest to biological oceanographers, but these two areas are amenable to observations from satellites. Temporal and spatial variability is a regular feature of marine ecosystems. The temporal and spatial variability of phytoplankton biomass and productivity which is ubiquitous at all time and space scales in the ocean must be characterized. Remote sensing from satellites addresses these problems with global observations of mesocale (2 to 20 days, 10 to 200 km) features over a long period of time.

  17. A Systematic Approach to Identify Markers of Distinctly Activated Human Macrophages

    Directory of Open Access Journals (Sweden)

    Bayan eSudan

    2015-05-01

    Full Text Available Polarization has been a useful concept for describing activated macrophage phenotypes and gene expression profiles. However, macrophage activation status within tumors and other settings are often inferred based on only a few markers. Complicating matters for relevance to human biology, many of the best studied macrophage activation markers have been best characterized in mice and sometimes are not similarly regulated in human macrophages. To identify novel markers of activated human macrophages, gene expression profiles for human macrophages of a single donor subjected to 33 distinct activating conditions were obtained and a set of putative activation markers were subsequently evaluated in macrophages from multiple donors using integrated fluidic circuit (IFC-based RT-PCR. Using unsupervised hierarchical clustering of the microarray screen, highly-altered transcripts (>4-fold change in expression sorted the macrophage transcription profiles into two major and 13 minor clusters. Among the 1874 highly-altered transcripts, over 100 were uniquely altered in one major or two related minor clusters. IFC PCR-derived data confirmed the microarray results and to show the kinetics of expression of potential macrophage activation markers. Transcripts encoding chemokines, cytokines, and cell surface were prominent in our analyses. The activation markers identified by this study could be used to better characterize tumor-associated macrophages from biopsies as well as other macrophage populations collected from human clinical samples.

  18. Molecular biology of the lung cancer

    International Nuclear Information System (INIS)

    Background. Lung cancer is one of the most common malignant diseases and leading cause of cancer death worldwide. The advances in molecular biology and genetics, including the modern microarray technology and rapid sequencing techniques, have enabled a remarkable progress into elucidating the lung cancer ethiopathogenesis. Numerous studies suggest that more than 20 different genetic and epigenetic alterations are accumulating during the pathogenesis of clinically evident pulmonary cancers as a clonal, multistep process. Thus far, the most investigated alterations are the inactivational mutations and losses of tumour suppressor genes and the overexpression of growth-promoting oncogenes. More recently, the acquired epigenetic inactivation of tumour suppressor genes by promoter hypermethylation has been recognized. The early clonal genetic abnormalities that occur in preneoplastic bronchial epithelium damaged by smoking or other carcinogenes are being identified. The molecular distinctions between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), as well as between tumors with different clinical outcomes have been described. These investigations lead to the hallmarks of lung cancer. Conclusions. It is realistic to expect that the molecular and cell culture-based investigations will lead to discoveries of new clinical applications with the potential to provide new avenues for early diagnosis, risk assessment, prevention, and most important, new more effective treatment approaches for the lung cancer patients. (author)

  19. A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide

    Directory of Open Access Journals (Sweden)

    Paiva Renata T

    2012-06-01

    Full Text Available Abstract Background Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modulation of this set of genes was then analyzed in the LPS stimulated cells treated with thalidomide. Results We identified 64 genes with altered expression induced by thalidomide using the rank product method. In addition, the lists of up-regulated and down-regulated genes were investigated by means of bioinformatics functional analysis, which allowed for the identification of biological processes affected by thalidomide. Confirmatory analysis was done in five of the identified genes using real time PCR. Conclusions The results showed some genes that can further our understanding of the biological mechanisms in the action of thalidomide. Of the five genes evaluated with real time PCR, three were down regulated and two were up regulated confirming the initial results of the microarray analysis.

  20. Biology Notes.

    Science.gov (United States)

    School Science Review, 1981

    1981-01-01

    Outlines a variety of laboratory procedures, techniques, and materials including construction of a survey frame for field biology, a simple tidal system, isolation and applications of plant protoplasts, tropisms, teaching lung structure, and a key to statistical methods for biologists. (DS)

  1. (Biological dosimetry)

    Energy Technology Data Exchange (ETDEWEB)

    Preston, R.J.

    1990-12-17

    The traveler attended the 1st International Conference on Biological Dosimetry in Madrid, Spain. This conference was organized to provide information to a general audience of biologists, physicists, radiotherapists, industrial hygiene personnel and individuals from related fields on the current ability of cytogenetic analysis to provide estimates of radiation dose in cases of occupational or environmental exposure. There is a growing interest in Spain in biological dosimetry because of the increased use of radiation sources for medical and occupational uses, and with this the anticipated and actual increase in numbers of overexposure. The traveler delivered the introductory lecture on Biological Dosimetry: Mechanistic Concepts'' that was intended to provide a framework by which the more applied lectures could be interpreted in a mechanistic way. A second component of the trip was to provide advice with regard to several recent cases of overexposure that had been or were being assessed by the Radiopathology and Radiotherapy Department of the Hospital General Gregorio Maranon'' in Madrid. The traveler had provided information on several of these, and had analyzed cells from some exposed or purportedly exposed individuals. The members of the biological dosimetry group were referred to individuals at REACTS at Oak Ridge Associated Universities for advice on follow-up treatment.

  2. Biology Notes.

    Science.gov (United States)

    School Science Review, 1984

    1984-01-01

    Presents information on the teaching of nutrition (including new information relating to many current O-level syllabi) and part 16 of a reading list for A- and S-level biology. Also includes a note on using earthworms as a source of material for teaching meiosis. (JN)

  3. Identifiability in stochastic models

    CERN Document Server

    1992-01-01

    The problem of identifiability is basic to all statistical methods and data analysis, occurring in such diverse areas as Reliability Theory, Survival Analysis, and Econometrics, where stochastic modeling is widely used. Mathematics dealing with identifiability per se is closely related to the so-called branch of ""characterization problems"" in Probability Theory. This book brings together relevant material on identifiability as it occurs in these diverse fields.

  4. Using biological pathway data with paxtools.

    Directory of Open Access Journals (Sweden)

    Emek Demir

    Full Text Available A rapidly growing corpus of formal, computable pathway information can be used to answer important biological questions including finding non-trivial connections between cellular processes, identifying significantly altered portions of the cellular network in a disease state and building predictive models that can be used for precision medicine. Due to its complexity and fragmented nature, however, working with pathway data is still difficult. We present Paxtools, a Java library that contains algorithms, software components and converters for biological pathways represented in the standard BioPAX language. Paxtools allows scientists to focus on their scientific problem by removing technical barriers to access and analyse pathway information. Paxtools can run on any platform that has a Java Runtime Environment and was tested on most modern operating systems. Paxtools is open source and is available under the Lesser GNU public license (LGPL, which allows users to freely use the code in their software systems with a requirement for attribution. Source code for the current release (4.2.0 can be found in Software S1. A detailed manual for obtaining and using Paxtools can be found in Protocol S1. The latest sources and release bundles can be obtained from biopax.org/paxtools.

  5. Transcriptome sequencing in prostate cancer identifies inter-tumor heterogeneity

    Directory of Open Access Journals (Sweden)

    Janet Mendonca

    2015-06-01

    Full Text Available Given the dearth of gene mutations in prostate cancer, [1] ,[2] it is likely that genomic rearrangements play a significant role in the evolution of prostate cancer. However, in the search for recurrent genomic alterations, "private alterations" have received less attention. Such alterations may provide insights into the evolution, behavior, and clinical outcome of an individual tumor. In a recent report in "Genome Biology" Wyatt et al. [3] defines unique alterations in a cohort of high-risk prostate cancer patient with a lethal phenotype. Utilizing a transcriptome sequencing approach they observe high inter-tumor heterogeneity; however, the genes altered distill into three distinct cancer-relevant pathways. Their analysis reveals the presence of several non-ETS fusions, which may contribute to the phenotype of individual tumors, and have significance for disease progression.

  6. Assessing the welfare of genetically altered mice.

    Science.gov (United States)

    Wells, D J; Playle, L C; Enser, W E J; Flecknell, P A; Gardiner, M A; Holland, J; Howard, B R; Hubrecht, R; Humphreys, K R; Jackson, I J; Lane, N; Maconochie, M; Mason, G; Morton, D B; Raymond, R; Robinson, V; Smith, J A; Watt, N

    2006-04-01

    In 2003, under the auspices of the main UK funders of biological and biomedical research, a working group was established with a remit to review potential welfare issues for genetically altered (GA) mice, to summarize current practice, and to recommend contemporary best practice for welfare assessments. The working group has produced a report which makes practical recommendations for GA mouse welfare assessment and dissemination of welfare information between establishments using a 'mouse passport'. The report can be found at www.nc3rs.org.uk/GAmice and www.lal.org.uk/gaa and includes templates for the recommended welfare assessment scheme and the mouse passport. An overview is provided below.

  7. Mapping biological systems to network systems

    CERN Document Server

    Rathore, Heena

    2016-01-01

    The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

  8. Mesoscopic biology

    Indian Academy of Sciences (India)

    G V Shivashankar

    2002-02-01

    In this paper we present a qualitative outlook of mesoscopic biology where the typical length scale is of the order of nanometers and the energy scales comparable to thermal energy. Novel biomolecular machines, governed by coded information at the level of DNA and proteins, operate at these length scales in biological systems. In recent years advances in technology have led to the study of some of the design principles of these machines; in particular at the level of an individual molecule. For example, the forces that operate in molecular interactions, the stochasticity involved in these interactions and their spatio-temporal dynamics are beginning to be explored. Understanding such design principles is opening new possibilities in mesoscopic physics with potential applications.

  9. Biological degradation of chernozems under irrigation

    Directory of Open Access Journals (Sweden)

    Oksana Naydyonova

    2014-12-01

    Full Text Available We studied the changes in the state of microbial cenosis of Ukraine’s chernozems under irrigation. Considerable part of Ukraine’s chernozems is located in the areas where humidification is insufficient and unstable. Irrigation is a soil-reclamation measure for chernozems of Ukrainian Forest-steppe and Steppe which enables getting the assured yield, especially vegetable and fodder crops. At the same time, irrigation is a powerful anthropogenic factor that affects the soil, causes a significant transformation of many of its properties and regimes including biological ones. Often these changes are negative. The purpose of our investigation was to identify changes in the state of microbial cenoses of chernozem soils under irrigation which depend on such factors as the quality of irrigation water, the duration and intensity of irrigation, the initial properties of soil, the structure of crop rotation, usage of fertilizing systems and agroameliorative techniques. We identified direction and evaluated a degree of changes in biological properties of chernozems under influence of irrigation in different agro-irrigational and soil-climatic conditions. In the long-term stationary field experiments we identified the following biological indices of irrigated soils and their non-irrigated analogues: a number of microorganisms which belong to main ecological-trophic groups, activity of soil enzymes (dehydrogenase, invertase, phenol oxidase, soil phytotoxic activity, cellulose destroying capacity of soil, indices of oligotrophy and mineralization, summary biological index (SBI and index of biological degradation (BDI. Results of researches showed that irrigation unbalanced the soil ecosystem and stipulated the forming of microbial cenosis with new parameters. Long-term intensive irrigation of typical chernozem (Kharkiv Region with fresh water under condition of 4-fields vegetable crop rotation led to the degradation changes of its microbial cenosis such as

  10. Crusts: biological

    Science.gov (United States)

    Belnap, Jayne; Elias, Scott A.

    2013-01-01

    Biological soil crusts, a community of cyanobacteria, lichens, mosses, and fungi, are an essential part of dryland ecosystems. They are critical in the stabilization of soils, protecting them from wind and water erosion. Similarly, these soil surface communities also stabilized soils on early Earth, allowing vascular plants to establish. They contribute nitrogen and carbon to otherwise relatively infertile dryland soils, and have a strong influence on hydrologic cycles. Their presence can also influence vascular plant establishment and nutrition.

  11. Biological programming

    OpenAIRE

    Ramsden, Jeremy J.; Bándi, Gergely

    2010-01-01

    Biology offers a tremendous set of concepts that are potentially very powerfully usable for the software engineer, but they have been barely exploited hitherto. In this position paper we propose a fresh attempt to create the building blocks of a programming technology that could be as successful as life. A key guiding principle is to develop and make use of unambiguous definitions of the essential features of life.

  12. Marine biology

    International Nuclear Information System (INIS)

    This book discusses both taxonomic and ecological topics on marine biology. Full coverage of marine organisms of all five kingdoms is provided, along with interesting and thorough discussion of all major marine habitats. Organization into six major parts allows flexibility. It also provides insight into important topics such as disposal of nuclear waste at sea, the idea that life began on the ocean floor, and how whales, krill, and people interact. A full-color photo chapter reviews questions, and exercises. The contents are: an overview marine biology: fundamental concepts/investigating life in the ocean; the physical ocean, the ocean floor, the nature of water, the nature and motion of ocean water; general ecology, conditions for life in the sea, biological productivity and energy transfer; marine organisms; monera, protista, mycota and metaphyta; the smaller marine animals, the large animals marine habitats, the intertidal zone/benthos of the continental shelf, the photic zone, the deep ocean, the ocean under stress, marine pollution, appendix a: the metric system and conversion factors/ appendix b: prefixes and suffixes/ appendix c: taxonomic classification of common marine organisms, and glossary, and index

  13. Marine biology

    Energy Technology Data Exchange (ETDEWEB)

    Thurman, H.V.; Webber, H.H.

    1984-01-01

    This book discusses both taxonomic and ecological topics on marine biology. Full coverage of marine organisms of all five kingdoms is provided, along with interesting and thorough discussion of all major marine habitats. Organization into six major parts allows flexibility. It also provides insight into important topics such as disposal of nuclear waste at sea, the idea that life began on the ocean floor, and how whales, krill, and people interact. A full-color photo chapter reviews questions, and exercises. The contents are: an overview marine biology: fundamental concepts/investigating life in the ocean; the physical ocean, the ocean floor, the nature of water, the nature and motion of ocean water; general ecology, conditions for life in the sea, biological productivity and energy transfer; marine organisms; monera, protista, mycota and metaphyta; the smaller marine animals, the large animals marine habitats, the intertidal zone/benthos of the continental shelf, the photic zone, the deep ocean, the ocean under stress, marine pollution, appendix a: the metric system and conversion factors/ appendix b: prefixes and suffixes/ appendix c: taxonomic classification of common marine organisms, and glossary, and index.

  14. Biological effects of space radiation and development of effective countermeasures

    Science.gov (United States)

    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.

  15. Identifying Unknown Proteins

    OpenAIRE

    Barker, Winona C.; Dayhoff, Margaret O.

    1983-01-01

    In this paper we discuss ways to identify a protein, both when its amino acid sequence is known and, particularly, prior to the determination of the complete sequence. If a similar sequence is in the Protein Sequence Database, an unknown may be identified on the basis of partial or ambiguous sequence data, or on the basis of amino acid composition. Identification in the early stages of structural determination can save time and scarce resources by preventing duplicate effort or by suggesting ...

  16. Genetic alterations and markers of melanoma

    Directory of Open Access Journals (Sweden)

    N. N. Mazurenko

    2014-01-01

    Full Text Available Melanoma remains the most deadly form of malignant skin disease with high risk of metastases. Metastatic melanoma is prognostic highly unfavorable and resistant to traditional chemotherapy and biologic treatment. There is a great progress in understanding of the molecular mechanisms underlying melanoma initiation and progression. The external (ultraviolet irradiation and internal (genetic factors are involved in melanoma genesis. 5–14 % of melanoma cases occur in familial context due to genetic predisposition risk factors. Among them rare germinal mutations in the cell cycle genes regulators CDKN2A and CDK4 and in the master gene of melanocyte homeostasis MITF, as well as single nucleotide polymorphisms of several low-penetrated genes, namely MC1R, have been identified. The main cell signaling pathways and oncogene driver mutations are involved in melanoma pathogenesis. RAS / RAF / MEK / ERK cascade is hyperactivated in 75 % of cutaneous melanoma cases. Activation of PI3K / AKT / mTOR signaling pathway is important for melanoma progression. Recent studies revealed that melanomas are genetically and phenotypically heterogeneous tumors. Spectrum of chromosomal alterations and activating mutations corresponding to tumor molecular portraits varies in melanomas of different location. Most of cutaneous melanomas contain BRAF (50 % or NRAS (20 % mutations, and NRAS mutations occur on chronically sun-exposed skin. Activating KIT mutations have been reported in approximately 20–30 % of certain subtypes of melanoma, including acral and mucosal, and melanoma that develop on photodamaged skin. Cutaneous metastatic melanoma derive from preexisting nevi in 25 % of cases, molecular mechanisms of nevi malignization are discussed. Deepsequencing approaches of melanoma samples of different melanoma types highlighted new melanoma driver genes, that are damaged due to tumorigenic effects of ultraviolet: PPP6C, RAC1, SNX31, TACC1 and STK19. The

  17. A review of the use of biological agents for chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Stübgen, Joerg-Patrick

    2013-03-15

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is a group of idiopathic, acquired, immune-mediated inflammatory demyelinating diseases of the peripheral nervous system. A majority of patients with CIDP respond to "first-line" treatment with IVIG, plasmapheresis and/or corticosteroids. There exists insufficient evidence to ascertain the benefit of treatment with "conventional" immunosuppressive drugs. The inconsistent efficacy, long-term financial burden and health risks of non-specific immune altering therapy have drawn recurrent attention to the possible usefulness of a variety of biological agents that target key aspects in the CIDP immunopathogenic pathways. This review aims to give an updated account of the scientific rationale and potential use of biological therapeutics in patients with CIDP. No specific treatment recommendations are given. The discovery, development and application of biological markers by modern molecular diagnostic techniques may help identify drug-naïve or treatment-resistant CIDP patients most likely to respond to targeted immunotherapy.

  18. Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function

    NARCIS (Netherlands)

    Ingólfsson, Helgi I; Thakur, Pratima; Herold, Karl F; Hobart, E Ashley; Ramsey, Nicole B; Periole, Xavier; de Jong, Djurre H; Zwama, Martijn; Yilmaz, Duygu; Hall, Katherine; Maretzky, Thorsten; Hemmings, Hugh C; Blobel, Carl; Marrink, Siewert J; Kocer, Armagan; Sack, Jon T; Andersen, Olaf S

    2014-01-01

    A wide variety of phytochemicals are consumed for their perceived health benefits. Many of these phytochemicals have been found to alter numerous cell functions, but the mechanisms underlying their biological activity tend to be poorly understood. Phenolic phytochemicals are particularly promiscuous

  19. Alteration kinetics of the glass-ceramic zirconolite and role of the alteration film Comparison with the SON68 glass

    Science.gov (United States)

    Martin, C.; Ribet, I.; Frugier, P.; Gin, S.

    2007-06-01

    The glass-ceramic zirconolite is being considered for specific conditioning of plutonium or the minor actinides. The actinides are distributed throughout the zirconolite crystals and the residual glass phase. Since zirconolite alteration is extremely limited, actinide release from the glass-ceramic material is mainly attributable to alteration of the residual glass. Specimens corresponding to the residual glass phase alone were therefore altered under different conditions to compare their kinetics with the one of the SON68 glass (inactive R7T7 type glass). Glass-ceramic zirconolite presents a more important rate decrease occuring more rapidly and that induces a quantity of glass altered at least 10 times as small as for SON68 glass. This slowdown of the alteration rate is attributed to the formation of an alteration film that has been the subject of a specific study. We have in particular identified a dense phase enriched in titanium and neodymium that probably influences deeply the kinetics.

  20. Biological Databases

    Directory of Open Access Journals (Sweden)

    Kaviena Baskaran

    2013-12-01

    Full Text Available Biology has entered a new era in distributing information based on database and this collection of database become primary in publishing information. This data publishing is done through Internet Gopher where information resources easy and affordable offered by powerful research tools. The more important thing now is the development of high quality and professionally operated electronic data publishing sites. To enhance the service and appropriate editorial and policies for electronic data publishing has been established and editors of article shoulder the responsibility.

  1. Altered fingerprints: analysis and detection.

    Science.gov (United States)

    Yoon, Soweon; Feng, Jianjiang; Jain, Anil K

    2012-03-01

    The widespread deployment of Automated Fingerprint Identification Systems (AFIS) in law enforcement and border control applications has heightened the need for ensuring that these systems are not compromised. While several issues related to fingerprint system security have been investigated, including the use of fake fingerprints for masquerading identity, the problem of fingerprint alteration or obfuscation has received very little attention. Fingerprint obfuscation refers to the deliberate alteration of the fingerprint pattern by an individual for the purpose of masking his identity. Several cases of fingerprint obfuscation have been reported in the press. Fingerprint image quality assessment software (e.g., NFIQ) cannot always detect altered fingerprints since the implicit image quality due to alteration may not change significantly. The main contributions of this paper are: 1) compiling case studies of incidents where individuals were found to have altered their fingerprints for circumventing AFIS, 2) investigating the impact of fingerprint alteration on the accuracy of a commercial fingerprint matcher, 3) classifying the alterations into three major categories and suggesting possible countermeasures, 4) developing a technique to automatically detect altered fingerprints based on analyzing orientation field and minutiae distribution, and 5) evaluating the proposed technique and the NFIQ algorithm on a large database of altered fingerprints provided by a law enforcement agency. Experimental results show the feasibility of the proposed approach in detecting altered fingerprints and highlight the need to further pursue this problem. PMID:21808092

  2. Identifying Knowledge and Communication

    Directory of Open Access Journals (Sweden)

    Eduardo Coutinho Lourenço de Lima

    2006-12-01

    Full Text Available In this paper, I discuss how the principle of identifying knowledge which Strawson advances in ‘Singular Terms and Predication’ (1961, and in ‘Identifying Reference and Truth-Values’ (1964 turns out to constrain communication. The principle states that a speaker’s use of a referring expression should invoke identifying knowledge on the part of the hearer, if the hearer is to understand what the speaker is saying, and also that, in so referring, speakers are attentive to hearers’ epistemic states. In contrasting it with Russell’s Principle (Evans 1982, as well as with the principle of identifying descriptions (Donnellan 1970, I try to show that the principle of identifying knowledge, ultimately a condition for understanding, makes sense only in a situation of conversation. This allows me to conclude that the cooperative feature of communication (Grice 1975 and reference (Clark andWilkes-Gibbs 1986 holds also at the understanding level. Finally, I discuss where Strawson’s views seem to be unsatisfactory, and suggest how they might be improved.

  3. Metal alloy identifier

    Science.gov (United States)

    Riley, William D.; Brown, Jr., Robert D.

    1987-01-01

    To identify the composition of a metal alloy, sparks generated from the alloy are optically observed and spectrographically analyzed. The spectrographic data, in the form of a full-spectrum plot of intensity versus wavelength, provide the "signature" of the metal alloy. This signature can be compared with similar plots for alloys of known composition to establish the unknown composition by a positive match with a known alloy. An alternative method is to form intensity ratios for pairs of predetermined wavelengths within the observed spectrum and to then compare the values of such ratios with similar values for known alloy compositions, thereby to positively identify the unknown alloy composition.

  4. Biological biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Jorge-Herrero, E. [Servicio de Cirugia Experimental. Clinica Puerta de Hierro, Madrid (Spain)

    1997-05-01

    There are a number of situations in which substances of biological origin are employed as biomaterials. Most of them are macromolecules derived from isolated connective tissue or the connective tissue itself in membrane form, in both cases, the tissue can be used in its natural form or be chemically treated. In other cases, certain blood vessels can be chemically pretreated and used as vascular prostheses. Proteins such as albumin, collagen and fibrinogen are employed to coat vascular prostheses. Certain polysaccharides have also been tested for use in controlled drug release systems. Likewise, a number of tissues, such as dura mater, bovine pericardium, procine valves and human valves, are used in the preparation of cardiac prostheses. We also use veins from animals or humans in arterial replacement. In none of these cases are the tissues employed dissimilar to the native tissues as they have been chemically modified, becoming a new bio material with different physical and biochemical properties. In short, we find that natural products are being utilized as biomaterials and must be considered as such; thus, it is necessary to study both their chemicobiological and physicomechanical properties. In the present report, we review the current applications, problems and future prospects of some of these biological biomaterials. (Author) 84 refs.

  5. A utilização de informantes-chave da comunidade na identificação de pessoas portadoras de alterações cinético-funcionais da cidade de Caxias do Sul, RS The use of key informants from within the community for identifying people with functional kinetic alterations in Caxias do Sul, Rio Grande do Sul State, Brazil

    Directory of Open Access Journals (Sweden)

    Alexandra Renosto

    2007-06-01

    Full Text Available OBJETIVO: Manter-se funcionalmente ativo em um determinado contexto social, parece ser um dos grandes desafios para a sociedade da atualidade. O objetivo deste trabalho foi estudar o perfil epidemiológico de portadores de alterações cinético-funcionais, a partir de informantes-chave da comunidade de Caxias do Sul (RS, considerando características socioeconômicas, socioculturais, familiares/ individuais e cuidados com a saúde, vinculando-as com a capacidade funcional. MATERIAL E MÉTODOS: Esta pesquisa compreendeu um estudo observacional descritivo. A população em estudo foi constituída pelos portadores de alterações cinético-funcionais provenientes de indicações de informantes-chave da comunidade, conhecidos como zeladoras de capelinha. Os instrumentos aplicados foram: questionário às zeladoras de capelinha, entrevista estruturada e Índice de Barthel aos incapacitados funcionais. RESULTADOS: Apenas 21,9% da população estudada que possui dependência funcional realiza tratamento fisioterapêutico. O uso de informantes-chave é uma alternativa viável no auxílio do diagnóstico funcional deste grupo populacional. As características da população em estudo supõem exclusão de atendimento fisioterapêutico e a necessidade de programas efetivos na abordagem do problema.PURPOSE: Remaining functionally active within a specific social context seems to be one of the hardest challenges faced by our society. The purpose of this paper is to study the epidemiological profiles of people with functional kinetic alterations as noted by key informants living in Caxias do Sul, Rio Grande do Sul State, Brazil, considering social, economic and cultural characteristics, as well as family/individual profiles and healthcare aspects, linked to functional capacities. METHODOLOGY: This research project included an observational descriptive study. The population studied consisted of people suffering from functional kinetic alterations noted by from

  6. Genetic Alterations in Glioma

    International Nuclear Information System (INIS)

    Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes

  7. Music alters visual perception.

    Directory of Open Access Journals (Sweden)

    Jacob Jolij

    Full Text Available BACKGROUND: Visual perception is not a passive process: in order to efficiently process visual input, the brain actively uses previous knowledge (e.g., memory and expectations about what the world should look like. However, perception is not only influenced by previous knowledge. Especially the perception of emotional stimuli is influenced by the emotional state of the observer. In other words, how we perceive the world does not only depend on what we know of the world, but also by how we feel. In this study, we further investigated the relation between mood and perception. METHODS AND FINDINGS: We let observers do a difficult stimulus detection task, in which they had to detect schematic happy and sad faces embedded in noise. Mood was manipulated by means of music. We found that observers were more accurate in detecting faces congruent with their mood, corroborating earlier research. However, in trials in which no actual face was presented, observers made a significant number of false alarms. The content of these false alarms, or illusory percepts, was strongly influenced by the observers' mood. CONCLUSIONS: As illusory percepts are believed to reflect the content of internal representations that are employed by the brain during top-down processing of visual input, we conclude that top-down modulation of visual processing is not purely predictive in nature: mood, in this case manipulated by music, may also directly alter the way we perceive the world.

  8. Male mating biology

    Directory of Open Access Journals (Sweden)

    Howell Paul I

    2009-11-01

    Full Text Available Abstract Before sterile mass-reared mosquitoes are released in an attempt to control local populations, many facets of male mating biology need to be elucidated. Large knowledge gaps exist in how both sexes meet in space and time, the correlation of male size and mating success and in which arenas matings are successful. Previous failures in mosquito sterile insect technique (SIT projects have been linked to poor knowledge of local mating behaviours or the selection of deleterious phenotypes during colonisation and long-term mass rearing. Careful selection of mating characteristics must be combined with intensive field trials to ensure phenotypic characters are not antagonistic to longevity, dispersal, or mating behaviours in released males. Success has been achieved, even when colonised vectors were less competitive, due in part to extensive field trials to ensure mating compatibility and effective dispersal. The study of male mating biology in other dipterans has improved the success of operational SIT programmes. Contributing factors include inter-sexual selection, pheromone based attraction, the ability to detect alterations in local mating behaviours, and the effects of long-term colonisation on mating competitiveness. Although great strides have been made in other SIT programmes, this knowledge may not be germane to anophelines, and this has led to a recent increase in research in this area.

  9. The aesthetics of chemical biology.

    Science.gov (United States)

    Parsons, Glenn

    2012-12-01

    Scientists and philosophers have long reflected on the place of aesthetics in science. In this essay, I review these discussions, identifying work of relevance to chemistry and, in particular, to the field of chemical biology. Topics discussed include the role of aesthetics in scientific theory choice, the aesthetics of molecular images, the beauty-making features of molecules, and the relation between the aesthetics of chemical biology and the aesthetics of industrial design.

  10. Researchers Discover Plants Biological Clock

    Institute of Scientific and Technical Information of China (English)

    王全良

    1996-01-01

    Scientists who created glow-in-the-dark plants by shooting up seedlingswith firefly DNA have identified the first biological clock gene in plants. Discovery of the timepiece gene, which controls such biological rhythmsas daily leaf movements and proe openings, flower-blooming schedules andphotosynthesis cycles, could lead to a host of applications in ornamental horti-culture, agriculture and even human health. Many researchers believe that

  11. TCGA and Its Vital Role in Understanding the Landscape of Somatic Alterations in Cancer - TCGA

    Science.gov (United States)

    Dr. Stephen Chanock, M.D., Director of the Division of Cancer Epidemiology & Genetics at the NCI, discusses how TCGA provides a strong foundation for understanding key biological alterations in cancer.

  12. Genomic alterations detected by comparative genomic hybridization in ovarian endometriomas

    Directory of Open Access Journals (Sweden)

    L.C. Veiga-Castelli

    2010-08-01

    Full Text Available Endometriosis is a complex and multifactorial disease. Chromosomal imbalance screening in endometriotic tissue can be used to detect hot-spot regions in the search for a possible genetic marker for endometriosis. The objective of the present study was to detect chromosomal imbalances by comparative genomic hybridization (CGH in ectopic tissue samples from ovarian endometriomas and eutopic tissue from the same patients. We evaluated 10 ovarian endometriotic tissues and 10 eutopic endometrial tissues by metaphase CGH. CGH was prepared with normal and test DNA enzymatically digested, ligated to adaptors and amplified by PCR. A second PCR was performed for DNA labeling. Equal amounts of both normal and test-labeled DNA were hybridized in human normal metaphases. The Isis FISH Imaging System V 5.0 software was used for chromosome analysis. In both eutopic and ectopic groups, 4/10 samples presented chromosomal alterations, mainly chromosomal gains. CGH identified 11q12.3-q13.1, 17p11.1-p12, 17q25.3-qter, and 19p as critical regions. Genomic imbalances in 11q, 17p, 17q, and 19p were detected in normal eutopic and/or ectopic endometrium from women with ovarian endometriosis. These regions contain genes such as POLR2G, MXRA7 and UBA52 involved in biological processes that may lead to the establishment and maintenance of endometriotic implants. This genomic imbalance may affect genes in which dysregulation impacts both eutopic and ectopic endometrium.

  13. Chromophore Deprotonation State Alters the Optical Properties of Blue Chromoprotein.

    Directory of Open Access Journals (Sweden)

    Cheng-Yi Chiang

    Full Text Available Chromoproteins (CPs have unique colors and can be used in biological applications. In this work, a novel blue CP with a maximum absorption peak (λmax at 608 nm was identified from the carpet anemone Stichodactyla gigantea (sgBP. In vivo expression of sgBP in zebrafish would change the appearance of the fishes to have a blue color, indicating the potential biomarker function. To enhance the color properties, the crystal structure of sgBP at 2.25 Å resolution was determined to allow structure-based protein engineering. Among the mutations conducted in the Gln-Tyr-Gly chromophore and chromophore environment, a S157C mutation shifted the λmax to 604 nm with an extinction coefficient (ε of 58,029 M-1·cm-1 and darkened the blue color expression. The S157C mutation in the sgBP chromophore environment could affect the color expression by altering the deprotonation state of the phenolic group in the chromophore. Our results provide a structural basis for the blue color enhancement of the biomarker development.

  14. Altered metabolism of growth hormone receptor mutant mice: a combined NMR metabonomics and microarray study.

    Directory of Open Access Journals (Sweden)

    Horst Joachim Schirra

    Full Text Available BACKGROUND: Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the metabolic consequences of altered growth hormone signalling in mutant mice that have truncations at position 569 and 391 of the intracellular domain of the growth hormone receptor, and thus exhibit either low (around 30% maximum or no growth hormone-dependent STAT5 signalling respectively. These mutations result in altered liver metabolism, obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: The analysis of metabolic changes was performed using microarray analysis of liver tissue and NMR metabonomics of urine and liver tissue. Data were analyzed using multivariate statistics and Gene Ontology tools. The metabolic profiles characteristic for each of the two mutant groups and wild-type mice were identified with NMR metabonomics. We found decreased urinary levels of taurine, citrate and 2-oxoglutarate, and increased levels of trimethylamine, creatine and creatinine when compared to wild-type mice. These results indicate significant changes in lipid and choline metabolism, and were coupled with increased fat deposition, leading to obesity. The microarray analysis identified changes in expression of metabolic enzymes correlating with alterations in metabolite concentration both in urine and liver. Similarity of mutant 569 to the wild-type was seen in young mice, but the pattern of metabolites shifted to that of the 391 mutant as the 569 mice became obese after six months age. CONCLUSIONS/SIGNIFICANCE: The metabonomic observations were consistent with the parallel analysis of gene expression and pathway mapping using microarray data, identifying metabolites and gene transcripts involved in hepatic metabolism, especially for taurine, choline and creatinine metabolism. The systems biology approach applied in this study provides a coherent picture of metabolic changes resulting from impaired STAT5 signalling by the growth hormone

  15. Biological Threats Detection Technologies

    International Nuclear Information System (INIS)

    Among many decisive factors, which can have the influence on the possibility of decreases the results of use biological agents should be mentioned obligatory: rapid detection and identification of biological factor used, the proper preventive treatment and the medical management. The aims of identification: to identify the factor used, to estimate the area of contamination, to evaluate the possible countermeasure efforts (antibiotics, disinfectants) and to assess the effectiveness of the decontamination efforts (decontamination of the persons, equipment, buildings, environment etc.). The objects of identification are: bacteria and bacteria's spores, viruses, toxins and genetically modified factors. The present technologies are divided into: based on PCR techniques (ABI PRISM, APSIS, BIOVERIS, RAPID), immuno (BADD, RAMP, SMART) PCR and immuno techniques (APDS, LUMINEX) and others (BDS2, LUNASCAN, MALDI). The selected technologies assigned to field conditions, mobile and stationary laboratories will be presented.(author)

  16. Biological scaling and physics

    Indian Academy of Sciences (India)

    A R P Rau

    2002-09-01

    Kleiber’s law in biology states that the specific metabolic rate (metabolic rate per unit mass) scales as -1/4 in terms of the mass of the organism. A long-standing puzzle is the (- 1/4) power in place of the usual expectation of (- 1/3) based on the surface to volume ratio in three-dimensions. While recent papers by physicists have focused exclusively on geometry in attempting to explain the puzzle, we consider here a specific law of physics that governs fluid flow to show how the (- 1/4) power arises under certain conditions. More generally, such a line of approach that identifies a specific physical law as involved and then examines the implications of a power law may illuminate better the role of physics in biology.

  17. Biological scaling and physics.

    Science.gov (United States)

    Rau, A R P

    2002-09-01

    Kleiber's law in biology states that the specific metabolic rate (metabolic rate per unit mass) scales as M- 1/4 in terms of the mass M of the organism. A long-standing puzzle is the (- 1/4) power in place of the usual expectation of (- 1/3) based on the surface to volume ratio in three-dimensions. While recent papers by physicists have focused exclusively on geometry in attempting to explain the puzzle, we consider here a specific law of physics that governs fluid flow to show how the (- 1/4) power arises under certain conditions. More generally, such a line of approach that identifies a specific physical law as involved and then examines the implications of a power law may illuminate better the role of physics in biology.

  18. Creating biological nanomaterials using synthetic biology

    International Nuclear Information System (INIS)

    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. (review)

  19. Creating biological nanomaterials using synthetic biology

    Directory of Open Access Journals (Sweden)

    MaryJoe K Rice

    2014-01-01

    Full Text Available 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.

  20. Identifying Fiscal Inflation

    OpenAIRE

    De Graeve, Ferre; Queijo von Heideken, Virginia

    2013-01-01

    Fiscal theorists warn about the risk of future inflation as a consequence of current fiscal imbalances in the US. Because actual inflation remains historically low and data on inflation expectations do not corroborate such risks, warnings for fiscal inflation are often ignored in policy and academic circles. This paper shows that a canonical NK- DSGE model enables identifying an anticipated component of inflation expectations that is closely related to fiscal policy. Estimation results sugges...

  1. Ultrafast Excited-State Dynamics in Biological Environments

    OpenAIRE

    Fürstenberg, Alexandre; Vauthey, Eric

    2007-01-01

    We discuss and illustrate by several examples how the ultrafast excited-state dynamics of a chromophore can be altered when changing its environment from a homogenous solution to a biological molecule such as proteins or nucleic acids.

  2. Microbial colonization and alteration of basaltic glass

    Directory of Open Access Journals (Sweden)

    J. Einen

    2006-03-01

    Full Text Available Microorganisms have been reported to be associated with the alteration of the glassy margin of seafloor pillow basalts (Thorseth et al., 2001, 2003; Lysnes et al., 2004. The amount of iron and other biological important elements present in basalts and the vast abundance of basaltic glass in the earth's crust, make glass alteration an important process in global element cycling. To gain further insight into microbial communities associated with glass alteration, five microcosm experiments mimicking seafloor conditions were inoculated with seafloor basalt and incubated for one year. Mineral precipitations, microbial attachment to the glass and glass alteration were visualized by scanning electron microscopy (SEM, and the bacterial community composition was fingerprinted by PCR and denaturing gradient gel electrophoresis (DGGE in combination with sequencing. SEM analysis revealed a microbial community with low morphological diversity of mainly biofilm associated and prosthecate microorganisms. Approximately 30 nm thick alteration rims developed on the glass in all microcosms after one year of incubation; this however was also seen in non inoculated controls. Calcium carbonate precipitates showed parallel, columnar and filamentous crystallization habits in the microcosms as well as in the sterile controls. DGGE analysis showed an alteration in bacterial community profiles in the five different microcosms, as a response to the different energy and redox regimes and time. In all microcosms a reduction in number of DGGE bands, in combination with an increase in cell abundance were recorded during the experiment. Sequence analysis showed that the microcosms were dominated by four groups of organisms with phylogenetic affiliation to four taxa: The Rhodospirillaceae, a family containing phototrophic marine organisms, in which some members are capable of heterotrophic growth in darkness and N2 fixation; the family Hyphomicrobiaceae, a group

  3. Structural Biology Fact Sheet

    Science.gov (United States)

    ... Home > Science Education > Structural Biology Fact Sheet Structural Biology Fact Sheet Tagline (Optional) Middle/Main Content Area What is structural biology? Structural biology is a field of science focused ...

  4. Experimental Alteration of Basalt to Support Interpretation of Remote Sensing and In Situ Meausrements from Mars

    Science.gov (United States)

    Bell, M. S.

    2014-01-01

    Major occurrences of hydrous alteration minerals on Mars have been found in Noachian impact craters formed in basaltic targets and detected using visible/near infrared (VNIR) spectroscopy. Until recently phyllosilicates were detected only in craters in the southern hemisphere [1, 2]. However, it has been reported that at least nine craters in the northern plains apparently excavated thick layers of lava and sediment to expose phyllosilicates [3] as well. The MER (Mars Exploration Rovers) rovers previously reported results of in situ measurement indicating the presence of alteration minerals on Mars [4,5] and it was recently reported that the Mars Curiosity rover has detected alteration phases in situ at Yellowknife Bay in Gale crater as well [6,7]. An important discovery for Mars geochronology is that the Chemistry and Mineralogy (CheMin) x-ray diffraction (XRD) instrument on Curiosity detected phyllosilicates indicating that phyllosilicate formation on Mars extended beyond the Noachian Epoch [8]. These discoveries indicate that Mars was globally altered by water in the past but does not constrain formation conditions for alteration phase occurrences, which have important implications for the evolution of the surface and the biological potential on Mars. Understanding the alteration assemblages produced by a range of conditions is vital for the interpretation of phyllosilicate spectral signatures as well as in situ measurements and to decipher the environment and evolution of early Mars. The martian surface has been intensely altered by meteorite impacts whose effects include brecciation and melting of target materials as well as the initiation of hydrothermal circulation in a hydrous target [9,10,11,12]. Impact effects may facilitate aqueous alteration of a basaltic target because the rate of silicate dissolution is a function of the degree of crystallinity, surface area, and temperature. The resultant alteration mineralogies from shocked basaltic target material

  5. Simulating Biological and Non-Biological Motion

    Science.gov (United States)

    Bruzzo, Angela; Gesierich, Benno; Wohlschlager, Andreas

    2008-01-01

    It is widely accepted that the brain processes biological and non-biological movements in distinct neural circuits. Biological motion, in contrast to non-biological motion, refers to active movements of living beings. Aim of our experiment was to investigate the mechanisms underlying mental simulation of these two movement types. Subjects had to…

  6. Biological Literacy in a College Biology Classroom.

    Science.gov (United States)

    Demastes, Sherry; Wandersee, James H.

    1992-01-01

    Examines the proposed definition of biological literacy as the understanding of a small number of pervasive biological principles appropriate to making informed personal and societal decisions. Utilizes the content of a major daily newspaper to adjust biology instruction to focus on this notion of biological literacy. Discusses benefits and…

  7. A Brief Introduction to Chinese Biological Biological

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Chinese Biological Abstracts sponsored by the Library, the Shanghai Institutes for Biological Sciences, the Biological Documentation and Information Network, all of the Chinese Academy of Sciences, commenced publication in 1987 and was initiated to provide access to the Chinese information in the field of biology.

  8. Random Cell Identifiers Assignment

    Directory of Open Access Journals (Sweden)

    Robert Bestak

    2012-01-01

    Full Text Available Despite integration of advanced functions that enable Femto Access Points (FAPs to be deployed in a plug-and-play manner, the femtocell concept still cause several opened issues to be resolved. One of them represents an assignment of Physical Cell Identifiers (PCIs to FAPs. This paper analyses a random based assignment algorithm in LTE systems operating in diverse femtocell scenarios. The performance of the algorithm is evaluated by comparing the number of confusions for various femtocell densities, PCI ranges and knowledge of vicinity. Simulation results show that better knowledge of vicinity can significantly reduce the number of confusions events.

  9. MicroRNA Expression Profiling Altered by Variant Dosage of Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Kuei-Fang Lee

    2014-01-01

    Full Text Available Various biological effects are associated with radiation exposure. Irradiated cells may elevate the risk for genetic instability, mutation, and cancer under low levels of radiation exposure, in addition to being able to extend the postradiation side effects in normal tissues. Radiation-induced bystander effect (RIBE is the focus of rigorous research as it may promote the development of cancer even at low radiation doses. Alterations in the DNA sequence could not explain these biological effects of radiation and it is thought that epigenetics factors may be involved. Indeed, some microRNAs (or miRNAs have been found to correlate radiation-induced damages and may be potential biomarkers for the various biological effects caused by different levels of radiation exposure. However, the regulatory role that miRNA plays in this aspect remains elusive. In this study, we profiled the expression changes in miRNA under fractionated radiation exposure in human peripheral blood mononuclear cells. By utilizing publicly available microRNA knowledge bases and performing cross validations with our previous gene expression profiling under the same radiation condition, we identified various miRNA-gene interactions specific to different doses of radiation treatment, providing new insights for the molecular underpinnings of radiation injury.

  10. Mutations in the catalytic loop HRD motif alter the activity and function of Drosophila Src64.

    Directory of Open Access Journals (Sweden)

    Taylor C Strong

    Full Text Available The catalytic loop HRD motif is found in most protein kinases and these amino acids are predicted to perform functions in catalysis, transition to, and stabilization of the active conformation of the kinase domain. We have identified mutations in a Drosophila src gene, src64, that alter the three HRD amino acids. We have analyzed the mutants for both biochemical activity and biological function during development. Mutation of the aspartate to asparagine eliminates biological function in cytoskeletal processes and severely reduces fertility, supporting the amino acid's critical role in enzymatic activity. The arginine to cysteine mutation has little to no effect on kinase activity or cytoskeletal reorganization, suggesting that the HRD arginine may not be critical for coordinating phosphotyrosine in the active conformation. The histidine to leucine mutant retains some kinase activity and biological function, suggesting that this amino acid may have a biochemical function in the active kinase that is independent of its side chain hydrogen bonding interactions in the active site. We also describe the phenotypic effects of other mutations in the SH2 and tyrosine kinase domains of src64, and we compare them to the phenotypic effects of the src64 null allele.

  11. Creating biological nanomaterials using synthetic biology

    OpenAIRE

    MaryJoe K Rice; Ruder, Warren C.

    2014-01-01

    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 bi...

  12. Ultraviolet-B radiation alters phenolic salicylate and flavenoid composition of Populus trichocarpa leaves

    Energy Technology Data Exchange (ETDEWEB)

    Warren, J. M. [USDA Forest Service, Forestry Science Laboratory, Corwallis, OR (United States); Bassman, J. H. [Washington State Univ., Dept. of Natural Resources Sciences, Pullman, WA (United States); Fellman, J. K.; Mattinson, D. S. [Washington State Univ., Dept. of Horticulture and Landscape Architecture, Pullman, WA (United States); Eigenbrode, S. [Idaho Univ., Dept. of Plant, Soil and Entomological Sciences, Moscow, ID (United States)

    2003-06-01

    Foliar phenolic composition of field- and greenhouse-grown black cottonwood was studied by subjecting samples to near zero, ambient and twice-ambient concentrations of biologically effective ultraviolet-B radiation. Phenolic compounds were extracted after three months, separated by liquid chromatography and identified and quantified by diode-array spectrometry and mass spectrometry. Phenolic compounds that were found to have increased in response to UV-B radiation were flavonoids, although increasing the level of radiation to ambient and twice ambient levels did not result in further flavonoid accumulation in either greenhouse or field samples. There was, however, an increase in salicortin, a non-flavonoid glycoside, and a salicylates that is important in plant-herbivore-predator relationships. It was concluded that enhanced solar UV-B radiation has the capacity to significantly alter trophic structure in some ecosystems by stimulating specific phenolic compounds. 74 refs., 1 tab., 6 figs.

  13. Bioerosion by chemosynthetic biological communities on Holocene submarine slide scars

    Science.gov (United States)

    Paull, C. K.; Ussler, W.; Greene, H. G.; Barry, J.; Keaten, R.

    2005-02-01

    Geomorphic, stratigraphic, and faunal observations of submarine slide scars that occur along the flanks of Monterey Canyon in 2.0 2.5 km water depths were made to identify the processes that continue to alter the surface of a submarine landslide scar after the initial slope failure. Deep-sea chemosynthetic biological communities and small caves are common on the sediment-free surfaces of the slide scars, especially along the headwall. The chemosynthetic organisms observed on slide scars in Monterey Canyon undergo a faunal succession based in part on their ability to maintain their access to the redox boundaries in the sediment on which they depend on as an energy source. By burrowing into the seafloor, these organisms are able to follow the retreating redox boundaries as geochemical re-equilibration occurs on the sole of the slide. As these organisms dig into the seafloor on the footwall, they often generate small caves and weaken the remaining seafloor. While chemosynthetic biological communities are typically used as indicators of fluid flow, these communities may be supported by methane and hydrogen sulfide that are diffusing out of the fresh seafloor exposed at the sole of the slide by the slope failure event. If so, these chemosynthetic biological communities may simply mark sites of recent seafloor exhumation, and are not reliable fluid seepage indicators.

  14. Fostering synergy between cell biology and systems biology.

    Science.gov (United States)

    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.

  15. Review: 2-mercaptoethanol alteration of in vitro immune functions of species other than murine.

    Science.gov (United States)

    Click, Robert E

    2014-01-15

    Descriptions that organosulfurs could alter biologically relevant cellular functions began some 40years ago when cell mediated and humoral murine in vitro immune responses were reported to be dramatically enhanced by any of four xenobiotic, sulfhydryl compounds-2-mercaptoethanol (2-ME), dithiothreitol, glutathione, and l-cysteine; the most effective of the four was 2-ME. These findings triggered a plethora of reports defining 2-ME benefits for a multitude of immunological processes, primarily with murine models. This led to investigations on 2-ME alterations of (a) immune functions in other species, (b) activities of other cell-types, and (c) in situ diseases. In addition, the early findings may have been instrumental in the identification of the previously undefined anticarcinogenic chemicals in specific foods as organosulfurs. Outside the plant organosulfurs, there are no comprehensive reviews of these areas to help define mechanisms by which organosulfurs function as well as identify potential alternative uses. Therefore, the present review will focus on 2-ME alterations of in vitro immune functions in species other than murine; namely, fish, amphibian, reptile, avian, whales, dolphins, rat, hamster, rabbit, guinea pig, feline, canine, porcine, ovine, bovine, and human. Processes, some unique to a given species, were in general, enhanced and in some cases dependent upon the presence of 2-ME. The largest benefits occurred in media that were serum free, followed by those in autologous serum and then fetal bovine serum supplemented medium. Concentrations of 2-ME were generally in the low μM range, with exceptions of those for salamander (20mM), turtles (70mM) and dolphins (7mM). The few studies designed to assess mechanisms found that changes induced by 2-ME were generally accompanied by alterations of reduced/oxidized glutathione cellular concentrations. The major benefit for most studies, however, was to increase the sensitivity of the culture environment, which

  16. Epigenetic alterations in gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    In-Seon CHOI; Tsung-Teh WU

    2005-01-01

    Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play important roles in gastric carcinogenesis. This review will briefly discuss the basic aspects of DNA methylation and CpG island methylation, in particular the epigenetic alterations of certain critical genes implicated in gastric carcinogenesis and its relevance of clinical implications.

  17. Cell biology perspectives in phage biology.

    Science.gov (United States)

    Ansaldi, Mireille

    2012-01-01

    Cellular biology has long been restricted to large cellular organisms. However, as the resolution of microscopic methods increased, it became possible to study smaller cells, in particular bacterial cells. Bacteriophage biology is one aspect of bacterial cell biology that has recently gained insight from cell biology. Despite their small size, bacteriophages could be successfully labeled and their cycle studied in the host cells. This review aims to put together, although non-extensively, several cell biology studies that recently pushed the elucidation of key mechanisms in phage biology, such as the lysis-lysogeny decision in temperate phages or genome replication and transcription, one step further.

  18. Tunable promoters in synthetic and systems biology

    DEFF Research Database (Denmark)

    Dehli, Tore; Solem, Christian; Jensen, Peter Ruhdal

    2012-01-01

    in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available......Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central...... for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression...

  19. Pulmonary alterations in Behcet's disease

    International Nuclear Information System (INIS)

    Purpose: This study aims to demonstrate pulmonary alterations (PA) in patients with Behcet's disease by using CT. Materials and methods: CTs of 50 patients with Behcet's disease and 20 others in a control group have been evaluated retrospectively for PA (septal, reticular, nodular, atelectatic opacities). Results: Eight out of 50 patients (16%) with Behcet's disease showed PA. Three out of 20 (15%) in the control group showed PA. No differences were observed between Behcet's disease patients and the control group regarding pulmonary alterations (p = 0.917). No differences were observed in the disease duration, ages and sex in either group in those with and without PA. Conclusion: Pulmonary alterations can be seen in patients with Behcet's disease, but these alterations are not significant.

  20. Dominating biological networks.

    Directory of Open Access Journals (Sweden)

    Tijana Milenković

    Full Text Available Proteins are essential macromolecules of life that carry out most cellular processes. Since proteins aggregate to perform function, and since protein-protein interaction (PPI networks model these aggregations, one would expect to uncover new biology from PPI network topology. Hence, using PPI networks to predict protein function and role of protein pathways in disease has received attention. A debate remains open about whether network properties of "biologically central (BC" genes (i.e., their protein products, such as those involved in aging, cancer, infectious diseases, or signaling and drug-targeted pathways, exhibit some topological centrality compared to the rest of the proteins in the human PPI network.To help resolve this debate, we design new network-based approaches and apply them to get new insight into biological function and disease. We hypothesize that BC genes have a topologically central (TC role in the human PPI network. We propose two different concepts of topological centrality. We design a new centrality measure to capture complex wirings of proteins in the network that identifies as TC those proteins that reside in dense extended network neighborhoods. Also, we use the notion of domination and find dominating sets (DSs in the PPI network, i.e., sets of proteins such that every protein is either in the DS or is a neighbor of the DS. Clearly, a DS has a TC role, as it enables efficient communication between different network parts. We find statistically significant enrichment in BC genes of TC nodes and outperform the existing methods indicating that genes involved in key biological processes occupy topologically complex and dense regions of the network and correspond to its "spine" that connects all other network parts and can thus pass cellular signals efficiently throughout the network. To our knowledge, this is the first study that explores domination in the context of PPI networks.

  1. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

    Science.gov (United States)

    Maroto Rey, José Pablo; Cillán Narvaez, Elena

    2013-06-01

    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  2. Alterations in the nuclear proteome of HIV-1 infected T-cells

    Energy Technology Data Exchange (ETDEWEB)

    DeBoer, Jason [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Jagadish, Teena; Haverland, Nicole A. [Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198 (United States); Madson, Christian J. [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); Ciborowski, Pawel [Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198 (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln 68583 (United States); Belshan, Michael, E-mail: michaelbelshan@creighton.edu [Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States); The Nebraska Center for Virology, University of Nebraska, Lincoln 68583 (United States)

    2014-11-15

    Virus infection of a cell involves the appropriation of host factors and the innate defensive response of the cell. The identification of proteins critical for virus replication may lead to the development of novel, cell-based inhibitors. In this study we mapped the changes in T-cell nuclei during human immunodeficiency virus type 1 (HIV-1) at 20 hpi. Using a stringent data threshold, a total of 13 and 38 unique proteins were identified in infected and uninfected cells, respectively, across all biological replicates. An additional 15 proteins were found to be differentially regulated between infected and control nuclei. STRING analysis identified four clusters of protein–protein interactions in the data set related to nuclear architecture, RNA regulation, cell division, and cell homeostasis. Immunoblot analysis confirmed the differential expression of several proteins in both C8166-45 and Jurkat E6-1 T-cells. These data provide a map of the response in host cell nuclei upon HIV-1 infection. - Highlights: • We identify changes in the expression of nuclear proteins during HIV-1 infection. • 163 nuclear proteins were found differentially regulated during HIV-1 infection. • Bioinformatic analysis identified several nuclear pathways altered by HIV infection. • Candidate factors were validated in two independent cell lines.

  3. Cardiovascular toxicities of biological therapies

    DEFF Research Database (Denmark)

    Ryberg, Marianne

    2013-01-01

    The development of biological therapy is based on growing knowledge regarding the molecular changes required in cells for the development and progression of cancer to occur. Molecular targeted therapy is designed to inhibit the major molecular pathways identified as essential for a specific devel...

  4. The landscape of somatic copy-number alteration across human cancers

    OpenAIRE

    Beroukhim, Rameen; Mermel, Craig H.; Porter, Dale; Wei, Guo; Raychaudhuri, Soumya; Donovan, Jerry; Barretina, Jordi; Boehm, Jesse S.; Dobson, Jennifer; Urashima, Mitsuyoshi; Mc Henry, Kevin T.; Pinchback, Reid M.; Ligon, Azra H.; Cho, Yoon-Jae; Haery, Leila

    2010-01-01

    A powerful way to discover key genes playing causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here, we report high-resolution analyses of somatic copy-number alterations (SCNAs) from 3131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across multiple cancer types, of which 122 cannot be explained by the presence of a known cancer target ge...

  5. Biological effects of radiation

    International Nuclear Information System (INIS)

    This fourth chapter presents: cell structure and metabolism; radiation interaction with biological tissues; steps of the production of biological effect of radiation; radiosensitivity of tissues; classification of biological effects; reversibility, transmissivity and influence factors; pre-natal biological effects; biological effects in therapy and syndrome of acute irradiation

  6. Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment?

    Science.gov (United States)

    Biological monitoring has become a standard approach to exposure assessment in occupational and environmental epidemiology. The use of biological effect markers to identify early adverse changes in target organs has also become widely adopted. Recently, nephrotoxicant research us...

  7. Digital Identifier Systems: Comparative Evaluation

    OpenAIRE

    Hamid Reza Khedmatgozar; Mehdi Alipour-Hafezi; Payam Hanafizadeh

    2015-01-01

    Identifier is one of the main elements in identifying an object in digital environment. Digital identifier systems were developed followed by a lot of problems such as violation of persistency and uniqueness of physical identifiers and URL in digital environment. These identifiers try to guarantee uniqueness and persistency of hostnames by using indirect names for Domain Name System (DNS). The main objective of this research is to identify qualified digital identifier system among other syste...

  8. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server

    2012-01-01

    Computational modeling is emerging as a powerful new approach for studying and manipulating biological systems. Many diverse methods have been developed to model, visualize, and rationally alter these systems at various length scales, from atomic resolution to the level of cellular pathways. Processes taking place at larger time and length scales, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. Computational Modeling of Biological Systems: From Molecules to Pathways provides an overview of established computational methods for the modeling of biologically and medically relevant systems. It is suitable for researchers and professionals working in the fields of biophysics, computational biology, systems biology, and molecular medicine.

  9. Systems Biology in Aging: Linking the Old and the Young

    OpenAIRE

    HOU, LEI; Huang, Jialiang; Green, Christopher D.; Boyd-Kirkup, Jerome; Zhang, Wei; Yu, Xiaoming; Gong, Wenxuan; Zhou, Bing; Jing-Dong J Han

    2012-01-01

    Aging can be defined as a process of progressive decline in the physiological capacity of an organism, manifested by accumulated alteration and destabilization at the whole system level. Systems biology approaches offer a promising new perspective to examine the old problem of aging. We begin this review by introducing the concepts of systems biology, and then illustrate the application of systems biology approaches to aging research, from gene expression profiling to network analysis. We the...

  10. Grand challenges in space synthetic biology

    OpenAIRE

    Menezes, Amor A.; Montague, Michael G.; Cumbers, John; Hogan, John A.; Arkin, Adam P.

    2015-01-01

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the...

  11. Culture, Urbanism and Changing Human Biology

    Science.gov (United States)

    Schell, L.M.

    2014-01-01

    Anthropologists have long known that human activity driven by culture changes the environment. This is apparent in the archaeological record and through the study of the modern environment. Perhaps the largest change since the paleolithic era is the organization of human populations in cities. New environments can reshape human biology through evolution as shown by the evolution of the hominid lineage. Evolution is not the only process capable of reshaping our biology. Some changes in our human biology are adaptive and evolutionary while others are pathological. What changes in human biology may be wrought by the modern urban environment? One significant new change in the environment is the introduction of pollutants largely through urbanization. Pollutants can affect human biology in myriad ways. Evidence shows that human growth, reproduction, and cognitive functioning can be altered by some pollutants, and altered in different ways depending on the pollutant. Thus, pollutants have significance for human biologists and anthropologists generally. Further, they illustrate the bio-cultural interaction characterizing human change. Humans adapt by changing the environment, a cultural process, and then change biologically to adjust to that new environment. This ongoing, interactive process is a fundamental characteristic of human change over the millennia. PMID:25598655

  12. Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment.

    Science.gov (United States)

    Ramo-Fernández, Laura; Schneider, Anna; Wilker, Sarah; Kolassa, Iris-Tatjana

    2015-10-01

    Survivors of war trauma or childhood maltreatment are at increased risk for trauma-spectrum disorders such as post-traumatic stress disorder (PTSD). In addition, traumatic stress has been associated with alterations in the neuroendocrine and the immune system, enhancing the risk for physical diseases. Traumatic experiences might even affect psychological as well as biological parameters in the next generation, i.e. traumatic stress might have transgenerational effects. This article outlines how epigenetic processes, which represent a pivotal biological mechanism for dynamic adaptation to environmental challenges, might contribute to the explanation of the long-lasting and transgenerational effects of trauma. In particular, epigenetic alterations in genes regulating the hypothalamus-pituitary-adrenal axis as well as the immune system have been observed in survivors of childhood and adult trauma. These changes could result in enduring alterations of the stress response as well as the physical health risk. Furthermore, the effects of parental trauma could be transmitted to the next generation by parental distress and the pre- and postnatal environment, as well as by epigenetic marks transmitted via the germline. While epigenetic research has a high potential of advancing our understanding of the consequences of trauma, the findings have to be interpreted with caution, as epigenetics only represent one piece of a complex puzzle of interacting biological and environmental factors. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Efflux Pump Control Alters Synthetic Gene Circuit Function.

    Science.gov (United States)

    Diao, Junchen; Charlebois, Daniel A; Nevozhay, Dmitry; Bódi, Zoltán; Pál, Csaba; Balázsi, Gábor

    2016-07-15

    Synthetic biology aims to design new biological systems for predefined purposes, such as the controlled secretion of biofuels, pharmaceuticals, or other chemicals. Synthetic gene circuits regulating an efflux pump from the ATP-binding cassette (ABC) protein family could achieve this. However, ABC efflux pumps can also drive out intracellular inducer molecules that control the gene circuits. This will introduce an implicit feedback that could alter gene circuit function in ways that are poorly understood. Here, we used two synthetic gene circuits inducible by tetracycline family molecules to regulate the expression of a yeast ABC pump (Pdr5p) that pumps out the inducer. Pdr5p altered the dose-responses of the original gene circuits substantially in Saccharomyces cerevisiae. While one aspect of the change could be attributed to the efflux pumping function of Pdr5p, another aspect remained unexplained. Quantitative modeling indicated that reduced regulator gene expression in addition to efflux pump function could fully explain the altered dose-responses. These predictions were validated experimentally. Overall, we highlight how efflux pumps can alter gene circuit dynamics and demonstrate the utility of mathematical modeling in understanding synthetic gene circuit function in new circumstances. PMID:27111147

  14. The biology of melanoma prognostic factors.

    NARCIS (Netherlands)

    Spatz, A.; Stock, N.; Batist, G.; Kempen, L.C.L.T. van

    2010-01-01

    Cutaneous melanoma still represents a paradox among all solid tumors. It is the cancer for which the best prognostic markers ever identified in solid tumors are available, yet there is very little understanding of their biological significance. This review focuses on recent biological data that shed

  15. Biology Education Research: Lessons and Future Directions

    OpenAIRE

    Singer, Susan R.; Nielsen, Natalie R.; Schweingruber, Heidi A.

    2013-01-01

    This feature draws on a 2012 National Research Council report to highlight some of the insights that discipline-based education research in general—and biology education research in particular—have provided into the challenges of undergraduate science education. It identifies strategies for overcoming those challenges and future directions for biology education research.

  16. Traceability of Biologics in The Netherlands

    DEFF Research Database (Denmark)

    Klein, Kevin; Scholl, Joep H G; Vermeer, Niels S;

    2016-01-01

    INTRODUCTION AND OBJECTIVE: Pharmacovigilance requirements for biologics mandate that EU Member States shall ensure that any biologic that is the subject of a suspected adverse drug reaction (ADR) is identifiable by brand name and batch number. Recent studies showed that brand name identification...

  17. Alterations in Cell Signaling Pathways in Breast Cancer Cells after Environmental Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kulp, K; McCutcheon-Maloney, S M; Bennett, L M

    2003-02-01

    Recent human epidemiological studies suggest that up to 75% of human cancers can be attributed to environmental exposures. Understanding the biologic impact of being exposed to a lifetime of complex environmental mixtures that may not be fully characterized is currently a major challenge. Functional endpoints may be used to assess the gross health consequences of complex mixture exposures from groundwater contamination, superfund sites, biologic releases, or nutritional sources. Such endpoints include the stimulation of cell growth or the induction of a response in an animal model. An environmental exposure that upsets normal cell growth regulation may have important ramifications for cancer development. Stimulating cell growth may alter an individual's cancer risk by changing the expression of genes and proteins that have a role in growth regulatory pathways within cells. Modulating the regulation of these genes and their products may contribute to the initiation, promotion or progression of disease in response to environmental exposure. We are investigating diet-related compounds that induce cell proliferation in breast cancer cell lines. These compounds, PhIP, Flor-Essence{reg_sign} and Essiac{reg_sign}, may be part of an everyday diet. PhIP is a naturally occurring mutagen that is formed in well-cooked muscle meats. PhIP consistently causes dose-dependent breast tumor formation in rats and consumption of well-done meat has been linked to increased risk of breast cancer in women. Flor-Essence{reg_sign} and Essiac{reg_sign} herbal tonics are complementary and alternative medicines used by women who have been diagnosed with breast cancer as an alternative therapy for disease treatment and prevention. The long-term goal of this work is to identify those cellular pathways that are altered by a chemical or biologic environmental exposure and understand how those changes correlate with and or predict changes in human health risk. This project addressed this goal

  18. Effect of single-point sequence alterations on the aggregationpropensity of a model protein

    Energy Technology Data Exchange (ETDEWEB)

    Bratko, Dusan; Cellmer, Troy; Prausnitz, John M.; Blanch, Harvey W.

    2005-10-07

    Sequences of contemporary proteins are believed to have evolved through process that optimized their overall fitness including their resistance to deleterious aggregation. Biotechnological processing may expose therapeutic proteins to conditions that are much more conducive to aggregation than those encountered in a cellular environment. An important task of protein engineering is to identify alternative sequences that would protect proteins when processed at high concentrations without altering their native structure associated with specific biological function. Our computational studies exploit parallel tempering simulations of coarse-grained model proteins to demonstrate that isolated amino-acid residue substitutions can result in significant changes in the aggregation resistance of the protein in a crowded environment while retaining protein structure in isolation. A thermodynamic analysis of protein clusters subject to competing processes of folding and association shows that moderate mutations can produce effects similar to those caused by changes in system conditions, including temperature, concentration, and solvent composition that affect the aggregation propensity. The range of conditions where a protein can resist aggregation can therefore be tuned by sequence alterations although the protein generally may retain its generic ability for aggregation.

  19. Genomic Effect of Triclosan on the Fetal Hypothalamus: Evidence for Altered Neuropeptide Regulation.

    Science.gov (United States)

    Rabaglino, Maria Belen; Chang, Eileen I; Richards, Elaine M; James, Margaret O; Keller-Wood, Maureen; Wood, Charles E

    2016-07-01

    Triclosan (TCS), an antibacterial compound commonly added to personal care products, could be an endocrine disruptor at low doses. Although TCS has been shown to alter fetal physiology, its effects in the developing fetal brain are unknown. We hypothesize that exposure to TCS during fetal life could affect fetal hypothalamic gene expression. The objective of this study was to use transcriptomics and systems analysis to identify significantly altered biological processes in the late gestation ovine fetal hypothalamus after direct or indirect exposure to low doses of TCS. For direct TCS exposure, chronically catheterized late gestation fetal sheep were infused with vehicle (n = 4) or TCS (250 μg/d; n = 4) iv. For indirect TCS exposure, TCS (100 μg/kg · d; n = 3) or vehicle (n = 3) was infused into the maternal circulation. Fetal hypothalami were collected after 2 days of infusion, and gene expression was measured through microarray. Hierarchical clustering of all samples according to gene expression profiles showed that samples from the TCS-treated animals clustered apart from the controls. Gene set enrichment analysis revealed that fetal hypothalamic genes stimulated by maternal and fetal TCS infusion were significantly enriching for cell cycle, reproductive process, and feeding behavior, whereas the inhibited genes were significantly enriching for chromatin modification and metabolism of steroids, lipoproteins, fatty acids, and glucose (P food intake pathways and metabolism. If these changes persist to postnatal life, they could result in adverse consequences in adulthood. PMID:27145008

  20. Identifying Botanical Mechanisms of Action

    Science.gov (United States)

    Toh, May Fern

    2010-01-01

    The biological mechanism of action for any botanical extract is a necessary part of discovery to determine pharmacological use and safety. Interestingly, many activities that are governed by endogenous compounds are not fully understood making the characterization of mechanisms elusive. For example, phytoestrogens are being consumed for menopausal symptoms while the biological action of estradiol are still being investigated. Therefore, long term efficacy and safety issues are a challenge in the field. As new activities are associated with new biological pathways, an important component of therapeutic discovery will need to be the re-evaluation of negative or less active natural products to determine their relative use as medicines. PMID:20837111

  1. Studies of Complex Biological Systems with Applications to Molecular Medicine: The Need to Integrate Transcriptomic and Proteomic Approaches

    Directory of Open Access Journals (Sweden)

    Elena Silvestri

    2011-01-01

    Full Text Available Omics approaches to the study of complex biological systems with potential applications to molecular medicine are attracting great interest in clinical as well as in basic biological research. Genomics, transcriptomics and proteomics are characterized by the lack of an a priori definition of scope, and this gives sufficient leeway for investigators (a to discern all at once a globally altered pattern of gene/protein expression and (b to examine the complex interactions that regulate entire biological processes. Two popular platforms in “omics” are DNA microarrays, which measure messenger RNA transcript levels, and proteomic analyses, which identify and quantify proteins. Because of their intrinsic strengths and weaknesses, no single approach can fully unravel the complexities of fundamental biological events. However, an appropriate combination of different tools could lead to integrative analyses that would furnish new insights not accessible through one-dimensional datasets. In this review, we will outline some of the challenges associated with integrative analyses relating to the changes in metabolic pathways that occur in complex pathophysiological conditions (viz. ageing and altered thyroid state in relevant metabolically active tissues. In addition, we discuss several new applications of proteomic analysis to the investigation of mitochondrial activity.

  2. A test of biological trait analysis with nematodes and an anthropogenic stressor.

    Science.gov (United States)

    Mitwally, Hanan M; Fleeger, John W

    2016-03-01

    Aquatic ecosystems are fundamentally altered by nutrient enrichment, and effective monitoring tools are needed to detect biological responses especially in the early stages of eutrophication. We tested the utility of biological trait analysis (BTA) to quantify the temporal responses of nematodes inhabiting salt marsh creeks that were experimentally enriched with nutrients for 6 years. Feeding, body shape, and tail shape traits were characterized on >6000 nematodes from annual samples from enriched and non-enriched sites. Here, we ask if trait combinations are more effective than single traits in detecting the magnitude and rate of change. We also sought to identify combinations of traits that best distinguish natural from nutrient-induced variation. BTA revealed that feeding, body shape, and all traits combined equally detected the response to nutrient enrichment. Compared to single traits however, BTAs were more sensitive to temporal trends and better distinguished natural variation from the response to nutrient enrichment. Tail shape traits (that might respond to altered sediment texture or geochemistry) were not affected by enrichment, and feeding traits yielded the greatest difference between enriched and reference communities indicating that changes in food resources drove responses. Feeding traits provided the highest quality information content in our study, and the use of feeding traits alone may adequately identify anthropogenic effects in many studies. However, we caution that body shape, tail shape, and feeding traits were strongly interrelated at our study site, and a diversity of trait groups may increase the information content of BTAs in more diverse habitats.

  3. Clinical and Biological Risk Factors for Neuropsychological Impairment in Alcohol Use Disorder.

    Science.gov (United States)

    Ritz, Ludivine; Coulbault, Laurent; Lannuzel, Coralie; Boudehent, Céline; Segobin, Shailendra; Eustache, Francis; Vabret, François; Pitel, Anne Lise; Beaunieux, Hélène

    2016-01-01

    The effects of alcoholism on cognitive and motor functioning are heterogeneous. While the role of some factors (patterns of alcohol consumption, eating habits or associated liver disease) has been hypothesized, the origins of this heterogeneity remain difficult to establish. The goals of the present study were thus to identify the clinical and biological risk factors for alcohol-related neuropsychological impairments and to determine the threshold beyond which these risk factors can be considered significant. Thirty alcoholic patients and 15 healthy controls had a blood test and underwent a neuropsychological examination. Alcohol severity measures, and liver, thiamine and malnutrition variables, were included in logistic regression models to determine the risk factors for cognitive and motor impairments (executive functions, visuospatial abilities, verbal episodic memory, ataxia), as well as those related to the severity of patients' overall neuropsychological profile (moderate or severe impairments). Liver fibrosis was found to be a risk factor for executive impairments and also for ataxia, when it was associated with long-term alcohol misuse and symptoms of withdrawal. Altered thiamine metabolism was solely predictive of verbal episodic memory impairments. This combination of biological abnormalities was associated with a profile of moderate neuropsychological impairments. Malnutrition was associated with a profile of more severe impairments. Malnutrition, altered liver function and thiamine metabolism explain, at least partially, the heterogeneity of alcohol-related neuropsychological impairments. Our findings could allow clinicians to identify patients at particular risk of severe neuropsychological impairments before the onset of irreversible and debilitating neurological complications. PMID:27617840

  4. A test of biological trait analysis with nematodes and an anthropogenic stressor.

    Science.gov (United States)

    Mitwally, Hanan M; Fleeger, John W

    2016-03-01

    Aquatic ecosystems are fundamentally altered by nutrient enrichment, and effective monitoring tools are needed to detect biological responses especially in the early stages of eutrophication. We tested the utility of biological trait analysis (BTA) to quantify the temporal responses of nematodes inhabiting salt marsh creeks that were experimentally enriched with nutrients for 6 years. Feeding, body shape, and tail shape traits were characterized on >6000 nematodes from annual samples from enriched and non-enriched sites. Here, we ask if trait combinations are more effective than single traits in detecting the magnitude and rate of change. We also sought to identify combinations of traits that best distinguish natural from nutrient-induced variation. BTA revealed that feeding, body shape, and all traits combined equally detected the response to nutrient enrichment. Compared to single traits however, BTAs were more sensitive to temporal trends and better distinguished natural variation from the response to nutrient enrichment. Tail shape traits (that might respond to altered sediment texture or geochemistry) were not affected by enrichment, and feeding traits yielded the greatest difference between enriched and reference communities indicating that changes in food resources drove responses. Feeding traits provided the highest quality information content in our study, and the use of feeding traits alone may adequately identify anthropogenic effects in many studies. However, we caution that body shape, tail shape, and feeding traits were strongly interrelated at our study site, and a diversity of trait groups may increase the information content of BTAs in more diverse habitats. PMID:26846290

  5. Human strongyloidiasis: identifying knowledge gaps, with emphasis on environmental control

    Directory of Open Access Journals (Sweden)

    Taylor MJ

    2014-08-01

    Full Text Available Michael J Taylor, Tara A Garrard, Francis J O'Donahoo, Kirstin E Ross Health and Environment, School of the Environment, Flinders University, Adelaide, SA, Australia Abstract: Strongyloides is a human parasitic nematode that is poorly understood outside a clinical context. This article identifies gaps within the literature, with particular emphasis on gaps that are hindering environmental control of Strongyloides. The prevalence and distribution of Strongyloides is unclear. An estimate of 100–370 million people infected worldwide has been proposed; however, inaccuracy of diagnosis, unreliability of prevalence mapping, and the fact that strongyloidiasis remains a neglected disease suggest that the higher figure of more than 300 million cases is likely to be a more accurate estimate. The complexity of Strongyloides life cycle means that laboratory cultures cannot be maintained outside of a host. This currently limits the range of laboratory-based research, which is vital to controlling Strongyloides through environmental alteration or treatment. Successful clinical treatment with antihelminthic drugs has meant that controlling Strongyloides through environmental control, rather than clinical intervention, has been largely overlooked. These control measures may encompass alteration of the soil environment through physical means, such as desiccation or removal of nutrients, or through chemical or biological agents. Repeated antihelminthic treatment of individuals with recurrent strongyloidiasis has not been observed to result in the selection of resistant strains; however, this has not been explicitly demonstrated, and relying on such assumptions in the long-term may prove to be shortsighted. It is ultimately naive to assume that continued administration of antihelminthics will be without any negative long-term effects. In Australia, strongyloidiasis primarily affects Indigenous communities, including communities from arid central Australia. This

  6. Neutron structural biology

    Energy Technology Data Exchange (ETDEWEB)

    Niimura, Nobuo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-03-01

    Neutron diffraction provides an experimental method of directly locating hydrogen atoms in protein which play important roles in physiological functions. However, there are relatively few examples of neutron crystallography in biology since it takes a lot of time to collect a sufficient number of Bragg reflections due to the low flux of neutrons illuminating the sample. In order to overcome the flux problem, we have successfully developed the neutron IP, where the neutron converter, {sup 6}Li or Gd, was mixed with a photostimulated luminescence material on flexible plastic support. Neutron Laue diffraction 2A data from tetragonal lysozyme were collected for 10 days with neutron imaging plates, and 960 hydrogen atoms in the molecule and 157 bound water molecules were identified. These results explain the proposed hydrolysis mechanism of the sugar by the lysozyme molecule and that lysozyme is less active at pH7.0. (author)

  7. The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing

    Institute of Scientific and Technical Information of China (English)

    Alexander W Wyatt; Fan Mo; Yuzhuo Wang; Colin C Collins

    2013-01-01

    Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity.In recent years,the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression.It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity,where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity.This review dissects our current understanding of prostate cancer ‘omics',including the sentinel role of copy number variation,the growing spectrum of oncogenic fusion genes,the potential influence of chromothripsis,and breakthroughs in defining mutation-associated subtypes.Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways,yet recurrent gene aberration appears rare.Therefore,it is critical that we continue to define individual tumour genomes,especially in the context of their expressed transcriptome.Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.

  8. Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

    Directory of Open Access Journals (Sweden)

    Jing Xia

    2014-01-01

    Full Text Available In late-onset Alzheimer’s disease (AD, multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC, hippocampus (HIP, posterior cingulate cortex (PCC, and middle temporal gyrus (MTG. We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with low topological overlap (TO of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.

  9. Art as Alterity in Education

    Science.gov (United States)

    Zhao, Guoping

    2014-01-01

    In education, art has often been perceived as entertainment and decoration and is the first subject to go when there are budget cuts or test-score pressures. Drawing on Emmanuel Lévinas's idea of the primacy of radical alterity that breaks the totality of our being, enables self-transformation and ethics, and ensures community as a totality…

  10. Grand challenges in space synthetic biology.

    Science.gov (United States)

    Menezes, Amor A; Montague, Michael G; Cumbers, John; Hogan, John A; Arkin, Adam P

    2015-12-01

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth. PMID:26631337

  11. Grand challenges in space synthetic biology.

    Science.gov (United States)

    Menezes, Amor A; Montague, Michael G; Cumbers, John; Hogan, John A; Arkin, Adam P

    2015-12-01

    Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth.

  12. Comparison of Modules of Wild Type and Mutant Huntingtin and TP53 Protein Interaction Networks: Implications in Biological Processes and Functions

    Science.gov (United States)

    Basu, Mahashweta; Bhattacharyya, Nitai P.; Mohanty, Pradeep K.

    2013-01-01

    Disease-causing mutations usually change the interacting partners of mutant proteins. In this article, we propose that the biological consequences of mutation are directly related to the alteration of corresponding protein protein interaction networks (PPIN). Mutation of Huntingtin (HTT) which causes Huntington's disease (HD) and mutations to TP53 which is associated with different cancers are studied as two example cases. We construct the PPIN of wild type and mutant proteins separately and identify the structural modules of each of the networks. The functional role of these modules are then assessed by Gene Ontology (GO) enrichment analysis for biological processes (BPs). We find that a large number of significantly enriched () GO terms in mutant PPIN were absent in the wild type PPIN indicating the gain of BPs due to mutation. Similarly some of the GO terms enriched in wild type PPIN cease to exist in the modules of mutant PPIN, representing the loss. GO terms common in modules of mutant and wild type networks indicate both loss and gain of BPs. We further assign relevant biological function(s) to each module by classifying the enriched GO terms associated with it. It turns out that most of these biological functions in HTT networks are already known to be altered in HD and those of TP53 networks are altered in cancers. We argue that gain of BPs, and the corresponding biological functions, are due to new interacting partners acquired by mutant proteins. The methodology we adopt here could be applied to genetic diseases where mutations alter the ability of the protein to interact with other proteins. PMID:23741403

  13. Synthetic biology: insights into biological computation.

    Science.gov (United States)

    Manzoni, Romilde; Urrios, Arturo; Velazquez-Garcia, Silvia; de Nadal, Eulàlia; Posas, Francesc

    2016-04-18

    Organisms have evolved a broad array of complex signaling mechanisms that allow them to survive in a wide range of environmental conditions. They are able to sense external inputs and produce an output response by computing the information. Synthetic biology attempts to rationally engineer biological systems in order to perform desired functions. Our increasing understanding of biological systems guides this rational design, while the huge background in electronics for building circuits defines the methodology. In this context, biocomputation is the branch of synthetic biology aimed at implementing artificial computational devices using engineered biological motifs as building blocks. Biocomputational devices are defined as biological systems that are able to integrate inputs and return outputs following pre-determined rules. Over the last decade the number of available synthetic engineered devices has increased exponentially; simple and complex circuits have been built in bacteria, yeast and mammalian cells. These devices can manage and store information, take decisions based on past and present inputs, and even convert a transient signal into a sustained response. The field is experiencing a fast growth and every day it is easier to implement more complex biological functions. This is mainly due to advances in in vitro DNA synthesis, new genome editing tools, novel molecular cloning techniques, continuously growing part libraries as well as other technological advances. This allows that digital computation can now be engineered and implemented in biological systems. Simple logic gates can be implemented and connected to perform novel desired functions or to better understand and redesign biological processes. Synthetic biological digital circuits could lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels. Biological computation not only provides possible biomedical and

  14. Synthetic biology: insights into biological computation.

    Science.gov (United States)

    Manzoni, Romilde; Urrios, Arturo; Velazquez-Garcia, Silvia; de Nadal, Eulàlia; Posas, Francesc

    2016-04-18

    Organisms have evolved a broad array of complex signaling mechanisms that allow them to survive in a wide range of environmental conditions. They are able to sense external inputs and produce an output response by computing the information. Synthetic biology attempts to rationally engineer biological systems in order to perform desired functions. Our increasing understanding of biological systems guides this rational design, while the huge background in electronics for building circuits defines the methodology. In this context, biocomputation is the branch of synthetic biology aimed at implementing artificial computational devices using engineered biological motifs as building blocks. Biocomputational devices are defined as biological systems that are able to integrate inputs and return outputs following pre-determined rules. Over the last decade the number of available synthetic engineered devices has increased exponentially; simple and complex circuits have been built in bacteria, yeast and mammalian cells. These devices can manage and store information, take decisions based on past and present inputs, and even convert a transient signal into a sustained response. The field is experiencing a fast growth and every day it is easier to implement more complex biological functions. This is mainly due to advances in in vitro DNA synthesis, new genome editing tools, novel molecular cloning techniques, continuously growing part libraries as well as other technological advances. This allows that digital computation can now be engineered and implemented in biological systems. Simple logic gates can be implemented and connected to perform novel desired functions or to better understand and redesign biological processes. Synthetic biological digital circuits could lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels. Biological computation not only provides possible biomedical and

  15. Translational environmental biology: cell biology informing conservation.

    Science.gov (United States)

    Traylor-Knowles, Nikki; Palumbi, Stephen R

    2014-05-01

    Typically, findings from cell biology have been beneficial for preventing human disease. However, translational applications from cell biology can also be applied to conservation efforts, such as protecting coral reefs. Recent efforts to understand the cell biological mechanisms maintaining coral health such as innate immunity and acclimatization have prompted new developments in conservation. Similar to biomedicine, we urge that future efforts should focus on better frameworks for biomarker development to protect coral reefs.

  16. Novel and highly recurrent chromosomal alterations in Sezary syndrome

    NARCIS (Netherlands)

    Vermeer, Maarten H.; van Doorn, Remco; Dijkman, Remco; Mao, Xin; Whittaker, Sean; Vader, Pieter C. van Voorst; Gerritsen, Marie-Jeanne P.; Geerts, Marie-Louise; Gellrich, Sylke; Soderberg, Ola; Leuchowius, Karl-Johan; Landegren, Ulf; Out-Luiting, Jacoba J.; Knijnenburg, Jeroen; Ijszenga, Marije; Szuhai, Karoly; Willemze, Rein; Tensen, Cornelis P.

    2008-01-01

    This study was designed to identify highly recurrent genetic alterations typical of Sezary syndrome (Sz), an aggressive cutaneous T-cell lymphoma/leukemia, possibly revealing pathogenetic mechanisms and novel therapeutic targets. High-resolution array-based comparative genomic hybridization was done

  17. Pictures of Synthetic Biology

    OpenAIRE

    Cserer, Amelie; Seiringer, Alexandra

    2009-01-01

    This article is concerned with the representation of Synthetic Biology in the media and by biotechnology experts. An analysis was made of German-language media articles published between 2004 and 2008, and interviews with biotechnology-experts at the Synthetic Biology conference SB 3.0 in Zurich 2007. The results have been reflected in terms of the definition of Synthetic Biology, applications of Synthetic Biology and the perspectives of opportunities and risks. In the media, Synthetic Biolog...

  18. Computational Systems Chemical Biology

    OpenAIRE

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

  19. Classification of Recombinant Biologics in the EU

    DEFF Research Database (Denmark)

    Klein, Kevin; De Bruin, Marie L; Broekmans, Andre W;

    2015-01-01

    before the data is aggregated at the European Union (EU) level, it is important that an unambiguous understanding of which medicinal products belong to the biological product category exists. This study aimed to identify the level of consistency between Member States regarding the classification...... to which products were classified as biologics by each Member State. We calculated the Fleiss kappa value to analyze interrater reliability. RESULTS: A considerable divergence was identified regarding the classification of the 146 recombinant biologics from the sample list: one Member State classified 100...... % of the recombinant biologics from the sample list as biologics, whereas the classification rates in the remaining four Member States ranged between 70 and 88 % for products available on the national market. The interrater reliability for 87 products available on the market in all five Member States was considered...

  20. Personalized identification of altered pathways in cancer using accumulated normal tissue data

    OpenAIRE

    Ahn, TaeJin; Lee, Eunjin; Huh, Nam; Park, Taesung

    2014-01-01

    Motivation: Identifying altered pathways in an individual is important for understanding disease mechanisms and for the future application of custom therapeutic decisions. Existing pathway analysis techniques are mainly focused on discovering altered pathways between normal and cancer groups and are not suitable for identifying the pathway aberrance that may occur in an individual sample. A simple way to identify individual’s pathway aberrance is to compare normal and tumor data from the same...

  1. Anthropogenic Noise and its Effect on Animal Communication: An Interface Between Comparative Psychology and Conservation Biology

    OpenAIRE

    Rabin, Lawrence A.; McCowan, Brenda; Hooper, Stacie L.; Owings, Donald H

    2003-01-01

    Conservation biology and comparative psychology rarely intersect, in part because conservation biology typically emphasizes populations whereas comparative psychology concentrates on individual organisms. However, both fields could benefit from their integration. Conservation biology can profit from an enhanced understanding of individual-level impacts of habitat alteration and the resulting implications for conservation mitigation strategies. Comparative psychology can gain from increased at...

  2. Identifying pelagic ecosystem indicators for management

    DEFF Research Database (Denmark)

    Trenkel, Verena; Hintzen, Niels; Rindorf, Anna;

    2013-01-01

    to pelagic fisheries to further explore the setting of management objectives. The objectives were identified through a participatory process including industry, management, scientist and NGO representatives. These objectives were used to identify appropriate driver, pressure and state indicators. The links......When exploiting fish populations under the ecosystem approach, aiming for MSY is not necessarily sufficient to ensure wider ecosystem sustainability. All of the large stocks of pelagic fish are managed through harvest control rules based on an MSY approach. Ensuring good environmental status...... will probably require further constraints to be imposed by management. Most of the current paradigm with regards to GES for fisheries has been based on demersal fish. Pelagic fisheries and fish are operationally and biologically respectively different. We use the example of applying the ecosystem approach...

  3. Electrostatic thin film chemical and biological sensor

    Science.gov (United States)

    Prelas, Mark A.; Ghosh, Tushar K.; Tompson, Jr., Robert V.; Viswanath, Dabir; Loyalka, Sudarshan K.

    2010-01-19

    A chemical and biological agent sensor includes an electrostatic thin film supported by a substrate. The film includes an electrostatic charged surface to attract predetermined biological and chemical agents of interest. A charge collector associated with said electrostatic thin film collects charge associated with surface defects in the electrostatic film induced by the predetermined biological and chemical agents of interest. A preferred sensing system includes a charge based deep level transient spectroscopy system to read out charges from the film and match responses to data sets regarding the agents of interest. A method for sensing biological and chemical agents includes providing a thin sensing film having a predetermined electrostatic charge. The film is exposed to an environment suspected of containing the biological and chemical agents. Quantum surface effects on the film are measured. Biological and/or chemical agents can be detected, identified and quantified based on the measured quantum surface effects.

  4. [Factors that alter taste perception].

    Science.gov (United States)

    Maffeis, E R; Silva-Netto, C R

    1990-01-01

    Dysfunction of taste perception is a significant problem for many individuals. Taste anomalies may affect health not only by directly affecting liquid and solid food intake, but also by creating a state of depression due to the loss of an important source of pleasure. Many factors alter taste perception, such as lesions of the oral mucosa, cigarette smoking, radiation, chemotherapy, renal disease, hepatitis, leprosy, hormones, nutrition, use of dentures, medications, and aging. Gum or ice chewing may temporarily help loss of taste. Patients should be encouraged to chew their food thoroughly, alternating the sides of the mouth, or alternating different foods. Unfortunately, in many cases there is no cure for this alteration, and patience is then the only possibility.

  5. Biological and Geographical application tool

    OpenAIRE

    Pereira, Miguel

    2007-01-01

    Monitoring and species identify is an essential step to natural resources management. Among these, biological resources aim special concern because data availability is highly limited by a number of sampling logistic constraints and catalog. As a matter of fact, data availability is one of important limitation to knowledge and, as a consequence the development of a new concept in natural resources. Data organization in digital format is a common practice in our days, and has the power to cont...

  6. Medulloblastoma: clinical and biologic aspects.

    OpenAIRE

    Packer, R. J.; Cogen, P.; Vezina, G.; Rorke, L. B.

    1999-01-01

    Medulloblastoma is the most common childhood primary CNS tumor, and treatment approaches have evolved over the past three decades. The biologic underpinnings of medulloblastoma are not fully characterized, but recent work has identified new, important directions for research. Stratification of patients with medulloblastoma into risk groups is the backbone of most ongoing therapeutic studies. Patients are usually characterized as being either average risk or poor risk, although an intermediate...

  7. NetDecoder: a network biology platform that decodes context-specific biological networks and gene activities.

    Science.gov (United States)

    da Rocha, Edroaldo Lummertz; Ung, Choong Yong; McGehee, Cordelia D; Correia, Cristina; Li, Hu

    2016-06-01

    The sequential chain of interactions altering the binary state of a biomolecule represents the 'information flow' within a cellular network that determines phenotypic properties. Given the lack of computational tools to dissect context-dependent networks and gene activities, we developed NetDecoder, a network biology platform that models context-dependent information flows using pairwise phenotypic comparative analyses of protein-protein interactions. Using breast cancer, dyslipidemia and Alzheimer's disease as case studies, we demonstrate NetDecoder dissects subnetworks to identify key players significantly impacting cell behaviour specific to a given disease context. We further show genes residing in disease-specific subnetworks are enriched in disease-related signalling pathways and information flow profiles, which drive the resulting disease phenotypes. We also devise a novel scoring scheme to quantify key genes-network routers, which influence many genes, key targets, which are influenced by many genes, and high impact genes, which experience a significant change in regulation. We show the robustness of our results against parameter changes. Our network biology platform includes freely available source code (http://www.NetDecoder.org) for researchers to explore genome-wide context-dependent information flow profiles and key genes, given a set of genes of particular interest and transcriptome data. More importantly, NetDecoder will enable researchers to uncover context-dependent drug targets. PMID:26975659

  8. Altered states: psychedelics and anesthetics.

    Science.gov (United States)

    Icaza, Eduardo E; Mashour, George A

    2013-12-01

    The psychedelic experience has been reported since antiquity, but there is relatively little known about the underlying neural mechanisms. A recent neuroimaging study on psilocybin revealed a pattern of decreased cerebral blood flow and functional disconnections that is surprisingly similar to that caused by various anesthetics. In this article, the authors review historical examples of psychedelic experiences induced by general anesthetics and then contrast the mechanisms by which these two drug classes generate altered states of consciousness. PMID:24061599

  9. [Molecular alterations in melanoma and targeted therapies].

    Science.gov (United States)

    Mourah, Samia; Lebbé, Céleste

    2014-12-01

    Melanoma is a skin cancer whose incidence is increasing steadily. The recent discovery of frequent and recurrent genetic alterations in cutaneous melanoma allowed a molecular classification of tumors into distinct subgroups, and paved the way for targeted therapy. Several signaling pathways are involved in the progression of this disease with oncogenic mutations affecting signaling pathways: MAPK, PI3K, cAMP and cyclin D1/CDK4. In each of these pathways, several potential therapeutic targets have been identified and specific inhibitors have already been developed and have shown clinical efficacy. The use of these inhibitors is often conditioned by tumors genotyping. In France, melanomas genotyping is supported by the platforms of the National Cancer Institute (INCA), which implemented a national program ensuring access to innovation for personalized medicine. The identification of new targets in melanoma supplies a very active dynamic development of innovative molecules contributing to changing the therapeutic landscape of this pathology. PMID:25776766

  10. [Molecular alterations in melanoma and targeted therapies].

    Science.gov (United States)

    Mourah, Samia; Lebbé, Céleste

    2014-12-01

    Melanoma is a skin cancer whose incidence is increasing steadily. The recent discovery of frequent and recurrent genetic alterations in cutaneous melanoma allowed a molecular classification of tumors into distinct subgroups, and paved the way for targeted therapy. Several signaling pathways are involved in the progression of this disease with oncogenic mutations affecting signaling pathways: MAPK, PI3K, cAMP and cyclin D1/CDK4. In each of these pathways, several potential therapeutic targets have been identified and specific inhibitors have already been developed and have shown clinical efficacy. The use of these inhibitors is often conditioned by tumors genotyping. In France, melanomas genotyping is supported by the platforms of the National Cancer Institute (INCA), which implemented a national program ensuring access to innovation for personalized medicine. The identification of new targets in melanoma supplies a very active dynamic development of innovative molecules contributing to changing the therapeutic landscape of this pathology.

  11. Buccal alterations in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Negrato Carlos

    2010-01-01

    Full Text Available Abstract Long standing hyperglycaemia besides damaging the kidneys, eyes, nerves, blood vessels, heart, can also impair the function of the salivary glands leading to a reduction in the salivary flow. When salivary flow decreases, as a consequence of an acute hyperglycaemia, many buccal or oral alterations can occur such as: a increased concentration of mucin and glucose; b impaired production and/or action of many antimicrobial factors; c absence of a metalloprotein called gustin, that contains zinc and is responsible for the constant maturation of taste papillae; d bad taste; e oral candidiasis f increased cells exfoliation after contact, because of poor lubrication; g increased proliferation of pathogenic microorganisms; h coated tongue; i halitosis; and many others may occur as a consequence of chronic hyperglycaemia: a tongue alterations, generally a burning mouth; b periodontal disease; c white spots due to demineralization in the teeth; d caries; e delayed healing of wounds; f greater tendency to infections; g lichen planus; h mucosa ulcerations. Buccal alterations found in diabetic patients, although not specific of this disease, have its incidence and progression increased when an inadequate glycaemic control is present.

  12. The nucleic acid revolution continues – will forensic biology become forensic molecular biology?

    OpenAIRE

    Gunn, Peter; Walsh, Simon; Roux, Claude

    2014-01-01

    Molecular biology has evolved far beyond that which could have been predicted at the time DNA identity testing was established. Indeed we should now perhaps be referring to “forensic molecular biology.” Aside from DNA’s established role in identifying the “who” in crime investigations, other developments in medical and developmental molecular biology are now ripe for application to forensic challenges. The impact of DNA methylation and other post-fertilization DNA modifications, plus the emer...

  13. Catchment-scale conservation units identified for the threatened Yarra pygmy perch (Nannoperca obscura in highly modified river systems.

    Directory of Open Access Journals (Sweden)

    Chris J Brauer

    Full Text Available Habitat fragmentation caused by human activities alters metapopulation dynamics and decreases biological connectivity through reduced migration and gene flow, leading to lowered levels of population genetic diversity and to local extinctions. The threatened Yarra pygmy perch, Nannoperca obscura, is a poor disperser found in small, isolated populations in wetlands and streams of southeastern Australia. Modifications to natural flow regimes in anthropogenically-impacted river systems have recently reduced the amount of habitat for this species and likely further limited its opportunity to disperse. We employed highly resolving microsatellite DNA markers to assess genetic variation, population structure and the spatial scale that dispersal takes place across the distribution of this freshwater fish and used this information to identify conservation units for management. The levels of genetic variation found for N. obscura are amongst the lowest reported for a fish species (mean heterozygosity of 0.318 and mean allelic richness of 1.92. We identified very strong population genetic structure, nil to little evidence of recent migration among demes and a minimum of 11 units for conservation management, hierarchically nested within four major genetic lineages. A combination of spatial analytical methods revealed hierarchical genetic structure corresponding with catchment boundaries and also demonstrated significant isolation by riverine distance. Our findings have implications for the national recovery plan of this species by demonstrating that N. obscura populations should be managed at a catchment level and highlighting the need to restore habitat and avoid further alteration of the natural hydrology.

  14. Biology Undergraduates' Misconceptions about Genetic Drift

    Science.gov (United States)

    Andrews, T. M.; Price, R. M.; Mead, L. S.; McElhinny, T. L.; Thanukos, A.; Perez, K. E.; Herreid, C. F.; Terry, D. R.; Lemons, P. P.

    2012-01-01

    This study explores biology undergraduates' misconceptions about genetic drift. We use qualitative and quantitative methods to describe students' definitions, identify common misconceptions, and examine differences before and after instruction on genetic drift. We identify and describe five overarching categories that include 16 distinct…

  15. Accounting for Ecosystem Alteration Doubles Estimates of Conservation Risk in the Conterminous United States

    OpenAIRE

    Randy Swaty; Kori Blankenship; Sarah Hagen; Joseph Fargione; Jim Smith; Jeannie Patton

    2011-01-01

    Previous national and global conservation assessments have relied on habitat conversion data to quantify conservation risk. However, in addition to habitat conversion to crop production or urban uses, ecosystem alteration (e.g., from logging, conversion to plantations, biological invasion, or fire suppression) is a large source of conservation risk. We add data quantifying ecosystem alteration on unconverted lands to arrive at a more accurate depiction of conservation risk for the conterminou...

  16. Exploring Cancer's Fractured Genomic Landscape: Searching for Cancer Drivers and Vulnerabilities in Somatic Copy Number Alterations

    OpenAIRE

    Zack, Travis Ian

    2014-01-01

    Somatic copy number alterations (SCNAs) are a class of alterations that lead to deviations from diploidy in developing and established tumors. A feature that distinguishes SCNAs from other alterations is their genomic footprint. The large genomic footprint of SCNAs in a typical cancer's genome presents both a challenge and an opportunity to find targetable vulnerabilities in cancer. Because a single event affects many genes, it is often challenging to identify the tumorigenic targets of SCNAs...

  17. Prospects of Biological Resources in Mitigating Agricultural Disasters

    Institute of Scientific and Technical Information of China (English)

    WANG Shaonan; YE Zhihua; YU Dazhao

    2001-01-01

    This paper analyzes the agricultural impacts of meteorological disasters, such as flood and drought, and biological disasters such as crop diseases, insect pests, weeds and rodents; and elaborates that efficacious development and utilization of biological resources are an effective way to preventing and mitigating agricultural disasters. Subjects for research on the development of biological resources are identified.

  18. Student Teachers' Conceptions of Teaching Biology

    Science.gov (United States)

    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…

  19. Seeing Cells: Teaching the Visual/Verbal Rhetoric of Biology

    Science.gov (United States)

    Dinolfo, John; Heifferon, Barbara; Temesvari, Lesly A.

    2007-01-01

    This pilot study obtained baseline information on verbal and visual rhetorics to teach microscopy techniques to college biology majors. We presented cell images to students in cell biology and biology writing classes and then asked them to identify textual, verbal, and visual cues that support microscopy learning. Survey responses suggest that…

  20. Nicotinic alteration of decision-making.

    Science.gov (United States)

    Naudé, Jérémie; Dongelmans, Malou; Faure, Philippe

    2015-09-01

    Addiction to nicotine is characterized by impulses, urges and lack of self-control towards cigarettes. A key element in the process of addiction is the development of habits oriented towards nicotine consumption that surpass flexible systems as a consequence of a gradual adaptation to chronic drug exposure. However, the long-term effects of nicotine on brain circuits also induce wide changes in decision-making processes, affecting behaviors unrelated to cigarettes. This review aims at providing an update on the implications of nicotine on general decision-making processes, with an emphasis on impulsivity and risk-taking. As impulsivity is a rather ambiguous behavioral trait, we build on economic and normative theories to better characterize these nicotine-induced alterations in decision-making. Nonetheless, experimental data are sparse and often contradictory. We will discuss how the latest findings on the neurobiological basis of choice behavior may help disentangling these issues. We focus on the role of nicotine acetylcholine receptors and their different subunits, and on the spatio-temporal dynamics (i.e. diversity of the neural circuits, short- and long-term effects) of both endogenous acetylcholine and nicotine action. Finally, we try to link these neurobiological results with neuro-computational models of attention, valuation and action, and of the role of acetylcholine in these decision processes. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. PMID:25498234

  1. Grays River Watershed and Biological Assessment Final Report 2006.

    Energy Technology Data Exchange (ETDEWEB)

    May, Christopher W.; McGrath, Kathleen E.; Geist, David R. [Pacific Northwest National Laboratory; Abbe, Timothy; Barton, Chase [Herrera Environmental Consultants, Inc.

    2008-02-04

    habitat conditions, and biological integrity. In addition, human land-use impacts are factored into the conceptual model because they can alter habitat quality and can disrupt natural habitat-forming processes. In this model (Figure S.1), aquatic habitat--both instream and riparian--is viewed as the link between watershed conditions and biologic responses. Based on this conceptual model, assessment of habitat loss and the resultant declines in salmonid populations can be conducted by relating current and historical (e.g., natural) habitat conditions to salmonid utilization, diversity, and abundance. In addition, assessing disrupted ecosystem functions and processes within the watershed can aid in identifying the causes of habitat change and the associated decline in biological integrity. In this same way, restoration, enhancement, and conservation projects can be identified and prioritized. A watershed assessment is primarily a landscape-scale evaluation of current watershed conditions and the associated hydrogeomorphic riverine processes. The watershed assessment conducted for this project focused on watershed processes that form and maintain salmonid habitat. Landscape metrics describing the level of human alteration of natural ecosystem attributes were used as indicators of water quality, hydrology, channel geomorphology, instream habitat, and biotic integrity. Ecological (watershed) processes are related to and can be predicted based on specific aspects of spatial pattern. This study evaluated the hydrologic regime, sediment delivery regime, and riparian condition of the sub-watersheds that comprise the upper Grays River watershed relative to their natural range of conditions. Analyses relied primarily on available geographic information system (GIS) data describing landscape characteristics such as climate, vegetation type and maturity, geology and soils, topography, land use, and road density. In addition to watershed-scale landscape characteristics, the study area

  2. Grays River Watershed and Biological Assessment, 2006 Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    May, Christopher; Geist, David [Pacific Northwest National Laboratory

    2007-04-01

    habitat conditions, and biological integrity. In addition, human land-use impacts are factored into the conceptual model because they can alter habitat quality and can disrupt natural habitat forming processes. In this model (Figure S.1), aquatic habitat--both instream and riparian--is viewed as the link between watershed conditions and biologic responses. Based on this conceptual model, assessment of habitat loss and the resultant declines in salmonid populations can be conducted by relating current and historical (e.g., natural) habitat conditions to salmonid utilization, diversity, and abundance. In addition, assessing disrupted ecosystem functions and processes within the watershed can aid in identifying the causes of habitat change and the associated decline in biological integrity. In this same way, restoration, enhancement, and conservation projects can be identified and prioritized. A watershed assessment is primarily a landscape-scale evaluation of current watershed conditions and the associated hydrogeomorphic riverine processes. The watershed assessment conducted for this project focused on watershed processes that form and maintain salmonid habitat. Landscape metrics describing the level of human alteration of natural ecosystem attributes were used as indicators of water quality, hydrology, channel geomorphology, instream habitat, and biotic integrity. Ecological (watershed) processes are related to and can be predicted based on specific aspects of spatial pattern. This study evaluated the hydrologic regime, sediment delivery regime, and riparian condition of the sub-watersheds that comprise the upper Grays River watershed relative to their natural range of conditions. Analyses relied primarily on available geographic information system (GIS) data describing landscape characteristics such as climate, vegetation type and maturity, geology and soils, topography, land use, and road density. In addition to watershed-scale landscape characteristics, the study area

  3. Biology of Blood

    Science.gov (United States)

    ... Mail Facebook TwitterTitle Google+ LinkedIn Home Blood Disorders Biology of Blood Overview of Blood Medical Dictionary Also ... Version. DOCTORS: Click here for the Professional Version Biology of Blood Overview of Blood Components of Blood ...

  4. Advances in Biological Science.

    Science.gov (United States)

    Oppenheimer, Steven B.; And Others

    1988-01-01

    Reviews major developments in areas that are at the cutting edge of biological research. Areas include: human anti-cancer gene, recombinant DNA techniques for the detection of Huntington disease carriers, and marine biology. (CW)

  5. Biology is simple.

    Science.gov (United States)

    Newman, Tim

    2015-12-30

    This paper explores the potential for simplicity to reveal new biological understanding. Borrowing selectively from physics thinking, and contrasting with Crick's reductionist philosophy, the author argues that greater emphasis on simplicity is necessary to advance biology and its applications.

  6. Engineering scalable biological systems

    OpenAIRE

    Lu, Timothy K.

    2010-01-01

    Synthetic biology is focused on engineering biological organisms to study natural systems and to provide new solutions for pressing medical, industrial, and environmental problems. At the core of engineered organisms are synthetic biological circuits that execute the tasks of sensing inputs, processing logic, and performing output functions. In the last decade, significant progress has been made in developing basic designs for a wide range of biological circuits in bacteria, yeast, and mammal...

  7. Systems interface biology

    OpenAIRE

    Francis J Doyle; Stelling, Jörg

    2006-01-01

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Henc...

  8. Biological Races in Humans

    OpenAIRE

    Templeton, Alan R.

    2013-01-01

    Races may exist in humans in a cultural sense, but biological concepts of race are needed to access their reality in a non-species-specific manner and to see if cultural categories correspond to biological categories within humans. Modern biological concepts of race can be implemented objectively with molecular genetic data through hypothesis-testing. Genetic data sets are used to see if biological races exist in humans and in our closest evolutionary relative, the chimpanzee. Using the two m...

  9. Upgrading Undergraduate Biology Education

    Science.gov (United States)

    Musante, Susan

    2011-01-01

    On many campuses throughout the country, undergraduate biology education is in serious need of an upgrade. During the past few decades, the body of biological knowledge has grown exponentially, and as a research endeavor, the practice of biology has evolved. Education research has also made great strides, revealing many new insights into how…

  10. Altering prolactin concentrations in sows.

    Science.gov (United States)

    Farmer, C

    2016-07-01

    Prolactin has a multiplicity of actions, but it is of particular importance in gestating and lactating animals. In sows, it is involved in the control of mammary development and also holds essential roles in the lactogenic and galactopoietic processes. Furthermore, low circulating concentrations of prolactin are associated with the agalactia syndrome. The crucial role of prolactin makes it important to understand the various factors that can alter its secretion. Regulation of prolactin secretion is largely under the negative control of dopamine, and dopamine agonists consistently decrease prolactin concentrations in sows. On the other hand, injections of dopamine antagonists can enhance circulating prolactin concentrations. Besides pharmacologic agents, many other factors can also alter prolactin concentrations in sows. The use of Chinese-derived breeds, for instance, leads to increased prolactin concentrations in lactating sows compared with standard European white breeds. Numerous husbandry and feeding practices also have a potential impact on prolactin concentrations in sows. Factors, such as provision of nest-building material prepartum, housing at farrowing, high ambient temperature, stress, transient weaning, exogenous thyrotropin-releasing factor, exogenous growth hormone-releasing factor, nursing frequency, prolonged photoperiod, fasting, increased protein and/or energy intake, altered energy sources, feeding high-fiber diets, sorghum ergot or plant extracts, were all studied with respect to their prolactinemic properties. Although some of these practices do indeed affect circulating prolactin concentrations, none leads to changes as drastic as those brought about by dopamine agonists or antagonists. It appears that the numerous factors regulating prolactin concentrations in sows are still not fully elucidated, and that studies to develop novel applicable ways of increasing prolactin concentrations in sows are warranted.

  11. A Systems Biology Analysis Unfolds the Molecular Pathways and Networks of Two Proteobacteria in Spaceflight and Simulated Microgravity Conditions

    Science.gov (United States)

    Roy, Raktim; Phani Shilpa, P.; Bagh, Sangram

    2016-09-01

    Bacteria are important organisms for space missions due to their increased pathogenesis in microgravity that poses risks to the health of astronauts and for projected synthetic biology applications at the space station. We understand little about the effect, at the molecular systems level, of microgravity on bacteria, despite their significant incidence. In this study, we proposed a systems biology pipeline and performed an analysis on published gene expression data sets from multiple seminal studies on Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium under spaceflight and simulated microgravity conditions. By applying gene set enrichment analysis on the global gene expression data, we directly identified a large number of new, statistically significant cellular and metabolic pathways involved in response to microgravity. Alteration of metabolic pathways in microgravity has rarely been reported before, whereas in this analysis metabolic pathways are prevalent. Several of those pathways were found to be common across studies and species, indicating a common cellular response in microgravity. We clustered genes based on their expression patterns using consensus non-negative matrix factorization. The genes from different mathematically stable clusters showed protein-protein association networks with distinct biological functions, suggesting the plausible functional or regulatory network motifs in response to microgravity. The newly identified pathways and networks showed connection with increased survival of pathogens within macrophages, virulence, and antibiotic resistance in microgravity. Our work establishes a systems biology pipeline and provides an integrated insight into the effect of microgravity at the molecular systems level.

  12. Altered Mental Status and Delirium.

    Science.gov (United States)

    Wilber, Scott T; Ondrejka, Jason E

    2016-08-01

    Older patients who present to the emergency department frequently have acute or chronic alterations of their mental status, including their level of consciousness and cognition. Recognizing both acute and chronic changes in cognition are important for emergency physicians. Delirium is an acute change in attention, awareness, and cognition. Numerous life-threatening conditions can cause delirium; therefore, prompt recognition and treatment are critical. The authors discuss an organized approach that can lead to a prompt diagnosis within the time constraints of the emergency department. PMID:27475019

  13. Genomic and Immunological Tumor Profiling Identifies Targetable Pathways and Extensive CD8+/PDL1+ Immune Infiltration in Inflammatory Breast Cancer Tumors.

    Science.gov (United States)

    Hamm, Christopher A; Moran, Diarmuid; Rao, Kakuturu; Trusk, Patricia B; Pry, Karen; Sausen, Mark; Jones, Siân; Velculescu, Victor E; Cristofanilli, Massimo; Bacus, Sarah

    2016-07-01

    Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that remains poorly understood at the molecular level. Comprehensive tumor profiling was performed to understand clinically actionable alterations in IBC. Targeted next-generation sequencing (NGS) and IHC were performed to identify activated pathways in IBC tumor tissues. siRNA studies examined the impact of IBC genomic variants in cellular models. IBC tumor tissues were further characterized for immune infiltration and immune checkpoint expression by IHC. Genomic analysis identified recurrent alterations in core biologic pathways, including activating and targetable variants in HER/PI3K/mTOR signaling. High rates of activating HER3 point mutations were discovered in IBC tumors. Cell line studies confirmed a role for mutant HER3 in IBC cell proliferation. Immunologic analysis revealed a subset of IBC tumors associated with high CD8(+)/PD-L1(+) lymphocyte infiltration. Immune infiltration positively correlated with an NGS-based estimate of neoantigen exposure derived from the somatic mutation rate and mutant allele frequency, iScore. Additionally, DNA mismatch repair alterations, which may contribute to higher iScores, occurred at greater frequency in tumors with higher immune infiltration. Our study identifies genomic alterations that mechanistically contribute to oncogenic signaling in IBC and provides a genetic basis for the selection of clinically relevant targeted and combination therapeutic strategies. Furthermore, an NGS-based estimate of neoantigen exposure developed in this study (iScore) may be a useful biomarker to predict immune infiltration in IBC and other cancers. The iScore may be associated with greater levels of response to immunotherapies, such as PD-L1/PD-1-targeted therapies. Mol Cancer Ther; 15(7); 1746-56. ©2016 AACR. PMID:27196778

  14. Genomic and Immunological Tumor Profiling Identifies Targetable Pathways and Extensive CD8+/PDL1+ Immune Infiltration in Inflammatory Breast Cancer Tumors.

    Science.gov (United States)

    Hamm, Christopher A; Moran, Diarmuid; Rao, Kakuturu; Trusk, Patricia B; Pry, Karen; Sausen, Mark; Jones, Siân; Velculescu, Victor E; Cristofanilli, Massimo; Bacus, Sarah

    2016-07-01

    Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that remains poorly understood at the molecular level. Comprehensive tumor profiling was performed to understand clinically actionable alterations in IBC. Targeted next-generation sequencing (NGS) and IHC were performed to identify activated pathways in IBC tumor tissues. siRNA studies examined the impact of IBC genomic variants in cellular models. IBC tumor tissues were further characterized for immune infiltration and immune checkpoint expression by IHC. Genomic analysis identified recurrent alterations in core biologic pathways, including activating and targetable variants in HER/PI3K/mTOR signaling. High rates of activating HER3 point mutations were discovered in IBC tumors. Cell line studies confirmed a role for mutant HER3 in IBC cell proliferation. Immunologic analysis revealed a subset of IBC tumors associated with high CD8(+)/PD-L1(+) lymphocyte infiltration. Immune infiltration positively correlated with an NGS-based estimate of neoantigen exposure derived from the somatic mutation rate and mutant allele frequency, iScore. Additionally, DNA mismatch repair alterations, which may contribute to higher iScores, occurred at greater frequency in tumors with higher immune infiltration. Our study identifies genomic alterations that mechanistically contribute to oncogenic signaling in IBC and provides a genetic basis for the selection of clinically relevant targeted and combination therapeutic strategies. Furthermore, an NGS-based estimate of neoantigen exposure developed in this study (iScore) may be a useful biomarker to predict immune infiltration in IBC and other cancers. The iScore may be associated with greater levels of response to immunotherapies, such as PD-L1/PD-1-targeted therapies. Mol Cancer Ther; 15(7); 1746-56. ©2016 AACR.

  15. Metabolic alterations in cancer cells and therapeutic implications

    Institute of Scientific and Technical Information of China (English)

    Naima Hammoudi; Kausar Begam Riaz Ahmed; Celia Garcia-Prieto; Peng Huang

    2011-01-01

    Cancer metabolism has emerged as an important area of research in recent years. Elucidation of the metabolic differences between cancer and normal cells and the underlying mechanisms will not only advance our understanding of fundamental cancer cell biology but also provide an important basis for the development of new therapeutic strategies and novel compounds to selectively eliminate cancer cells by targeting their unique metabolism. This article reviews several important metabolic alterations in cancer cells, with an emphasis on increased aerobic glycolysis (the Warburg effect) and glutamine addiction, and discusses the mechanisms that may contribute to such metabolic changes. In addition, metabolic alterations in cancer stem cells, mitochondrial metabolism and its influence on drug sensitivity, and potential therapeutic strategies and agents that target cancer metabolism are also discussed.

  16. Altered Transendothelial Transport of Hormones as a Contributor to Diabetes

    Directory of Open Access Journals (Sweden)

    Nanyoung Yoon

    2014-04-01

    Full Text Available The vascular endothelium is a dynamic structure responsible for the separation and regulated movement of biological material between circulation and interstitial fluid. Hormones and nutrients can move across the endothelium either via a transcellular or paracellular route. Transcellular endothelial transport is well understood and broadly acknowledged to play an important role in the normal and abnormal physiology of endothelial function. However, less is known about the role of the paracellular route. Although the concept of endothelial dysfunction in diabetes is now widely accepted, we suggest that alterations in paracellular transport should be studied in greater detail and incorporated into this model. In this review we provide an overview of endothelial paracellular permeability and discuss its potential importance in contributing to the development of diabetes and associated complications. Accordingly, we also contend that if better understood, altered endothelial paracellular permeability could be considered as a potential therapeutic target for diabetes.

  17. Identifying tumor cell growth inhibitors by combinatorial chemistry and zebrafish assays.

    Directory of Open Access Journals (Sweden)

    Jing Xiang

    Full Text Available Cyclin-dependent kinases (CDKs play important roles in regulating cell cycle progression, and altered cell cycles resulting from over-expression or abnormal activation of CDKs observed in many human cancers. As a result, CDKs have become extensive studied targets for developing chemical inhibitors for cancer therapies; however, protein kinases share a highly conserved ATP binding pocket at which most chemical inhibitors bind, therefore, a major challenge in developing kinase inhibitors is achieving target selectivity. To identify cell growth inhibitors with potential applications in cancer therapy, we used an integrated approach that combines one-pot chemical synthesis in a combinatorial manner to generate diversified small molecules with new chemical scaffolds coupled with growth inhibition assay using developing zebrafish embryos. We report the successful identification of a novel lead compound that displays selective inhibitory effects on CDK2 activity, cancer cell proliferation, and tumor progression in vivo. Our approaches should have general applications in developing cell proliferation inhibitors using an efficient combinatorial chemical genetic method and integrated biological assays. The novel cell growth inhibitor we identified should have potential as a cancer therapeutic agent.

  18. DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features.

    Science.gov (United States)

    Arribas, Alberto J; Rinaldi, Andrea; Mensah, Afua A; Kwee, Ivo; Cascione, Luciano; Robles, Eloy F; Martinez-Climent, Jose A; Oscier, David; Arcaini, Luca; Baldini, Luca; Marasca, Roberto; Thieblemont, Catherine; Briere, Josette; Forconi, Francesco; Zamò, Alberto; Bonifacio, Massimiliano; Mollejo, Manuela; Facchetti, Fabio; Dirnhofer, Stephan; Ponzoni, Maurilio; Bhagat, Govind; Piris, Miguel A; Gaidano, Gianluca; Zucca, Emanuele; Rossi, Davide; Bertoni, Francesco

    2015-03-19

    Splenic marginal zone lymphoma is a rare lymphoma. Loss of 7q31 and somatic mutations affecting the NOTCH2 and KLF2 genes are the commonest genomic aberrations. Epigenetic changes can be pharmacologically reverted; therefore, identification of groups of patients with specific epigenomic alterations might have therapeutic relevance. Here we integrated genome-wide DNA-promoter methylation profiling with gene expression profiling, and clinical and biological variables. An unsupervised clustering analysis of a test series of 98 samples identified 2 clusters with different degrees of promoter methylation. The cluster comprising samples with higher-promoter methylation (High-M) had a poorer overall survival compared with the lower (Low-M) cluster. The prognostic relevance of the High-M phenotype was confirmed in an independent validation set of 36 patients. In the whole series, the High-M phenotype was associated with IGHV1-02 usage, mutations of NOTCH2 gene, 7q31-32 loss, and histologic transformation. In the High-M set, a number of tumor-suppressor genes were methylated and repressed. PRC2 subunit genes and several prosurvival lymphoma genes were unmethylated and overexpressed. A model based on the methylation of 3 genes (CACNB2, HTRA1, KLF4) identified a poorer-outcome patient subset. Exposure of splenic marginal zone lymphoma cell lines to a demethylating agent caused partial reversion of the High-M phenotype and inhibition of proliferation. PMID:25612624

  19. Review of biological network data and its applications.

    Science.gov (United States)

    Yu, Donghyeon; Kim, Minsoo; Xiao, Guanghua; Hwang, Tae Hyun

    2013-12-01

    Studying biological networks, such as protein-protein interactions, is key to understanding complex biological activities. Various types of large-scale biological datasets have been collected and analyzed with high-throughput technologies, including DNA microarray, next-generation sequencing, and the two-hybrid screening system, for this purpose. In this review, we focus on network-based approaches that help in understanding biological systems and identifying biological functions. Accordingly, this paper covers two major topics in network biology: reconstruction of gene regulatory networks and network-based applications, including protein function prediction, disease gene prioritization, and network-based genome-wide association study.

  20. Mapping Hydrothermal Alterations in the Muteh Gold Mining Area in Iran by using ASTER satellite Imagery data

    Science.gov (United States)

    Asadi Haroni, Hooshang; Hassan Tabatabaei, Seyed

    2016-04-01

    Muteh gold mining area is located in 160 km NW of Isfahan town. Gold mineralization is meso-thermal type and associated with silisic, seresitic and carbonate alterations as well as with hematite and goethite. Image processing and interpretation were applied on the ASTER satellite imagery data of about 400 km2 at the Muteh gold mining area to identify hydrothermal alterations and iron oxides associated with gold mineralization. After applying preprocessing methods such as radiometric and geometric corrections, image processing methods of Principal Components Analysis (PCA), Least Square Fit (Ls-Fit) and Spectral Angle Mapper (SAM) were applied on the ASTER data to identify hydrothermal alterations and iron oxides. In this research reference spectra of minerals such as chlorite, hematite, clay minerals and phengite identified from laboratory spectral analysis of collected samples were used to map the hydrothermal alterations. Finally, identified hydrothermal alteration and iron oxides were validated by visiting and sampling some of the mapped hydrothermal alterations.

  1. Accounting for ecosystem alteration doubles estimates of conservation risk in the conterminous United States.

    Science.gov (United States)

    Swaty, Randy; Blankenship, Kori; Hagen, Sarah; Fargione, Joseph; Smith, Jim; Patton, Jeannie

    2011-01-01

    Previous national and global conservation assessments have relied on habitat conversion data to quantify conservation risk. However, in addition to habitat conversion to crop production or urban uses, ecosystem alteration (e.g., from logging, conversion to plantations, biological invasion, or fire suppression) is a large source of conservation risk. We add data quantifying ecosystem alteration on unconverted lands to arrive at a more accurate depiction of conservation risk for the conterminous United States. We quantify ecosystem alteration using a recent national assessment based on remote sensing of current vegetation compared with modeled reference natural vegetation conditions. Highly altered (but not converted) ecosystems comprise 23% of the conterminous United States, such that the number of critically endangered ecoregions in the United States is 156% higher than when calculated using habitat conversion data alone. Increased attention to natural resource management will be essential to address widespread ecosystem alteration and reduce conservation risk. PMID:21850248

  2. Accounting for ecosystem alteration doubles estimates of conservation risk in the conterminous United States.

    Directory of Open Access Journals (Sweden)

    Randy Swaty

    Full Text Available Previous national and global conservation assessments have relied on habitat conversion data to quantify conservation risk. However, in addition to habitat conversion to crop production or urban uses, ecosystem alteration (e.g., from logging, conversion to plantations, biological invasion, or fire suppression is a large source of conservation risk. We add data quantifying ecosystem alteration on unconverted lands to arrive at a more accurate depiction of conservation risk for the conterminous United States. We quantify ecosystem alteration using a recent national assessment based on remote sensing of current vegetation compared with modeled reference natural vegetation conditions. Highly altered (but not converted ecosystems comprise 23% of the conterminous United States, such that the number of critically endangered ecoregions in the United States is 156% higher than when calculated using habitat conversion data alone. Increased attention to natural resource management will be essential to address widespread ecosystem alteration and reduce conservation risk.

  3. Synthetic biological networks

    International Nuclear Information System (INIS)

    Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics. (review article)

  4. Use of biological indicators in TMDL assessment and implementation

    OpenAIRE

    Yagow, G.; Wilson, B.; Srivastava, P; Obropta, C. C.

    2006-01-01

    Most states in the U.S. have a general water quality standard intended to protect water from all potential pollutants not specifically named or identified in other standards. Biological indicators are used, in part, to assess the level of water quality with respect to this general standard. Under EPA's Total Maximum Daily Load (TMDL) program, impaired waters based on a biological assessment require an additional step compared with non-biological TMDLs. In non-biological TMDLs, the "pollutant"...

  5. Integrated Design of Antibodies for Systems Biology Using Ab Designer

    OpenAIRE

    Pisitkun, Trairak; Dummer, Patrick; Somparn, Poorichaya; Hirankarn, Nattiya; Kopp, Jeffrey B.; Knepper, Mark A.

    2014-01-01

    In the current era of large-scale biology, systems biology has evolved as a powerful approach to identify complex interactions within biological systems. In addition to high throughput identification and quantification techniques, methods based on high-quality mono-specific antibodies remain an essential element of the approach. To assist the large-scale design and production of peptide-directed antibodies for systems biology studies, we developed a fully integrated online application, AbDesi...

  6. Identifying mechanistic similarities in drug responses

    KAUST Repository

    Zhao, C.

    2012-05-15

    Motivation: In early drug development, it would be beneficial to be able to identify those dynamic patterns of gene response that indicate that drugs targeting a particular gene will be likely or not to elicit the desired response. One approach would be to quantitate the degree of similarity between the responses that cells show when exposed to drugs, so that consistencies in the regulation of cellular response processes that produce success or failure can be more readily identified.Results: We track drug response using fluorescent proteins as transcription activity reporters. Our basic assumption is that drugs inducing very similar alteration in transcriptional regulation will produce similar temporal trajectories on many of the reporter proteins and hence be identified as having similarities in their mechanisms of action (MOA). The main body of this work is devoted to characterizing similarity in temporal trajectories/signals. To do so, we must first identify the key points that determine mechanistic similarity between two drug responses. Directly comparing points on the two signals is unrealistic, as it cannot handle delays and speed variations on the time axis. Hence, to capture the similarities between reporter responses, we develop an alignment algorithm that is robust to noise, time delays and is able to find all the contiguous parts of signals centered about a core alignment (reflecting a core mechanism in drug response). Applying the proposed algorithm to a range of real drug experiments shows that the result agrees well with the prior drug MOA knowledge. © The Author 2012. Published by Oxford University Press. All rights reserved.

  7. Positioning Genomics in Biology Education: Content Mapping of Undergraduate Biology Textbooks

    Directory of Open Access Journals (Sweden)

    Naomi L. B. Wernick

    2014-07-01

    Full Text Available 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.

  8. TWO STAGE FRAMEWORK FOR ALTERED FINGERPRINT MATCHING

    OpenAIRE

    T. R. Anoop; M.G. Mini

    2015-01-01

    Fingerprint alteration is the process of masking one’s identity from personal identification systems especially in boarder control security systems. Failure of matching the altered fingerprint of the criminals against the watch list of fingerprints can help them to break the security system. This fact leads to the need of a method for altered fingerprint matching. This paper presents a two stage method for altered fingerprint matching. In first stage, approximated global ridge orientation fie...

  9. Computational systems chemical biology.

    Science.gov (United States)

    Oprea, Tudor I; May, Elebeoba E; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology (SCB) (Nat Chem Biol 3: 447-450, 2007).The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules, and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology/systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology, and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology.

  10. Quantum biological information theory

    CERN Document Server

    Djordjevic, Ivan B

    2016-01-01

    This book is a self-contained, tutorial-based introduction to quantum information theory and quantum biology. It serves as a single-source reference to the topic for researchers in bioengineering, communications engineering, electrical engineering, applied mathematics, biology, computer science, and physics. The book provides all the essential principles of the quantum biological information theory required to describe the quantum information transfer from DNA to proteins, the sources of genetic noise and genetic errors as well as their effects. Integrates quantum information and quantum biology concepts; Assumes only knowledge of basic concepts of vector algebra at undergraduate level; Provides a thorough introduction to basic concepts of quantum information processing, quantum information theory, and quantum biology; Includes in-depth discussion of the quantum biological channel modelling, quantum biological channel capacity calculation, quantum models of aging, quantum models of evolution, quantum models o...

  11. Systems Biology of Industrial Microorganisms

    Science.gov (United States)

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

  12. New Criteria to Identify Spectrum

    Indian Academy of Sciences (India)

    A Jensen; M Krishna

    2005-05-01

    In this paper we give some new criteria for identifying the components of a probability measure, in its Lebesgue decomposition. This enables us to give new criteria to identify spectral types of self-adjoint operators on Hilbert spaces, especially those of interest.

  13. New criteria to identify spectrum

    DEFF Research Database (Denmark)

    Jensen, Arne; Krishna, M.

    2005-01-01

    In this paper we give some new criteria for identifying the components of a probability measure, in its Lebesgue decomposition. This enables us to give new criteria to identify spectral types of self-adjoint operators on Hilbert spaces, especially those of interest....

  14. Ultrastructural alterations in adult Schistosoma mansoni caused by artemether

    Directory of Open Access Journals (Sweden)

    Shuhua Xiao

    2002-07-01

    Full Text Available Progress has been made over the last decade with the development and clinical use of artemether as an agent against major human schistosome parasites. The tegument has been identified as a key target of artemether, implying detailed studies on ultrastructural damage induced by this compound. We performed a temporal examination, employing a transmission electron microscope to assess the pattern and extent of ultrastructural alterations in adult Schistosoma mansoni harboured in mice treated with a single dose of 400 mg/kg artemether. Eight hours post-treatment, damage to the tegument and subtegumental structures was seen. Tegumental alterations reached a peak 3 days after treatment and were characterized by swelling, fusion of distal cytoplasma, focal lysis of the tegumental matrix and vacuolisation. Tubercles and sensory organelles frequently degenerated or collapsed. Typical features of subtegumental alterations, including muscle fibres, syncytium and parenchyma tissues, were focal or extensive lysis, vacuolisation and degeneration of mitochondria. Severe alterations were also observed in gut epithelial cells and vitelline cells of female worms. Our findings of artemether-induced ultrastructural alterations in adult S. mansoni confirm previous results obtained with juvenile S. mansoni and S. japonicum of different ages.

  15. Eosinophils in glioblastoma biology

    Directory of Open Access Journals (Sweden)

    Curran Colleen S

    2012-01-01

    Full Text Available Abstract Glioblastoma multiforme (GBM is the most common primary brain tumor in adults. The development of this malignant glial lesion involves a multi-faceted process that results in a loss of genetic or epigenetic gene control, un-regulated cell growth, and immune tolerance. Of interest, atopic diseases are characterized by a lack of immune tolerance and are inversely associated with glioma risk. One cell type that is an established effector cell in the pathobiology of atopic disease is the eosinophil. In response to various stimuli, the eosinophil is able to produce cytotoxic granules, neuromediators, and pro-inflammatory cytokines as well as pro-fibrotic and angiogenic factors involved in pathogen clearance and tissue remodeling and repair. These various biological properties reveal that the eosinophil is a key immunoregulatory cell capable of influencing the activity of both innate and adaptive immune responses. Of central importance to this report is the observation that eosinophil migration to the brain occurs in response to traumatic brain injury and following certain immunotherapeutic treatments for GBM. Although eosinophils have been identified in various central nervous system pathologies, and are known to operate in wound/repair and tumorstatic models, the potential roles of eosinophils in GBM development and the tumor immunological response are only beginning to be recognized and are therefore the subject of the present review.

  16. Network-based analysis of affected biological processes in type 2 diabetes models.

    Directory of Open Access Journals (Sweden)

    Manway Liu

    2007-06-01

    Full Text Available Type 2 diabetes mellitus is a complex disorder associated with multiple genetic, epigenetic, developmental, and environmental factors. Animal models of type 2 diabetes differ based on diet, drug treatment, and gene knockouts, and yet all display the clinical hallmarks of hyperglycemia and insulin resistance in peripheral tissue. The recent advances in gene-expression microarray technologies present an unprecedented opportunity to study type 2 diabetes mellitus at a genome-wide scale and across different models. To date, a key challenge has been to identify the biological processes or signaling pathways that play significant roles in the disorder. Here, using a network-based analysis methodology, we identified two sets of genes, associated with insulin signaling and a network of nuclear receptors, which are recurrent in a statistically significant number of diabetes and insulin resistance models and transcriptionally altered across diverse tissue types. We additionally identified a network of protein-protein interactions between members from the two gene sets that may facilitate signaling between them. Taken together, the results illustrate the benefits of integrating high-throughput microarray studies, together with protein-protein interaction networks, in elucidating the underlying biological processes associated with a complex disorder.

  17. New Molecular Features of Colorectal Cancer Identified - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Investigators from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) who comprehensively analyzed 95 human colorectal tumor samples, have determined how gene alterations identified in previous analyses of the same samples

  18. Climate change and physical disturbance manipulations result in distinct biological soil crust communities.

    Science.gov (United States)

    Steven, Blaire; Kuske, Cheryl R; Gallegos-Graves, La Verne; Reed, Sasha C; Belnap, Jayne

    2015-11-01

    Biological soil crusts (biocrusts) colonize plant interspaces in many drylands and are critical to soil nutrient cycling. Multiple climate change and land use factors have been shown to detrimentally impact biocrusts on a macroscopic (i.e., visual) scale. However, the impact of these perturbations on the bacterial components of the biocrusts remains poorly understood. We employed multiple long-term field experiments to assess the impacts of chronic physical (foot trampling) and climatic changes (2°C soil warming, altered summer precipitation [wetting], and combined warming and wetting) on biocrust bacterial biomass, composition, and metabolic profile. The biocrust bacterial communities adopted distinct states based on the mechanism of disturbance. Chronic trampling decreased biomass and caused small community compositional changes. Soil warming had little effect on biocrust biomass or composition, while wetting resulted in an increase in the cyanobacterial biomass and altered bacterial composition. Warming combined with wetting dramatically altered bacterial composition and decreased Cyanobacteria abundance. Shotgun metagenomic sequencing identified four functional gene categories that differed in relative abundance among the manipulations, suggesting that climate and land use changes affected soil bacterial functional potential. This study illustrates that different types of biocrust disturbance damage biocrusts in macroscopically similar ways, but they differentially impact the resident soil bacterial communities, and the communities' functional profiles can differ depending on the disturbance type. Therefore, the nature of the perturbation and the microbial response are important considerations for management and restoration of drylands.

  19. Transcriptomic analysis using olive varieties and breeding progenies identify candidate genes involved in plant architecture

    Directory of Open Access Journals (Sweden)

    Juan José eGonzález Plaza

    2016-03-01

    Full Text Available Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2,252 differentially expressed genes associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  20. Transcriptomic Analysis Using Olive Varieties and Breeding Progenies Identifies Candidate Genes Involved in Plant Architecture.

    Science.gov (United States)

    González-Plaza, Juan J; Ortiz-Martín, Inmaculada; Muñoz-Mérida, Antonio; García-López, Carmen; Sánchez-Sevilla, José F; Luque, Francisco; Trelles, Oswaldo; Bejarano, Eduardo R; De La Rosa, Raúl; Valpuesta, Victoriano; Beuzón, Carmen R

    2016-01-01

    Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2252 differentially expressed genes (DEGs) associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  1. Characterizing genomic alterations in cancer by complementary functional associations | Office of Cancer Genomics

    Science.gov (United States)

    Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment.

  2. Author Identifiers in Scholarly Repositories

    CERN Document Server

    Warner, Simeon

    2010-01-01

    Bibliometric and usage-based analyses and tools highlight the value of information about scholarship contained within the network of authors, articles and usage data. Less progress has been made on populating and using the author side of this network than the article side, in part because of the difficulty of unambiguously identifying authors. I briefly review a sample of author identifier schemes, and consider use in scholarly repositories. I then describe preliminary work at arXiv to implement public author identifiers, services based on them, and plans to make this information useful beyond the boundaries of arXiv.

  3. Network modeling identifies molecular functions targeted by miR-204 to suppress head and neck tumor metastasis.

    Directory of Open Access Journals (Sweden)

    Younghee Lee

    2010-04-01

    Full Text Available Due to the large number of putative microRNA gene targets predicted by sequence-alignment databases and the relative low accuracy of such predictions which are conducted independently of biological context by design, systematic experimental identification and validation of every functional microRNA target is currently challenging. Consequently, biological studies have yet to identify, on a genome scale, key regulatory networks perturbed by altered microRNA functions in the context of cancer. In this report, we demonstrate for the first time how phenotypic knowledge of inheritable cancer traits and of risk factor loci can be utilized jointly with gene expression analysis to efficiently prioritize deregulated microRNAs for biological characterization. Using this approach we characterize miR-204 as a tumor suppressor microRNA and uncover previously unknown connections between microRNA regulation, network topology, and expression dynamics. Specifically, we validate 18 gene targets of miR-204 that show elevated mRNA expression and are enriched in biological processes associated with tumor progression in squamous cell carcinoma of the head and neck (HNSCC. We further demonstrate the enrichment of bottleneckness, a key molecular network topology, among miR-204 gene targets. Restoration of miR-204 function in HNSCC cell lines inhibits the expression of its functionally related gene targets, leads to the reduced adhesion, migration and invasion in vitro and attenuates experimental lung metastasis in vivo. As importantly, our investigation also provides experimental evidence linking the function of microRNAs that are located in the cancer-associated genomic regions (CAGRs to the observed predisposition to human cancers. Specifically, we show miR-204 may serve as a tumor suppressor gene at the 9q21.1-22.3 CAGR locus, a well established risk factor locus in head and neck cancers for which tumor suppressor genes have not been identified. This new strategy

  4. Computational systems biology in cancer brain metastasis.

    Science.gov (United States)

    Peng, Huiming; Tan, Hua; Zhao, Weiling; Jin, Guangxu; Sharma, Sambad; Xing, Fei; Watabe, Kounosuke; Zhou, Xiaobo

    2016-01-01

    Brain metastases occur in 20-40% of patients with advanced malignancies. A better understanding of the mechanism of this disease will help us to identify novel therapeutic strategies. In this review, we will discuss the systems biology approaches used in this area, including bioinformatics and mathematical modeling. Bioinformatics has been used for identifying the molecular mechanisms driving brain metastasis and mathematical modeling methods for analyzing dynamics of a system and predicting optimal therapeutic strategies. We will illustrate the strategies, procedures, and computational techniques used for studying systems biology in cancer brain metastases. We will give examples on how to use a systems biology approach to analyze a complex disease. Some of the approaches used to identify relevant networks, pathways, and possibly biomarkers in metastasis will be reviewed into details. Finally, certain challenges and possible future directions in this area will also be discussed.

  5. Genetic alterations in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Muhammad Wasif Saif; Lena Karapanagiotou; Kostas Syrigos

    2007-01-01

    The diagnosis of pancreatic cancer is devastating for patients and their relatives as the incidence rate is approximately the same as mortality rate. Only a small percentage, which ranges from 0.4% to 4% of patients who have been given this diagnosis, will be alive at five years. At the time of diagnosis, 80% of pancreatic cancer patients have unresectable or metastatic disease.Moreover, the therapeutic alternatives offered by chemotherapy or radiotherapy are few, if not zero. For all these reasons, there is an imperative need of analyzing and understanding the primitive lesions that lead to invasive pancreatic adenocarcinoma. Molecular pathology of these lesions is the key of our understanding of the mechanisms underlying the development of this cancer and will probably help us in earlier diagnosis and better therapeutic results. This review focuses on medical research on pancreatic cancer models and the underlying genetic alterations.

  6. Peripheral whole blood microRNA alterations in major depression and bipolar disorder.

    Science.gov (United States)

    Maffioletti, Elisabetta; Cattaneo, Annamaria; Rosso, Gianluca; Maina, Giuseppe; Maj, Carlo; Gennarelli, Massimo; Tardito, Daniela; Bocchio-Chiavetto, Luisella

    2016-08-01

    Major depression (MD) and bipolar disorder (BD) are severe and potentially life-threating mood disorders whose etiology is to date not completely understood. MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein synthesis post-transcriptionally by base-pairing to target gene mRNAs. Growing evidence indicated that miRNAs might play a key role in the pathogenesis of neuropsychiatric disorders and in the action of psychotropic drugs. On these bases, in this study we evaluated the expression levels of 1733 mature miRNAs annotated in miRBase v.17, through a microarray technique, in the blood of 20 MD and 20 BD patients and 20 healthy controls, in order to identify putative miRNA signatures associated with mood disorders. We found that 5 miRNAs (hsa-let-7a-5p, hsa-let-7d-5p, hsa-let-7f-5p, hsa-miR-24-3p and hsa-miR-425-3p) were specifically altered in MD patients and 5 (hsa-miR-140-3p, hsa-miR-30d-5p, hsa-miR-330-5p, hsa-miR-378a-5p and hsa-miR-21-3p) in BD patients, whereas 2 miRNAs (hsa-miR-330-3p and hsa-miR-345-5p) were dysregulated in both the diseases. The bioinformatic prediction of the genes targeted by the altered miRNAs revealed the possible involvement of neural pathways relevant for psychiatric disorders. In conclusion, the observed results indicate a dysregulation of miRNA blood expression in mood disorders and could indicate new avenues for a better understanding of their pathogenetic mechanisms. The identified alterations may represent potential peripheral biomarkers to be complemented with other clinical and biological features for the improvement of diagnostic accuracy.

  7. Alteration of Heterogeneous Ice Nucleation Properties Induced by Particle Aging

    Science.gov (United States)

    Sullivan, R. C.; Polen, M.; Beydoun, H.; Lawlis, E.; Ahern, A.; Jahn, L.; Hill, T. C. J.

    2015-12-01

    Aerosol particles that can serve as ice nuclei frequently experience rapid and extensive chemical aging during atmospheric transport. This is known to significantly alter some ice nucleation modes of the few types of ice nucleation particle systems where aging effects have been simulated, such as for mineral dust. Yet much of our understanding of atmospheric particle freezing properties is derived from measurements of fresh or unaged particles. We know almost nothing regarding how atmospheric aging might alter the freezing properties of biomass burning aerosol or biological particle nucleants. We have investigated the effects of simulated aging using a chamber reactor on the heterogeneous ice nucleation properties of biomass burning aerosol (BBA) and ice-active bacteria particles. Some types of aging were found to enhance the freezing ability of BBA, exhibited as a shift in a portion of the droplet freezing curve to warmer temperatures by a few °C. Ice-active bacteria were found to consistently loose their most ice-active nucleants after repeated aging cycles. The bacterial systems always retained significantly efficient ice active sites that still allowed them to induce freezing at mild/warm temperatures, despite this decrease in freezing ability. A comprehensive series of online single-particle mass spectrometry and offline spectromicroscopic analysis of individual particles was used to determine how the aging altered the aerosol's composition, and gain mechanistic insights into how this in turn altered the freezing properties. Our new ice nucleation framework that uses a continuous distribution of ice active site ability (contact angle) was used to interpret the droplet freezing spectra and understand how aging alters the internal and external variability, and rigidity, of the ice active sites.

  8. Identifying Occupationally Specific Affective Behaviors.

    Science.gov (United States)

    Pucel, David J.

    1993-01-01

    Data from two groups of cosmetology instructors (n=15) and two groups of machinist instructors (n=17) validated the Occupational Affective Behavior Analysis instrument as capable of identifying affective behaviors viewed as important to success in a given occupation. (SK)

  9. Alkaline phosphatases and aminopeptidases are altered in a Cry11Aa resistant strain of Aedes aegypti.

    Science.gov (United States)

    Lee, Su-Bum; Aimanova, Karlygash G; Gill, Sarjeet S

    2014-11-01

    Bacillus thuringiensis subsp. israelensis (Bti) is widely used for the biological control of mosquito populations. However, the mechanism of Bti toxins is still not fully understood. To further elucidate the mechanism of Bti toxins, we developed an Aedes aegypti resistant strain that shows high-level resistance to Cry11Aa toxin. After 27 selections with Cry11Aa toxin, the larvae showed a 124-fold resistance ratio for Cry11Aa (strain G30). G30 larvae showed cross-resistance to Cry4Aa (66-fold resistance), less to Cry4Ba (13-fold), but not to Cry11Ba (2-fold). Midguts from these resistant larvae did not show detectable difference in the processing of the Cry11Aa toxin compared to that in susceptible larvae (WT). Brush border membrane vesicles (BBMV) from resistant larvae bound slightly less Cry11Aa compared to WT BBMV. To identify potential proteins associated with Cry11A resistance, not only transcript changes in the larval midgut were analyzed using Illumina sequencing and qPCR, but alterations of previously identified receptor proteins were investigated using immunoblots. The transcripts of 375 genes were significantly increased and those of 208 genes were down regulated in the resistant larvae midgut compared to the WT. None of the transcripts for previously identified receptors of Cry11Aa (Aedes cadherin, ALP1, APN1, and APN2) were altered in these analyses. The genes for the identified functional receptors in resistant larvae midgut did not contain any mutation in their sequences nor was there any change in their transcript expression levels compared to WT. However, ALP proteins were expressed at reduced levels (∼ 40%) in the resistant strain BBMV. APN proteins and their activity were also slightly reduced in resistance strain. The transcript levels of ALPs (AAEL013330 and AAEL015070) and APNs (AAEL008158, AAEL008162) were significantly reduced. These results strongly suggest that ALPs and APNs could be associated with Cry11Aa resistance in Ae. aegypti. PMID

  10. Algorithms to identify failure pattern

    OpenAIRE

    Poudel, Bhuwan Krishna Som

    2013-01-01

    This project report was written for ?Algorithms to Identify Failure Pattern? at NTNU (Norwegian University of Science and Technology), IME (Faculty of Information Technology, Mathematics and Electrical Engineering) and IDI (Department of Computer Science).In software application, there are three types of failure pattern: point pattern, block pattern and stripe pattern. The purpose of the report is to prepare an algorithm that identifies the pattern in a software application. Only theoretical ...

  11. Branching processes in biology

    CERN Document Server

    Kimmel, Marek

    2015-01-01

    This book provides a theoretical background of branching processes and discusses their biological applications. Branching processes are a well-developed and powerful set of tools in the field of applied probability. The range of applications considered includes molecular biology, cellular biology, human evolution and medicine. The branching processes discussed include Galton-Watson, Markov, Bellman-Harris, Multitype, and General Processes. As an aid to understanding specific examples, two introductory chapters, and two glossaries are included that provide background material in mathematics and in biology. The book will be of interest to scientists who work in quantitative modeling of biological systems, particularly probabilists, mathematical biologists, biostatisticians, cell biologists, molecular biologists, and bioinformaticians. The authors are a mathematician and cell biologist who have collaborated for more than a decade in the field of branching processes in biology for this new edition. This second ex...

  12. Individual Identifiability Predicts Population Identifiability in Forensic Microsatellite Markers.

    Science.gov (United States)

    Algee-Hewitt, Bridget F B; Edge, Michael D; Kim, Jaehee; Li, Jun Z; Rosenberg, Noah A

    2016-04-01

    Highly polymorphic genetic markers with significant potential for distinguishing individual identity are used as a standard tool in forensic testing [1, 2]. At the same time, population-genetic studies have suggested that genetically diverse markers with high individual identifiability also confer information about genetic ancestry [3-6]. The dual influence of polymorphism levels on ancestry inference and forensic desirability suggests that forensically useful marker sets with high levels of individual identifiability might also possess substantial ancestry information. We study a standard forensic marker set-the 13 CODIS loci used in the United States and elsewhere [2, 7-9]-together with 779 additional microsatellites [10], using direct population structure inference to test whether markers with substantial individual identifiability also produce considerable information about ancestry. Despite having been selected for individual identification and not for ancestry inference [11], the CODIS markers generate nontrivial model-based clustering patterns similar to those of other sets of 13 tetranucleotide microsatellites. Although the CODIS markers have relatively low values of the F(ST) divergence statistic, their high heterozygosities produce greater ancestry inference potential than is possessed by less heterozygous marker sets. More generally, we observe that marker sets with greater individual identifiability also tend toward greater population identifiability. We conclude that population identifiability regularly follows as a byproduct of the use of highly polymorphic forensic markers. Our findings have implications for the design of new forensic marker sets and for evaluations of the extent to which individual characteristics beyond identification might be predicted from current and future forensic data.

  13. Germline CDKN2A/ARF alterations in human melanoma

    OpenAIRE

    Hashemi, Jamileh

    2002-01-01

    Approximately 10% of cases of human cutaneous malignant melanoma (CMM) have been estimated to occur in individuals with a familial predisposition, frequently in association with dysplastic nevus syndrome (DNS). The genetics of familial melanoma is complex and heterogeneous. To date only two melanoma predisposing genes have been identified. The CDKN2A/ARF locus on human chromosome 9p21 encodes two distinct cell cycle regulatory proteins, p16 and p14ARF. Germline alterations i...

  14. Vascular transcriptional alterations produced by juvenile obesity in Ossabaw swine

    OpenAIRE

    Padilla, Jaume; Jenkins, Nathan T.; Lee, Sewon; Zhang, Hanrui; Cui, Jian; Zuidema, Mozow Y.; Zhang, Cuihua; Hill, Michael A; Perfield, James W.; Jamal A. Ibdah; Booth, Frank W.; Davis, J Wade; Laughlin, M. Harold; Rector, R. Scott

    2013-01-01

    We adopted a transcriptome-wide microarray analysis approach to determine the extent to which vascular gene expression is altered as a result of juvenile obesity and identify obesity-responsive mRNAs. We examined transcriptional profiles in the left anterior descending coronary artery (LAD), perivascular fat adjacent to the LAD, and descending thoracic aorta between obese (n = 5) and lean (n = 6) juvenile Ossabaw pigs (age = 22 wk). Obesity was experimentally induced by feeding the animals a ...

  15. Ultrastructural alterations in adult Schistosoma mansoni caused by artemether

    OpenAIRE

    Xiao Shuhua; Shen Binggui; Utzinger Jürg; Chollet Jacques; Tanner Marcel

    2002-01-01

    Progress has been made over the last decade with the development and clinical use of artemether as an agent against major human schistosome parasites. The tegument has been identified as a key target of artemether, implying detailed studies on ultrastructural damage induced by this compound. We performed a temporal examination, employing a transmission electron microscope to assess the pattern and extent of ultrastructural alterations in adult Schistosoma mansoni harboured in mice treated wit...

  16. Foundations of biology

    OpenAIRE

    Sikorav, Jean-Louis; Braslau, Alan; Goldar, Arach

    2014-01-01

    It is often stated that there are no laws in biology, where everything is contingent and could have been otherwise, being solely the result of historical accidents. Furthermore, the customary introduction of fundamental biological entities such as individual organisms, cells, genes, catalysts and motors remains largely descriptive; constructive approaches involving deductive reasoning appear, in comparison, almost absent. As a consequence, both the logical content and principles of biology ne...

  17. Introducing Aquatic Biology

    OpenAIRE

    Kinne, Otto; Browman, Howard I.; Seaman, Matthias

    2007-01-01

    The Inter-Research Science Center (IR) journals Marine Ecology Progress Series (MEPS) and Aquatic Microbial Ecology (AME) have been receiving increasing numbers of high-quality manuscripts that are principally biological, rather than ecological. With regret, we have had to turn these submissions away. Also, leading limnologists have for many years suggested that IR should provide an outlet for top quality articles on freshwater biology and ecology. Aquatic Biology (...

  18. Glycobiology Current Molecular Biology

    OpenAIRE

    Sabire KARAÇALI

    2003-01-01

    Carbohydrate chemistry evolved into carbohydrate biochemistry and gradually into the biology of carbohydrates, or glycobiology, at the end of the last century. Glycobiology is the new research area of modern molecular biology, and it investigates the structure, biosynthesis and biological functions of glycans. The numbers, linkage types (a or b), positions, binding points and functional group differences of monosaccharides create microheterogeneity. Thus, numerous glycoforms with precise stru...

  19. Synthetic biology: mapping the scientific landscape.

    Directory of Open Access Journals (Sweden)

    Paul Oldham

    Full Text Available This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves.

  20. Perception of biological motion in visual agnosia

    Directory of Open Access Journals (Sweden)

    Elisabeth eHuberle

    2012-08-01

    Full Text Available Over the past twenty-five years, visual processing has been discussed in the context of the dual stream hypothesis consisting of a ventral (‘what' and a dorsal ('where' visual information processing pathway. Patients with brain damage of the ventral pathway typically present with signs of visual agnosia, the inability to identify and discriminate objects by visual exploration, but show normal perception of motion perception. A dissociation between the perception of biological motion and non-biological motion has been suggested: Perception of biological motion might be impaired when 'non-biological' motion perception is intact and vice versa. The impact of object recognition on the perception of biological motion remains unclear. We thus investigated this question in a patient with severe visual agnosia, who showed normal perception of non-biological motion. The data suggested that the patient's perception of biological motion remained largely intact. However, when tested with objects constructed of coherently moving dots (‘Shape-from-Motion’, recognition was severely impaired. The results are discussed in the context of possible mechanisms of biological motion perception.

  1. Perception of biological motion in visual agnosia.

    Science.gov (United States)

    Huberle, Elisabeth; Rupek, Paul; Lappe, Markus; Karnath, Hans-Otto

    2012-01-01

    Over the past 25 years, visual processing has been discussed in the context of the dual stream hypothesis consisting of a ventral ("what") and a dorsal ("where") visual information processing pathway. Patients with brain damage of the ventral pathway typically present with signs of visual agnosia, the inability to identify and discriminate objects by visual exploration, but show normal perception of motion perception. A dissociation between the perception of biological motion and non-biological motion has been suggested: perception of biological motion might be impaired when "non-biological" motion perception is intact and vice versa. The impact of object recognition on the perception of biological motion remains unclear. We thus investigated this question in a patient with severe visual agnosia, who showed normal perception of non-biological motion. The data suggested that the patient's perception of biological motion remained largely intact. However, when tested with objects constructed of coherently moving dots ("Shape-from-Motion"), recognition was severely impaired. The results are discussed in the context of possible mechanisms of biological motion perception.

  2. Biological aerosol background characterization

    Science.gov (United States)

    Blatny, Janet; Fountain, Augustus W., III

    2011-05-01

    To provide useful information during military operations, or as part of other security situations, a biological aerosol detector has to respond within seconds or minutes to an attack by virulent biological agents, and with low false alarms. Within this time frame, measuring virulence of a known microorganism is extremely difficult, especially if the microorganism is of unknown antigenic or nucleic acid properties. Measuring "live" characteristics of an organism directly is not generally an option, yet only viable organisms are potentially infectious. Fluorescence based instruments have been designed to optically determine if aerosol particles have viability characteristics. Still, such commercially available biological aerosol detection equipment needs to be improved for their use in military and civil applications. Air has an endogenous population of microorganisms that may interfere with alarm software technologies. To design robust algorithms, a comprehensive knowledge of the airborne biological background content is essential. For this reason, there is a need to study ambient live bacterial populations in as many locations as possible. Doing so will permit collection of data to define diverse biological characteristics that in turn can be used to fine tune alarm algorithms. To avoid false alarms, improving software technologies for biological detectors is a crucial feature requiring considerations of various parameters that can be applied to suppress alarm triggers. This NATO Task Group will aim for developing reference methods for monitoring biological aerosol characteristics to improve alarm algorithms for biological detection. Additionally, they will focus on developing reference standard methodology for monitoring biological aerosol characteristics to reduce false alarm rates.

  3. Expression and structural-functional alterations of α-1-acid glycoprotein at the pathological state

    Directory of Open Access Journals (Sweden)

    Kulinich A. O.

    2010-07-01

    Full Text Available The review analyzes up-to-date knowledge on structure and biological functions of α-acid glycoprotein. The special attention is given to alterations of fucosylation, sialylation and branching of orosomucoid at the acute, chronic inflammation and oncotransformations.

  4. MATERNAL ATRAZINE (ATR) ALTERS HYPOTHALAMIC DOPAMINE (HYP-DA) AND SERUM PROLACTIN (SPRL) IN MALE PUPS

    Science.gov (United States)

    Maternal Atrazine (ATR) alters hypothalamic dopamine (HYP-DA) and serum prolactin (sPRL) in male pups. 1Christopher Langdale, 2Tammy Stoker and 2Ralph Cooper. 1 Dept. of Cell Biology, North Carolina State University College of Veterinary Medicine, Raleigh, NC. 2 Endocrinology ...

  5. Data for mitochondrial proteomic alterations in the developing rat brain.

    Science.gov (United States)

    Villeneuve, Lance M; Stauch, Kelly L; Fox, Howard S

    2014-12-01

    Mitochondria are a critical organelle involved in many cellular processes, and due to the nature of the brain, neuronal cells are almost completely reliant on these organelles for energy generation. Due to the fact that biomedical research tends to investigate disease state pathogenesis, one area of mitochondrial research commonly overlooked is homeostatic responses to energy demands. Therefore, to elucidate mitochondrial alterations occurring during the developmentally important phase of E18 to P7 in the brain, we quantified the proteins in the mitochondrial proteome as well as proteins interacting with the mitochondria. We identified a large number of significantly altered proteins involved in a variety of pathways including glycolysis, mitochondrial trafficking, mitophagy, and the unfolded protein response. These results are important because we identified alterations thought to be homeostatic in nature occurring within mitochondria, and these results may be used to identify any abnormal deviations in the mitochondrial proteome occurring during this period of brain development. A more comprehensive analysis of this data may be obtained from the article "Proteomic analysis of mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands" in the Journal of Proteomics. PMID:26217684

  6. [Autism, genetics and synaptic function alterations].

    Science.gov (United States)

    Perche, O; Laumonnier, F; Baala, L; Ardourel, M-Y; Menuet, A; Robin, V; Mortaud, S; Montécot-Dubourg, C; Richard, O; Pichon, J; Briault, S

    2010-10-01

    Autism is a neurodevelopmental disorder characterized by a deficit of language and communication both associated with a restricted repertoire of activities and interests. The current prevalence of autistic disorder stricto sensu is estimated at 1/500 whereas autism spectrum disorders (ASD) increases up to 1/150 to 1/200. Mental deficiency (MD) and epilepsy are present in numerous autistic individuals. Consequently, autism is as a major public health issue. Autism was first considered as a non biological disease; however various rational approaches for analysing epidemiological data suggested the possibility of the influence of genetic factors. In 2003, this hypothesis was clearly illustrated by the characterization of genetic mutations transmitted through a mendelian manner. Subsequently, the glutamate synapse appeared as a preferential causal target in autism because the identified genes encoded proteins present in this structure. Strikingly, the findings that an identical genetic dysfunction of the synapse might also explain some MD suggested the possibility of a genetic comorbidity between these neurodevelopmental conditions. To date, various identified genes are considered indifferently as "autism" or "MD" genes. The characterization of mutations in the NLGN4X gene in patients with Asperger syndrome, autism without MD, or MD without autism, was the first example. It appears that a genetic continuum between ASD on one hand, and between autism and MD on the other hand, is present. Consequently, it is likely that genes already involved in MD will be found mutated in autistic patients and will represent future target for finding new factors in autism.

  7. Biological effects of ionizing radiation

    International Nuclear Information System (INIS)

    In this review radiation produced by the nuclear industry is placed into context with other sources of radiation in our world. Human health effects of radiation, derivation of standards and risk estimates are reviewed in this document. The implications of exposing the worker and the general population to radiation generated by nuclear power are assessed. Effects of radiation are also reviewed. Finally, gaps in our knowledge concerning radiation are identified and current research on biological effects, on environmental aspects, and on dosimetry of radiation within AECL and Canada is documented in this report. (author)

  8. Triclosan exposure alters postembryonic development in a Pacific tree frog (Pseudacris regilla) Amphibian Metamorphosis Assay (TREEMA)

    International Nuclear Information System (INIS)

    The Amphibian Metamorphosis Assay (AMA), developed for Xenopus laevis, is designed to identify chemicals that disrupt thyroid hormone (TH)-mediated biological processes. We adapted the AMA for use on an ecologically-relevant North American species, the Pacific tree frog (Pseudacris regilla), and applied molecular endpoints to evaluate the effects of the antibacterial agent, triclosan (TCS). Premetamorphic (Gosner stage 26–28) tadpoles were immersed for 21 days in solvent control, 1.5 μg/L thyroxine (T4), 0.3, 3 and 30 μg/L (nominal) TCS, or combined T4/TCS treatments. Exposure effects were scored by morphometric (developmental stage, wet weight, and body, snout-vent and hindlimb lengths) and molecular (mRNA abundance using quantitative real time polymerase chain reaction) criteria. T4 treatment alone accelerated development concomitant with altered levels of TH receptors α and β, proliferating cell nuclear antigen, and gelatinase B mRNAs in the brain and tail. We observed TCS-induced perturbations in all of the molecular and morphological endpoints indicating that TCS exposure disrupts coordination of postembryonic tadpole development. Clear alterations in molecular endpoints were evident at day 2 whereas the earliest morphological effects appeared at day 4 and were most evident at day 21. Although TCS alone (3 and 30 μg/L) was protective against tadpole mortality, this protection was lost in the presence of T4. The Pacific tree frog is the most sensitive species examined to date displaying disruption of TH-mediated development by a common antimicrobial agent.

  9. Triclosan exposure alters postembryonic development in a Pacific tree frog (Pseudacris regilla) Amphibian Metamorphosis Assay (TREEMA)

    Energy Technology Data Exchange (ETDEWEB)

    Marlatt, Vicki L. [Nautilus Environmental, 8864 Commerce Court, Burnaby, B.C. V5A 4N7 (Canada); Veldhoen, Nik [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055 Stn CSC, Victoria, B.C. V8W 3P6 (Canada); Lo, Bonnie P. [Nautilus Environmental, 8864 Commerce Court, Burnaby, B.C. V5A 4N7 (Canada); Bakker, Dannika; Rehaume, Vicki; Vallee, Kurtis [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055 Stn CSC, Victoria, B.C. V8W 3P6 (Canada); Haberl, Maxine; Shang, Dayue; Aggelen, Graham C. van; Skirrow, Rachel C. [Pacific and Yukon Laboratory for Environmental Testing, Emergencies Operational Analytical Laboratories and Research Support Division, Environment Canada, 2645 Dollarton Highway, North Vancouver, B.C. V7H 1B1 (Canada); Elphick, James R. [Nautilus Environmental, 8864 Commerce Court, Burnaby, B.C. V5A 4N7 (Canada); Helbing, Caren C., E-mail: chelbing@uvic.ca [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055 Stn CSC, Victoria, B.C. V8W 3P6 (Canada)

    2013-01-15

    The Amphibian Metamorphosis Assay (AMA), developed for Xenopus laevis, is designed to identify chemicals that disrupt thyroid hormone (TH)-mediated biological processes. We adapted the AMA for use on an ecologically-relevant North American species, the Pacific tree frog (Pseudacris regilla), and applied molecular endpoints to evaluate the effects of the antibacterial agent, triclosan (TCS). Premetamorphic (Gosner stage 26-28) tadpoles were immersed for 21 days in solvent control, 1.5 {mu}g/L thyroxine (T{sub 4}), 0.3, 3 and 30 {mu}g/L (nominal) TCS, or combined T{sub 4}/TCS treatments. Exposure effects were scored by morphometric (developmental stage, wet weight, and body, snout-vent and hindlimb lengths) and molecular (mRNA abundance using quantitative real time polymerase chain reaction) criteria. T{sub 4} treatment alone accelerated development concomitant with altered levels of TH receptors {alpha} and {beta}, proliferating cell nuclear antigen, and gelatinase B mRNAs in the brain and tail. We observed TCS-induced perturbations in all of the molecular and morphological endpoints indicating that TCS exposure disrupts coordination of postembryonic tadpole development. Clear alterations in molecular endpoints were evident at day 2 whereas the earliest morphological effects appeared at day 4 and were most evident at day 21. Although TCS alone (3 and 30 {mu}g/L) was protective against tadpole mortality, this protection was lost in the presence of T{sub 4}. The Pacific tree frog is the most sensitive species examined to date displaying disruption of TH-mediated development by a common antimicrobial agent.

  10. Biological features and biomarkers in hepatocellularcarcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Similar to other cancers, a multistep process of carcinogenesisis observed in hepatocellular carcinoma (HCC).Although the mechanisms underlying the developmentof HCC have been investigated in terms of oncology,virology, and stem cell biology, the whole picture ofhepatocarcinogenesis remains to be elucidated. Recentprogress in molecular biology has provided clues tothe underlying cause of various diseases. In particular,sequencing technologies, such as whole genome andexome sequencing analyses, have made an impacton genomic research on a variety of cancers includingHCC. Comprehensive genomic analyses have detectednumerous abnormal genetic alterations, such asmutations and copy number alterations. Based on thesefindings, signaling pathways and cancer-related genesinvolved in hepatocarcinogenesis could be analyzed indetail. Simultaneously, a number of novel biomarkers,both from tissue and blood samples, have been recentlyreported. These biomarkers have been successfullyapplied to early diagnosis and prognostic prediction ofpatients with HCC. In this review, we focus on the recentdevelopments in molecular cancer research on HCC andexplain the biological features and novel biomarkers.

  11. Sparse Linear Identifiable Multivariate Modeling

    DEFF Research Database (Denmark)

    Henao, Ricardo; Winther, Ole

    2011-01-01

    In this paper we consider sparse and identifiable linear latent variable (factor) and linear Bayesian network models for parsimonious analysis of multivariate data. We propose a computationally efficient method for joint parameter and model inference, and model comparison. It consists of a fully...... Bayesian hierarchy for sparse models using slab and spike priors (two-component δ-function and continuous mixtures), non-Gaussian latent factors and a stochastic search over the ordering of the variables. The framework, which we call SLIM (Sparse Linear Identifiable Multivariate modeling), is validated...... computational complexity. We attribute this mainly to the stochastic search strategy used, and to parsimony (sparsity and identifiability), which is an explicit part of the model. We propose two extensions to the basic i.i.d. linear framework: non-linear dependence on observed variables, called SNIM (Sparse Non-linear...

  12. Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults.

    Science.gov (United States)

    Salaverria, Itziar; Philipp, Claudia; Oschlies, Ilske; Kohler, Christian W; Kreuz, Markus; Szczepanowski, Monika; Burkhardt, Birgit; Trautmann, Heiko; Gesk, Stefan; Andrusiewicz, Miroslaw; Berger, Hilmar; Fey, Miriam; Harder, Lana; Hasenclever, Dirk; Hummel, Michael; Loeffler, Markus; Mahn, Friederike; Martin-Guerrero, Idoia; Pellissery, Shoji; Pott, Christiane; Pfreundschuh, Michael; Reiter, Alfred; Richter, Julia; Rosolowski, Maciej; Schwaenen, Carsten; Stein, Harald; Trümper, Lorenz; Wessendorf, Swen; Spang, Rainer; Küppers, Ralf; Klapper, Wolfram; Siebert, Reiner

    2011-07-01

    The prognosis of germinal center-derived B-cell (GCB) lymphomas, including follicular lymphoma and diffuse large-B-cell lymphoma (DLBCL), strongly depends on age. Children have a more favorable outcome than adults. It is not known whether this is because of differences in host characteristics, treatment protocols, or tumor biology, including the presence of chromosomal alterations. By screening for novel IGH translocation partners in pediatric and adult lymphomas, we identified chromosomal translocations juxtaposing the IRF4 oncogene next to one of the immunoglobulin (IG) loci as a novel recurrent aberration in mature B-cell lymphoma. FISH revealed 20 of 427 lymphomas to carry an IG/IRF4-fusion. Those were predominantly GCB-type DLBCL or follicular lymphoma grade 3, shared strong expression of IRF4/MUM1 and BCL6, and lacked PRDM1/BLIMP1 expression and t(14;18)/BCL2 breaks. BCL6 aberrations were common. The gene expression profile of IG/IRF4-positive lymphomas differed from other subtypes of DLBCL. A classifier for IG/IRF4 positivity containing 27 genes allowed accurate prediction. IG/IRF4 positivity was associated with young age and a favorable outcome. Our results suggest IRF4 translocations to be primary alterations in a molecularly defined subset of GCB-derived lymphomas. The probability for this subtype of lymphoma significantly decreases with age, suggesting that diversity in tumor biology might contribute to the age-dependent differences in prognosis of lymphoma. PMID:21487109

  13. Semi-automatic classification of skeletal morphology in genetically altered mice using flat-panel volume computed tomography.

    Directory of Open Access Journals (Sweden)

    Christian Dullin

    2007-07-01

    Full Text Available Rapid progress in exploring the human and mouse genome has resulted in the generation of a multitude of mouse models to study gene functions in their biological context. However, effective screening methods that allow rapid noninvasive phenotyping of transgenic and knockout mice are still lacking. To identify murine models with bone alterations in vivo, we used flat-panel volume computed tomography (fpVCT for high-resolution 3-D imaging and developed an algorithm with a computational intelligence system. First, we tested the accuracy and reliability of this approach by imaging discoidin domain receptor 2- (DDR2- deficient mice, which display distinct skull abnormalities as shown by comparative landmark-based analysis. High-contrast fpVCT data of the skull with 200 microm isotropic resolution and 8-s scan time allowed segmentation and computation of significant shape features as well as visualization of morphological differences. The application of a trained artificial neuronal network to these datasets permitted a semi-automatic and highly accurate phenotype classification of DDR2-deficient compared to C57BL/6 wild-type mice. Even heterozygous DDR2 mice with only subtle phenotypic alterations were correctly determined by fpVCT imaging and identified as a new class. In addition, we successfully applied the algorithm to classify knockout mice lacking the DDR1 gene with no apparent skull deformities. Thus, this new method seems to be a potential tool to identify novel mouse phenotypes with skull changes from transgenic and knockout mice on the basis of random mutagenesis as well as from genetic models. However for this purpose, new neuronal networks have to be created and trained. In summary, the combination of fpVCT images with artificial neuronal networks provides a reliable, novel method for rapid, cost-effective, and noninvasive primary screening tool to detect skeletal phenotypes in mice.

  14. Football refereeing: Identifying innovative methods

    Directory of Open Access Journals (Sweden)

    Reza MohammadKazemi

    2014-08-01

    Full Text Available The aim of the present study is to identify the potentials innovation in football industry. Data were collected from 10 national and international referees, assistant referees and referees’ supervisors in Iran. In this study, technological innovations are identified that assist better refereeing performances. The analysis revealed a significant relationship between using new technologies and referees ‘performance. The results indicate that elite referees, assistant referees and supervisors agreed to use new technological innovations during the game. According to their comments, this kind of technology causes the referees’ performance development.

  15. Hindlimb unloading alters ligament healing

    Science.gov (United States)

    Provenzano, Paolo P.; Martinez, Daniel A.; Grindeland, Richard E.; Dwyer, Kelley W.; Turner, Joanne; Vailas, Arthur C.; Vanderby, Ray Jr

    2003-01-01

    We investigated the hypothesis that hindlimb unloading inhibits healing in fibrous connective tissue such as ligament. Male rats were assigned to 3- and 7-wk treatment groups with three subgroups each: sham control, ambulatory healing, and hindlimb-suspended healing. Ambulatory and suspended animals underwent surgical rupture of their medial collateral ligaments, whereas sham surgeries were performed on control animals. After 3 or 7 wk, mechanical and/or morphological properties were measured in ligament, muscle, and bone. During mechanical testing, most suspended ligaments failed in the scar region, indicating the greatest impairment was to ligament and not to bone-ligament insertion. Ligament testing revealed significant reductions in maximum force, ultimate stress, elastic modulus, and low-load properties in suspended animals. In addition, femoral mineral density, femoral strength, gastrocnemius mass, and tibialis anterior mass were significantly reduced. Microscopy revealed abnormal scar formation and cell distribution in suspended ligaments with extracellular matrix discontinuities and voids between misaligned, but well-formed, collagen fiber bundles. Hence, stress levels from ambulation appear unnecessary for formation of fiber bundles yet required for collagen to form structurally competent continuous fibers. Results support our hypothesis that hindlimb unloading impairs healing of fibrous connective tissue. In addition, this study provides compelling morphological evidence explaining the altered structure-function relationship in load-deprived healing connective tissue.

  16. Protamine alterations in human spermatozoa.

    Science.gov (United States)

    Jodar, Meritxell; Oliva, Rafael

    2014-01-01

    Protamines are the major nuclear proteins in sperm cells, having a crucial role in the correct packaging of the paternal DNA. The fact that protamine haploinsufficiency in mice resulted in abnormal chromatin packaging and male infertility suggested that the protamines could also be important candidates in explaining some of the idiopathic male infertility cases in humans. The first clinical studies focused on analyzing protamines at the protein level. Various studies have found the presence of an altered amount of protamines in some infertile patients, in contrast to the normal situation in fertile individuals where the two protamines, protamine 1 and protamine 2, are both present in approximately equal quantities. Subsequently, the protamine genes were the subject of various mutational genetic screening studies in search of variants that could be associated with deregulation in the protamine expression observed. The results of these protamine mutational studies showed that the presence of high penetrant mutations is a very rare cause of male infertility. However, some variants and some haplotypes described may behave as risk factors for male infertility. More recently, the presence of RNA in the mature sperm cell has also been investigated. The present chapter will introduce the basic aspects of protamine evolution and function and review the various articles published to date on the relationship between the protamines studied at the DNA, RNA, and protein levels and male infertility. PMID:23955674

  17. Integrated Biological Control

    International Nuclear Information System (INIS)

    Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects; and microorganisms such as molds that adversely affect the quality of the workplace environment). Biological control activities may be either preventive (apriori) or in response to existing contamination spread (aposteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and apriori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, aposteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response

  18. Biological pretreatment sewages water

    OpenAIRE

    Veselý, Václav

    2009-01-01

    Bachelor's thesis deals with waste water purification at the stage of pre-inflow of water into the biological waste water treatment plants. It is divided into two parts, a theoretical and calculation. The theoretical part deals about sewage water and the method of biological treatment. Design proposal is part of the activation tank for quantity EO.

  19. Experimenting with Mathematical Biology

    Science.gov (United States)

    Sanft, Rebecca; Walter, Anne

    2016-01-01

    St. Olaf College recently added a Mathematical Biology concentration to its curriculum. The core course, Mathematics of Biology, was redesigned to include a wet laboratory. The lab classes required students to collect data and implement the essential modeling techniques of formulation, implementation, validation, and analysis. The four labs…

  20. Biological Macromolecule Crystallization Database

    Science.gov (United States)

    SRD 21 Biological Macromolecule Crystallization Database (Web, free access)   The Biological Macromolecule Crystallization Database and NASA Archive for Protein Crystal Growth Data (BMCD) contains the conditions reported for the crystallization of proteins and nucleic acids used in X-ray structure determinations and archives the results of microgravity macromolecule crystallization studies.

  1. Bioinformatics and School Biology

    Science.gov (United States)

    Dalpech, Roger

    2006-01-01

    The rapidly changing field of bioinformatics is fuelling the need for suitably trained personnel with skills in relevant biological "sub-disciplines" such as proteomics, transcriptomics and metabolomics, etc. But because of the complexity--and sheer weight of data--associated with these new areas of biology, many school teachers feel…

  2. Evolving Human Alteration of the Carbon Cycle: the Watershed Continuum

    Science.gov (United States)

    Kaushal, S.; Delaney Newcomb, K.; Newcomer Johnson, T.; Pennino, M. J.; Smith, R. M.; Beaulieu, J. J.; Belt, K.; Grese, M.; Blomquist, J.; Duan, S.; Findlay, S.; Likens, G.; Mayer, P. M.; Murthy, S.; Utz, R.; Yepsen, M.

    2014-12-01

    Watersheds experiencing land development are constantly evolving, and their biogeochemical signatures are expected to evolve across both space and time in drainage waters. We investigate how land development influences spatial and temporal evolution of the carbon cycle from small streams to major rivers in the Eastern U.S. Along the watershed continuum, we show that there is spatial evolution in: (1) the amount, chemical form, and bioavailability of carbon; (2) carbon retention/release at the reach scale; and (3) ecosystem metabolism of carbon from headwaters to coastal waters. Over shorter time scales, the interaction between land use and climate variability alters magnitude and frequency of carbon "pulses" in watersheds. Amounts and forms of carbon pulses in agricultural and urban watersheds respond similarly to climate variability due to headwater alteration and loss of ecosystem services to buffer runoff and temperature changes. Over longer time scales, land use change has altered organic carbon concentrations in tidal waters of Chesapeake Bay, and there have been increased bicarbonate alkalinity concentrations in rivers throughout the Eastern U.S. due to human activities. In summary, our analyses indicates that the form and reactivity of carbon have evolved over space and time along the watershed continuum with major implications for downstream ecosystem metabolism, biological oxygen demand, carbon dioxide production, and river alkalinization.

  3. Mutant p53: multiple mechanisms define biologic activity in cancer

    Directory of Open Access Journals (Sweden)

    Michael Paul Kim

    2015-11-01

    Full Text Available The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of p53 alterations involve missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may acquire novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in multiple model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 are reviewed and their limitations discussed.

  4. Can we trust current estimates for biological nitrogen fixation?

    Science.gov (United States)

    Bellenger, Jean-Philippe; Kraepiel, Anne

    2016-04-01

    Biological nitrogen fixation (BNF) consists on the reduction of atmospheric dinitrogen (N2) into bioavailable ammonium. This reaction accounts for up to 97% of nitrogen (N) input in unmanaged terrestrial ecosystems. Closing the N budget is a long standing challenge in many ecosystems. Recent studies have highlighted that current methods used to assess BNF are affected by critical biases. These findings challenge our confidence in many N budgets and call for a profound reconsideration of our methodological approaches. Beside these methodological issues, our ability to properly assess BNF might be further altered as a result of a misconception regarding the importance of BNF enzymatic diversity in nature. BNF is catalyzed by the enzyme nitrogenase (Nase) for which three isoforms have been identified so far; the molybdenum (Mo), vanadium (V) and iron-only (Fe) isoforms. Currently BNF is mostly considered to primarily depend on the Mo isoform. The contribution of the alternative Nases (V and Fe isoforms) to BNF in natural habitats has been mostly overlooked. However, recent findings have challenged this traditional view of the Nases hierarchy (Mo isoform predominance) with deep implications for BNF assessment in the field. Here, I will present an overview of recent findings, provided by various research groups, challenging current methods used to assess BNF. I will also present a summary of recent studies highlighting the importance of alternative Nases in nature. I will finally illustrate how altering our view on the Mo-Nase predominance can deeply affect our confidence in current BNF estimates. I will conclude by presenting new methodological approaches that will contribute to significantly improve our ability to understand and estimate BNF in the field by improving our capacity to access BNF spatio-temporal variability and enzymatic diversity.

  5. Optics of Biological Particles

    CERN Document Server

    Hoekstra, Alfons; Videen, Gorden

    2007-01-01

    This book covers the optics of single biological particles, both theory and experiment, with emphasis on Elastic Light Scattering and Fluorescence. It deals with the optics of bacteria (bio-aerosols), marine particles (selected phytoplankton communities) and red and white blood cells. Moreover, there are dedicated chapters on a general theory for scattering by a cell, and modelling and simulation of scattering by inhomogeneous biological cells. Finally, one chapter is dedicated to astro-biological signatures, discussing the possibilities for detecting non-terrestrial biological material. The volume has up-to-date discussions on new experimental and numerical techniques, and many examples of applications of these techniques in real-life systems, as used to detect and characterize e.g. biological warfare agents or human blood cells.

  6. Frontiers in mathematical biology

    CERN Document Server

    1994-01-01

    Volume 100, which is the final volume of the LNBM series serves to commemorate the acievements in two decades of this influential collection of books in mathematical biology. The contributions, by the leading mathematical biologists, survey the state of the art in the subject, and offer speculative, philosophical and critical analyses of the key issues confronting the field. The papers address fundamental issues in cell and molecular biology, organismal biology, evolutionary biology, population ecology, community and ecosystem ecology, and applied biology, plus the explicit and implicit mathematical challenges. Cross-cuttting issues involve the problem of variation among units in nonlinear systems, and the related problems of the interactions among phenomena across scales of space, time and organizational complexity.

  7. Identifying the Gifted Child Humorist.

    Science.gov (United States)

    Fern, Tami L.

    1991-01-01

    This study attempted to identify gifted child humorists among 1,204 children in grades 3-6. Final identification of 13 gifted child humorists was determined through application of such criteria as funniness, originality, and exemplary performance or product. The influence of intelligence, development, social factors, sex differences, family…

  8. Identifying Two-Sided Markets

    NARCIS (Netherlands)

    Filistrucchi, L.; Geradin, D.A.A.G.; van Damme, E.E.C.

    2012-01-01

    Abstract: We review the burgeoning literature on two-sided markets focusing on the different definitions that have been proposed. In particular, we show that the well-known definition given by Evans is a particular case of the more general definition proposed by Rochet and Tirole. We then identify t

  9. Identifying high-risk medication

    DEFF Research Database (Denmark)

    Sædder, Eva; Brock, Birgitte; Nielsen, Lars Peter;

    2014-01-01

    salicylic acid, and beta-blockers; 30 drugs or drug classes caused 82 % of all serious MEs. The top ten drugs involved in fatal events accounted for 73 % of all drugs identified. CONCLUSION: Increasing focus on seven drugs/drug classes can potentially reduce hospitalizations, extended hospitalizations...

  10. Current dichotomy between traditional molecular biological and omic research in cancer biology and pharmacology.

    Science.gov (United States)

    Reinhold, William C

    2015-12-10

    There is currently a split within the cancer research community between traditional molecular biological hypothesis-driven and the more recent "omic" forms or research. While the molecular biological approach employs the tried and true single alteration-single response formulations of experimentation, the omic employs broad-based assay or sample collection approaches that generate large volumes of data. How to integrate the benefits of these two approaches in an efficient and productive fashion remains an outstanding issue. Ideally, one would merge the understandability, exactness, simplicity, and testability of the molecular biological approach, with the larger amounts of data, simultaneous consideration of multiple alterations, consideration of genes both of known interest along with the novel, cross-sample comparisons among cell lines and patient samples, and consideration of directed questions while simultaneously gaining exposure to the novel provided by the omic approach. While at the current time integration of the two disciplines remains problematic, attempts to do so are ongoing, and will be necessary for the understanding of the large cell line screens including the Developmental Therapeutics Program's NCI-60, the Broad Institute's Cancer Cell Line Encyclopedia, and the Wellcome Trust Sanger Institute's Cancer Genome Project, as well as the the Cancer Genome Atlas clinical samples project. Going forward there is significant benefit to be had from the integration of the molecular biological and the omic forms or research, with the desired goal being improved translational understanding and application. PMID:26677427

  11. Hyperglycaemia Alters Thymic Epithelial Cell Function

    Directory of Open Access Journals (Sweden)

    Vera Alexandrovna Abramova

    2013-07-01

    Full Text Available Insulin-dependent diabetes mellitus (IDDM is considered to be a consequence of unchecked auto-immune processes. Alterations in immune system responses are thought to be the cause of the disease, but the possibility that altered metabolite levels (glucose can establish the disease by specifically acting on and altering thymus stroma functions has not been investigated. Therefore, the direct effect of hyperglycaemia (HG on central tolerance mechanisms as a causative agent needs to be investigated.

  12. Rural Electric Network Alteration Spurs Cable Production

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    <正>Most aluminum cable enterprises in Yunnan and Zhejiang focus their production capacity on overhead cables needed in rural electric network alteration. During the 12th Five-Year Plan period, China launched the rural electric network alteration & upgrade project. As of the middle of 2011, the budget of the central government for the rural electric network alteration & upgrade project planned by the National Development and Reform Commission has reached up to RMB 64.96 billion.

  13. Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins.

    Science.gov (United States)

    Chan, Yuk-Kit; Zhang, Huoming; Liu, Pei; Tsao, Sai-Wah; Lung, Maria Li; Mak, Nai-Ki; Ngok-Shun Wong, Ricky; Ying-Kit Yue, Patrick

    2015-10-15

    Exosomes, a group of secreted extracellular nanovesicles containing genetic materials and signaling molecules, play a critical role in intercellular communication. During tumorigenesis, exosomes have been demonstrated to promote tumor angiogenesis and metastasis while their biological functions in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and NP460) were isolated using ultracentrifugation. The molecular profile and biophysical characteristics of exosomes were verified by Western blotting, sucrose density gradient and electron microscopy. We showed that the C666-1 exosomes (10 and 20 μg/ml) could significantly increase the tubulogenesis, migration and invasion of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was used to identify the differentially expressed proteins in C666-1 exosomes. Among the 640 identified proteins, 51 and 89 proteins were considered as up- and down-regulated (≥ 1.5-fold variations) in C666-1 exosomes compared to the normal counterparts, respectively. As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1 and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes. Taken together, these data strongly indicated the critical roles of identified angiogenic proteins in the involvement of exosomes-induced angiogenesis, which could potentially be developed as therapeutic targets in future.

  14. Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins

    KAUST Repository

    Chan, Yuk-kit

    2015-04-01

    Exosomes, a group of secreted extracellular nanovesicles containing genetic materials and signaling molecules, play a critical role in intercellular communication. During tumorigenesis, exosomes have been demonstrated to promote tumor angiogenesis and metastasis while their biological functions in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and NP460) were isolated using ultracentrifugation. The molecular profile and biophysical characteristics of exosomes were verified by Western blotting, sucrose density gradient, and electron microscopy. We showed that the C666-1 exosomes (10 and 20 μg/ml) could significantly increase the tubulogenesis, migration and invasion of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was used to identify the differentially expressed proteins in C666-1 exosomes. Among the 640 identified proteins, 51 and 89 proteins were considered as up- and down-regulated (≥ 1.5-fold variations) in C666-1 exosomes compared to the normal counterparts, respectively. As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1, and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes. Taken together, these data strongly indicated the critical roles of identified angiogenic proteins in the involvement of exosomes-induced angiogenesis, which could potentially be developed as therapeutic targets in future. This article is protected by copyright. All rights reserved.

  15. Biology and management of ependymomas.

    Science.gov (United States)

    Wu, Jing; Armstrong, Terri S; Gilbert, Mark R

    2016-07-01

    Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The tumor biology is typically more associated with the site of origin rather than being age-specific. Genetically distinct subgroups have been identified by genomic studies based on locations in classic grade II and III ependymomas. They are supratentorial ependymomas with C11orf95-RELA fusion or YAP1 fusion, infratentorial ependymomas with or without a hypermethylated phenotype (CIMP), and spinal cord ependymomas. Myxopapillary ependymomas and subependymomas have different biology than ependymomas with typical WHO grade II or III histology. Surgery and radiotherapy are the mainstays of treatment, while the role of chemotherapy has not yet been established. An in-depth understanding of tumor biology, developing reliable animal models that accurately reflect tumor molecule features, and high throughput drug screening are essential for developing new therapies. Collaborative efforts between scientists, physicians, and advocacy groups will enhance the translation of laboratory findings into clinical trials. Improvements in disease control underscore the need to incorporate assessment and management of patients' symptoms to ensure that treatment advances translate into improvement in quality of life. PMID:27022130

  16. Synthetic biology and biosecurity: challenging the "myths".

    Science.gov (United States)

    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

  17. Identifying novel drug indications through automated reasoning.

    Directory of Open Access Journals (Sweden)

    Luis Tari

    Full Text Available BACKGROUND: 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. METHODOLOGY: 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. CONCLUSION/SIGNIFICANCE: 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

  18. Altered Practice Altered Stories Altered Lives: Three Considerations for Translating Organizational Communication Scholarship into Practice.

    Science.gov (United States)

    Tracy, Sarah J.

    2002-01-01

    Offers three "unabashedly normative" considerations for translating organizational communication scholarship to practice: identifying a problem, incorporating participant voices, and presenting research to practitioners. Suggests that by engaging in these practices scholars can create alternative organizational stories and in doing so create space…

  19. Cold-induced thermoregulation and biological aging.

    Science.gov (United States)

    Florez-Duquet, M; McDonald, R B

    1998-04-01

    Aging is associated with diminished cold-induced thermoregulation (CIT). The mechanisms accounting for this phenomenon have yet to be clearly elucidated but most likely reflect a combination of increased heat loss and decreased metabolic heat production. The inability of the aged subject to reduce heat loss during cold exposure is associated with diminished reactive tone of the cutaneous vasculature and, to a lesser degree, alterations in the insulative properties of body fat. Cold-induced metabolic heat production via skeletal muscle shivering thermogenesis and brown adipose tissue nonshivering thermogenesis appears to decline with age. Few investigations have directly linked diminished skeletal muscle shivering thermogenesis with the age-related reduction in cold-induced thermoregulatory capacity. Rather, age-related declines in skeletal muscle mass and metabolic activity are cited as evidence for decreased heat production via shivering. Reduced mass, GDP binding to brown fat mitochondria, and uncoupling protein (UCP) levels are cited as evidence for attenuated brown adipose tissue cold-induced nonshivering thermogenic capacity during aging. The age-related reduction in brown fat nonshivering thermogenic capacity most likely reflects altered cellular signal transduction rather than changes in neural and hormonal signaling. The discussion in this review focuses on how alterations in CIT during the life span may offer insight into possible mechanisms of biological aging. Although the preponderance of evidence presented here demonstrates that CIT declines with chronological time, the mechanism reflecting this attenuated function remains to be elucidated. The inability to draw definitive conclusions regarding biological aging and CIT reflects the lack of a clear definition of aging. It is unlikely that the mechanisms accounting for the decline in cold-induced thermoregulation during aging will be determined until biological aging is more precisely defined.

  20. Systems biology in aging: linking the old and the young.

    Science.gov (United States)

    Hou, Lei; Huang, Jialiang; Green, Christopher D; Boyd-Kirkup, Jerome; Zhang, Wei; Yu, Xiaoming; Gong, Wenxuan; Zhou, Bing; Han, Jing-Dong J

    2012-11-01

    Aging can be defined as a process of progressive decline in the physiological capacity of an organism, manifested by accumulated alteration and destabilization at the whole system level. Systems biology approaches offer a promising new perspective to examine the old problem of aging. We begin this review by introducing the concepts of systems biology, and then illustrate the application of systems biology approaches to aging research, from gene expression profiling to network analysis. We then introduce the network that can be constructed using known lifespan and aging regulators, and conclude with a look forward to the future of systems biology in aging research. In summary, systems biology is not only a young field that may help us understand aging at a higher level, but also an important platform that can link different levels of knowledge on aging, moving us closer to a more comprehensive control of systematic decline during aging. PMID:23633915

  1. Altered cingulostriatal coupling in obsessive-compulsive disorder.

    Science.gov (United States)

    Beucke, Jan Carl; Kaufmann, Christian; Linnman, Clas; Gruetzmann, Rosa; Endrass, Tanja; Deckersbach, Thilo; Dougherty, Darin D; Kathmann, Norbert

    2012-01-01

    Neurobiological models of obsessive-compulsive disorder (OCD) assume abnormalities in corticostriatal networks involving cingulate and orbitofrontal cortices, but the connectivity within these systems is rarely addressed in experimental imaging studies in this patient group. Using an established monetary reinforcement paradigm known to involve the cingulate cortex and the ventral striatum, the present study sought to test for altered corticostriatal coupling in OCD patients anticipating potential punishment. The anterior midcingulate cortex (aMCC), a region integrating negative emotion, pain, and cognitive control, was chosen as a seed region due to its particular relevance in OCD, representing the neurosurgical target for cingulotomy, and showing increased responses to errors in OCD patients. Results from psychophysiological interaction analyses revealed that significantly altered, inverse coupling occurs between the aMCC and the ventral striatum when OCD patients anticipate potential punishment. This abnormality links the two major contemporary neurosurgical OCD target sites, and provides direct experimental evidence of altered corticostriatal connectivity in OCD. Noteworthy, an abnormal aMCC coupling with cortical areas outside of traditional corticostriatal circuitry was identified besides the alteration in the cingulostriatal pathway. In conclusion, these findings support the importance of applying connectivity methods to study corticostriatal networks in OCD, and favor the application of effective connectivity methods to study corticostriatal abnormalities in OCD patients performing tasks that involve symptom provocation and reinforcement learning. PMID:22823561

  2. Microarray-bioinformatics analysis of altered genomic expression profiles between human fetal and infant myocardium

    Institute of Scientific and Technical Information of China (English)

    KONG Bo; LIU Ying-long; L(U) Xiao-dong

    2008-01-01

    Background The physiological differences between fetal and postnatal heart have been well characterized at the cellular level. However, the genetic mechanisms governing and regulating these differences have only been partially elucidated. Elucidation of the differentially expressed genes profile before and after birth has never been systematically proposed and analyzed.Methods The human oligonuclectide microarray and bioinformatics analysis approaches were applied to isolate and classify the differentially expressed genes between fetal and infant cardiac tissue samples. Quantitative real-time PCR was used to confirm the results from the microarray.Results Two hundred and forty-two differentially expressed genes were discovered and classified into 13 categories, including genes related to energy metabolism, myocyte hyperplasia, development, muscle contraction, protein synthesis and degradation, extraceUular matrix components, transcription factors, apoptosis, signal pathway molecules, organelle organization and several other biological processes. Moreover, 95 genes were identified which had not previously been reported to be expressed in the heart.Conclusions The study systematically analyzed the alteration of the gene expression profile between the human fetal and infant myocardium. A number of genes were discovered which had not been reported to be expressed in the heart. The data provided insight into the physical development mechanisms of the heart before and after birth.KONG Bo and LU Xiao-dong contributed equally to this study.

  3. Genistein alters growth but is not toxic to the rat prostate.

    Science.gov (United States)

    Fritz, Wayne A; Eltoum, Isam-Eldin; Cotroneo, Michelle S; Lamartiniere, Coral A

    2002-10-01

    The mortality of clinical prostate cancer is lower in Asian populations than in American or European men. Asian men typically consume more soy than their Western counterparts, leading to the investigation of individual components, particularly phytoestrogens, as protective factors against prostate cancer. Genistein, the predominant isoflavone in soy, has been reported to reduce the incidence of prostate cancer in animal models, but the underlying biological action remains to be elucidated. The purpose of this investigation was to identify the effects of the phytoestrogen, genistein and the synthetic estrogen diethylstilbestrol (DES), as a control, on development and function of the rat dorsolateral prostate (DLP) when given in the diet. The effects of testosterone and dihydrotestosterone (DHT) injections were also tested. Analysis of individual lobes of the DLP revealed that 1000 mg/kg, but not 250 mg/kg, of a genistein AIN-76A diet slightly reduced lateral prostate type 1 (LP1) bud perimeter. However, expression of the secretory dorsal protein 1 (DP1) and 5alpha-reductase type II activity were not altered in the prostate. This suggested that prostate differentiation, and not toxicity, had occurred. DES in the diet reduced and testosterone injections elevated relative prostate weights and perimeters of the dorsal, LP1, lateral prostate type 2 and DP1 expression. DHT increased relative prostate weights but did not significantly increase individual lobe perimeter. Unlike DES, maximally tolerated doses of genistein in the diet were not toxic to the rat prostate. PMID:12368387

  4. Managing biological diversity

    Science.gov (United States)

    Samson, Fred B.; Knopf, Fritz L.

    1993-01-01

    Biological diversity is the variety of life and accompanying ecological processes (Off. Technol. Assess. 1987, Wilcove and Samson 1987, Keystone 1991). Conservation of biological diversity is a major environmental issue (Wilson 1988, Counc. Environ. Quality 1991). The health and future of the earth's ecological systems (Lubchenco et al. 1991), global climate change (Botkin 1990), and an ever-increasing rate in loss of species, communities, and ecological systems (Myers 1990) are among issues drawing biological diversity to the mainstream of conservation worldwide (Int. Union Conserv. Nat. and Nat. Resour. [IUCN] et al. 1991). The legal mandate for conserving biological diversity is now in place (Carlson 1988, Doremus 1991). More than 19 federal laws govern the use of biological resources in the United States (Rein 1991). The proposed National Biological Diversity Conservation and Environmental Research Act (H.R. 585 and S.58) notes the need for a national biological diversity policy, would create a national center for biological diversity research, and recommends a federal interagency strategy for ecosystem conservation. There are, however, hard choices ahead for the conservation of biological diversity, and biologists are grappling with how to set priorities in research and management (Roberts 1988). We sense disillusion among field biologists and managers relative to how to operationally approach the seemingly overwhelming charge of conserving biological diversity. Biologists also need to respond to critics like Hunt (1991) who suggest a tree farm has more biological diversity than an equal area of old-growth forest. At present, science has played only a minor role in the conservation of biological diversity (Weston 1992) with no unified approach available to evaluate strategies and programs that address the quality and quantity of biological diversity (Murphy 1990, Erwin 1992). Although actions to conserve biological diversity need to be clearly defined by

  5. The cell biology of fat expansion

    Science.gov (United States)

    Rutkowski, Joseph M.; Stern, Jennifer H.

    2015-01-01

    Adipose tissue is a complex, multicellular organ that profoundly influences the function of nearly all other organ systems through its diverse metabolite and adipokine secretome. Adipocytes are the primary cell type of adipose tissue and play a key role in maintaining energy homeostasis. The efficiency with which adipose tissue responds to whole-body energetic demands reflects the ability of adipocytes to adapt to an altered nutrient environment, and has profound systemic implications. Deciphering adipocyte cell biology is an important component of understanding how the aberrant physiology of expanding adipose tissue contributes to the metabolic dysregulation associated with obesity. PMID:25733711

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

    Science.gov (United States)

    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.

  7. Biology and Mathematics

    Directory of Open Access Journals (Sweden)

    Bascompte, Jordi

    2007-06-01

    Full Text Available Biology has become the new “physics” of mathematics, one of the areas of greatest mathematical applications. In turn, mathematics has provided powerful tools and metaphors to approach the astonishing complexity of biological systems. This has allowed the development of sound theoretical frameworks. Here, I summarize some of the most significant contributions of mathematics to biology, ranging from population genetics, to developmental biology, and to networks of species interactions.La biología se ha convertido en la nueva “física” de las matemáticas, una de las áreas con mayores aplicaciones. Las matemáticas, por su parte, han proporcionado herramientas y metáforas muy poderosas para abordar la increíble complejidad de los sistemas biológicos. Esto ha permitido la génesis de marcos conceptuales sólidos. En este artículo resumo algunas de las aplicaciones más exitosas de las matemáticas a la biología que van desde la genética de poblaciones a la biología del desarrollo y las redes de interacciones ecológicas.

  8. Biological and Chemical Security

    Energy Technology Data Exchange (ETDEWEB)

    Fitch, P J

    2002-12-19

    The LLNL Chemical & Biological National Security Program (CBNP) provides science, technology and integrated systems for chemical and biological security. Our approach is to develop and field advanced strategies that dramatically improve the nation's capabilities to prevent, prepare for, detect, and respond to terrorist use of chemical or biological weapons. Recent events show the importance of civilian defense against terrorism. The 1995 nerve gas attack in Tokyo's subway served to catalyze and focus the early LLNL program on civilian counter terrorism. In the same year, LLNL began CBNP using Laboratory-Directed R&D investments and a focus on biodetection. The Nunn-Lugar-Domenici Defense Against Weapons of Mass Destruction Act, passed in 1996, initiated a number of U.S. nonproliferation and counter-terrorism programs including the DOE (now NNSA) Chemical and Biological Nonproliferation Program (also known as CBNP). In 2002, the Department of Homeland Security was formed. The NNSA CBNP and many of the LLNL CBNP activities are being transferred as the new Department becomes operational. LLNL has a long history in national security including nonproliferation of weapons of mass destruction. In biology, LLNL had a key role in starting and implementing the Human Genome Project and, more recently, the Microbial Genome Program. LLNL has over 1,000 scientists and engineers with relevant expertise in biology, chemistry, decontamination, instrumentation, microtechnologies, atmospheric modeling, and field experimentation. Over 150 LLNL scientists and engineers work full time on chemical and biological national security projects.

  9. Rapid classification of biological components

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Vicki S. (Idaho Falls, ID); Barrett, Karen B. (Meridian, ID); Key, Diane E. (Idaho Falls, ID)

    2010-03-23

    A method is disclosed for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an illustrative embodiment of the invention, the analyte is a drug, such as marijuana, cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method involves attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein the locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to antigens in the array, thereby forming immune complexes; washing away antibodies that do not form immune complexes; and detecting the immune complexes, thereby forming an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to a subject's identity.

  10. Rapid classification of biological components

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Vicki S.; Barrett, Karen B.; Key, Diane E.

    2013-10-15

    A method is disclosed for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an illustrative embodiment of the invention, the analyte is a drug, such as marijuana, cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method involves attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein the locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to antigens in the array, thereby forming immune complexes; washing away antibodies that do not form immune complexes; and detecting the immune complexes, thereby forming an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to a subject's identity.

  11. Rapid classification of biological components

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Vicki S. (Idaho Falls, ID); Barrett, Karen B. (Meridian, ID); Key, Diane E. (Idaho Falls, ID)

    2010-03-23

    A method is disclosed for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an illustrative embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method involves attaching antigens of the surface of a solid support in a preselected pattern to form an array wherein the locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to antigens in the array, thereby forming immune complexes; washing away antibodies that do not form immune complexes; and detecting the immune complexes, thereby forming an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to a subject's identity.

  12. Rapid classification of biological components

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Vicki S.; Barrett, Karen B.; Key, Diane E.

    2006-01-24

    A method is disclosed for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an illustrative embodiment of the invention, the analyte is a drug, such as marijuana, cocaine, methamphetamine, methyltestosterone, or mesterolone. The method involves attaching antigens to the surface of a solid support in a preselected pattern to form an array wherein the locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to antigens in the array, thereby forming immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, thereby forming an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  13. Rapid classification of biological components

    Science.gov (United States)

    Thompson, Vicki S.; Barrett, Karen B.; Key, Diane E.

    2013-10-15

    A method is disclosed for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an illustrative embodiment of the invention, the analyte is a drug, such as marijuana, cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method involves attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein the locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to antigens in the array, thereby forming immune complexes; washing away antibodies that do not form immune complexes; and detecting the immune complexes, thereby forming an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to a subject's identity.

  14. Identifying Emotion from Natural Walking

    OpenAIRE

    Cui, Liqing; Li, Shun; Zhang, Wan; Zhang, Zhan; Zhu, Tingshao

    2015-01-01

    Emotion identification from gait aims to automatically determine persons affective state, it has attracted a great deal of interests and offered immense potential value in action tendency, health care, psychological detection and human-computer(robot) interaction.In this paper, we propose a new method of identifying emotion from natural walking, and analyze the relevance between the traits of walking and affective states. After obtaining the pure acceleration data of wrist and ankle, we set a...

  15. Identifying High Performance ERP Projects

    OpenAIRE

    Stensrud, Erik; Myrtveit, Ingunn

    2002-01-01

    Learning from high performance projects is crucial for software process improvement. Therefore, we need to identify outstanding projects that may serve as role models. It is common to measure productivity as an indicator of performance. It is vital that productivity measurements deal correctly with variable returns to scale and multivariate data. Software projects generally exhibit variable returns to scale, and the output from ERP projects is multivariate. We propose to use Data Envelopment ...

  16. Suitability of the cellular viability technique as a control tool of the chlorine dosage on the activated sludge of a biological process affected by bulking

    International Nuclear Information System (INIS)

    This work demonstrates the suitability of the cellular viability technique as a control tool of the chlorine dosage on the activated sludge of a biological process affected by the overabundance of the filamentous bacteria (Thiothrix-021N). This technique was used to establish the chlorine dosage according to the observed damages on cellular membranes of both, floc-forming bacteria as well as filamentous bacteria. To identify the filamentous bacteria responsible for the macro-structural alteration of the flocs, several criteria were, met, including morphologic characteristics as well as conventional microbiological stains: Gram, Neisser and polyhydroxy alkanoates. FISH was used to confirm the obtained results, providing a definitive identification of the filamentous bacteria responsible for the alteration. (Author) 11 refs

  17. The role of the ALK receptor in cancer biology.

    Science.gov (United States)

    Hallberg, B; Palmer, R H

    2016-09-01

    A vast array of oncogenic variants has been identified for anaplastic lymphoma kinase (ALK). Therefore, there is a need to better understand the role of ALK in cancer biology in order to optimise treatment strategies. This review summarises the latest research on the receptor tyrosine kinase ALK, and how this information can guide the management of patients with cancer that is ALK-positive. A variety of ALK gene alterations have been described across a range of tumour types, including point mutations, deletions and rearrangements. A wide variety of ALK fusions, in which the kinase domain of ALK and the amino-terminal portion of various protein partners are fused, occur in cancer, with echinoderm microtubule-associated protein-like 4 (EML4)-ALK being the most prevalent in non-small-cell lung cancer (NSCLC). Different ALK fusion proteins can mediate different signalling outputs, depending on properties such as subcellular localisation and protein stability. The ALK fusions found in tumours lack spatial and temporal regulation, which can also affect dimerisation and substrate specificity. Two ALK tyrosine kinase inhibitors (TKIs), crizotinib and ceritinib, are currently approved in Europe for use in ALK-positive NSCLC and several others are in development. These ALK TKIs bind slightly differently within the ATP-binding pocket of the ALK kinase domain and are associated with the emergence of different resistance mutation patterns during therapy. This emphasises the need to tailor the sequence of ALK TKIs according to the ALK signature of each patient. Research into the oncogenic functions of ALK, and fast paced development of ALK inhibitors, has substantially improved outcomes for patients with ALK-positive NSCLC. Limited data are available surrounding the physiological ligand-stimulated activation of ALK signalling and further research is needed. Understanding the role of ALK in tumour biology is key to further optimising therapeutic strategies for ALK

  18. Modification-specific proteomics in plant biology

    DEFF Research Database (Denmark)

    Ytterberg, A Jimmy; Jensen, Ole N

    2010-01-01

    and proteomics. In general, methods for PTM characterization are developed to study yeast and mammalian biology and later adopted to investigate plants. Our point of view is that it is advantageous to enrich for PTMs on the peptide level as part of a quantitative proteomics strategy to not only identify the PTM...

  19. Milk inhibits the biological activity of ricin

    Science.gov (United States)

    Ricin is a highly toxic protein produced by the castor plant Ricinus communis. The toxin is relatively easy to isolate and can be used as a biological weapon. There is great interest in identifying effective inhibitors for ricin. In this study, we demonstrated by three independent assays that compon...

  20. Fragment Produced by Nuclear Reaction of Heavy Ions Interacted with Tissue-equivalent Biological Material

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In heavy ion therapy and radiation biological effects the nuclear fragments from the heavy ion collisions may cause a significant alteration of the radiation field. Nuclear collision between beam particles and tissue nuclei along the penetration path of high-energy ions in tissue or biological-equivalent material causes a loss

  1. Neutron in biology

    Energy Technology Data Exchange (ETDEWEB)

    Niimura, Nobuo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-11-01

    Neutron in biology can provide an experimental method of directly locating relationship of proteins and DNA. However, there are relatively few experimental study of such objects since it takes a lot of time to collect a sufficient number of Bragg reflections and inelastic spectra due to the low flux of neutron illuminating the sample. Since a next generation neutron source of JAERI will be 5MW spallation neutron source and its effective neutron flux will be 10{sup 2} to 10{sup 3} times higher than the one of JRR-3M, neutron in biology will open a completely new world for structural biology. (author)

  2. Patenting humans: clones, chimeras, and biological artifacts.

    Science.gov (United States)

    Hurlbut, William B

    2005-01-01

    The momentum of advances in biology is evident in the history of patents on life forms. As we proceed forward with greater understanding and technological control of developmental biology there will be many new and challenging dilemmas related to patenting of human parts and partial trajectories of human development. These dilemmas are already evident in the current conflict over the moral status of the early human embryo. In this essay, recent evidence from embryological studies is considered and the unbroken continuity of organismal development initiated at fertilization is asserted as clear and reasonable grounds for moral standing. Within this frame of analysis, it is proposed that through a technique of Altered Nuclear Transfer, non-organismal entities might be created from which embryonic stem cells could be morally procured. Criteria for patenting of such non-organismal entities are considered.

  3. Biology and Treatment of Rhabdoid Tumor.

    Science.gov (United States)

    Geller, James I; Roth, Jacquelyn J; Biegel, Jaclyn A

    2015-01-01

    Rhabdoid tumor is a rare, highly aggressive malignancy that primarily affects infants and young children. These tumors typically arise in the brain and kidney, although extrarenal, non-central nervous system tumors in almost all soft-tissue sites have been described. SMARCB1 is a member of the SWI/SNF chromatin-remodeling complex and functions as a tumor suppressor in the vast majority of rhabdoid tumors. Patients with germline mutations or deletions affecting SMARCB1 are predisposed to the development of rhabdoid tumors, as well as the genetic disorder schwannomatosis. The current hypothesis is that rhabdoid tumors are driven by epigenetic dysregulation, as opposed to the alteration of a specific biologic pathway. The strategies for novel therapeutic approaches based on what is currently known about rhabdoid tumor biology are presented. PMID:26349416

  4. Biology and Medicine Division annual report, 1987

    International Nuclear Information System (INIS)

    Modern biology is characterized by rapid change. The development of new tools and the results derived from their application to various biological systems require significant shifts in our concepts and the strategies that are adopted to analyze and elucidate mechanisms. In parallel with exciting new scientific developments our organizational structure and programmatic emphases have altered. These changes and developments have enabled the life sciences at LBL to be better positioned to create and respond to new opportunities. The work summarized in this annual report reflects a vital multifaceted research program that is in the vanguard of the areas represented. We are committed to justifying the confidence expressed by LBL through the new mission statement and reorganizational changes designed to give greater prominence to the life sciences

  5. Biology and Medicine Division annual report, 1987

    Energy Technology Data Exchange (ETDEWEB)

    1988-04-01

    Modern biology is characterized by rapid change. The development of new tools and the results derived from their application to various biological systems require significant shifts in our concepts and the strategies that are adopted to analyze and elucidate mechanisms. In parallel with exciting new scientific developments our organizational structure and programmatic emphases have altered. These changes and developments have enabled the life sciences at LBL to be better positioned to create and respond to new opportunities. The work summarized in this annual report reflects a vital multifaceted research program that is in the vanguard of the areas represented. We are committed to justifying the confidence expressed by LBL through the new mission statement and reorganizational changes designed to give greater prominence to the life sciences.

  6. Biological research for radiation protection

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Gyu; Kim, Kug Chan; Shim, Hae Won; Oh, Tae Jeong; Park, Seon Young; Lee, Kang Suk

    2000-04-01

    The work scope of Biological research for the radiation protection had contained the search of biological microanalytic methods for assessing the health effect by {gamma}-radiation and toxic agents, the standardization of human T-lymphocyte cell culture and polymerase chain reaction, T-cell clonal assay, and the quantification of mutation frequency in the hypoxanthine (guanine) phosphoribosyl transferase (HPRT) gene locus by single exposure or combined exposure. Especially, the polymerase chain reaction methods using reverse transcriptase has been developed to analyze the mutant gene induced by {gamma}-radiation and chemical (pentachlorophenol) agent exposure, and to investigate the point mutations in the HPRT gene locus of T-lymphocytes. The HPRT T-cell clonal assay revealed that it could not differentiate {gamma}-irradiation from pentachlorophenol, because the frequency of somatic mutations induced by both damaging agents increased in a dose-dependent manner. The analysis of DNA sequence alterations of HPRT mutant clones clearly showed that both damaging agents induced different mutational spectra in the HPRT locus of T-cells. The large deletions, which account for 75 percent of the analyzed mutants, are characteristic mutations induced by {gamma}-irradiation. By contrast, point mutations such as base substitutions and insertion, come up to 97 percent in the case of pentachlorophenol-treated cells. The point mutation frequencies at 190 base pair and 444 base pair positions are 3-6 folds as high as in those at other mutation positions. It may be that these mutation sites are hot spots induced by pentachlorophenol. These results suggest that the HPRT mutation spectrum can be used as a potential bio marker for assessing a specific environmental risk. (author)

  7. Biological research for radiation protection

    International Nuclear Information System (INIS)

    The work scope of Biological research for the radiation protection had contained the search of biological microanalytic methods for assessing the health effect by γ-radiation and toxic agents, the standardization of human T-lymphocyte cell culture and polymerase chain reaction, T-cell clonal assay, and the quantification of mutation frequency in the hypoxanthine (guanine) phosphoribosyl transferase (HPRT) gene locus by single exposure or combined exposure. Especially, the polymerase chain reaction methods using reverse transcriptase has been developed to analyze the mutant gene induced by γ-radiation and chemical (pentachlorophenol) agent exposure, and to investigate the point mutations in the HPRT gene locus of T-lymphocytes. The HPRT T-cell clonal assay revealed that it could not differentiate γ-irradiation from pentachlorophenol, because the frequency of somatic mutations induced by both damaging agents increased in a dose-dependent manner. The analysis of DNA sequence alterations of HPRT mutant clones clearly showed that both damaging agents induced different mutational spectra in the HPRT locus of T-cells. The large deletions, which account for 75 percent of the analyzed mutants, are characteristic mutations induced by γ-irradiation. By contrast, point mutations such as base substitutions and insertion, come up to 97 percent in the case of pentachlorophenol-treated cells. The point mutation frequencies at 190 base pair and 444 base pair positions are 3-6 folds as high as in those at other mutation positions. It may be that these mutation sites are hot spots induced by pentachlorophenol. These results suggest that the HPRT mutation spectrum can be used as a potential bio marker for assessing a specific environmental risk. (author)

  8. Integrating biological knowledge into variable selection: an empirical Bayes approach with an application in cancer biology

    OpenAIRE

    Hill Steven M; Neve Richard M; Bayani Nora; Kuo Wen-Lin; Ziyad Safiyyah; Spellman Paul T; Gray Joe W; Mukherjee Sach

    2012-01-01

    Abstract Background An important question in the analysis of biochemical data is that of identifying subsets of molecular variables that may jointly influence a biological response. Statistical variable selection methods have been widely used for this purpose. In many settings, it may be important to incorporate ancillary biological information concerning the variables of interest. Pathway and network maps are one example of a source of such information. However, although ancillary informatio...

  9. A Molecular Biology Database Digest

    OpenAIRE

    Bry, François; Kröger, Peer

    2000-01-01

    Computational Biology or Bioinformatics has been defined as the application of mathematical and Computer Science methods to solving problems in Molecular Biology that require large scale data, computation, and analysis [18]. As expected, Molecular Biology databases play an essential role in Computational Biology research and development. This paper introduces into current Molecular Biology databases, stressing data modeling, data acquisition, data retrieval, and the integration...

  10. A kernel version of multivariate alteration detection

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Vestergaard, Jacob Schack

    2013-01-01

    Based on the established methods kernel canonical correlation analysis and multivariate alteration detection we introduce a kernel version of multivariate alteration detection. A case study with SPOT HRV data shows that the kMAD variates focus on extreme change observations....

  11. A genetic code alteration is a phenotype diversity generator in the human pathogen Candida albicans.

    Directory of Open Access Journals (Sweden)

    Isabel Miranda

    Full Text Available BACKGROUND: The discovery of genetic code alterations and expansions in both prokaryotes and eukaryotes abolished the hypothesis of a frozen and universal genetic code and exposed unanticipated flexibility in codon and amino acid assignments. It is now clear that codon identity alterations involve sense and non-sense codons and can occur in organisms with complex genomes and proteomes. However, the biological functions, the molecular mechanisms of evolution and the diversity of genetic code alterations remain largely unknown. In various species of the genus Candida, the leucine CUG codon is decoded as serine by a unique serine tRNA that contains a leucine 5'-CAG-3'anticodon (tRNA(CAG(Ser. We are using this codon identity redefinition as a model system to elucidate the evolution of genetic code alterations. METHODOLOGY/PRINCIPAL FINDINGS: We have reconstructed the early stages of the Candida genetic code alteration by engineering tRNAs that partially reverted the identity of serine CUG codons back to their standard leucine meaning. Such genetic code manipulation had profound cellular consequences as it exposed important morphological variation, altered gene expression, re-arranged the karyotype, increased cell-cell adhesion and secretion of hydrolytic enzymes. CONCLUSION/SIGNIFICANCE: Our study provides the first experimental evidence for an important role of genetic code alterations as generators of phenotypic diversity of high selective potential and supports the hypothesis that they speed up evolution of new phenotypes.

  12. Large Pelagics Biological Survey

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Large Pelagics Biological Survey (LPBS) collects additional length and weight information and body parts such as otoliths, caudal vertebrae, dorsal spines, and...

  13. Hammond Bay Biological Station

    Data.gov (United States)

    Federal Laboratory Consortium — Hammond Bay Biological Station (HBBS), located near Millersburg, Michigan, is a field station of the USGS Great Lakes Science Center (GLSC). HBBS was established by...

  14. The Biology of Behaviour.

    Science.gov (United States)

    Broom, D. M.

    1981-01-01

    Discusses topics to aid in understanding animal behavior, including the value of the biological approach to psychology, functional systems, optimality and fitness, universality of environmental effects on behavior, and evolution of social behavior. (DS)

  15. Laboratory of Biological Modeling

    Data.gov (United States)

    Federal Laboratory Consortium — The Laboratory of Biological Modeling is defined by both its methodologies and its areas of application. We use mathematical modeling in many forms and apply it to...

  16. Insecticides and Biological Control

    Science.gov (United States)

    Furness, G. O.

    1972-01-01

    Use of insecticides has been questioned due to their harmful effects on edible items. Biological control of insects along with other effective practices for checking spread of parasites on crops are discussed. (PS)

  17. Chemistry and biology data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Chemical monitoring data and biological data from field collected samples. This dataset is associated with the following publication: Biales , A., D. Denton , D....

  18. Fishery Biology Database (AGDBS)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Basic biological data are the foundation on which all assessments of fisheries resources are built. These include parameters such as the size and age composition of...

  19. Mammalian cell biology

    International Nuclear Information System (INIS)

    This section contains summaries of research on mechanisms of lethality and radioinduced changes in mammalian cell properties, new cell systems for the study of the biology of mutation and neoplastic transformation, and comparative properties of ionizing radiations

  20. Enhanced Biological Sampling Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This is a database of a variety of biological, reproductive, and energetic data collected from fish on the continental shelf in the northwest Atlantic Ocean....

  1. Precision Measurement in Biology

    Science.gov (United States)

    Quake, Stephen

    Is biology a quantitative science like physics? I will discuss the role of precision measurement in both physics and biology, and argue that in fact both fields can be tied together by the use and consequences of precision measurement. The elementary quanta of biology are twofold: the macromolecule and the cell. Cells are the fundamental unit of life, and macromolecules are the fundamental elements of the cell. I will describe how precision measurements have been used to explore the basic properties of these quanta, and more generally how the quest for higher precision almost inevitably leads to the development of new technologies, which in turn catalyze further scientific discovery. In the 21st century, there are no remaining experimental barriers to biology becoming a truly quantitative and mathematical science.

  2. Mechanical Biological Treatment

    DEFF Research Database (Denmark)

    Bilitewski, B-; Oros, Christiane; Christensen, Thomas Højlund

    2011-01-01

    The basic processes and technologies of composting and anaerobic digestion, as described in the previous chapters, are usually used for specific or source-separated organic waste flows. However, in the 1990s mechanical biological waste treatment technologies (MBT) were developed for unsorted...... or residual waste (after some recyclables removed at the source). The concept was originally to reduce the amount of waste going to landfill, but MBT technologies are today also seen as plants recovering fuel as well as material fractions. As the name suggests the technology combines mechanical treatment...... technologies (screens, sieves, magnets, etc.) with biological technologies (composting, anaerobic digestion). Two main technologies are available: Mechanical biological pretreatment (MBP), which first removes an RDF fraction and then biologically treats the remaining waste before most of it is landfilled...

  3. [Systems biology of cancer].

    Science.gov (United States)

    Barillot, Emmanuel; Calzone, Laurence; Zinovyev, Andrei

    2009-01-01

    Cancer Systems Biology is now accepted and recognized as a promising field both in biological and clinical research. It relies on a rigorous formalization of regulation networks into precise and unambiguous languages. It provides both detailed and modular views of the complex biological system of interest (which in cancer research is typically an interaction network governing essential cellular events such as proliferation, differentiation, cell death...) in order to facilitate the interpretation of molecular profiles of tumors. The translation of these networks into mathematical models allows prediction of the evolution of the system in time and under certain perturbations. As a result, it can not only propose specific target points for pharmaceutical purposes, but also anticipate the evolution of tumors as well as their classifications. These characteristics emphasize the important role of Systems Biology of Cancer in the future of biomedical research.

  4. Thermodynamics of Biological Processes

    Science.gov (United States)

    Garcia, Hernan G.; Kondev, Jane; Orme, Nigel; Theriot, Julie A.; Phillips, Rob

    2012-01-01

    There is a long and rich tradition of using ideas from both equilibrium thermodynamics and its microscopic partner theory of equilibrium statistical mechanics. In this chapter, we provide some background on the origins of the seemingly unreasonable effectiveness of ideas from both thermodynamics and statistical mechanics in biology. After making a description of these foundational issues, we turn to a series of case studies primarily focused on binding that are intended to illustrate the broad biological reach of equilibrium thinking in biology. These case studies include ligand-gated ion channels, thermodynamic models of transcription, and recent applications to the problem of bacterial chemotaxis. As part of the description of these case studies, we explore a number of different uses of the famed Monod–Wyman–Changeux (MWC) model as a generic tool for providing a mathematical characterization of two-state systems. These case studies should provide a template for tailoring equilibrium ideas to other problems of biological interest. PMID:21333788

  5. EDITORIAL: Physical Biology

    Science.gov (United States)

    Roscoe, Jane

    2004-06-01

    Physical Biology is a new peer-reviewed publication from Institute of Physics Publishing. Launched in 2004, the journal will foster the integration of biology with the traditionally more quantitative fields of physics, chemistry, computer science and other math-based disciplines. Its primary aim is to further the understanding of biological systems at all levels of complexity, ranging from the role of structure and dynamics of a single molecule to cellular networks and organisms. The journal encourages the development of a new biology-driven physics based on the extraordinary and increasingly rich data arising in biology, and provides research directions for those involved in the creation of novel bio-engineered systems. Physical Biology will publish a stimulating combination of full length research articles, communications, perspectives, reviews and tutorials from a wide range of disciplines covering topics such as: Single-molecule studies and nanobiotechnology Molecular interactions and protein folding Charge transfer and photobiology Ion channels; structure, function and ion regulation Molecular motors and force generation Subcellular processes Biological networks and neural systems Modeling aspects of molecular and cell biology Cell-cell signaling and interaction Biological patterns and development Evolutionary processes Novel tools and methods in physical biology Experts in the areas encompassed by the journal's scope have been appointed to the Editorial Scientific Committee and the composition of the Committee will be updated regularly to reflect the developments in this new and exciting field. Physical Biology is free online to everyone in 2004; you are invited to take advantage of this offer by visiting the journal homepage at http://physbio.iop.org This special print edition of Physical Biology is a combination of issues 1 and 2 of this electronic-only journal and it brings together an impressive range of articles in the fields covered, including a popular

  6. Multiscale Biological Materials

    DEFF Research Database (Denmark)

    Frølich, Simon

    2016-01-01

    Materials formed by organisms, also known as biological materials, exhibit outstanding structural properties. The range of materials formed in nature is remarkable and their functions include support, protection, motion, sensing, storage, and maintenance of physiological homeostasis. These complex...... materials are characterized by their hierarchical and composite design, where features with sizes ranging from nanometers to centimeters provide the basis for the functionality of the material. Understanding of biological materials is, while very interesting from a basic research perspective, also valuable...... as inspiration for the development of new materials for medical and technological applications. In order to successfully mimic biological materials we must first have a thorough understanding of their design. As such, the purpose of the characterization of biological materials can be defined as the establishment...

  7. Synthetic biology: A foundation for multi-scale molecular biology

    OpenAIRE

    Bower, Adam G; McClintock, Maria K; Stephen S. Fong

    2010-01-01

    The field of synthetic biology has made rapid progress in a number of areas including method development, novel applications and community building. In seeking to make biology “engineerable,” synthetic biology is increasing the accessibility of biological research to researchers of all experience levels and backgrounds. One of the underlying strengths of synthetic biology is that it may establish the framework for a rigorous bottom-up approach to studying biology starting at the DNA level. Bu...

  8. Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions

    Directory of Open Access Journals (Sweden)

    Kerstin Pannek

    2014-01-01

    Conclusion: This study shows that network-based analysis of structural connectivity can identify alterations in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

  9. Noise in Biology

    OpenAIRE

    Tsimring, Lev S

    2014-01-01

    Noise permeates biology on all levels, from the most basic molecular, sub-cellular processes to the dynamics of tissues, organs, organisms, and populations. The functional roles of noise in biological processes can vary greatly. Along with standard, entropy-increasing effects of producing random mutations, diversifying phenotypes in isogenic populations, limiting information capacity of signaling relays, it occasionally plays more surprising constructive roles by accelerating the pace of evol...

  10. Synthetic biology and biosecurity.

    Science.gov (United States)

    Robienski, Jürgen; Simon, Jürgen

    2014-01-01

    This article discusses the conflict fields and legal questions of synthetic biology, esp. concerning biosecurity. A respective jurisprudential discussion has not taken place yet in Germany apart from few statements and recommendations. But in Germany, Europe and the USA, it is generally accepted that a broad discussion is necessary. This is esp. true for the question of biosecurity and the possible dangers arising from Synthetic Biology. PMID:25845204

  11. Systems cell biology.

    Science.gov (United States)

    Mast, Fred D; Ratushny, Alexander V; Aitchison, John D

    2014-09-15

    Systems cell biology melds high-throughput experimentation with quantitative analysis and modeling to understand many critical processes that contribute to cellular organization and dynamics. Recently, there have been several advances in technology and in the application of modeling approaches that enable the exploration of the dynamic properties of cells. Merging technology and computation offers an opportunity to objectively address unsolved cellular mechanisms, and has revealed emergent properties and helped to gain a more comprehensive and fundamental understanding of cell biology.

  12. Sleep deprivation alters valuation signals in the ventromedial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Camilo eLibedinsky

    2011-10-01

    Full Text Available Even a single night of total sleep-deprivation (SD can have dramatic effects on economic decision making. Here we tested the novel hypothesis that SD influences economic decisions by altering the valuation process. Using functional magnetic resonance imaging (fMRI we identified value signals related to the anticipation and the experience of monetary and social rewards (attractive female faces. We then derived decision value signals that were predictive of each participant’s willingness to exchange money for brief views of attractive faces in an independent market task. Strikingly, SD altered decision value signals in ventromedial prefrontal cortex (VMPFC in proportion to the corresponding change in economic preferences. These changes in preference were independent of the effects of SD on attention and vigilance. Our results provide novel evidence that signals in VMPFC track the current state of the individual, and thus reflect not static but constructed preferences.

  13. Rich in life but poor in data: the known knowns and known unknowns of modelling how soil biology drives soil structure

    Science.gov (United States)

    Hallett, Paul; Ogden, Mike

    2015-04-01

    Soil biology has a fascinating capacity to manipulate pore structure by altering or overcoming hydrological and mechanical properties of soil. Many have postulated, quite rightly, that this capacity of soil biology to 'engineer' its habitat drives its diversity, improves competitiveness and increases resilience to external stresses. A large body of observational research has quantified pore structure evolution accompanied by the growth of organisms in soil. Specific compounds that are exuded by organisms or the biological structures they create have been isolated and found to correlate well with observed changes to pore structure or soil stability. This presentation will provide an overview of basic mechanical and hydrological properties of soil that are affected by biology, and consider missing data that are essential to model how they impact soil structure evolution. Major knowledge gaps that prevent progress will be identified and suggestions will be made of how research in this area should progress. We call for more research to gain a process based understanding of structure formation by biology, to complement observational studies of soil structure before and after imposed biological activity. Significant advancement has already been made in modelling soil stabilisation by plant roots, by combining data on root biomechanics, root-soil interactions and soil mechanical properties. Approaches for this work were developed from earlier materials science and geotechnical engineering research, and the same ethos should be adopted to model the impacts of other biological compounds. Fungal hyphae likely reinforce soils in a similar way to plant roots, with successful biomechanical measurements of these micron diameter structures achieved with micromechanical test frames. Extending root reinforcement models to fungi would not be a straightforward exercise, however, as interparticle bonding and changes to pore water caused by fungal exudates could have a major impact on

  14. 14 CFR 26.45 - Holders of type certificates-Alterations and repairs to alterations.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Holders of type certificates-Alterations... AIRPLANES Aging Airplane Safety-Damage Tolerance Data for Repairs and Alterations § 26.45 Holders of type... alteration data developed by the holder of a type certificate, the holder must— (1) Review...

  15. Peripheral Skin Temperature and Circadian Biological Clock in Shift Nurses after a Day off

    OpenAIRE

    Massimo Bracci; Veronica Ciarapica; Alfredo Copertaro; Mariella Barbaresi; Nicola Manzella; Marco Tomasetti; Simona Gaetani; Federica Monaco; Monica Amati; Matteo Valentino; Venerando Rapisarda; Lory Santarelli

    2016-01-01

    The circadian biological clock is essentially based on the light/dark cycle. Some people working with shift schedules cannot adjust their sleep/wake cycle to the light/dark cycle, and this may result in alterations of the circadian biological clock. This study explored the circadian biological clock of shift and daytime nurses using non-invasive methods. Peripheral skin temperature, cortisol and melatonin levels in saliva, and Per2 expression in pubic hair follicle cells were investigated for...

  16. Controlling Sulfuryl-Transfer Biology.

    Science.gov (United States)

    Cook, Ian; Wang, Ting; Wang, Wei; Kopp, Felix; Wu, Peng; Leyh, Thomas S

    2016-05-19

    In humans, the cytosolic sulfotransferases (SULTs) catalyze regiospecific transfer of the sulfuryl moiety (-SO3) from 3'-phosphoadenosine 5'-phosphosulfate to thousands of metabolites, including numerous signaling small molecules, and thus regulates their activities and half-lives. Imbalances in the in vivo set points of these reactions leads to disease. Here, with the goal of controlling sulfonation in vivo, molecular ligand-recognition principles in the SULT and nuclear receptor families are integrated in creating a strategy that can prevent sulfonation of a compound without significantly altering its receptor affinity, or inhibiting SULTS. The strategy is validated by using it to control the sulfonation and estrogen receptor (ER) activating activity of raloxifene (a US Food and Drug Administration-approved selective estrogen receptor modulator) and its derivatives. Preventing sulfonation is shown to enhance ER-activation efficacy 10(4)-fold in studies using Ishikawa cells. The strategy offers the opportunity to control sulfuryl transfer on a compound-by-compound basis, to enhance the efficacy of sulfonated drugs, and to explore the biology of sulfuryl transfer with unprecedented precision. PMID:27203377

  17. Molecular Biology of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    HuanXi; JanBrabender; RalfMetzger; PaulM.Schneider

    2004-01-01

    There have been many new developments in our understanding of esophageal carcinoma biology over the past several years. Information regarding both of the major forms of this disease, adenocarcinoma and squamous cell carcinoma, has accumulated in conjunction with data on precursor conditions such as Barrett's esophagus. Interesting and promising findings have included overexpression of proto-oncogenes,loss of heterozygosity at multiple chromosomal loci, tumor suppressor gene inactivation, epigenetic silencing by DNA methylation, and mutations and deletions involving the tumor suppressor gene p53. Important cancer pathways, the cyclin kinase inhibitor cascade and the DNA mismatch repair process, implicated in the genesis of multiple tumor types have also been inculpated in esophageal carcinogenesis. Alterations in the p16 and p15 cyclin kinase inhibitors including point mutations and homozygous deletions have been reported in primary esophageal tumors. Further developments in the field of molecular carcinogenesis of esophageal malignancies promise to yield improvements in prevention, early detection, prognostic categorization, and perhaps gene-based therapy of this deadly disease.

  18. Biosimilars: Company Strategies to Capture Value from the Biologics Market

    Directory of Open Access Journals (Sweden)

    Juan Leonardo Martínez-Hurtado

    2012-12-01

    Full Text Available Patents for several biologic blockbusters will expire in the next few years. The arrival of biosimilars, the biologic equivalent of chemical generics, will have an impact on the current biopharmaceuticals market. Five core capabilities have been identified as paramount for those companies aiming to enter the biosimilars market: research and development, manufacturing, supporting activities, marketing, and lobbying. Understanding the importance of each of these capabilities will be key to maximising the value generated from the biologics patent cliff.

  19. Screening and identifying antagonistic bacteria against Rhizoctonia solani and their biological control effects on soil-born damping-off disease of cucumber%土传黄瓜立枯病高效拮抗菌的筛选鉴定及其生物效应

    Institute of Scientific and Technical Information of China (English)

    黄新琦; 雍晓雨; 沈其荣; 杨兴明

    2012-01-01

    In this study,more than 400 bacterial strains were isolated from rhizosphere soil of cucumber,and the dual culture method was used to screen bacterial antagonists against Rhizoctonia solani.Sixteen strains of bacterial antagonists were isolated and their inhabiting zone against R.solani ranged from 0.81 cm to 1.93 cm.Based on the results of morphologic characteristics,physiological and biochemical properties and phylogenetic analysis of 16S rDNA,three strains(N33,N34 and N43) with inhabiting zone more than 1.6 cm were identified as Pseudomonas sp,Bacillus sp.and Bacillus sp.,respectively.Through application of the three antagonists in cropping substrate of cucumber seedlings,their promotion effect on cucumber seedlings and control efficiency on damping-off disease were tested.All of the three isolates could promote the growth of cucumber seedlings and suppress cucumber seedlings from damping-off disease.Among of them,N43 showed the best effect on increasing the fresh weight of shoot by 62.16% and preventing the disease with a control efficiency of 62%,compared with control.%采用平板对峙法从黄瓜根际土壤中分离出的400余株细菌菌株中筛选出16株对立枯丝核菌Rhizoctonia solani具有拮抗效果的菌株,抑菌带直径在0.81~1.93 cm之间。并从中选出3株抑菌带直径在1.6cm以上的菌株N33、N35和N43,结合形态、生理生化特性及16S rDNA序列比对分析,鉴定N33菌株为假单胞菌属Pseudomonas sp.,N35和N43菌株为芽胞杆菌属Bacillus sp.。通过在黄瓜育苗基质中添加选育的高效拮抗菌株,观测其对黄瓜苗生长的促进作用以及对立枯病的防治作用,3株菌株均具有促进黄瓜苗期生长和防治苗期立枯病的作用,其中N43菌株促生及防病效果均最显著,地上部鲜重比对照处理增加62.16%,防治效果达62%。

  20. How stress alters memory in 'smart' snails.

    Directory of Open Access Journals (Sweden)

    Sarah Dalesman

    Full Text Available Cognitive ability varies within species, but whether this variation alters the manner in which memory formation is affected by environmental stress is unclear. The great pond snail, Lymnaea stagnalis, is commonly used as model species in studies of learning and memory. The majority of those studies used a single laboratory strain (i.e. the Dutch strain originating from a wild population in the Netherlands. However, our recent work has identified natural populations that demonstrate significantly enhanced long-term memory (LTM formation relative to the Dutch strain following operant conditioning of aerial respiratory behaviour. Here we assess how two populations with enhanced memory formation (i.e. 'smart' snails, one from Canada (Trans Canada 1: TC1 and one from the U.K. (Chilton Moor: CM respond to ecologically relevant stressors. In control conditions the Dutch strain forms memory lasting 1-3 h following a single 0.5 h training session in our standard calcium pond water (80 mg/l [Ca(2+], whereas the TC1 and CM populations formed LTM lasting 5+ days following this training regime. Exposure to low environmental calcium pond water (20 mg/l [Ca(2+], which blocks LTM in the Dutch strain, reduced LTM retention to 24 h in the TC1 and CM populations. Crowding (20 snails in 100 ml immediately prior to training blocks LTM in the Dutch strain, and also did so in TC1 and CM populations. Therefore, snails with enhanced cognitive ability respond to these ecologically relevant stressors in a similar manner to the Dutch strain, but are more robust at forming LTM in a low calcium environment. Despite the two populations (CM and TC1 originating from different continents, LTM formation was indistinguishable in both control and stressed conditions. This indicates that the underlying mechanisms controlling cognitive differences among populations may be highly conserved in L. stagnalis.