Sample records for biomarkers 0f bacterial

  1. Cloning and sequencing of the genes coding for the A and B subunits of vacuolar-type Na(+)-ATPase from Enterococcus hirae. Coexistence of vacuolar- and F0F1-type ATPases in one bacterial cell. (United States)

    Takase, K; Yamato, I; Kakinuma, Y


    The eubacterium Enterococcus hirae ATCC 9790 possesses a H(+)-translocating ATPase, and the deduced amino acid sequences of the genes coding for this enzyme have indicated that it is a typical F0F1-type ATPase (Shibata, C., Ehara, T., Tomura, K., Igarashi, K., and Kobayashi, H. (1992) J. Bacteriol. 174, 6117-6124). We cloned the ntpA and ntpB genes coding for the A and B subunits, respectively, of Na(+)-translocating ATPase from the same bacterium, and the full amino acid sequences of the two subunits were deduced from the nucleotide sequence. The A (593 amino acid residues) and B (458 amino acid residues) subunits were highly homologous (48-60% identical) to the A (large or alpha) and the B (small or beta) subunits, respectively, of vacuolar-type H(+)-ATPases which have been found in eukaryotic endomembrane systems (Neurospora crassa, Saccharomyces cerevisiae, Arabidopsis thaliana, and carrot) and archaebacterial cell membranes (Sulfolobus acidocaldarius and Methanosarcina barkeri). The A and B subunits of Na(+)-ATPase showed about 23-28% identities with the beta and alpha subunits of E. hirae F1-ATPase and of Escherichia coli F1-ATPase, respectively. These results indicate that E. hirae Na(+)-ATPase belongs to the vacuolar-type ATPase. This is the first demonstration that both genes for V- and F-type ATPases are functionally expressed in one bacterial cell.

  2. What bacteria leave behind: bacterial organic matter quality and biomarker signals

    DEFF Research Database (Denmark)

    Piil, Kristoffer; Schramm, Andreas; Niggemann, Jutta;

    WHAT BACTERIA LEAVE BEHIND: BACTERIAL ORGANIC MATTER QUALITY AND BIOMARKER SIGNALS Knowledge of the cellular content of bacterial biomarkers (D-amino acids and muramic acid) provides us with a powerful tool to trace production and fate of bacterially derived organic matter. The biochemical...... composition of prokaryotic cells was studied by re-growing a mixed community of native sediment bacteria in anoxic sediment pore water. Cellular concentrations of L- and D-amino acids and amino sugars were determined by high performance liquid chromatography (HPLC). The proportion of Archaea, Gram positive...

  3. Soluble triggering receptor expressed on myeloid cells 1: a biomarker for bacterial meningitis

    NARCIS (Netherlands)

    R.M. Determann; M. Weisfelt; J. de Gans; A. van der Ende; M.J. Schultz; D. van de Beek


    Objective: To evaluate whether soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in CSF can serve as a biomarker for the presence of bacterial meningitis and outcome in patients with this disease. Design: Retrospective study of diagnostic accuracy. Setting and patients: CSF was coll

  4. Identification and dynamic modeling of biomarkers for bacterial uptake and effect of sulfonamide antimicrobials

    NARCIS (Netherlands)

    Richter, M.K.; Focks, A.; Siegfried, B.; Rentsch, D.; Krauss, M.


    The effects of sulfathiazole (STA) on Escherichia coli with glucose as a growth substrate was investigated to elucidate the effect-based reaction of sulfonamides in bacteria and to identify biomarkers for bacterial uptake and effect. The predominant metabolite was identified as pterine-sulfathiazole

  5. Cytokines and Chemokines as Biomarkers of Community-Acquired Bacterial Infection

    Directory of Open Access Journals (Sweden)

    Michal Holub


    Full Text Available Routinely used biomarkers of bacterial etiology of infection, such as C-reactive protein and procalcitonin, have limited usefulness for evaluation of infections since their expression is enhanced by a number of different conditions. Therefore, several inflammatory cytokines and chemokines were analyzed with sera from patients hospitalized for moderate bacterial and viral infectious diseases. In total, 57 subjects were enrolled: 21 patients with community-acquired bacterial infections, 26 patients with viral infections, and 10 healthy subjects (control cohorts. The laboratory analyses were performed using Luminex technology, and the following molecules were examined: IL-1Ra, IL-2, IL-4, IL-6, IL-8, TNF-α, INF-γ, MIP-1β, and MCP-1. Bacterial etiology of infection was associated with significantly (P<0.001 elevated serum concentrations of IL-1Ra, IL-2, IL-6, and TNF-α in comparison to levels observed in the sera of patients with viral infections. In the patients with bacterial infections, IL-1Ra and IL-8 demonstrated positive correlation with C-reactive protein, whereas, IL-1Ra, TNF-α, and MCP-1 correlated with procalcitonin. Furthermore, elevated levels of IL-1Ra, IL-6, and TNF-α decreased within 3 days of antibiotic therapy to levels observed in control subjects. The results show IL-1Ra as a potential useful biomarker of community-acquired bacterial infection.

  6. Biomarkers for Tuberculosis Based on Secreted, Species-Specific, Bacterial Small Molecules. (United States)

    Pan, Shih-Jung; Tapley, Asa; Adamson, John; Little, Tessa; Urbanowski, Michael; Cohen, Keira; Pym, Alexander; Almeida, Deepak; Dorasamy, Afton; Layre, Emilie; Young, David C; Singh, Ravesh; Patel, Vinod B; Wallengren, Kristina; Ndung'u, Thumbi; Wilson, Douglas; Moody, D Branch; Bishai, William


    Improved biomarkers are needed for tuberculosis. To develop tests based on products secreted by tubercle bacilli that are strictly associated with viability, we evaluated 3 bacterial-derived, species-specific, small molecules as biomarkers: 2 mycobactin siderophores and tuberculosinyladenosine. Using liquid chromatography-tandem mass spectrometry, we demonstrated the presence of 1 or both mycobactins and/or tuberculosinyladenosine in serum and whole lung tissues from infected mice and sputum, cerebrospinal fluid (CSF), or lymph nodes from infected patients but not uninfected controls. Detection of the target molecules distinguished host infection status in 100% of mice with both serum and lung as the target sample. In human subjects, we evaluated detection of the bacterial small molecules (BSMs) in multiple body compartments in 3 patient cohorts corresponding to different forms of tuberculosis. We detected at least 1 of the 3 molecules in 90%, 71%, and 40% of tuberculosis patients' sputum, CSF, and lymph node samples, respectively. In paucibacillary forms of human tuberculosis, which are difficult to diagnose even with culture, detection of 1 or more BSM was rapid and compared favorably to polymerase chain reaction-based detection. Secreted BSMs, detectable in serum, warrant further investigation as a means for diagnosis and therapeutic monitoring in patients with tuberculosis.

  7. Transcriptional activity around bacterial cell death reveals molecular biomarkers for cell viability

    Directory of Open Access Journals (Sweden)

    Schuren Frank H


    Full Text Available Abstract Background In bacteriology, the ability to grow in selective media and to form colonies on nutrient agar plates is routinely used as a retrospective criterion for the detection of living bacteria. However, the utilization of indicators for bacterial viability-such as the presence of specific transcripts or membrane integrity-would overcome bias introduced by cultivation and reduces the time span of analysis from initiation to read out. Therefore, we investigated the correlation between transcriptional activity, membrane integrity and cultivation-based viability in the Gram-positive model bacterium Bacillus subtilis. Results We present microbiological, cytological and molecular analyses of the physiological response to lethal heat stress under accurately defined conditions through systematic sampling of bacteria from a single culture exposed to gradually increasing temperatures. We identified a coherent transcriptional program including known heat shock responses as well as the rapid expression of a small number of sporulation and competence genes, the latter only known to be active in the stationary growth phase. Conclusion The observed coordinated gene expression continued even after cell death, in other words after all bacteria permanently lost their ability to reproduce. Transcription of a very limited number of genes correlated with cell viability under the applied killing regime. The transcripts of the expressed genes in living bacteria – but silent in dead bacteria-include those of essential genes encoding chaperones of the protein folding machinery and can serve as molecular biomarkers for bacterial cell viability.

  8. Vaginal Biogenic Amines: Biomarkers of Bacterial Vaginosis or Precursors to Vaginal Dysbiosis?

    Directory of Open Access Journals (Sweden)

    Tiffanie Maree Nelson


    Full Text Available Bacterial vaginosis (BV is the most common vaginal disorder among reproductive age women. One clinical indicator of BV is a ‘fishy’ odor. This odor has been associated with increases in several biogenic amines (BAs that may serve as important biomarkers. Within the vagina, BA production has been linked to various vaginal taxa, yet their genetic capability to synthesize BAs is unknown. Using a bioinformatics approach, we show that relatively few vaginal taxa are predicted to be capable of producing BAs. Many of these taxa (Dialister, Prevotella, Parvimonas, Megasphaera, Peptostreptococcus, and Veillonella spp. are more abundant in the vaginal microbial community state type (CST IV, which is depleted in lactobacilli. Several of the major Lactobacillus species (L. crispatus, L. jensenii, and L. gasseri were identified as possessing gene sequences for proteins predicted to be capable of putrescine production. Finally, we show in a small cross sectional study of 37 women that the BAs putrescine, cadaverine and tyramine are significantly higher in CST IV over CSTs I and III. These data support the hypothesis that BA production is conducted by few vaginal taxa and may be important to the outgrowth of BV-associated (vaginal dysbiosis vaginal bacteria.

  9. Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study

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    Andreas eDix


    Full Text Available Sepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to classify if a sample contains a bacterial, fungal, or mock-infection. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97% for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83% for an additional test dataset comprising Cryptococcus neoformans infections. Furthermore, the classifier is robust to Gaussian noise, indicating correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances.

  10. Custom database development and biomarker discovery methods for MALDI-TOF mass spectrometry-based identification of high-consequence bacterial pathogens. (United States)

    Tracz, Dobryan M; Tyler, Andrea D; Cunningham, Ian; Antonation, Kym S; Corbett, Cindi R


    A high-quality custom database of MALDI-TOF mass spectral profiles was developed with the goal of improving clinical diagnostic identification of high-consequence bacterial pathogens. A biomarker discovery method is presented for identifying and evaluating MALDI-TOF MS spectra to potentially differentiate biothreat bacteria from less-pathogenic near-neighbour species.

  11. Towards an understanding of a0-f0 mixing

    CERN Document Server

    Hanhart, Christoph; Pelaez, Jose R


    We investigate the isospin-violating mixing of the light scalar mesons a0(980) and f0(980) within the unitarized chiral approach. Isospin-violating effects are considered to leading order in the quark mass differences and electromagnetism. In this approach both mesons are generated through meson-meson dynamics. Thus our results might be considered as benchmark results for the mixing phenomenon within a framework consistent with chiral symmetry and unitarity, where these resonances are not predominantly q q-bar states. Amongst the possible experimental signals, we discuss observable consequences for the reaction J/Psi -> phi pi0 eta in detail. In particular we demonstrate that the effect of a0-f0 mixing is by far the most important isospin-breaking effect in the resonance region and can indeed be extracted from experiment.

  12. Sediment biomarker, bacterial community characterization of high arsenic aquifers in Jianghan Plain, China (United States)

    Ye, Hengpeng; Yang, Zeyu; Wu, Xiang; Wang, Jingwen; Du, Dongyun; Cai, Jian; Lv, Kangle; Chen, Huiyun; Mei, Jingkun; Chen, Mengqi; Du, Hong


    Representative biomarkers (e.g., n-alkanes), diversity and microbial community in the aquifers contaminated by high concentration of arsenic (As) in different sediment depth (0–30 m) in Jianghan Plain, Hubei, China, were analyzed to investigate the potential mechanism of As enrichment in groundwater. The concentration of As was abundant in top soil and sand, but not in clay. The analysis of the distribution of n-alkanes, CPI values, and wax to total n-alkane ratio (Wax(n)%) indicated that the organic matter (OM) from fresh terrestrial plants were abundant in the shallow sediment. However, n-alkanes have suffered from significant biodegradation from the depth of 16 m to 30 m. The deposition of fresh terrestrial derived organic matters may facilitate the release of As from sediment to groundwater in the sediment of 0–16 m. However, the petroleum derived organic matters may do the favor to the release of As in the deeper section of borehole (16 m to 30 m). The 16S rRNA gene sequences identification indicated that Acidobacteria, Actinomycetes and Hydrogenophaga are abundant in the sediments with high arsenic. Therefore, microbes and organic matters from different sources may play important roles in arsenic mobilization in the aquifers of the study area. PMID:28165031

  13. Short- and long-term biomarkers for bacterial robustness: a framework for quantifying correlations between cellular indicators and adaptive behavior.

    Directory of Open Access Journals (Sweden)

    Heidy M W den Besten

    Full Text Available The ability of microorganisms to adapt to changing environments challenges the prediction of their history-dependent behavior. Cellular biomarkers that are quantitatively correlated to stress adaptive behavior will facilitate our ability to predict the impact of these adaptive traits. Here, we present a framework for identifying cellular biomarkers for mild stress induced enhanced microbial robustness towards lethal stresses. Several candidate-biomarkers were selected by comparing the genome-wide transcriptome profiles of our model-organism Bacillus cereus upon exposure to four mild stress conditions (mild heat, acid, salt and oxidative stress. These candidate-biomarkers--a transcriptional regulator (activating general stress responses, enzymes (removing reactive oxygen species, and chaperones and proteases (maintaining protein quality--were quantitatively determined at transcript, protein and/or activity level upon exposure to mild heat, acid, salt and oxidative stress for various time intervals. Both unstressed and mild stress treated cells were also exposed to lethal stress conditions (severe heat, acid and oxidative stress to quantify the robustness advantage provided by mild stress pretreatment. To evaluate whether the candidate-biomarkers could predict the robustness enhancement towards lethal stress elicited by mild stress pretreatment, the biomarker responses upon mild stress treatment were correlated to mild stress induced robustness towards lethal stress. Both short- and long-term biomarkers could be identified of which their induction levels were correlated to mild stress induced enhanced robustness towards lethal heat, acid and/or oxidative stress, respectively, and are therefore predictive cellular indicators for mild stress induced enhanced robustness. The identified biomarkers are among the most consistently induced cellular components in stress responses and ubiquitous in biology, supporting extrapolation to other microorganisms

  14. Soil water availability and microsite mediate fungal and bacterial phospholipid fatty acid biomarker abundances in Mojave Desert soils exposed to elevated atmospheric CO2 (United States)

    Jin, V. L.; Schaeffer, S. M.; Ziegler, S. E.; Evans, R. D.


    Changes in the rates of nitrogen (N) cycling, microbial carbon (C) substrate use, and extracellular enzyme activities in a Mojave Desert ecosystem exposed to elevated atmospheric CO2 suggest shifts in the size and/or functional characteristics of microbial assemblages in two dominant soil microsites: plant interspaces and under the dominant shrub Larrea tridentata. We used ester-linked phospholipid fatty acid (PLFA) biomarkers as a proxy for microbial biomass to quantify spatial and temporal differences in soil microbial communities from February 2003 to May 2005. Further, we used the 13C signature of the fossil CO2 source for elevated CO2 plots to trace recent plant C inputs into soil organic matter (SOM) and broad microbial groups using δ13C (‰). Differences between individual δ13CPLFA and δ13CSOM for fungal biomarkers indicated active metabolism of newer C in elevated CO2 soils. Total PLFA-C was greater in shrub microsites compared to plant interspaces, and CO2 treatment differences within microsites increased under higher soil water availability. Total, fungal, and bacterial PLFA-C increased with decreasing soil volumetric water content (VWC) in both microsites, suggesting general adaptations to xeric desert conditions. Increases in fungal-to-bacterial PLFA-C ratio with decreasing VWC reflected functional group-specific responses to changing soil water availability. While temporal and spatial extremes in resource availability in desert ecosystems contribute to the difficulty in identifying common trends or mechanisms driving microbial responses in less extreme environments, we found that soil water availability and soil microsite interacted with elevated CO2 to shift fungal and bacterial biomarker abundances in Mojave Desert soils.

  15. Serum anti-Helicobacter pylori immunoglobulin G titer correlates with grade of histological gastritis, mucosal bacterial density, and levels of serum biomarkers. (United States)

    Tu, Huakang; Sun, Liping; Dong, Xiao; Gong, Yuehua; Xu, Qian; Jing, Jingjing; Yuan, Yuan


    OBJECTIVE. Clinical implications of serum anti-Helicobacter pylori immunoglobulin G (IgG) titer were unclear. This study investigated the associations of serum anti-H. pylori IgG titer with grade of histological gastritis, mucosal bacterial density and levels of serum biomarkers, including pepsinogen (PG) I, PGII, PGI/II ratio and gastrin-17. MATERIAL AND METHODS. Study participants were from a screening program in northern China. Serum anti-H. pylori IgG measurements were available for 5922 patients with superficial gastritis. Serum anti-H. pylori IgG titer and serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. RESULTS. In patients with mild, moderate or severe superficial gastritis, the mean serum anti-H. pylori IgG titers were 17.3, 33.4 and 54.4 EIU (p for trend gastritis, mucosal bacterial density and concentrations of serum PGI, PGII and gastrin-17, and negatively with PGI/II ratio.

  16. Pleural effusion adenosine deaminase: a candidate biomarker to discriminate between Gram-negative and Gram-positive bacterial infections of the pleural space

    Directory of Open Access Journals (Sweden)

    Ruolin Li


    Full Text Available OBJECTIVES: Delay in the treatment of pleural infection may contribute to its high mortality. In this retrospective study, we aimed to evaluate the diagnostic accuracy of pleural adenosine deaminase in discrimination between Gram-negative and Gram-positive bacterial infections of the pleural space prior to selecting antibiotics. METHODS: A total of 76 patients were enrolled and grouped into subgroups according to Gram staining: 1 patients with Gram-negative bacterial infections, aged 53.2±18.6 years old, of whom 44.7% had empyemas and 2 patients with Gram-positive bacterial infections, aged 53.5±21.5 years old, of whom 63.1% had empyemas. The pleural effusion was sampled by thoracocentesis and then sent for adenosine deaminase testing, biochemical testing and microbiological culture. The Mann-Whitney U test was used to examine the differences in adenosine deaminase levels between the groups. Correlations between adenosine deaminase and specified variables were also quantified using Spearman’s correlation coefficient. Moreover, receiver operator characteristic analysis was performed to evaluate the diagnostic accuracy of pleural effusion adenosine deaminase. RESULTS: Mean pleural adenosine deaminase levels differed significantly between Gram-negative and Gram-positive bacterial infections of the pleural space (191.8±32.1 U/L vs 81.0±16.9 U/L, p<0.01. The area under the receiver operator characteristic curve was 0.689 (95% confidence interval: 0.570, 0.792, p<0.01 at the cutoff value of 86 U/L. Additionally, pleural adenosine deaminase had a sensitivity of 63.2% (46.0-78.2%; a specificity of 73.7% (56.9-86.6%; positive and negative likelihood ratios of 2.18 and 0.50, respectively; and positive and negative predictive values of 70.6% and 66.7%, respectively. CONCLUSIONS: Pleural effusion adenosine deaminase is a helpful alternative biomarker for early and quick discrimination of Gram-negative from Gram-positive bacterial infections of the

  17. Biofilms as "Connectors" for Oral and Systems Medicine: A New Opportunity for Biomarkers, Molecular Targets, and Bacterial Eradication. (United States)

    Sintim, Herman O; Gürsoy, Ulvi Kahraman


    Oral health and systems medicine are intimately related but have remained, sadly, as isolated knowledge communities for decades. Are there veritable connector knowledge domains that can usefully link them together on the critical path to biomarker research and "one health"? In this context, it is noteworthy that bacteria form surface-attached communities on most biological surfaces, including the oral cavity. Biofilm-forming bacteria contribute to periodontal diseases and recent evidences point to roles of these bacteria in systemic diseases as well, with cardiovascular diseases, obesity, and cancer as notable examples. Interestingly, the combined mass of microorganisms such as bacteria are so large that when we combine all plants and animals on earth, the total biomass of bacteria is still bigger. They literally do colonize everywhere, not only soil and water but our skin, digestive tract, and even oral cavity are colonized by bacteria. Hence efforts to delineate biofilm formation mechanisms of oral bacteria and microorganisms and the development of small molecules to inhibit biofilm formation in the oral cavity is very timely for both diagnostics and therapeutics. Research on biofilms can benefit both oral and systems medicine. Here, we examine, review, and synthesize new knowledge on the current understanding of oral biofilm formation, the small molecule targets that can inhibit biofilm formation in the mouth. We suggest new directions for both oral and systems medicine, using various omics technologies such as SILAC and RNAseq, that could yield deeper insights, biomarkers, and molecular targets to design small molecules that selectively aim at eradication of pathogenic oral bacteria. Ultimately, devising new ways to control and eradicate bacteria in biofilms will open up novel diagnostic and therapeutic avenues for oral and systemic diseases alike.

  18. Diversification of nitrogen fixing bacterial community using nifH gene as a biomarker in different geographical soils of Western Indian Himalayas. (United States)

    Singh, Chhug; Soni, Ravindra; Jain, Sourabh; Roy, Subhadip; Goel, Reeta


    Six soil samples (Pantnagar, Chamoli, Almora, Ranichauri, Pithoragarh and Badrinath) belonging to different geographical locations of Western Himalayas in India, were analyzed to diversify the nitrogen fixing bacterial community using nifH gene biomarker DNA from soil samples were isolated and amplified using nifH gene specific primers. Genomic DNA and PCR amplified products were then individually subjected to restriction digestion with tetra to octacutter enzymes (AluI, MspI, BgIII, XbaI, HindIII, HaeIII, AluI, MspI and PasI. Further restriction pattern was studied by preparing dendograms on the basis of similarity matrix and compared for the nifH community. It was observed that temperate region soils (Ranichauri and Pithoragarh) were negative for nifH marker while subalpine region (Badrinath) and tarai region soils (Pantnagar) documented similar nifH community. Moreover; the direct genomic DNA restriction analysis indicated that subalpine region soil (Badrinath) was most diversified.

  19. Search for the decay $B^0_s\\to\\overline{D}^0f_0(980)$

    CERN Document Server

    Aaij, Roel; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Birnkraut, Alex; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casanova Mohr, Raimon; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Ruscio, Francesco; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gascon, David; Gaspar, Clara; Gastaldi, Ugo; Gauld, Rhorry; Gavardi, Laura; Gazzoni, Giulio; Geraci, Angelo; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Gianì, Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, Vladimir; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Humair, Thibaud; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Matthieu, Kecke; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Janine; Müller, Katharina; Müller, Vanessa; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Ninci, Daniele; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz, Hugo; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skillicorn, Ian; Skwarnicki, Tomasz; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Sterpka, Christopher Francis; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szumlak, Tomasz; T'Jampens, Stephane; Tekampe, Tobias; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Todd, Jacob; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wiedner, Dirk; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang


    A search for $B_s^0 \\to \\overline{D}^{0} f_{0}(980)$ decays is performed using $3.0\\, {\\rm fb}^{-1}$ of $pp$ collision data recorded by the LHCb experiment during 2011 and 2012. The $f_{0}(980)$ meson is reconstructed through its decay to the $\\pi^{+}\\pi^{-}$ final state in the mass window $900\\, {\\rm MeV}/c^{2} < m(\\pi^{+}\\pi^{-}) < 1080\\, {\\rm MeV}/c^{2}$. No significant signal is observed. The first upper limits on the branching fraction of $\\mathcal{B}(B_s^0 \\to \\overline{D}^{0} f_{0}(980)) < 3.1\\,(3.4) \\times 10^{-6}$ are set at $90\\%$ ($95\\%$) confidence level.

  20. Observation of the isospin-violating decay J/psi -> phi pi(0)f(0) (980)

    NARCIS (Netherlands)

    Ablikim, M.; Achasov, M. N.; Ai, X.C.; Albayrak, O.; Albrecht, M.; Ambrose, D.J.; Amoroso, A.; Bondarenko, O.; Haddadi, Z.; Kavatsyuk, M.; Loehner, H.; Messchendorp, J.G.; Tiemens, M.


    Using a sample of 1.31 x 10(9) J/psi events collected with the BESIII detector at the BEPCII collider, the decays J/psi -> phi pi(+)pi(-)pi(0) and J/psi -> phi pi(0)pi(0)pi(0) are investigated. The isospin- violating decay J/psi -> phi pi(0)f(0)(980) with f(0)(980)-> pi pi is observed for the first

  1. Preliminary results on correlation in daily f0F2 and M(3000F2 variations

    Directory of Open Access Journals (Sweden)

    Y Nissopoulos


    Full Text Available A statistical analysis of the hourly daily values of the factor M(3000F2 and the F2-layer critical frequency f0F2 is carried out first for each hour of the day through-out a given month of a given year at a given station (hour-to-hour variation and then for each day of a given month and year at a given station (day-to-day variation. This analysis shows that these ionospheric characteristics are poorly correlated. It is concluded that the daily values of the first characteristic cannot be estimated from the second by using a simple linear equation.

  2. Procalcitonine als biomarker voor infecties

    NARCIS (Netherlands)

    de Jonge, J C; de Lange, D W; Bij de Vaate, E A; van Leeuwen, H; Arends, J E


    - Inappropriate use of antibiotics in patients without bacterial infection contributes significantly to worldwide antibiotic resistance.- The goal of this review is to summarise evidence from randomised trials investigating the value of the biomarker procalcitonin (PCT) in patients with symptoms of

  3. Statistical properties of the deviations of f 0 F 2 from monthly medians

    Directory of Open Access Journals (Sweden)

    Y. Tulunay


    Full Text Available The deviations of hourly f 0 F 2 from monthly medians for 20 stations in Europe during the period 1958-1998 are studied. Spectral analysis is used to show that, both for original data (for each hour and for the deviations from monthly medians, the deterministic components are the harmonics of 11 years (solar cycle, 1 year and its harmonics, 27 days and 12 h 50.49 m (2nd harmonic of lunar rotation period L 2 periodicities. Using histograms for one year samples, it is shown that the deviations from monthly medians are nearly zero mean (mean < 0.5 and approximately Gaussian (relative difference range between %10 to %20 and their standard deviations are larger for daylight hours (in the range 5-7. It is shown that the amplitude distribution of the positive and negative deviations is nearly symmetrical at night hours, but asymmetrical for day hours. The positive and negative deviations are then studied separately and it is observed that the positive deviations are nearly independent of R12 except for high latitudes, but negative deviations are modulated by R12 . The 90% confidence interval for negative deviations for each station and each hour is computed as a linear model in terms of R12. After correction for local time, it is shown that for all hours the confidence intervals increase with latitude but decrease above 60N. Long-term trend analysis showed that there is an increase in the amplitude of positive deviations from monthly means irrespective of the solar conditions. Using spectral analysis it is also shown that the seasonal dependency of negative deviations is more accentuated than the seasonal dependency of positive deviations especially at low latitudes. In certain stations, it is also observed that the 4th harmonic of 1 year corresponding to a periodicity of 3 months, which is missing in f 0 F 2 data, appears in the spectra of negative variations.

  4. A method for f0F2 monitoring over Spain using the El Arenosillo digisonde current observations

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    G. Miro


    Full Text Available Ionosphere monitoring implies: observations, prediction and mapping of ionospheric parameters. A case with one available (El Arenosillo ionosonde is considered. Some statistical methods for f0F2 short-term (1-24 h in advance prediction are compared. The analysis of multi-dimensional regression for Df0F2 (relative deviation from running median with Ap, F10.7 and previous Df0F2 observations has shown that inclusion of additional terms with Ap and F10.7 improves the prediction accuracy for lead time more than 15 h. For lead time 1-6 h a linear regression with earlier observed Df0F2 provides the f0F2 forecast with Relative Mean Deviation (RMD 6-11%. This is acceptable from a practical point of view. A 24-h forecast can be done with RMD 10-11%. Multi-regressional methods provide better prediction accuracy than the usual 10-day running median or quasi-inertial method based on such median. Hourly f0F2 values may be used to calculate the effective index R12eff used as input to the ITU-R monthly median model. This allows the ITU-R model to "breathe" following hour-to-hour f0F2 variations. Then standard surfering methods may be applied for f0F2 mapping over the whole area. The f0F2 mapping accuracy based on the hourly R12eff index is shown to be 9-11% depending on solar activity level.

  5. Correlations in daily deviations from the median of f0F2, M(3000F2 and VF

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    T. D. Xenos


    Full Text Available The statistical analysis of the hourly daily deviations from the corresponding monthly-median values of the factor M(3000F2 and of the critical frequency of the F2-layer, f0F2, reveals that the correlation between these parameters is poor. A similar analysis between the hourly daily deviations from the corresponding monthly-median of the height h’F and the f0F2 leads to similar results. These results indicate that the factor M(3000F2, the height h’F and the critical frequency f0F2 may have a different daily variability.

  6. An L0(F,R)-valued Function's Intermediate Value Theorem and Its Applications to Random Uniform Convexity

    Institute of Scientific and Technical Information of China (English)

    Tie Xin GUO; Xiao Lin ZENG


    Let (Ω,F,P) be a probability space and L0(F,R) the algebra of equivalence classes of realvalued random variables on (Ω,F,P).When L0(F,R) is endowed with the topology of convergence in probability,we prove an intermediate value theorem for a continuous local function from L0(F,R) to L0(F,R).As applications of this theorem,we first give several useful expressions for modulus of random convexity,then we prove that a complete random normed module (S,‖· ‖) is random uniformly convex itf LF(S) is uniformly convex for each fixed positive number p such that 1 < p < +oo.

  7. Observation of the isospin-violating decay $J/\\psi \\to \\phi\\pi^{0}f_{0}(980)$

    CERN Document Server

    Ablikim, M; Ai, X C; Albayrak, O; Albrecht, M; Ambrose, D J; Amoroso, A; An, F F; An, Q; Bai, J Z; Ferroli, R Baldini; Ban, Y; Bennett, D W; Bennett, J V; Bertani, M; Bettoni, D; Bian, J M; Bianchi, F; Boger, E; Bondarenko, O; Boyko, I; Briere, R A; Cai, H; Cai, X; Cakir, O; Calcaterra, A; Cao, G F; Cetin, S A; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, H Y; Chen, J C; Chen, M L; Chen, S J; Chen, X; Chen, X R; Chen, Y B; Cheng, H P; Chu, X K; Cibinetto, G; Cronin-Hennessy, D; Dai, H L; Dai, J P; Dbeyssi, A; De dovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; De Mori, F; Ding, Y; Dong, C; Dong, J; Dong, L Y; Dong, M Y; Du, S X; Duan, P F; Fan, J Z; Fang, J; Fang, S S; Fang, X; Fang, Y; Fava, L; Feldbauer, F; Felici, G; Feng, C Q; Fioravanti, E; Fritsch, M; Fu, C D; Gao, Q; Gao, X Y; Gao, Y; Gao, Z; Garzia, I; Geng, C; Goetzen, K; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, Y; Guo, Y P; Haddadi, Z; ner, A Haf; Han, S; Han, Y L; Hao, X Q; Harris, F A; He, K L; He, Z Y; Held, T; Heng, Y K; Hou, Z L; Hu, C; Hu, H M; Hu, J F; Hu, T; Hu, Y; Huang, G M; Huang, G S; Huang, H P; Huang, J S; Huang, X T; Huang, Y; Hussain, T; Ji, Q; Ji, Q P; Ji, X B; Ji, X L; Jiang, L L; Jiang, L W; Jiang, X S; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; ansson, T Joh; Julin, A; Kalantar-Nayestanaki, N; Kang, X L; Kang, X S; Kavatsyuk, M; Ke, B C; Kliemt, R; Kloss, B; Kolcu, O B; Kopf, B; Kornicer, M; Kuehn, W; Kupsc, A; Lange, J S; Lara, M; Larin, P; Leng, C; Li, C H; Li, Cheng; Li, D M; Li, F; Li, G; Li, H B; Li, J C; Li, Jin; Li, K; Li, Lei; Li, P R; Li, T; Li, W D; Li, W G; Li, X L; Li, X M; Li, X N; Li, X Q; Li, Z B; Liang, H; Liang, Y F; Liang, Y T; Liao, G R; Lin, D X; Liu, B J; iu, C X L; Liu, F H; Liu, Fang; Liu, Feng; Liu, H B; Liu, H H; Liu, H M; Liu, J; Liu, J P; Liu, J Y; Liu, K; Liu, K Y; Liu, L D; Liu, P L; Liu, Q; Liu, S B; Liu, X; Liu, X X; Liu, Y B; Liu, Z A; Liu, Zhiqiang; u, Zhiqing Li; Loehner, H; Lou, X C; Lu, H J; Lu, J G; Lu, R Q; Lu, Y; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lv, M; Lyu, X R; Ma, F C; Ma, H L; Ma, L L; Ma, Q M; Ma, T; Ma, X N; Ma, X Y; Maas, F E; Maggiora, M; ik, Q A Mal; Mao, Y J; Mao, Z P; Marcello, S; Messchendorp, J G; Min, J; Min, T J; Mitchell, R E; Mo, X H; Mo, Y J; Morales, C Morales; Moriya, K; Muchnoi, N Yu; Muramatsu, H; Nefedov, Y; Nerling, F; Nikolaev, I B; Ning, Z; Nisar, S; Niu, S L; Niu, X Y; Olsen, S L; Ouyang, Q; Pacetti, S; Patteri, P; Pelizaeus, M; Peng, H P; Peters, K; son, J Petters; Ping, J L; Ping, R G; Poling, R; Prasad, V; Pu, Y N; Qi, M; Qian, S; Qiao, C F; Qin, L Q; Qin, N; Qin, X S; Qin, Y; Qin, Z H; Qiu, J F; Rashid, K H; Redmer, C F; Ren, H L; Ripka, M; Rong, G; Rosner, Ch; Ruan, X D; Santoro, V; Sarantsev, A; Savrié, M; Schoenning, K; Schumann, S; Shan, W; Shao, M; Shen, C P; Shen, P X; Shen, X Y; Sheng, H Y; Song, W M; Song, X Y; Sosio, S; Spataro, S; Sun, G X; Sun, J F; Sun, S S; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Tapan, I; Thorndike, E H; Tiemens, M; Toth, D; Ullrich, M; Uman, I; arner, G S V; Wang, B; Wang, B L; Wang, D; Wang, D Y; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, S G; Wang, W; Wang, X F; Wang, Y D; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z H; Wang, Z Y; r, T Webe; Wei, D H; Wei, J B; Weidenkaff, P; Wen, S P; Wiedner, U; Wolke, M; Wu, L H; Wu, Z; Xia, L G; Xia, Y; Xiao, D; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, L; Xu, Q J; Xu, Q N; Xu, X P; Yan, L; Yan, W B; Yan, W C; Yan, Y H; Yang, H X; Yang, L; Yang, Y; Yang, Y X; Ye, H; Ye, M; Ye, M H; Yin, J H; Yu, B X; Yu, C X; Yu, H W; Yu, J S; Yuan, C Z; Yuan, W L; Yuan, Y; Yuncu, A; Zafar, A A; Zallo, A; Zeng, Y; Zhang, B X; Zhang, B Y; Zhang, C; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J J; Zhang, J L; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, K; Zhang, L; Zhang, S H; Zhang, X Y; Zhang, Y; Zhang, Y H; Zhang, Y T; Zhang, Z H; Zhang, Z P; Zhang, Z Y; Zhao, G; Zhao, J W; Zhao, J Y; Zhao, J Z; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, Q W; Zhao, S J; Zhao, T C; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, W J; Zheng, Y H; Zhong, B; Zhou, L; Zhou, Li; Zhou, X; Zhou, X K; Zhou, X R; Zhou, X Y; Zhu, K; Zhu, K J; Zhu, S; Zhu, X L; Zhu, Y C; Zhu, Y S; Zhu, Z A; Zhuang, J; Zotti, L; Zou, B S; Zou, J H


    Using a sample of 1.31 billion $J/\\psi$ events collected with the BESIII detector at the BEPCII collider, the decays $J/\\psi \\to \\phi \\pi^{+}\\pi^{-}\\pi^{0}$ and $J/\\psi \\to \\phi \\pi^{0}\\pi^{0}\\pi^{0}$ are investigated. The isospin violating decay $J/\\psi \\to \\phi \\pi^{0} f_{0}(980)$ with $f_{0}(980) \\to \\pi\\pi$, is observed for the first time. The width of the $f_{0}(980)$ obtained from the dipion mass spectrum is found to be much smaller than the world average value. In the $\\pi^{0} f_{0}(980)$ mass spectrum, there is evidence of $f_1(1285)$ production. By studying the decay $J/\\psi \\to \\phi\\eta'$, the branching fractions of $\\eta' \\to \\pi^{+}\\pi^{-}\\pi^{0}$ and $\\eta' \\to \\pi^{0}\\pi^{0}\\pi^{0}$, as well as their ratio, are also measured.

  8. The F(0F(1-ATP synthase complex contains novel subunits and is essential for procyclic Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Alena Zíková


    Full Text Available The mitochondrial F(0F(1 ATP synthase is an essential multi-subunit protein complex in the vast majority of eukaryotes but little is known about its composition and role in Trypanosoma brucei, an early diverged eukaryotic pathogen. We purified the F(0F(1 ATP synthase by a combination of affinity purification, immunoprecipitation and blue-native gel electrophoresis and characterized its composition and function. We identified 22 proteins of which five are related to F(1 subunits, three to F(0 subunits, and 14 which have no obvious homology to proteins outside the kinetoplastids. RNAi silencing of expression of the F(1 alpha subunit or either of the two novel proteins showed that they are each essential for the viability of procyclic (insect stage cells and are important for the structural integrity of the F(0F(1-ATP synthase complex. We also observed a dramatic decrease in ATP production by oxidative phosphorylation after silencing expression of each of these proteins while substrate phosphorylation was not severely affected. Our procyclic T. brucei cells were sensitive to the ATP synthase inhibitor oligomycin even in the presence of glucose contrary to earlier reports. Hence, the two novel proteins appear essential for the structural organization of the functional complex and regulation of mitochondrial energy generation in these organisms is more complicated than previously thought.

  9. Procalcitonin as a Serum Biomarker for Differentiation of Bacterial Meningitis From Viral Meningitis in Children: Evidence From a Meta-Analysis. (United States)

    Henry, Brandon Michael; Roy, Joyeeta; Ramakrishnan, Piravin Kumar; Vikse, Jens; Tomaszewski, Krzysztof A; Walocha, Jerzy A


    Several studies have explored the use of serum procalcitonin (PCT) in differentiating between bacterial and viral etiologies in children with suspected meningitis. We pooled these studies into a meta-analysis to determine the PCT diagnostic accuracy. All major databases were searched through March 2015. No date or language restrictions were applied. Eight studies (n = 616 pediatric patients) were included. Serum PCT assay was found to be very accurate for differentiating the etiology of pediatric meningitis with pooled sensitivity and specificity of 0.96 (95% CI = 0.92-0.98) and 0.89 (95% CI = 0.86-0.92), respectively. The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and area under the curve (AUC) for PCT were 7.5 (95% CI = 5.6-10.1), 0.08(95% CI = 0.04-0.14), 142.3 (95% CI = 59.5-340.4), and 0.97 (SE = 0.01), respectively. In 6 studies, PCT was found to be superior than CRP, whose DOR was only 16.7 (95%CI = 8.8-31.7). Our meta-analysis demonstrates that serum PCT assay is a highly accurate and powerful test for rapidly differentiating between bacterial and viral meningitis in children.

  10. Genetic Evidence for the Involvement of the S-Layer Protein Gene sap and the Sporulation Genes spo0A, spo0B, and spo0F in Phage AP50c Infection of Bacillus anthracis


    Roger D Plaut; Beaber, John W.; Zemansky, Jason; Kaur, Ajinder P.; George, Matroner; Biswas, Biswajit; Henry, Matthew; Bishop-Lilly, Kimberly A.; Mokashi, Vishwesh; Hannah, Ryan M.; Pope, Robert K.; Timothy D. Read; Stibitz, Scott; Calendar, Richard; Sozhamannan, Shanmuga


    In order to better characterize the Bacillus anthracis typing phage AP50c, we designed a genetic screen to identify its bacterial receptor. Insertions of the transposon mariner or targeted deletions of the structural gene for the S-layer protein Sap and the sporulation genes spo0A, spo0B, and spo0F in B. anthracis Sterne resulted in phage resistance with concomitant defects in phage adsorption and infectivity. Electron microscopy of bacteria incubated with AP50c revealed phage particles assoc...


    Institute of Scientific and Technical Information of China (English)


    How to Improve Your Oral English by "Listening, Speaking, Reading and Writing" Abstract:the learning of oral Englisn becomes and more important in the 21st century. The essay probes in to the relationship between oral English and listening, reading and writing, and put forward the method to improve oral English by listening, speaking, reading and writing.

  12. F0F1-ATP-Synthase aus Escherichia coli: Untersuchung verschiedener Proteinsysteme mit ESR-Spektroskopie


    Kraft, Gerhard


    Das Enzym F0F1-ATP-Synthase katalysiert die Phosphorylierung von ADP zu ATP unter Ausnutzung des durch die Atmungskette entstehenden Protonengradienten an Membranen. Hierbei pumpt der membranintegrale F0-Teil des Proteins Protonen durch die Membran und induziert die ATP-Synthese, welche auf dem peripheren, wasserlöslichen F1-Teil des Proteins (F1-ATPase) stattfindet. F0 besteht aus drei Proteinuntereinheiten der Stöchiometrie a b_2 c_9-12, während F1 aus fünf Untereinheiten der Stöchiometrie ...

  13. Measurements of the branching fraction and CP-violation asymmetries in B0-->f0(980)K0S. (United States)

    Aubert, B; Barate, R; Boutigny, D; Couderc, F; Gaillard, J-M; Hicheur, A; Karyotakis, Y; Lees, J P; Tisserand, V; Zghiche, A; Palano, A; Pompili, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Borgland, A W; Breon, A B; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Day, C T; Gill, M S; Gritsan, A V; Groysman, Y; Jacobsen, R G; Kadel, R W; Kadyk, J; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Mir, L M; Oddone, P J; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Shelkov, V G; Wenzel, W A; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Morgan, S E; Watson, A T; Fritsch, M; Goetzen, K; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Steinke, M; Boyd, J T; Chevalier, N; Cottingham, W N; Kelly, M P; Latham, T E; Wilson, F F; Cuhadar-Donszelmann, T; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Thiessen, D; Khan, A; Kyberd, P; Teodorescu, L; Blinov, V E; Druzhinin, V P; Golubev, V B; Ivanchenko, V N; Kravchenko, E A; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Yushkov, A N; Best, D; Bruinsma, M; Chao, M; Eschrich, I; Kirkby, D; Lankford, A J; Mandelkern, M; Mommsen, R K; Roethel, W; Stoker, D P; Buchanan, C; Hartfiel, B L; Foulkes, S D; Gary, J W; Shen, B C; Wang, K; del Re, D; Hadavand, H K; Hill, E J; MacFarlane, D B; Paar, H P; Rahatlou, Sh; Sharma, V; Berryhill, J W; Campagnari, C; Dahmes, B; Levy, S L; Long, O; Lu, A; Mazur, M A; Richman, J D; Verkerke, W; Beck, T W; Eisner, A M; Heusch, C A; Lockman, W S; Schalk, T; Schmitz, R E; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Dubois-Felsmann, G P; Dvoretskii, A; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Ryd, A; Samuel, A; Yang, S; Jayatilleke, S; Mancinelli, G; Meadows, B T; Sokoloff, M D; Abe, T; Blanc, F; Bloom, P; Chen, S; Ford, W T; Nauenberg, U; Olivas, A; Rankin, P; Smith, J G; Zhang, J; Zhang, L; Chen, A; Harton, J L; Soffer, A; Toki, W H; Wilson, R J; Zeng, Q L; Altenburg, D; Brandt, T; Brose, J; Dickopp, M; Feltresi, E; Hauke, A; Lacker, H M; Müller-Pfefferkorn, R; Nogowski, R; Otto, S; Petzold, A; Schubert, J; Schubert, K R; Schwierz, R; Spaan, B; Sundermann, J E; Bernard, D; Bonneaud, G R; Brochard, F; Grenier, P; Schrenk, S; Thiebaux, Ch; Vasileiadis, G; Verderi, M; Bard, D J; Clark, P J; Lavin, D; Muheim, F; Playfer, S; Xie, Y; Andreotti, M; Azzolini, V; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Piemontese, L; Sarti, A; Treadwell, E; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Patteri, P; Piccolo, M; Zallo, A; Buzzo, A; Capra, R; Contri, R; Crosetti, G; Lo Vetere, M; Macri, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Bailey, S; Brandenburg, G; Morii, M; Won, E; Dubitzky, R S; Langenegger, U; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Gaillard, J R; Morton, G W; Nash, J A; Taylor, G P; Charles, M J; Grenier, G J; Mallik, U; Cochran, J; Crawley, H B; Lamsa, J; Meyer, W T; Prell, S; Rosenberg, E I; Yi, J; Davier, M; Grosdidier, G; Höcker, A; Laplace, S; Le Diberder, F; Lepeltier, V; Lutz, A M; Petersen, T C; Plaszczynski, S; Schune, M H; Tantot, L; Wormser, G; Cheng, C H; Lange, D J; Simani, M C; Wright, D M; Bevan, A J; Chavez, C A; Coleman, J P; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Parry, R J; Payne, D J; Sloane, R J; Touramanis, C; Back, J J; Cormack, C M; Harrison, P F; Di Lodovico, F; Mohanty, G B; Brown, C L; Cowan, G; Flack, R L; Flaecher, H U; Green, M G; Jackson, P S; McMahon, T R; Ricciardi, S; Salvatore, F; Winter, M A; Brown, D; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Hart, P A; Hodgkinson, M C; Lafferty, G D; Lyon, A J; Williams, J C; Farbin, A; Hulsbergen, W D; Jawahery, A; Kovalskyi, D; Lae, C K; Lillard, V; Roberts, D A; Blaylock, G; Dallapiccola, C; Flood, K T; Hertzbach, S S; Kofler, R; Koptchev, V B; Moore, T B; Saremi, S; Staengle, H; Willocq, S; Cowan, R; Sciolla, G; Taylor, F; Yamamoto, R K; Mangeol, D J J; Patel, P M; Robertson, S H; Lazzaro, A; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Reidy, J; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Taras, P; Nicholson, H; Cavallo, N; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Baak, M; Bulten, H; Raven, G; Wilden, L; Jessop, C P; LoSecco, J M; Gabriel, T A; Allmendinger, T; Brau, B; Gan, K K; Honscheid, K; Hufnagel, D; Kagan, H; Kass, R; Pulliam, T; Rahimi, A M; Ter-Antonyan, R; Wong, Q K; Brau, J; Frey, R; Igonkina, O; Potter, C T; Sinev, N B; Strom, D; Torrence, E; Colecchia, F; Dorigo, A; Galeazzi, F; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Tiozzo, G; Voci, C; Benayoun, M; Briand, H; Chauveau, J; David, P; de la Vaissière, Ch; Del Buono, L; Hamon, O; John, M J J


    We present measurements of the branching fraction and CP-violating asymmetries in the decay B0-->f0(980)K0S. The results are obtained from a data sample of 123 x 10(6) Upsilon(4S)-->BB decays. From a time-dependent maximum likelihood fit, we measure the branching fraction B(B0-->f0(980)(-->pi+pi-)K0)=(6.0+/-0.9+/-0.6+/-1.2)x10(-6), the mixing-induced CP violation parameter S=-1.62(+0.56)(-0.51)+/-0.09+/-0.04, and the direct CP violation parameter C=0.27+/-0.36+/-0.10+/-0.07, where the first errors are statistical, the second systematic, and the third due to model uncertainties. We measure the f0(980) mass and width to be mf0(980)=(980.6+/-4.1+/-0.5+/-4.0) MeV/c2 and Gammaf0(980)=(43(+12)(-9)+/-3+/-9) MeV/c2, respectively.

  14. Nuclear factor YY1 activates the mammalian F0F1 ATP synthase alpha-subunit gene. (United States)

    Breen, G A; Vander Zee, C A; Jordan, E M


    Analysis of the promoters of the bovine and human nuclear-encoded mitochondrial F0F1 ATP synthase alpha-subunit genes (ATPA) has identified several positive cis-acting regulatory regions that are important for basal promoter activity in human HeLa cells. We have previously determined that the binding of a protein factor, termed ATPF1, to an E-box sequence (CANNTG) located within one of these cis-acting regions is critical for transcriptional activation of the ATPA gene. In this article, we describe a second positive cis-acting regulatory element of the ATPA gene that is important for expression of the ATPA gene. We show that this cis-acting element also contains a binding site for a protein present in HeLa cells. On the basis of electrophoretic mobility shift patterns, oligonucleotide competition assays, and immunological cross-reactivity, we conclude that this protein factor is Yin-Yang 1 (YY1). Experiments carried out to examine the functional role of YY1 within the context of the ATPA promoter demonstrated that YY1 acts as a positive regulator of the ATPA gene. For example, when the YY1 binding site of the ATPA promoter was placed upstream of a reporter gene it was found to activate transcription in transient transfection assays. In addition, disruption of the YY1 binding site in the ATPA gene resulted in a loss of transcriptional activity. Furthermore, in cotransfection experiments overexpression of YY1 in trans was found to activate transcription of ATPA promoter-CAT constructs. Thus, at least two positive trans-acting regulatory factors, ATPF1 and YY1, are important for expression of the bovine and human F0F1 ATP synthase alpha-subunit genes.

  15. Imaging Biomarkers or Biomarker Imaging?

    Directory of Open Access Journals (Sweden)

    Markus Mitterhauser


    Full Text Available Since biomarker imaging is traditionally understood as imaging of molecular probes, we highly recommend to avoid any confusion with the previously defined term “imaging biomarkers” and, therefore, only use “molecular probe imaging (MPI” in that context. Molecular probes (MPs comprise all kinds of molecules administered to an organism which inherently carry a signalling moiety. This review highlights the basic concepts and differences of molecular probe imaging using specific biomarkers. In particular, PET radiopharmaceuticals are discussed in more detail. Specific radiochemical and radiopharmacological aspects as well as some legal issues are presented.

  16. Design, construction, operation, and evaluation of solar systems for industrial process-heat applications in the intermediate-temperature range (212/sup 0/F to 550/sup 0/F). Environmental assessment

    Energy Technology Data Exchange (ETDEWEB)



    The environmental impacts are assessed for a proposed 50,000 square foot field of single axis tracking, concentrating solar collectors along the Ohio River in southern Ohio. The facility is planned to produce process steam for use in the production of polystyrene. Absorbed solar energy would heat an aliphatic hydrocarbon synthetic heat transfer fluid to a maximum temperature of 500/sup 0/F. The existing environment is briefly described, particularly regarding air quality. The potential environmental impacts of the solar process heat system on the air, water, soil, endangered species and archaeological and historical resources are examined, including risks due to flood and glare and a comparison of alternatives. Also included are a Consent Judgment relating to two coal-fired boilers in violation of EPA regulations, property data of Gulf Synfluid 4CS (a candidate heat transfer fluid), piping and instrumentation diagrams and schematics, site grade and drainage plan, geological survey map, subsurface soil investigation, Ohio endangered species list, Ohio Archaeological Counsel certification list, and a study of heat transfer fluids and their properties. (LEW)

  17. A method for f{sub 0}F{sub 2} monitoring over Spain using the El Arenosillo digisonde current observations

    Energy Technology Data Exchange (ETDEWEB)

    Mikhailov, A. [Institute of Terrestial Magnetism, Ionosphere and Radio Wave Propagation, Russian Academy of Sciences, Troitsk, Moscow Region (Russian Federation); La Morena de, B.A.; Miro, G.; Marin, D. [National Institute of Aerospace Technology, Mazagon, Huelva (Spain)


    Ionosphere monitoring implies: observations, prediction and mapping of ionospheric parameter. A case with one available (El Arenosillo) ionosonde is considered. Some statistical methods for f{sub 0}F{sub 2} short-term (1-24 h in advance) prediction are compared. The analysis of multi-dimensional regression for {delta}f{sub 0}F{sub 2} (relative deviation for running median) with A{sub p}, F{sub 10}.{sub 7} and previous {delta}f{sub 0}F{sub 2} observations has shown that inclusion of additional terms with A{sub p} and F{sub 10}.{sub 7} improves the prediction accuracy for lead time more than 15 h. For lead time 1-6 h a linear regression with earlier observed {delta}f{sub 0}F{sub 2} provides the f{sub 0}F{sub 2} forecast with Relative Mean Deviation (RMD) 6-11%. This is acceptable from a practical point of view. A 24-h forecast can be done with RMD 10-11%. Multi-regressional methods provide better prediction accuracy than the usual 10-day running median or quasi-inertial method based on such median. Hourly f{sub 0}F{sub 2} values may be used to calculate the effective index R{sub 12e}ff used as input to the ITU-R monthly median model. This allows the ITU-R model to 'breathe' following hour-to-hour f{sub 0}F{sub 2} variations. Mapping accuracy based on the hourly R{sub 12e}ff index is shown to be 9-11% depending on solar activity level.

  18. Self-welding evaluation of type 304 and A286 stainless steel in the temperature range 800/sup 0/-1140/sup 0/F in flowing sodium

    Energy Technology Data Exchange (ETDEWEB)

    Chang, J.Y.; Flagella, P.N.; Schrock, S.L.


    This paper covers two material combinations, Type 304 SS vs Type 304 SS and Type 304 SS vs A286, tested at temperatures from 800 to 1140/sup 0/F for time periods up to six months in flowing sodium. Contact stresses ranged from 2 to 30 ksi on contact areas for 0.63 to 1.00 in./sup 2/. Tests were performed in either tensile or shear modes on the flat-on-flat samples. Surface morphologies of the sample before and after the test were presented. Self-welding of Type 304 SS was significant at temperatures above 1080/sup 0/F while no self-welding was detected at 800/sup 0/F. Sliding friction coefficient ( data for a Type 304 SS couple at 800/sup 0/F under compressive stresses from 2000 to 30,000 psi in sodium could be correlated quite accurately by W/sigma = 0.08e/sup, where W is the waviness height in microinches and sigma is the compressive stress in kilo-pound per square inch. One self-weld couple of Type 304 SS/Type 304 SS exposed at 1080/sup 0/F for 3 months was not separated but rather removed intact from the test apparatus and examined in cross-section. Scanning electron micrographs of the contacted area revealed that portions of the original interface were no longer discernible. (auth)

  19. A Prediction Method for△f0F2min of a Single Station From Interplanetary Parameters Based on Statistical Study

    Institute of Scientific and Technical Information of China (English)

    LI Zheng; WEI Fengsi; FENG Xueshang; GUO Jianpeng; XU Xiaojun


    Using 86 CME-interplanetary shock events,the correlation between the peak values of (a) the solar wind parameters(Bz,Ey,Pdyn) and the geomagnetic indices(SYM-H,ASY-H,Kp), (b) the coupling functions(Borovsky,Akasofu,Newell) and the geomagnetic indices,(c) the solar wind parameters/coupling functions/geomagnetic indices and the ionospheric parameter(△f0F2min), are investigated.The statistical results show that in group(a),Bz min and SYM-Hmin have the best correlation,that in group(b),the best correlation is between the peak values of Akasofu function (Amin) and SYM-Hmin,and that in group(c),the best correlation is between (pmax and △f0F2min). Based on the statistical results,a method for predicting f0F2 of a single station is attempted to be set up.The input is modified B_(z min) and the outputs are SYM-Hmin and △f0F2min.Then 25 CME-IPS events that caused geomagnetic storms in 1998 and 2009 are used to check the prediction method. The results show that our method can be used to predict SYM-Hmin and △f0F2min

  20. D0 Silicon Upgrade: Heat Transfer and Thermal Bowing Calculations of the D0 F-Diskl

    Energy Technology Data Exchange (ETDEWEB)

    Ratzmann, Paul M.; /Fermilab


    Shown in Figure 1 is a side view of the D0 F-disk assembly. SVX II chips are mounted to a flex copper/kapton Circuit, which is glued to a beryllium substrate. Figure 1 shows the top and bottom disk assemblies mounted on the cooling channel. However the disks are not mounted directly opposite one another as shown, but alternately rotate through 30{sup o} wedges mounted on either side of the cooling channel. The assumed channel temperature for these calculations is 0 C, as in the cases of the ladder cooling calculations, ref. [1] and [2]. The assumed SVX II chip power is 0.400 W. The finite difference method is used to calculate the temperature profiles of the various components. It is described in Ref. [1]. Each disk is read out using SVX II chips on both sides of the silicon. The silicon is 59.2 mm wide at its widest location. The SVX II chip location opposite the cooling channel has 8 chips mounted on the hybrid. and there are 6 SVX II chips mounted outboard of the cooling channel on the same side as the cooling channel. The SVX II chips mounted on the same side as the cooling channel read out the silicon via a jumper which passes between the beryllium substrate and the cooling channel. Currently there are two substrate materials under consideration for the jumper; kapton/copper and silicon/aluminum. The two materials have different thermal properties. so both will be considered in this note in order to compare their performance in the two different assemblies. The silicon jumper is assumed to be 0.3 mm thick with a thermal conductivity of 0.15 W/mm-K. The kapton/copper flex circuit is assumed to be 0.075 mm in thickness, with 1/2 oz copper traces (a thickness of 0.017 mm copper with 0.4 W/m-K thermal conductivity) along the length. The thermal conductivity of kapton is 0.12E-3 W/mm-K [3]. The F-Disk region is occupied by cables which extend from the barrel ladders. The cables dissipate power [4] and will contribute to warming the gas. The SVX IT chips on both the

  1. Genetic evidence for the involvement of the S-layer protein gene sap and the sporulation genes spo0A, spo0B, and spo0F in Phage AP50c infection of Bacillus anthracis. (United States)

    Plaut, Roger D; Beaber, John W; Zemansky, Jason; Kaur, Ajinder P; George, Matroner; Biswas, Biswajit; Henry, Matthew; Bishop-Lilly, Kimberly A; Mokashi, Vishwesh; Hannah, Ryan M; Pope, Robert K; Read, Timothy D; Stibitz, Scott; Calendar, Richard; Sozhamannan, Shanmuga


    In order to better characterize the Bacillus anthracis typing phage AP50c, we designed a genetic screen to identify its bacterial receptor. Insertions of the transposon mariner or targeted deletions of the structural gene for the S-layer protein Sap and the sporulation genes spo0A, spo0B, and spo0F in B. anthracis Sterne resulted in phage resistance with concomitant defects in phage adsorption and infectivity. Electron microscopy of bacteria incubated with AP50c revealed phage particles associated with the surface of bacilli of the Sterne strain but not with the surfaces of Δsap, Δspo0A, Δspo0B, or Δspo0F mutants. The amount of Sap in the S layer of each of the spo0 mutant strains was substantially reduced compared to that of the parent strain, and incubation of AP50c with purified recombinant Sap led to a substantial reduction in phage activity. Phylogenetic analysis based on whole-genome sequences of B. cereus sensu lato strains revealed several closely related B. cereus and B. thuringiensis strains that carry sap genes with very high similarities to the sap gene of B. anthracis. Complementation of the Δsap mutant in trans with the wild-type B. anthracis sap or the sap gene from either of two different B. cereus strains that are sensitive to AP50c infection restored phage sensitivity, and electron microscopy confirmed attachment of phage particles to the surface of each of the complemented strains. Based on these data, we postulate that Sap is involved in AP50c infectivity, most likely acting as the phage receptor, and that the spo0 genes may regulate synthesis of Sap and/or formation of the S layer.

  2. Biomarkers in Veterinary Medicine. (United States)

    Myers, Michael J; Smith, Emily R; Turfle, Phillip G


    This article summarizes the relevant definitions related to biomarkers; reviews the general processes related to biomarker discovery and ultimate acceptance and use; and finally summarizes and reviews, to the extent possible, examples of the types of biomarkers used in animal species within veterinary clinical practice and human and veterinary drug development. We highlight opportunities for collaboration and coordination of research within the veterinary community and leveraging of resources from human medicine to support biomarker discovery and validation efforts for veterinary medicine.

  3. Combination of biomarkers

    DEFF Research Database (Denmark)

    Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger;


    The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

  4. Bacterial Vaginosis (United States)

    ... Issues > Conditions > Sexually Transmitted > Bacterial Vaginosis Health Issues Listen Español Text Size Email Print Share Bacterial Vaginosis Page Content Bacterial vaginosis (BV) is the most common vaginal infection in sexually active teenaged girls . It appears to be caused by ...

  5. New sepsis biomarkers

    Directory of Open Access Journals (Sweden)

    Dolores Limongi


    Full Text Available Sepsis remains a leading cause of death in the intensive care units and in all age groups worldwide. Early recognition and diagnosis are key to achieving improved outcomes. Therefore, novel biomarkers that might better inform clinicians treating such patients are surely needed. The main attributes of successful biomarkers would be high sensitivity, specificity, possibility of bedside monitoring and financial accessibility. A panel of sepsis biomarkers along with currently used laboratory tests will facilitate earlier diagnosis, timely treatment and improved outcome may be more effective than single biomarkers. In this review, we summarize the most recent advances on sepsis biomarkers evaluated in clinical and experimental studies.

  6. New sepsis biomarkers

    Institute of Scientific and Technical Information of China (English)

    Dolores Limongi; Cartesio D’Agostini; Marco Ciotti


    Sepsis remains a leading cause of death in the intensive care units and in all age groups worldwide. Early recognition and diagnosis are key to achieving improved outcomes.Therefore, novel biomarkers that might better inform clinicians treating such patients are surely needed. The main attributes of successful biomarkers would be high sensitivity,specificity, possibility of bedside monitoring and financial accessibility. A panel of sepsis biomarkers along with currently used laboratory tests will facilitate earlier diagnosis,timely treatment and improved outcome may be more effective than single biomarkers. In this review, we summarize the most recent advances on sepsis biomarkers evaluated in clinical and experimental studies.

  7. New sepsis biomarkers

    Institute of Scientific and Technical Information of China (English)

    Dolores Limongi; Cartesio DAgostini; Marco Ciotti


    Sepsis remains a leading cause of death in the intensive care units and in all age groups worldwide. Early recognition and diagnosis are key to achieving improved outcomes. Therefore, novel biomarkers that might better inform clinicians treating such patients are surely needed. The main attributes of successful biomarkers would be high sensitivity, specificity, possibility of bedside monitoring and financial accessibility. A panel of sepsis biomarkers along with currently used laboratory tests will facilitate earlier diagnosis, timely treatment and improved outcome may be more effective than single biomarkers. In this review, we summarize the most recent advances on sepsis biomarkers evaluated in clinical and experimental studies.

  8. Caracterización genética de la ATPasa F0F1 de "streptococcus pneumoniae" : blanco de acción de antimicrobianos


    Martín Galiano, Antonio Javier


    Streptococcus pneumoniae es una de las bacterias patógenas con mayor índice de mortalidad a escala mundial. Es uno de los principales agentes etiológicos de la neumonía, otitis media, bacteiremia y meningitis. El control de las patologías que produce está dificultado por el gran porcentaje de aislados clínicos resistentes a compuestos antimicrobianos y a que la efectividad de la vacunación no es completa en los grupos de riesgo. Se observó un incremento en la actividad de la ATPasa F0F1 de S....

  9. Biomarkers in clinical medicine. (United States)

    Chen, Xiao-He; Huang, Shuwen; Kerr, David


    Biomarkers have been used in clinical medicine for decades. With the rise of genomics and other advances in molecular biology, biomarker studies have entered a whole new era and hold promise for early diagnosis and effective treatment of many diseases. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention (1). They can be classified into five categories based on their application in different disease stages: 1) antecedent biomarkers to identify the risk of developing an illness, 2) screening biomarkers to screen for subclinical disease, 3) diagnostic biomarkers to recognize overt disease, 4) staging biomarkers to categorise disease severity, and 5) prognostic biomarkers to predict future disease course, including recurrence, response to therapy, and monitoring efficacy of therapy (1). Biomarkers can indicate a variety of health or disease characteristics, including the level or type of exposure to an environmental factor, genetic susceptibility, genetic responses to environmental exposures, markers of subclinical or clinical disease, or indicators of response to therapy. This chapter will focus on how these biomarkers have been used in preventive medicine, diagnostics, therapeutics and prognostics, as well as public health and their current status in clinical practice.

  10. Measurement of Inclusive $\\rho^{0}, f_{0}(980), f_{2}(1270), K^{*0}_{2}(1430)$ and $f'_{2}(1525)$ Production in $Z^0$ Decays

    CERN Document Server

    Abreu, P; Adye, T; Adzic, P; Ajinenko, I; Albrecht, Z; Alderweireld, T; Alekseev, G D; Alemany, R; Allmendinger, T; Allport, P P; Almehed, S; Amaldi, Ugo; Amato, S; Anassontzis, E G; Andersson, P; Andreazza, A; Andringa, S; Antilogus, P; Apel, W D; Arnoud, Y; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barbiellini, Guido; Barbier, R; Bardin, Dimitri Yuri; Barker, G; Baroncelli, A; Battaglia, Marco; Baubillier, M; Becks, K H; Begalli, M; Beillière, P; Belokopytov, Yu A; Benvenuti, Alberto C; Bérat, C; Berggren, M; Bertini, D; Bertrand, D; Besançon, M; Bianchi, F; Bigi, M; Bilenky, S M; Bizouard, M A; Bloch, D; Blom, H M; Bonesini, M; Bonivento, W; Boonekamp, M; Booth, P S L; Borgland, A W; Borisov, G; Bosio, C; Botner, O; Boudinov, E; Bouquet, B; Bourdarios, C; Bowcock, T J V; Boyko, I; Bozovic, I; Bozzo, M; Branchini, P; Brenke, T; Brenner, R A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschmann, P; Cabrera, S; Caccia, M; Calvi, M; Camporesi, T; Canale, V; Carena, F; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Chabaud, V; Charpentier, P; Chaussard, L; Checchia, P; Chelkov, G A; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Chudoba, J; Cieslik, K; Collins, P; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Cowell, J H; Crawley, H B; Crennell, D J; Crépé, S; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Damgaard, G; Davenport, Martyn; Da Silva, W; Deghorain, A; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; de Boer, Wim; De Brabandere, S; De Clercq, C; De Lotto, B; De Min, A; De Paula, L S; Dijkstra, H; Di Ciaccio, Lucia; Dolbeau, J; Doroba, K; Dracos, M; Drees, J; Dris, M; Duperrin, A; Durand, J D; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Ellert, M; Elsing, M; Engel, J P; Erzen, B; Espirito-Santo, M C; Falk, E; Fanourakis, G K; Fassouliotis, D; Fayot, J; Feindt, Michael; Ferrari, P; Ferrer, A; Ferrer-Ribas, E; Fichet, S; Firestone, A; Flagmeyer, U; Föth, H; Fokitis, E; Fontanelli, F; Franek, B J; Frodesen, A G; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gamblin, S; Gandelman, M; García, C; Gaspar, C; Gaspar, M; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Gerdyukov, L N; Ghodbane, N; Gil, I; Glege, F; Gokieli, R; Golob, B; Gómez-Ceballos, G; Gonçalves, P; González-Caballero, I; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Grahl, J; Graziani, E; Green, C; Grimm, H J; Gris, P; Grosdidier, G; Grzelak, K; Günther, M; Guy, J; Hahn, F; Hahn, S; Haider, S; Hallgren, A; Hamacher, K; Hansen, J; Harris, F J; Hedberg, V; Heising, S; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Heuser, J M; Higón, E; Holmgren, S O; Holt, P J; Hoorelbeke, S; Houlden, M A; Hrubec, Josef; Huet, K; Hughes, G J; Hultqvist, K; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, C; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, P E; Joram, C; Juillot, P; Kapusta, F; Karafasoulis, K; Katsanevas, S; Katsoufis, E C; Keränen, R; Kersevan, Borut P; Khomenko, B A; Khovanskii, N N; Kiiskinen, A P; King, B J; Kinvig, A; Kjaer, N J; Klapp, O; Klein, H; Kluit, P M; Kokkinias, P; Koratzinos, M; Kostyukhin, V; Kourkoumelis, C; Kuznetsov, O; Krammer, Manfred; Kriznic, E; Krstic, J; Krumshtein, Z; Kubinec, P; Kurowska, J; Kurvinen, K L; Lamsa, J; Lane, D W; Langefeld, P; Lapin, V; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Leinonen, L; Leisos, A; Leitner, R; Lenzen, Georg; Lepeltier, V; Lesiak, T; Lethuillier, M; Libby, J; Liko, D; Lipniacka, A; Lippi, I; Lörstad, B; Loken, J G; Lopes, J H; López, J M; López-Fernandez, R; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J N; Mahon, J R; Maio, A; Malek, A; Malmgren, T G M; Malychev, V; Mandl, F; Marco, J; Marco, R P; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Masik, J; Mazzucato, F; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; McPherson, G; Meroni, C; Meyer, W T; Myagkov, A; Migliore, E; Mirabito, L; Mitaroff, Winfried A; Mjörnmark, U; Moa, T; Moch, M; Møller, R; Mönig, K; Monge, M R; Moreau, X; Morettini, P; Morton, G A; Müller, U; Münich, K; Mulders, M; Mulet-Marquis, C; Muresan, R; Murray, W J; Muryn, B; Myatt, Gerald; Myklebust, T; Naraghi, F; Navarria, Francesco Luigi; Navas, S; Nawrocki, K; Negri, P; Neufeld, N; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nikolenko, M; Nomokonov, V P; Normand, Ainsley; Nygren, A; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Orazi, G; Österberg, K; Ouraou, A; Paganoni, M; Paiano, S; Pain, R; Paiva, R; Palacios, J; Palka, H; Papadopoulou, T D; Papageorgiou, K; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Pegoraro, M; Peralta, L; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Phillips, H T; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Rakoczy, D; Ratoff, P N; Read, A L; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Reinhardt, R; Renton, P B; Resvanis, L K; Richard, F; Rídky, J; Rinaudo, G; Røhne, O M; Romero, A; Ronchese, P; Rosenberg, E I; Rosinsky, P; Roudeau, Patrick; Rovelli, T; Royon, C; Ruhlmann-Kleider, V; Ruiz, A; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sajot, G; Salt, J; Sampsonidis, D; Sannino, M; Schneider, H; Schwemling, P; Schwickerath, U; Schyns, M A E; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Sekulin, R L; Shellard, R C; Sheridan, A; Siebel, M; Simard, L C; Simonetto, F; Sissakian, A N; Smadja, G; Smirnova, O G; Smith, G R; Sokolov, A; Sopczak, André; Sosnowski, R; Spassoff, Tz; Spiriti, E; Sponholz, P; Squarcia, S; Stampfer, D; Stanescu, C; Stanic, S; Stevenson, K; Stocchi, A; Strauss, J; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Chikilev, O G; Tegenfeldt, F; Terranova, F; Thomas, J; Timmermans, J; Tinti, N; Tkatchev, L G; Todorova, S; Tomaradze, A G; Tomé, B; Tonazzo, A; Tortora, L; Tranströmer, G; Treille, D; Tristram, G; Trochimczuk, M; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tzamarias, S; Überschär, B; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; van Apeldoorn, G W; van Dam, P; Van Doninck, W K; Van Eldik, J; Van Lysebetten, A; Van Vulpen, I B; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Verzi, V; Vilanova, D; Vitale, L; Vlasov, E; Vodopyanov, A S; Vollmer, C F; Voulgaris, G; Vrba, V; Wahlen, H; Walck, C; Weiser, C; Wicke, D; Wickens, J H; Wilkinson, G R; Winter, M; Witek, M; Wolf, G; Yi, J; Yushchenko, O P; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, N I; Zucchelli, G C; Zumerle, G


    DELPHI results are presented on the inclusive production of the neutral mesons$\\rho^0$, $f_0(980)$, $f_2(1270)$, K$^{*0}_2(1430)$ and $f^{'}_2(1525)$ in hadronic Z$^0$ decays. They are based on about 2 million multihadronic events collected in 1994 and 1995, using the particle identification capabilities of the DELPHI Ring Imaging Cherenkov detectors and measured ionization losses in the Time Projection Chamber. The total production rates per hadronic Z$^0$ decay have been determined to be: $1.19 \\pm 0.10$ for $\\rho^0$; $0.164 \\pm 0.021$ for $f_0(980)$;$0.214 \\pm 0.038$ for $f_2(1270)$; 0:073 \\pm 0:023 for $K^{*0}_2 (1430)$; and 0:012 \\pm 0:006 for $f_{2}$(1525). The total production rates for all mesons and differential cross-sections for the $\\rho^{0}$, $f_{0}$(980) and $f_{2}$(1270) are compared with the results of other LEP experiments and with models.

  11. Biomarkers for Parkinson's disease. (United States)

    Sherer, Todd B


    Biomarkers for detecting the early stages of Parkinson's disease (PD) could accelerate development of new treatments. Such biomarkers could be used to identify individuals at risk for developing PD, to improve early diagnosis, to track disease progression with precision, and to test the efficacy of new treatments. Although some progress has been made, there are many challenges associated with developing biomarkers for detecting PD in its earliest stages.

  12. Respiratory Toxicity Biomarkers (United States)

    The advancement in high throughput genomic, proteomic and metabolomic techniques have accelerated pace of lung biomarker discovery. A recent growth in the discovery of new lung toxicity/disease biomarkers have led to significant advances in our understanding of pathological proce...

  13. On consensus biomarker selection

    Directory of Open Access Journals (Sweden)

    Gambin Anna


    Full Text Available Abstract Background Recent development of mass spectrometry technology enabled the analysis of complex peptide mixtures. A lot of effort is currently devoted to the identification of biomarkers in human body fluids like serum or plasma, based on which new diagnostic tests for different diseases could be constructed. Various biomarker selection procedures have been exploited in recent studies. It has been noted that they often lead to different biomarker lists and as a consequence, the patient classification may also vary. Results Here we propose a new approach to the biomarker selection problem: to apply several competing feature ranking procedures and compute a consensus list of features based on their outcomes. We validate our methods on two proteomic datasets for the diagnosis of ovarian and prostate cancer. Conclusion The proposed methodology can improve the classification results and at the same time provide a unified biomarker list for further biological examinations and interpretation.

  14. Biomarkers of Reflux Disease. (United States)

    Kia, Leila; Pandolfino, John E; Kahrilas, Peter J


    Gastroesophageal reflux disease (GERD) encompasses an array of disorders unified by the reflux of gastric contents. Because there are many potential disease manifestations, esophageal and extraesophageal, there is no single biomarker of the entire disease spectrum; a set of GERD biomarkers that each quantifies specific aspects of GERD-related pathology might be needed. We review recent reports of biomarkers of GERD, specifically in relation to endoscopically negative esophageal disease and excluding conventional pH-impedance monitoring. We consider histopathologic biomarkers, baseline impedance, and serologic assays to determine that most markers are based on manifestations of impaired esophageal mucosal integrity, which is based on increased ionic and molecular permeability, and/or destruction of tight junctions. Impaired mucosal integrity quantified by baseline mucosal impedance, proteolytic fragments of junctional proteins, or histopathologic features has emerged as a promising GERD biomarker.

  15. Biomarkers in Parkinson's disease. (United States)

    Morgan, John C; Mehta, Shyamal H; Sethi, Kapil D


    Biomarkers are objectively measured characteristics that are indicators of normal biological processes, pathogenic processes, or responses to therapeutic interventions. To date, clinical assessment remains the gold standard in the diagnosis of Parkinson's disease (PD) and clinical rating scales are well established as the gold standard for tracking progression of PD. Researchers have identified numerous potential biomarkers that may aid in the differential diagnosis of PD and/or tracking disease progression. Clinical, genetic, blood and cerebrospinal fluid (proteomics, transcriptomics, metabolomics), and neuroimaging biomarkers may provide useful tools in the diagnosis of PD and in measuring disease progression and response to therapies. Some potential biomarkers are inexpensive and do not require much technical expertise, whereas others are expensive or require specialized equipment and technical skills. Many potential biomarkers in PD show great promise; however, they need to be assessed for their sensitivity and specificity over time in large and varied samples of patients with and without PD.

  16. Bacterial gastroenteritis (United States)

    Bacterial gastroenteritis is present when bacteria cause an infection of the stomach and intestines ... has not been treated Many different types of bacteria can cause ... Campylobacter jejuni E coli Salmonella Shigella Staphylococcus ...

  17. [Biomarkers in Alzheimer's disease]. (United States)

    García-Ribas, G; López-Sendón Moreno, J L; García-Caldentey, J


    The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is already known that these pathological processes of AD starts decades before the first symptoms, so these biomarkers may provide means of early disease detection. At least three stages of AD could be identified: preclinical AD, mild cognitive impairment due to AD, and dementia due to AD. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review the actual research on blood-based biomarkers. Recent studies on healthy elderly subjects and on carriers of dominantly inherited AD mutations have also found biomarker changes that allow separate groups in these preclinical stages. These studies may aid for segregate populations in clinical trials and objectively evaluate if there are changes over the pathological processes of AD. Limits to widespread use of CSF biomarkers, apart from the invasive nature of the process itself, is the higher coefficient of variation for the analyses between centres. It requires strict pre-analytical and analytical procedures that may make feasible multi-centre studies and global cut-off points for the different stages of AD.

  18. Microbial ecology of the stratified water column of the Black Sea as revealed by a comprehensive biomarker study

    DEFF Research Database (Denmark)

    Wakeham, Stuart G.; Amann, Rudi; Freemann, Katherine H.;


    ) and sulfate reducing bacteria. We also measured a wide range of bacterial and archaeal lipid biomarkers. Depth distributions of diagnostic biomarkers are matched with zonation of microbial processes, including aerobic bacterial oxidation of methane, oxidation of ammonium by bacteria and archaea, metal...... reduction, and sulfide oxidation at the chemocline, and bacterial sulfate reduction and anaerobic oxidation of methane by archaea in the anoxic zone. Cell densities for archaea and sulfate reducing bacteria are estimated based on water column biomarker concentrations and compared with CARD-FISH results....

  19. Metabolic products as biomarkers (United States)

    Melancon, M.J.; Alscher, R.; Benson, W.; Kruzynski, G.; Lee, R.F.; Sikka, H.C.; Spies, R.B.; Huggett, Robert J.; Kimerle, Richard A.; Mehrle, Paul M.=; Bergman, Harold L.


    Ideally, endogenous biomarkers would indicate both exposure and environmental effects of toxic chemicals; however, such comprehensive biochemical and physiological indices are currently being developed and, at the present time, are unavailable for use in environmental monitoring programs. Continued work is required to validate the use of biochemical and physiological stress indices as useful components of monitoring programs. Of the compounds discussed only phytochelatins and porphyrins are currently in biomarkers in a useful state; however, glutathione,metallothioneins, stress ethylene, and polyamines are promising as biomarkers in environmental monitoring.

  20. Commentary: statistics for biomarkers. (United States)

    Lovell, David P


    This short commentary discusses Biomarkers' requirements for the reporting of statistical analyses in submitted papers. It is expected that submitters will follow the general instructions of the journal, the more detailed guidance given by the International Committee of Medical Journal Editors, the specific guidelines developed by the EQUATOR network, and those of various specialist groups. Biomarkers expects that the study design and subsequent statistical analyses are clearly reported and that the data reported can be made available for independent assessment. The journal recognizes that there is continuing debate about different approaches to statistical science. Biomarkers appreciates that the field continues to develop rapidly and encourages the use of new methodologies.

  1. Regulation of the nuclear gene that encodes the alpha-subunit of the mitochondrial F0F1-ATP synthase complex. Activation by upstream stimulatory factor 2. (United States)

    Breen, G A; Jordan, E M


    We have previously identified several positive cis-acting regulatory regions in the promoters of the bovine and human nuclear-encoded mitochondrial F0F1-ATP synthase alpha-subunit genes (ATPA). One of these cis-acting regions contains the sequence 5'-CACGTG-3' (an E-box), to which a number of transcription factors containing a basic helix-loop-helix motif can bind. This E-box element is required for maximum activity of the ATPA promoter in HeLa cells. The present study identifies the human transcription factor, upstream stimulatory factor 2 (USF2), as a nuclear factor that binds to the ATPA E-box and demonstrates that USF2 plays a critical role in the activation of the ATPA gene in vivo. Evidence includes the following. Antiserum directed against USF2 recognized factors present in HeLa nuclear extracts that interact with the ATPA promoter in mobility shift assays. Wild-type USF2 proteins synthesized from expression vectors trans-activated the ATPA promoter through the E-box, whereas truncated USF2 proteins devoid of the amino-terminal activation domains did not. Importantly, expression of a dominant-negative mutant of USF2 lacking the basic DNA binding domain but able to dimerize with endogenous USF proteins significantly reduced the level of activation of the ATPA promoter caused by ectopically coexpressed USF2, demonstrating the importance of endogenous USF2 in activation of the ATPA gene.

  2. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg;


    BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps...... in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

  3. Biomarker time out. (United States)

    Petzold, Axel; Bowser, Robert; Calabresi, Paolo; Zetterberg, Henrik; Uitdehaag, Bernard M J


    The advancement of knowledge relies on scientific investigations. The timing between asking a question and data collection defines if a study is prospective or retrospective. Prospective studies look forward from a point in time, are less prone to bias and are considered superior to retrospective studies. This conceptual framework conflicts with the nature of biomarker research. New candidate biomarkers are discovered in a retrospective manner. There are neither resources nor time for prospective testing in all cases. Relevant sources for bias are not covered. Ethical questions arise through the time penalty of an overly dogmatic concept. The timing of sample collection can be separated from testing biomarkers. Therefore the moment of formulating a hypothesis may be after sample collection was completed. A conceptual framework permissive to asking research questions without the obligation to bow to the human concept of calendar time would simplify biomarker research, but will require new safeguards against bias.

  4. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung


    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  5. Biomarkers for neuromyelitis optica. (United States)

    Chang, Kuo-Hsuan; Ro, Long-Sun; Lyu, Rong-Kuo; Chen, Chiung-Mei


    Neuromyelitis optica (NMO) is an acquired, heterogeneous inflammatory disorder, which is characterized by recurrent optic neuritis and longitudinally extensive spinal cord lesions. The discovery of the serum autoantibody marker, anti-aquaporin 4 (anti-AQP4) antibody, revolutionizes our understanding of pathogenesis of NMO. In addition to anti-AQP4 antibody, other biomarkers for NMO are also reported. These candidate biomarkers are particularly involved in T helper (Th)17 and astrocytic damages, which play a critical role in the development of NMO lesions. Among them, IL-6 in the peripheral blood is associated with anti-AQP4 antibody production. Glial fibrillary acidic protein (GFAP) in CSF demonstrates good correlations with clinical severity of NMO relapses. Detecting these useful biomarkers may be useful in the diagnosis and evaluation of disease activity of NMO. Development of compounds targeting these biomarkers may provide novel therapeutic strategies for NMO. This article will review the related biomarker studies in NMO and discuss the potential therapeutics targeting these biomarkers.

  6. Bacterial Adhesion & Blocking Bacterial Adhesion

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk


    tract to the microbial flocs in waste water treatment facilities. Microbial biofilms may however also cause a wide range of industrial and medical problems, and have been implicated in a wide range of persistent infectious diseases, including implantassociated microbial infections. Bacterial adhesion...... is the first committing step in biofilm formation, and has therefore been intensely scrutinized. Much however, still remains elusive. Bacterial adhesion is a highly complex process, which is influenced by a variety of factors. In this thesis, a range of physico-chemical, molecular and environmental parameters......, which influence the transition from a planktonic lifestyle to a sessile lifestyle, have been studied. Protein conditioning film formation was found to influence bacterial adhesion and subsequent biofilm formation considerable, and an aqueous extract of fish muscle tissue was shown to significantly...

  7. Bacterial lipases

    NARCIS (Netherlands)

    Jaeger, Karl-Erich; Ransac, Stéphane; Dijkstra, Bauke W.; Colson, Charles; Heuvel, Margreet van; Misset, Onno


    Many different bacterial species produce lipases which hydrolyze esters of glycerol with preferably long-chain fatty acids. They act at the interface generated by a hydrophobic lipid substrate in a hydrophilic aqueous medium. A characteristic property of lipases is called interfacial activation, mea

  8. Bacterial Ecology

    DEFF Research Database (Denmark)

    Fenchel, Tom


    Bacterial ecology is concerned with the interactions between bacteria and their biological and nonbiological environments and with the role of bacteria in biogeochemical element cycling. Many fundamental properties of bacteria are consequences of their small size. Thus, they can efficiently exploit...

  9. Biomarkers intersect with the exposome. (United States)

    Rappaport, Stephen M


    The exposome concept promotes use of omic tools for discovering biomarkers of exposure and biomarkers of disease in studies of diseased and healthy populations. A two-stage scheme is presented for profiling omic features in serum to discover molecular biomarkers and then for applying these biomarkers in follow-up studies. The initial component, referred to as an exposome-wide-association study (EWAS), employs metabolomics and proteomics to interrogate the serum exposome and, ultimately, to identify, validate and differentiate biomarkers of exposure and biomarkers of disease. Follow-up studies employ knowledge-driven designs to explore disease causality, prevention, diagnosis, prognosis and treatment.

  10. Distribution, origin and transformation of amino sugars sand bacterial contribution to estuarine particulate organic matter

    Digital Repository Service at National Institute of Oceanography (India)

    Khodse, V.B.; Bhosle, N.B.

    Amino sugars including bacterial biomarker muramic acid(Mur) were investigated in suspended particulate matter(SPM) to understand their distribution, origin, and biogeochemical cycling and the contribution of bacteria to particulate organic matter...

  11. Application of solar energy for the generation and supply of industrial-process low-to intermediate-pressure steam ranging from 300/sup 0/F-550/sup 0/F (high-temperature steam). Final report, September 30, 1978-June 30, 1979

    Energy Technology Data Exchange (ETDEWEB)

    Matteo, M.; Kull, J.; Luddy, W.; Youngblood, S.


    A detailed design was developed for a solar industrial process heat system to be installed at the ERGON, Inc. Bulk Oil Storage Terminal in Mobile, Alabama. The 1874 m/sup 2/ (20160 ft/sup 2/) solar energy collector field will generate industrial process heat at temperatures ranging from 150 to 290/sup 0/C (300 to 550/sup 0/F). The heat will be used to reduce the viscosity of stored No. 6 fuel oil, making it easier to pump from storage to transport tankers. Heat transfer oil is circulated in a closed system, absorbing heat in the collector field and delivering it through immersed heat exchangers to the stored fuel oil. The solar energy system will provide approximately 44 percent of the process heat required.

  12. Biomarkers for systemic lupus erythematosus. (United States)

    Ahearn, Joseph M; Liu, Chau-Ching; Kao, Amy H; Manzi, Susan


    The urgent need for lupus biomarkers was demonstrated in September 2011 during a Workshop sponsored by the Food and Drug Administration: Potential Biomarkers Predictive of Disease Flare. After 2 days of discussion and more than 2 dozen presentations from thought leaders in both industry and academia, it became apparent that highly sought biomarkers to predict lupus flare have not yet been identified. Even short of the elusive biomarker of flare, few biomarkers for systemic lupus erythematosus (SLE) diagnosis, monitoring, and stratification have been validated and employed for making clinical decisions. This lack of reliable, specific biomarkers for SLE hampers proper clinical management of patients with SLE and impedes development of new lupus therapeutics. As such, the intensity of investigation to identify lupus biomarkers is climbing a steep trajectory, lending cautious optimism that a validated panel of biomarkers for lupus diagnosis, monitoring, stratification, and prediction of flare may soon be in hand.

  13. [Bacterial vaginosis]. (United States)

    Romero Herrero, Daniel; Andreu Domingo, Antonia


    Bacterial vaginosis (BV) is the main cause of vaginal dysbacteriosis in the women during the reproductive age. It is an entity in which many studies have focused for years and which is still open for discussion topics. This is due to the diversity of microorganisms that cause it and therefore, its difficult treatment. Bacterial vaginosis is probably the result of vaginal colonization by complex bacterial communities, many of them non-cultivable and with interdependent metabolism where anaerobic populations most likely play an important role in its pathogenesis. The main symptoms are an increase of vaginal discharge and the unpleasant smell of it. It can lead to serious consequences for women, such as an increased risk of contracting sexually transmitted infections including human immunodeficiency virus and upper genital tract and pregnancy complications. Gram stain is the gold standard for microbiological diagnosis of BV, but can also be diagnosed using the Amsel clinical criteria. It should not be considered a sexually transmitted disease but it is highly related to sex. Recurrence is the main problem of medical treatment. Apart from BV, there are other dysbacteriosis less characterized like aerobic vaginitis of which further studies are coming slowly but are achieving more attention and consensus among specialists.

  14. Biomarkers in Barrett's esophagus. (United States)

    Reid, Brian J; Blount, Patricia L; Rabinovitch, Peter S


    This article provides a framework for clinicians who are attempting the difficult task of interpreting the Barrett's biomarker literature with the goal of improving care for their patients. Although many articles. including more that 60 proposed biomarkers, have been published on this subject, only a few describe phase 3 and 4 studies that are of interest to the clinical gastroenterologist (Table 1). For year, dysplasia grade has been the sole means of risk stratification for patients with BE, and it likely will continue to be used in the foreseeable future. The current authors believe that dysplasia classification can be valuable using the team management approach and quality controls described previously. Significant problems, however, have emerged in phase 2 through 4 studies of dysplasia that make it imperative for the Barrett's field to incorporate additional biomarkers as they are validated. These problems include poor reproducibility of dysplasia interpretations, poor predictive value for negative, indefinite, and low-grade dysplasia, and inconsistent results for HGD in different centers, all of which makes it virtually impossible to develop national guidelines for surveillance. Some studies have even suggested that endoscopic biopsy surveillance using dysplasia may not be worthwhile. Currently, flow cytometric tetraploidy and aneuploidy have progressed furthest in biomarker validation (see Table 1). With proper handling, endoscopic biopsy specimens can be shipped to reference laboratories that have the instruments, computer analytic methods, and expertise to reproducibly detect tetraploidy and aneuploidy. The results of phase 4 studies indicate that flow cytometry appears to be useful in detecting a subset of patients who do not have HGD and yet have an increased risk of progression to cancer that cannot be identified by dysplasia grade. For many reasons, the authors anticipate that the number of validated biomarkers will increase substantially in the

  15. Emerging Biomarkers in Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Mairéad G.; Sahebjam, Solmaz; Mason, Warren P., E-mail: [Pencer Brain Tumor Centre, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada)


    Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6)-methlyguanine-DNA-methyltransferase (MGMT) promoter and deoxyribonucleic acid (DNA) methylation, loss of heterozygosity (LOH) of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH) mutations, epidermal growth factor receptor (EGFR), epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, phosphatase and tensin homolog (PTEN), p16INK4a gene, cytochrome c oxidase (CcO), phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA]), microRNAs (miRNAs), cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future.

  16. Role of serum procalcitonin level in early diagnosis of bacterial pneumonia in children, a hospital based study

    Directory of Open Access Journals (Sweden)

    Sheikh Mohd Saleem


    Conclusions: Serum PCT is an important biomarker for prompt diagnosis of bacterial infection and a sensitive indicator to distinguish bacterial from non-bacterial pneumonia. Evaluating serum PCT levels helps in early use of antibiotic therapy and prognosis of underlying disease. [Int J Res Med Sci 2016; 4(5.000: 1518-1521

  17. Neuroimaging Biomarkers for Psychosis (United States)

    Hager, Brandon M.


    Background Biomarkers provide clinicians with a predictable model for the diagnosis, treatment and follow-up of medical ailments. Psychiatry has lagged behind other areas of medicine in the identification of biomarkers for clinical diagnosis and treatment. In this review, we investigated the current state of neuroimaging as it pertains to biomarkers for psychosis. Methods We reviewed systematic reviews and meta-analyses of the structural (sMRI), functional (fMRI), diffusion-tensor (DTI), Positron emission tomography (PET) and spectroscopy (MRS) studies of subjects at-risk or those with an established schizophrenic illness. Only articles reporting effect-sizes and confidence intervals were included in an assessment of robustness. Results Out of the identified meta-analyses and systematic reviews, 21 studies met the inclusion criteria for assessment. There were 13 sMRI, 4 PET, 3 MRS, and 1 DTI studies. The search terms included in the current review encompassed familial high risk (FHR), clinical high risk (CHR), First episode (FES), Chronic (CSZ), schizophrenia spectrum disorders (SSD), and healthy controls (HC). Conclusions Currently, few neuroimaging biomarkers can be considered ready for diagnostic use in patients with psychosis. At least in part, this may be related to the challenges inherent in the current symptom-based approach to classifying these disorders. While available studies suggest a possible value of imaging biomarkers for monitoring disease progression, more systematic research is needed. To date, the best value of imaging data in psychoses has been to shed light on questions of disease pathophysiology, especially through the characterization of endophenotypes. PMID:25883891

  18. Biomarkers of Selenium Status

    Directory of Open Access Journals (Sweden)

    Gerald F. Combs, Jr.


    Full Text Available The essential trace element, selenium (Se, has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic potential; and very high Se intakes can produce adverse effects. This hierarchy of biological activities calls for biomarkers informative at different levels of Se exposure. Some Se-biomarkers, such as the selenoproteins and particularly GPX3 and SEPP1, provide information about function directly and are of value in identifying nutritional Se deficiency and tracking responses of deficient individuals to Se-treatment. They are useful under conditions of Se intake within the range of regulated selenoprotein expression, e.g., for humans <55 μg/day and for animals <20 μg/kg diet. Other Se-biomarkers provide information indirectly through inferences based on Se levels of foods, tissues, urine or feces. They can indicate the likelihood of deficiency or adverse effects, but they do not provide direct evidence of either condition. Their value is in providing information about Se status over a wide range of Se intake, particularly from food forms. There is need for additional Se biomarkers particularly for assessing Se status in non-deficient individuals for whom the prospects of cancer risk reduction and adverse effects risk are the primary health considerations. This would include determining whether supranutritional intakes of Se may be required for maximal selenoprotein expression in immune surveillance cells. It would also include developing methods to determine low molecular weight Se-metabolites, i.e., selenoamino acids and methylated Se-metabolites, which to date have not been detectable in biological specimens. Recent analytical advances using tandem liquid chromatography-mass spectrometry suggest prospects for detecting these metabolites.

  19. Bacterial hydrodynamics

    CERN Document Server

    Lauga, Eric


    Bacteria predate plants and animals by billions of years. Today, they are the world's smallest cells yet they represent the bulk of the world's biomass, and the main reservoir of nutrients for higher organisms. Most bacteria can move on their own, and the majority of motile bacteria are able to swim in viscous fluids using slender helical appendages called flagella. Low-Reynolds-number hydrodynamics is at the heart of the ability of flagella to generate propulsion at the micron scale. In fact, fluid dynamic forces impact many aspects of bacteriology, ranging from the ability of cells to reorient and search their surroundings to their interactions within mechanically and chemically-complex environments. Using hydrodynamics as an organizing framework, we review the biomechanics of bacterial motility and look ahead to future challenges.

  20. IDBD: infectious disease biomarker database. (United States)

    Yang, In Seok; Ryu, Chunsun; Cho, Ki Joon; Kim, Jin Kwang; Ong, Swee Hoe; Mitchell, Wayne P; Kim, Bong Su; Oh, Hee-Bok; Kim, Kyung Hyun


    Biomarkers enable early diagnosis, guide molecularly targeted therapy and monitor the activity and therapeutic responses across a variety of diseases. Despite intensified interest and research, however, the overall rate of development of novel biomarkers has been falling. Moreover, no solution is yet available that efficiently retrieves and processes biomarker information pertaining to infectious diseases. Infectious Disease Biomarker Database (IDBD) is one of the first efforts to build an easily accessible and comprehensive literature-derived database covering known infectious disease biomarkers. IDBD is a community annotation database, utilizing collaborative Web 2.0 features, providing a convenient user interface to input and revise data online. It allows users to link infectious diseases or pathogens to protein, gene or carbohydrate biomarkers through the use of search tools. It supports various types of data searches and application tools to analyze sequence and structure features of potential and validated biomarkers. Currently, IDBD integrates 611 biomarkers for 66 infectious diseases and 70 pathogens. It is publicly accessible at and

  1. Early diagnosis of complex diseases by molecular biomarkers, network biomarkers, and dynamical network biomarkers. (United States)

    Liu, Rui; Wang, Xiangdong; Aihara, Kazuyuki; Chen, Luonan


    Many studies have been carried out for early diagnosis of complex diseases by finding accurate and robust biomarkers specific to respective diseases. In particular, recent rapid advance of high-throughput technologies provides unprecedented rich information to characterize various disease genotypes and phenotypes in a global and also dynamical manner, which significantly accelerates the study of biomarkers from both theoretical and clinical perspectives. Traditionally, molecular biomarkers that distinguish disease samples from normal samples are widely adopted in clinical practices due to their ease of data measurement. However, many of them suffer from low coverage and high false-positive rates or high false-negative rates, which seriously limit their further clinical applications. To overcome those difficulties, network biomarkers (or module biomarkers) attract much attention and also achieve better performance because a network (or subnetwork) is considered to be a more robust form to characterize diseases than individual molecules. But, both molecular biomarkers and network biomarkers mainly distinguish disease samples from normal samples, and they generally cannot ensure to identify predisease samples due to their static nature, thereby lacking ability to early diagnosis. Based on nonlinear dynamical theory and complex network theory, a new concept of dynamical network biomarkers (DNBs, or a dynamical network of biomarkers) has been developed, which is different from traditional static approaches, and the DNB is able to distinguish a predisease state from normal and disease states by even a small number of samples, and therefore has great potential to achieve "real" early diagnosis of complex diseases. In this paper, we comprehensively review the recent advances and developments on molecular biomarkers, network biomarkers, and DNBs in particular, focusing on the biomarkers for early diagnosis of complex diseases considering a small number of samples and high

  2. Bacterial vaginosis -- aftercare (United States)

    ... this page: // Bacterial vaginosis - aftercare To use the sharing features on this ... to back after you use the bathroom. Preventing Bacterial Vaginosis You can help prevent bacterial vaginosis by: Not ...

  3. Pregnancy Complications: Bacterial Vaginosis (United States)

    ... Complications & Loss > Pregnancy complications > Bacterial vaginosis and pregnancy Bacterial vaginosis and pregnancy E-mail to a friend Please ... this page It's been added to your dashboard . Bacterial vaginosis (also called BV or vaginitis) is an infection ...

  4. Biomarker Identification Using Text Mining

    Directory of Open Access Journals (Sweden)

    Hui Li


    Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

  5. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma


    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  6. Chiral Biomarkers in Meteorites (United States)

    Hoover, Richard B.


    The chirality of organic molecules with the asymmetric location of group radicals was discovered in 1848 by Louis Pasteur during his investigations of the rotation of the plane of polarization of light by crystals of sodium ammonium paratartrate. It is well established that the amino acids in proteins are exclusively Levorotary (L-aminos) and the sugars in DNA and RNA are Dextrorotary (D-sugars). This phenomenon of homochirality of biological polymers is a fundamental property of all life known on Earth. Furthermore, abiotic production mechanisms typically yield recemic mixtures (i.e. equal amounts of the two enantiomers). When amino acids were first detected in carbonaceous meteorites, it was concluded that they were racemates. This conclusion was taken as evidence that they were extraterrestrial and produced by abiologically. Subsequent studies by numerous researchers have revealed that many of the amino acids in carbonaceous meteorites exhibit a significant L-excess. The observed chirality is much greater than that produced by any currently known abiotic processes (e.g. Linearly polarized light from neutron stars; Circularly polarized ultraviolet light from faint stars; optically active quartz powders; inclusion polymerization in clay minerals; Vester-Ulbricht hypothesis of parity violations, etc.). This paper compares the measured chirality detected in the amino acids of carbonaceous meteorites with the effect of these diverse abiotic processes. IT is concluded that the levels observed are inconsistent with post-arrival biological contamination or with any of the currently known abiotic production mechanisms. However, they are consistent with ancient biological processes on the meteorite parent body. This paper will consider these chiral biomarkers in view of the detection of possible microfossils found in the Orgueil and Murchison carbonaceous meteorites. Energy dispersive x-ray spectroscopy (EDS) data obtained on these morphological biomarkers will be

  7. Towards Improved Biomarker Research

    DEFF Research Database (Denmark)

    Kjeldahl, Karin

    This thesis takes a look at the data analytical challenges associated with the search for biomarkers in large-scale biological data such as transcriptomics, proteomics and metabolomics data. These studies aim to identify genes, proteins or metabolites which can be associated with e.g. a diet, dis...... is used both for regression and classification purposes. This method has proven its strong worth in the multivariate data analysis throughout an enormous range of applications; a very classic data type is near infrared (NIR) data, but many similar data types have also be very successful...

  8. Which biomarkers reveal neonatal sepsis?

    Directory of Open Access Journals (Sweden)

    Kun Wang

    Full Text Available We address the identification of optimal biomarkers for the rapid diagnosis of neonatal sepsis. We employ both canonical correlation analysis (CCA and sparse support vector machine (SSVM classifiers to select the best subset of biomarkers from a large hematological data set collected from infants with suspected sepsis from Yale-New Haven Hospital's Neonatal Intensive Care Unit (NICU. CCA is used to select sets of biomarkers of increasing size that are most highly correlated with infection. The effectiveness of these biomarkers is then validated by constructing a sparse support vector machine diagnostic classifier. We find that the following set of five biomarkers capture the essential diagnostic information (in order of importance: Bands, Platelets, neutrophil CD64, White Blood Cells, and Segs. Further, the diagnostic performance of the optimal set of biomarkers is significantly higher than that of isolated individual biomarkers. These results suggest an enhanced sepsis scoring system for neonatal sepsis that includes these five biomarkers. We demonstrate the robustness of our analysis by comparing CCA with the Forward Selection method and SSVM with LASSO Logistic Regression.

  9. Epigenetic biomarkers in liver cancer. (United States)

    Banaudha, Krishna K; Verma, Mukesh


    Liver cancer (hepatocellular carcinoma or HCC) is a major cancer worldwide. Research in this field is needed to identify biomarkers that can be used for early detection of the disease as well as new approaches to its treatment. Epigenetic biomarkers provide an opportunity to understand liver cancer etiology and evaluate novel epigenetic inhibitors for treatment. Traditionally, liver cirrhosis, proteomic biomarkers, and the presence of hepatitis viruses have been used for the detection and diagnosis of liver cancer. Promising results from microRNA (miRNA) profiling and hypermethylation of selected genes have raised hopes of identifying new biomarkers. Some of these epigenetic biomarkers may be useful in risk assessment and for screening populations to identify who is likely to develop cancer. Challenges and opportunities in the field are discussed in this chapter.

  10. Biomarkers in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bennike, Tue; Birkelund, Svend; Stensballe, Allan


    with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future...... development of preventive and treatment strategies. Thus, the clinical use of a panel of biomarkers represents a diagnostic and prognostic tool of potentially great value. The technological development in recent years within proteomic research (determination and quantification of the complete protein content......) has made the discovery of novel biomarkers feasible. Several IBD-associated protein biomarkers are known, but none have been successfully implemented in daily use to distinguish CD and UC patients. The intestinal tissue remains an obvious place to search for novel biomarkers, which blood, urine...

  11. Novel and unique diagnostic biomarkers for Bacillus anthracis infection. (United States)

    Sela-Abramovich, Sagit; Chitlaru, Theodor; Gat, Orit; Grosfeld, Haim; Cohen, Ofer; Shafferman, Avigdor


    A search for bacterium-specific biomarkers in peripheral blood following infection with Bacillus anthracis was carried out with rabbits, using a battery of specific antibodies generated by DNA vaccination against 10 preselected highly immunogenic bacterial antigens which were identified previously by a genomic/proteomic/serologic screen of the B. anthracis secretome. Detection of infection biomarkers in the circulation of infected rabbits could be achieved only after removal of highly abundant serum proteins by chromatography using a random-ligand affinity column. Besides the toxin component protective antigen, the following three secreted proteins were detected in the circulation of infected animals: the chaperone and protease HtrA (BA3660), an NlpC/P60 endopeptidase (BA1952), and a protein of unknown function harboring two SH3 (Src homology 3) domains (BA0796). The three proteins could be detected in plasma samples from infected animals exhibiting 10(3) to 10(5) CFU/ml blood and also in standard blood cultures at 3 to 6 h post-bacterial inoculation at a bacteremic level as low as 10(3) CFU/ml. Furthermore, the three biomarkers appear to be present only in the secretome of B. anthracis, not in those of the related pathogens B. thuringiensis and B. cereus. To the best of our knowledge, this is the first report of direct detection of B. anthracis-specific proteins, other than the toxin components, in the circulation of infected animals.

  12. Biomarkers for lymphoma (United States)

    Zangar, Richard C.; Varnum, Susan M.


    A biomarker, method, test kit, and diagnostic system for detecting the presence of lymphoma in a person are disclosed. The lymphoma may be Hodgkin's lymphoma or non-Hodgkin's lymphoma. The person may be a high-risk subject. In one embodiment, a plasma sample from a person is obtained. The level of at least one protein listed in Table S3 in the plasma sample is measured. The level of at least one protein in the plasma sample is compared with the level in a normal or healthy subject. The lymphoma is diagnosed based upon the level of the at least one protein in the plasma sample in comparison to the normal or healthy level.

  13. Molecular biomarkers of neurodegeneration. (United States)

    Höglund, Kina; Salter, Hugh


    Neuronal dysfunction and degeneration are central events of a number of major diseases with significant unmet need. Neuronal dysfunction may not necessarily be the result of cell death, but may also be due to synaptic damage leading to impaired neuronal cell signaling or long-term potentiation. Once degeneration occurs, it is unclear whether axonal or synaptic loss comes first or whether this precedes neuronal cell death. In this review we summarize the pathophysiology of four major neurodegenerative diseases; Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig's disease) For each of these diseases, we describe how biochemical biomarkers are currently understood in relation to the pathophysiology and in terms of neuronal biology, and we discuss the clinical and diagnostic utility of these potential tools, which are at present limited. We discuss how markers may be used to drive drug development and clinical practice.

  14. Inflammatory biomarkers for AMD. (United States)

    Stanton, Chloe M; Wright, Alan F


    Age-related macular degeneration (AMD) is the leading cause of blindness worldwide, affecting an estimated 50 million individuals aged over 65 years.Environmental and genetic risk-factors implicate chronic inflammation in the etiology of AMD, contributing to the formation of drusen, retinal pigment epithelial cell dysfunction and photoreceptor cell death. Consistent with a role for chronic inflammation in AMD pathogenesis, several inflammatory mediators, including complement components, chemokines and cytokines, are elevated at both the local and systemic levels in AMD patients. These mediators have diverse roles in the alternative complement pathway, including recruitment of inflammatory cells, activation of the inflammasome, promotion of neovascularisation and in the resolution of inflammation. The utility of inflammatory biomarkers in assessing individual risk and progression of the disease is controversial. However, understanding the role of these inflammatory mediators in AMD onset, progression and response to treatment may increase our knowledge of disease pathogenesis and provide novel therapeutic options in the future.

  15. [Novel biomarkers for diabetic nephropathy]. (United States)

    Araki, Shin-ichi


    Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. An early clinical sign of this complication is an increase of urinary albumin excretion, called microalbuminuria, which is not only a predictor of the progression of nephropathy, but also an independent risk factor for cardiovascular disease. Although microalbuminuria is clinically important to assess the prognosis of diabetic patients, it may be insufficient as an early and specific biomarker of diabetic nephropathy because of a large day-to-day variation and lack of a good correlation of microalbuminuria with renal dysfunction and pathohistological changes. Thus, more sensitive and specific biomarkers are needed to improve the diagnostic capability of identifying patients at high risk. The factors involved in renal tubulo-interstitial damage, the production and degradation of extracellular matrix, microinflammation, etc., are investigated as candidate molecules. Despite numerous efforts so far, the assessment of these biomarkers is still a subject of ongoing investigations. Recently, a variety of omics and quantitative techniques in systems biology are rapidly emerging in the field of biomarker discovery, including proteomics, transcriptomics, and metabolomics, and they have been applied to search for novel putative biomarkers of diabetic nephropathy. Novel biomarkers or their combination with microalbuminuria provide a better diagnostic accuracy than microalbuminuria alone, and may be useful for establishing personal medicine. Furthermore, the identification of novel biomarkers may provide insight into the mechanisms underlying diabetic nephropathy.

  16. mRNA biomarkers selection based on Partial Least Square algorithm in order to further predict Bacillus weihenstephanensis acid resistance. (United States)

    Desriac, Noémie; Coroller, Louis; Jannic, Frederic; Postollec, Florence; Sohier, Danièle


    In order to integrate omics data to quantitative microbiological risk assessment in foods, gene expressions may serve as bacterial behaviour biomarkers. In this study an integrative approach encompassing predictive modelling and mRNAs quantifications, was followed to select molecular biomarkers to further predict the acid resistance of Bacillus weihenstephanensis. A multivariate analysis was performed to correlate the acid bacterial resistance and the gene expression of vegetative cells with or without exposure to stressing conditions. This mathematical method provides the advantage to take gene expressions and their interactions into account. The use of the Partial Least Squares algorithm allowed the selection of nine genes as acid resistance biomarkers among thirty targeted genes. According to their involvement in the general acid stress response of Bacillus, these genes were assigned to three different biological modules namely, metabolic rearrangements, general stress response and oxidative stress response. The oxidative stress response appeared as the major activated biological module in B. weihenstephanensis cells submitted to acid stress conditions. Furthermore, as a firstly described model, the developed concept showed promising results to further be used to predict bacterial resistance using gene expression. Thus, this study underlines the possibility to integrate the bacterial physiology state, using omics biomarkers, into bacterial behaviour modelling and provide mechanistic understanding in acid bacterial resistance mechanisms.

  17. Biomarkers for monitoring efficacy of bioremediation by microbial inoculants

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, J.K.; Elvang, A.M. [Stockholm University (Sweden). Arrhenius Laboratories for Natural Sciences; Bjorklof, K.; Jorgensen, K.S. [Finnish Environment Institute, Helsinki (Finland). Research Laboratory


    Bioaugmentation of contaminated sites with microbes that are adapted or genetically engineered for degradation of specific toxic compounds is an area that is currently being explored as a clean-up option. Biomarkers have been developed to track the survival and efficacy of specific bacteria that are used as inocula for bioremediation of contaminated soil. Examples of biomarkers include the Iuc gene, encoding firefly luciferase and the gfp gene, encoding the green fluorescent protein (GFP). The luc gene was used to tag different bacteria used for bioremediation of gasoline or chlorophenols. The bacteria were monitored on the basis of luciferase activity in cell extracts from soil. The gfp gene was also used to monitor bacteria during degradation of chlorophenol in soil, based on fluorescence of the GFP protein. Other biomarkers can also be used for monitoring of microbial inocula used for bioaugmentation of contaminated sites. The choice of biomarker and monitoring system depends on the particular site, bacterial strain and sensitivity and specificity of detection required. (author)

  18. Development of Parkinson's disease biomarkers. (United States)

    Prakash, Kumar M; Tan, Eng-King


    Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting over 6 million people worldwide. It is anticipated that the number of affected individuals may increase significantly in the most populous nations by 2030. During the past 20 years, much progress has been made in identifying and assessing various potential clinical, biochemical, imaging and genetic biomarkers for PD. Despite the wealth of information, development of a validated biomarker for PD is still ongoing. It is hoped that reliable and well-validated biomarkers will provide critical clues to assist in the diagnosis and management of Parkinson's disease patients in the near future.

  19. Integrated Detection of Pathogens and Host Biomarkers for Wounds

    Energy Technology Data Exchange (ETDEWEB)

    Jaing, C


    The increasing incidence and complications arising from combat wounds has necessitated a reassessment of methods for effective treatment. Infection, excessive inflammation, and incidence of drug-resistant organisms all contribute toward negative outcomes for afflicted individuals. The organisms and host processes involved in wound progression, however, are incompletely understood. We therefore set out, using our unique technical resources, to construct a profile of combat wounds which did or did not successfully resolve. We employed the Lawrence Livermore Microbial Detection Array and identified a number of nosocomial pathogens present in wound samples. Some of these identities corresponded with bacterial isolates previously cultured, while others were not obtained via standard microbiology. Further, we optimized proteomics protocols for the identification of host biomarkers indicative of various stages in wound progression. In combination with our pathogen data, our biomarker discovery efforts will provide a profile corresponding to wound complications, and will assist significantly in treatment of these complex cases.

  20. Improving tuberculosis diagnostics with biomarkers

    Directory of Open Access Journals (Sweden)

    Shu CC


    Full Text Available Chin-Chung Shu,1,2 Jann-Yuan Wang,2 Li-Na Lee,2,3 Chong-Jen Yu,2 Kwen-Tay Luh3 1Department of Traumatology, 2Department of Internal Medicine, 3Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan Abstract: Although many laboratory methods have been developed to expedite the diagnosis of active tuberculosis (TB and Mycobacterium tuberculosis (Mtb infection, delays in diagnosis remain a major problem in clinical practice. Biomarkers may contribute favorably or unfavorably to TB diagnosis in a clinical suspect TB case with inconclusive diagnostic findings. A good understanding of the effectiveness and practical limitations of these biomarkers is important to improve diagnosis. This review summarizes currently used biomarkers, mainly as validation, and focuses on latent TB infection, active pulmonary TB, and tuberculous pleural effusion. Keywords: tuberculosis, biomarker, diagnosis, latent tuberculosis infection, pleural effusion 

  1. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An


    Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

  2. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille


    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  3. Biomarkers in Prostate Cancer Epidemiology


    Mudit Verma; Mukesh Verma; Payal Patel


    Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high ris...

  4. Biomarkers of satiation and satiety. (United States)

    de Graaf, Cees; Blom, Wendy A M; Smeets, Paul A M; Stafleu, Annette; Hendriks, Henk F J


    This review's objective is to give a critical summary of studies that focused on physiologic measures relating to subjectively rated appetite, actual food intake, or both. Biomarkers of satiation and satiety may be used as a tool for assessing the satiating efficiency of foods and for understanding the regulation of food intake and energy balance. We made a distinction between biomarkers of satiation or meal termination and those of meal initiation related to satiety and between markers in the brain [central nervous system (CNS)] and those related to signals from the periphery to the CNS. Various studies showed that physicochemical measures related to stomach distension and blood concentrations of cholecystokinin and glucagon-like peptide 1 are peripheral biomarkers associated with meal termination. CNS biomarkers related to meal termination identified by functional magnetic resonance imaging and positron emission tomography are indicators of neural activity related to sensory-specific satiety. These measures cannot yet serve as a tool for assessing the satiating effect of foods, because they are not yet feasible. CNS biomarkers related to satiety are not yet specific enough to serve as biomarkers, although they can distinguish between extreme hunger and fullness. Three currently available biomarkers for satiety are decreases in blood glucose in the short term (2-4 d) negative energy balance; and ghrelin concentrations, which have been implicated in both short-term and long-term energy balance. The next challenge in this research area is to identify food ingredients that have an effect on biomarkers of satiation, satiety, or both. These ingredients may help consumers to maintain their energy intake at a level consistent with a healthy body weight.

  5. Analysis of biomarker data a practical guide

    CERN Document Server

    Looney, Stephen W


    A "how to" guide for applying statistical methods to biomarker data analysis Presenting a solid foundation for the statistical methods that are used to analyze biomarker data, Analysis of Biomarker Data: A Practical Guide features preferred techniques for biomarker validation. The authors provide descriptions of select elementary statistical methods that are traditionally used to analyze biomarker data with a focus on the proper application of each method, including necessary assumptions, software recommendations, and proper interpretation of computer output. In addition, the book discusses

  6. Relationship of proton motive force and the F(0)F (1)-ATPase with bio-hydrogen production activity of Rhodobacter sphaeroides: effects of diphenylene iodonium, hydrogenase inhibitor, and its solvent dimethylsulphoxide. (United States)

    Hakobyan, Lilit; Gabrielyan, Lilit; Trchounian, Armen


    Rhodobacter sphaeroides MDC 6521 was able to produce bio-hydrogen (H(2)) in anaerobic conditions under illumination. In this study the effects of the hydrogenase inhibitor-diphenylene iodonium (Ph(2)I) and its solvent dimethylsulphoxide (DMSO) on growth characteristics and H(2) production by R. sphaeroides were investigated. The results point out the concentration dependent DMSO effect: in the presence of 10 mM DMSO H(2) yield was ~6 fold lower than that of the control. The bacterium was unable to produce H(2) in the presence of Ph(2)I. In order to examine the mediatory role of proton motive force (∆p) or the F(0)F(1)-ATPase in H(2) production by R. sphaeroides, the effects of Ph(2)I and DMSO on ∆p and its components (membrane potential (∆ψ) and transmembrane pH gradient), and ATPase activity were determined. In these conditions ∆ψ was of -98 mV and the reversed ∆pH was +30 mV, resulting in ∆p of -68 mV. Ph(2)I decreased ∆ψ in concentrations of 20 μM and higher; lower concentrations of Ph(2)I as DMSO had no valuable effect on ∆ψ. The R. sphaeroides membrane vesicles demonstrated significant ATPase activity sensitive to N,N'-dicyclohexylcarbodiimide. The 10-20 μM Ph(2)I did not affect the ATPase activity, whereas 40 μM Ph(2)I caused a marked inhibition (~2 fold) in ATPase activity. The obtained results provide novel evidence on the involvement of hydrogenase and the F(0)F(1)-ATPase in H(2) production by R. sphaeroides. Moreover, these data indicate the role of hydrogenase and the F(0)F(1)-ATPase in ∆p generation. In addition, DMSO might increase an interaction of nitrogenase with CO(2), decreasing nitrogenase activity and affecting H(2) production.

  7. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria


    Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach...... that imposes selection pressure for resistant bacteria. New approaches are urgently needed. Targeting bacterial virulence functions directly is an attractive alternative. An obvious target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in colonization, invasion, and biofilm formation....... As such, adhesion represents the Achilles heel of crucial pathogenic functions. It follows that interference with adhesion can reduce bacterial virulence. Here, we illustrate this important topic with examples of techniques being developed that can inhibit bacterial adhesion. Some of these will become...

  8. Transcriptional control of the F0F1-ATP synthase operon of Corynebacterium glutamicum: SigmaH factor binds to its promoter and regulates its expression at different pH values. (United States)

    Barriuso-Iglesias, Mónica; Barreiro, Carlos; Sola-Landa, Alberto; Martín, Juan F


    Corynebacterium glutamicum used in the amino acid fermentation industries is an alkaliphilic microorganism. Its F(0)F(1)-ATPase operon (atpBEFHAGDC) is expressed optimally at pH 9.0 forming a polycistronic (7.5 kb) and a monocistronic (1.2 kb) transcripts both starting upstream of the atpB gene. Expression of this operon is controlled by the SigmaH factor. The sigmaH gene (sigH) was cloned and shown to be co-transcribed with a small gene, cg0877, encoding a putative anti-sigma factor. A mutant deleted in the sigH gene expressed the atpBEFHAGDC operon optimally at pH 7.0 at difference of the wild-type strain (optimal expression at pH 9.0). These results suggested that the SigmaH factor is involved in pH control of expression of the F(0) F(1) ATPase operon. The SigmaH protein was expressed in Escherichia coli fused to the GST (glutathione-S-transferase) and purified to homogeneity by affinity chromatography on a GSTrap HP column. The fused protein was identified by immunodetection with anti-GST antibodies. DNA-binding studies by electrophoretic mobility shift assays showed that the SigH protein binds to a region of the atpB promoter containing the sigmaH recognition sequence (-35)TTGGAT…18nt…GTTA(-10). SigmaH plays an important role in the cascade of control of pH stress in Corynebacterium.

  9. Biomarkers of silicosis: Potential candidates

    Directory of Open Access Journals (Sweden)

    Tiwari R


    Full Text Available Silica dust is widely prevalent in the atmosphere and more common than the other types of dust, thus making silicosis the most frequently occurring pneumoconiosis. In India also, studies carried out by National Institute of Occupational Health have shown high prevalence of silicosis in small factories and even in nonoccupational exposed subjects. The postero-anterior chest radiographs remain the key tool in diagnosing and assessing the extent and severity of interstitial lung disease. Although Computed Tomography detects finer anatomical structure than radiography it could not get popularity because of its cost. On the basis of histological features of silicosis many potential biomarkers such as Cytokines, Tumor Necrosis Factor, Interleukin 1, Angiotensin Converting Enzyme, Serum Copper, Fas ligand (FasL, etc. have been tried. However, further studies are needed to establish these potential biomarkers as true biomarker of silicosis.

  10. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan


    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  11. Utility of immune response-derived biomarkers in the differential diagnosis of inflammatory disorders. (United States)

    ten Oever, Jaap; Netea, Mihai G; Kullberg, Bart-Jan


    Differentiating between inflammatory disorders is difficult, but important for a rational use of antimicrobial agents. Biomarkers reflecting the host immune response may offer an attractive strategy to predict the etiology of an inflammatory process and can thus be of help in decision making. We performed a review of the literature to evaluate the diagnostic value of inflammatory biomarkers in adult patients admitted to the hospital with suspected systemic acute infections. Elevated procalcitonin (PCT) concentrations indicate a bacterial infection in febrile patients with an auto-immune disease, rather than a disease flare. CD64 expression on neutrophils can discriminate between non-infectious systemic inflammation and sepsis, and limited evidence suggests the same for decoy receptor 3. PCT is useful for both diagnosing bacterial infection complicating influenza and guiding antibiotic treatment in lower respiratory tract infections in general. In undifferentiated illnesses, increased CD35 expression on neutrophils distinguishes bacterial from viral infections. Compared to bacterial infections, invasive fungal infections are characterized by low concentrations of PCT. No biomarker predicting a specific infecting agent could be identified.

  12. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R


    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...... sizes has been conducted. METHODS: Here, we performed a comprehensive review of meta-analyses of peripheral nongenetic biomarkers that could discriminate individuals with MDD from nondepressed controls. PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched through April 10, 2015. RESULTS: From 15...

  13. Proteomics in Discovery of Hepatocellular Carcinoma Biomarkers

    Institute of Scientific and Technical Information of China (English)


    Objective: To discover new proteomic biomarkers of hepatocellular carcinoma. Methods: Surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry was used to discover biomarkers for differentiating hepatocellular carcinoma and chronic liver disease. A population of 50 patients with hepatocellular carcinoma and 33 patients with chronic liver disease was studied. Results: Twelve proteomic biomarkers of hepatocellular carcinoma were detected in this study. Three proteomic biomarkers were highly expressed in hepatocellular carcinoma and nine proteomic biomarkers were highly expressed in chronic liver disease. The most valuable proteomic biomarker with m/z=11498 had no similar diagnostic value as α-fetoprotein. Conclusion:Some of the twelve proteomic biomarkers may become new biomarkers of hepatocellular carcinoma.

  14. Biomarker Detection using PS2-Thioaptamers Project (United States)

    National Aeronautics and Space Administration — AM Biotechnologies (AM) will develop a system to detect and quantify bone demineralization biomarkers as outlined in SBIR Topic "Technologies to Detect Biomarkers"....

  15. The consequences of lead acetate intake on exposure and integrity biomarkers of reproductive system in female rats at sexual maturity (two generation study

    Directory of Open Access Journals (Sweden)

    Eugenia Dumitrescu


    Full Text Available The aim of the study was the assessment of lead toxic impact on female reproductive systemintegrity and performances biomarkers. The objectives were: the evaluation of lead levels in ovary,Fallopian tubes and uterus (exposure biomarker and the structural changes in ovary, Fallopian tubesand uterus (integrity biomarker at sexual maturity consecutive exposure to lead acetate (50, 100, 150ppb Pb in drinking water along two generation (F0, F1. The study pointed out significant increase of leadlevel in ovaries, Fallopian tubes and uterus comparative to the control group and direct corelation, withdifferent degrees of significance, with the exposure level; severe congestive and degenerative changes inovary (destruction of parenchymatosa zone, vacuolar epithelial cells, passive vascular congestion,edematous follicle without oocytes, follicle with oocytes and uterus (necrosis of uterine glands,destruction of uterine lining cells, total detachments of the superficial layers of the epithelia, hypertrophyof the epithelia.

  16. Peritonitis - spontaneous bacterial (United States)

    Spontaneous bacterial peritonitis (SBP); Ascites - peritonitis; Cirrhosis - peritonitis ... who are on peritoneal dialysis for kidney failure. Peritonitis may have other causes . These include infection from ...

  17. Biomarkers of environmental benzene exposure

    Energy Technology Data Exchange (ETDEWEB)

    Weisel, C.; Yu, R.; Roy, A.; Georgopoulos, P. [Environmental and Occupational Health Sciences Institute, Piscataway, NJ (United States)


    Environmental exposures to benzene result in increases in body burden that are reflected in various biomarkers of exposure, including benzene in exhaled breath, benzene in blood and urinary trans-trans-muconic acid and S-phenylmercapturic acid. A review of the literature indicates that these biomarkers can be used to distinguish populations with different levels of exposure (such as smokers from nonsmokers and occupationally exposed from environmentally exposed populations) and to determine differences in metabolism. Biomarkers in humans have shown that the percentage of benzene metabolized by the ring-opening pathway is greater at environmental exposures than that at higher occupational exposures, a trend similar to that found in animal studies. This suggests that the dose-response curve is nonlinear; that potential different metabolic mechanisms exist at high and low doses; and that the validity of a linear extrapolation of adverse effects measured at high doses to a population exposed to lower, environmental levels of benzene is uncertain. Time-series measurements of the biomarker, exhaled breath, were used to evaluate a physiologically based pharmacokinetic (PBPK) model. Biases were identified between the PBPK model predictions and experimental data that were adequately described using an empirical compartmental model. It is suggested that a mapping of the PBPK model to a compartmental model can be done to optimize the parameters in the PBPK model to provide a future framework for developing a population physiologically based pharmacokinetic model. 44 refs., 3 figs., 1 tab.

  18. Biomarkers of satiation and satiety

    NARCIS (Netherlands)

    Graaf, C. de; Blom, W.A.M.; Smeets, P.A.M.; Stafleu, A.; Hendriks, H.F.J.


    This review's objective is to give a critical summary of studies that focused on physiologic measures relating to subjectively rated appetite, actual food intake, or both. Biomarkers of satiation and satiety may be used as a tool for assessing the satiating efficiency of foods and for understanding

  19. Biomarkers in sarcoidosis: a review

    Directory of Open Access Journals (Sweden)

    Ahmadzai H


    Full Text Available Hasib Ahmadzai,1,2 Wei Sheng Joshua Loke,1 Shuying Huang,1 Cristan Herbert,1 Denis Wakefield,3 Paul S Thomas2 1Inflammation and Infection Research Centre (IIRC, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; 2Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, Sydney, NSW, Australia; 3Immunology of the Eye Clinic, St Vincent's Clinic, Darlinghurst, Sydney, NSW, Australia Abstract: Sarcoidosis is a systemic granulomatous disease of undetermined etiology invariably affecting the lungs and thoracic lymph nodes. It has been termed an “immune paradox”, as there is peripheral anergy despite exaggerated inflammation at disease sites. The disease is usually self-limiting, although some individuals experience unremitting inflammation that may progress into pulmonary fibrosis and death. The inflammatory process is largely a T helper-1-driven immune response. Given its heterogeneous clinical manifestations, diagnosis is usually a clinical conundrum. Clinical and radiological findings alone are often inadequate to confirm the diagnosis. At present, sarcoidosis is usually a diagnosis of exclusion, confirmed by histological evidence of noncaseating granulomas in the absence of known granulomagenic agents. This has compelled researchers to look for disease-specific biomarkers that can help diagnose sarcoidosis and delineate its disease course, severity, and prognosis. In this review we highlight various investigations used to diagnose sarcoidosis, outline proposed biomarkers, and discuss novel methods of sampling biomarkers. Keywords: sarcoidosis, biomarkers, inflammatory markers, exhaled breath condensate, proteomics, granuloma

  20. Biomarkers of (osteo)arthritis. (United States)

    Mobasheri, Ali; Henrotin, Yves


    Arthritic diseases are a major cause of disability and morbidity, and cause an enormous burden for health and social care systems globally. Osteoarthritis (OA) is the most common form of arthritis. The key risk factors for the development of OA are age, obesity, joint trauma or instability. Metabolic and endocrine diseases can also contribute to the pathogenesis of OA. There is accumulating evidence to suggest that OA is a whole-organ disease that is influenced by systemic mediators, inflammaging, innate immunity and the low-grade inflammation induced by metabolic syndrome. Although all joint tissues are implicated in disease progression in OA, articular cartilage has received the most attention in the context of aging, injury and disease. There is increasing emphasis on the early detection of OA as it has the capacity to target and treat the disease more effectively. Indeed it has been suggested that this is the era of "personalized prevention" for OA. However, the development of strategies for the prevention of OA require new and sensitive biomarker tools that can detect the disease in its molecular and pre-radiographic stage, before structural and functional alterations in cartilage integrity have occurred. There is also evidence to support a role for biomarkers in OA drug discovery, specifically the development of disease modifying osteoarthritis drugs. This Special Issue of Biomarkers is dedicated to recent progress in the field of OA biomarkers. The papers in this Special Issue review the current state-of-the-art and discuss the utility of OA biomarkers as diagnostic and prognostic tools.

  1. Cancer Biomarkers | Division of Cancer Prevention (United States)

    [[{"fid":"175","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Cancer Biomarkers Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Cancer Biomarkers Research Group Homepage Logo","field_folder[und]":"15"},"type":"media","attributes":{"alt":"Cancer Biomarkers Research Group Homepage Logo","title":"Cancer Biomarkers Research Group Homepage Logo","height":"266","width":"400","style":"width: 400px; height: 266px;","class":"i | Research to identify, develop and validate biomarkers for early cancer detection and risk assessment.

  2. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria


    Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach that ...... valuable weapons for preventing pathogen contamination and fighting infectious diseases in the future....

  3. Implementation of proteomic biomarkers: making it work (United States)

    Mischak, Harald; Ioannidis, John PA; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia


    While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. PMID:22519700

  4. Vimentin in Bacterial Infections

    DEFF Research Database (Denmark)

    Mak, Tim N; Brüggemann, Holger


    Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate...... filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge...... about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria...

  5. Meeting Report--NASA Radiation Biomarker Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Straume, Tore; Amundson, Sally A,; Blakely, William F.; Burns, Frederic J.; Chen, Allen; Dainiak, Nicholas; Franklin, Stephen; Leary, Julie A.; Loftus, David J.; Morgan, William F.; Pellmar, Terry C.; Stolc, Viktor; Turteltaub, Kenneth W.; Vaughan, Andrew T.; Vijayakumar, Srinivasan; Wyrobek, Andrew J.


    A summary is provided of presentations and discussions from the NASA Radiation Biomarker Workshop held September 27-28, 2007, at NASA Ames Research Center in Mountain View, California. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including for long-duration space travel. Topics discussed include the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage following large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass-spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. Summary conclusions are provided at the end of the report.

  6. Blood-based biomarkers for Parkinson's disease. (United States)

    Chahine, Lama M; Stern, Matthew B; Chen-Plotkin, Alice


    There is a pressing need for biomarkers to diagnose Parkinson's disease (PD), assess disease severity, and prognosticate course. Various types of biologic specimens are potential candidates for identifying biomarkers--defined here as surrogate indicators of physiological or pathophysiological states--but blood has the advantage of being minimally invasive to obtain. There are, however, several challenges to identifying biomarkers in blood. Several candidate biomarkers identified in other diseases or in other types of biological fluids are being pursued as blood-based biomarkers in PD. In addition, unbiased discovery is underway using techniques including metabolomics, proteomics, and gene expression profiling. In this review, we summarize these techniques and discuss the challenges and successes of blood-based biomarker discovery in PD. Blood-based biomarkers that are discussed include α-synuclein, DJ-1, uric acid, epidermal growth factor, apolipoprotein-A1, and peripheral inflammatory markers.

  7. Oral Fluids that Detect Cardiovascular Disease Biomarkers (United States)

    Foley, Joseph D.; Sneed, J. Darrell; Steinhubl, Steven R; Kolasa, Justin; Ebersole, Jeffrey L.; Lin, Yushun; Kryscio, Richard J.; McDevitt, John T.; Campbell, Charles L.; Miller, Craig S.


    Objective To determine the utility of oral fluids for assessment of coronary and cardiovascular (CVD) health. Study Design Twenty-nine patients with pre-existing CVD disease underwent an invasive cardiac procedure (alcohol septal ablation or percutaneous coronary intervention) and provided unstimulated whole saliva (UWS), sublingual swabs (LS), gingival swabs (GS) and serum at 0, 8, 16, 24, 48 hr. Concentrations of 13 relevant biomarkers were determined and correlated with levels in serum and the oral fluids. Results Concentrations of the majority of biomarkers were higher in UWS than LS and GS. Coronary and CVD disease biomarkers in UWS correlated better with serum than LS and GS based on group status and measures of time effect. Seven biomarkers demonstrated time effect changes consistent with serum biomarkers, including C-reactive protein and troponin I. Conclusions Changes in serum biomarker profiles are reflected in oral fluids suggesting that oral fluid biomarkers could aid in the assessment of cardiac ischemia/necrosis. PMID:22769406

  8. Troponins Biomarkers Of Miocardic Injury

    Directory of Open Access Journals (Sweden)

    Ana Consuelo González Patiño


    Full Text Available Biomarkers or Biological markers are tools that for their availability, economy, specificity and sensitivity are useful in the diagnosis, prognosis and monitoring of canine and feline patients with cardiovascular alterations; widely used and standardized in human cardiology, presented as an excellent complement, of easy access, for specialized tests such as Doppler ultrasound and electrocardiography that, sometimes, are not available in everyday clinical practice. The cardiac troponins are sensitive and specific biomarkers in the detection of different abnormalities that affect the integrity of the myocardium, these are minimally invasive tests, inexpensive and would provide valuable information in the treatment of cardiac patients; therefore, the possibility of making these part of the protocol in the routine evaluation of patients, with suspect of heart disease should be considered.

  9. Genetic biomarkers in hypertrophic cardiomyopathy. (United States)

    Coats, Caroline J; Elliott, Perry M


    Hypertrophic cardiomyopathy is a common inherited heart muscle disorder associated with sudden cardiac death, arrhythmias and heart failure. Genetic mutations can be identified in approximately 60% of patients; these are commonest in genes that encode proteins of the cardiac sarcomere. Similar to other Mendelian diseases these mutations are characterized by incomplete penetrance and variable clinical expression. Our knowledge of this genetic diversity is rapidly evolving as high-throughput DNA sequencing technology is now used to characterize an individual patient's disease. In addition, the genomic basis of several multisystem diseases associated with a hypertrophic cardiomyopathy phenotype has been elucidated. Genetic biomarkers can be helpful in making an accurate diagnosis and in identifying relatives at risk of developing the condition. In the clinical setting, genetic testing and genetic screening should be used pragmatically with appropriate counseling. Here we review the current role of genetic biomarkers in hypertrophic cardiomyopathy, highlight recent progress in the field and discuss future challenges.

  10. Biomarkers in acute lung injury. (United States)

    Mokra, Daniela; Kosutova, Petra


    Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS.

  11. Glycoscience aids in biomarker discovery

    Directory of Open Access Journals (Sweden)

    Serenus Hua1,2 & Hyun Joo An1,2,*


    Full Text Available The glycome consists of all glycans (or carbohydrates within abiological system, and modulates a wide range of important biologicalactivities, from protein folding to cellular communications.The mining of the glycome for disease markers representsa new paradigm for biomarker discovery; however, this effortis severely complicated by the vast complexity and structuraldiversity of glycans. This review summarizes recent developmentsin analytical technology and methodology as applied tothe fields of glycomics and glycoproteomics. Mass spectrometricstrategies for glycan compositional profiling are described, as arepotential refinements which allow structure-specific profiling.Analytical methods that can discern protein glycosylation at aspecific site of modification are also discussed in detail.Biomarker discovery applications are shown at each level ofanalysis, highlighting the key role that glycoscience can play inhelping scientists understand disease biology.

  12. Candidate immune biomarkers for radioimmunotherapy. (United States)

    Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric


    Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy.

  13. Swiftly Decreasing Cerebrospinal Fluid Cathelicidin Concentration Predicts Improved Outcome in Childhood Bacterial Meningitis. (United States)

    Savonius, Okko; Helve, Otto; Roine, Irmeli; Andersson, Sture; Fernández, Josefina; Peltola, Heikki; Pelkonen, Tuula


    We investigated cerebrospinal fluid (CSF) cathelicidin concentrations in childhood bacterial meningitis on admission and during antimicrobial treatment. CSF cathelicidin concentrations on admission correlated with CSF white cell counts and protein levels but not with bacterial etiology. A greater decrease in the concentration in response to treatment was associated with a better outcome. Since the CSF cathelicidin concentration reflects the degree of central nervous system (CNS) inflammation, it may be used as a novel biomarker in childhood bacterial meningitis. An early decrease during treatment likely signals more rapid mitigation of the disease process and thus a better outcome.

  14. [Proteomic biomarkers in Parkinson's disease]. (United States)

    Bandrés, Sara; Durán, Raquel; Barrero, Francisco; Ramírez, Manuel; Vives, Francisco


    Parkinson's disease (PD) is a neurodegenerative disorder that affects movement and is caused by the death of the dopaminergic neurons in the compact part of the substantia nigra. Its diagnosis is essentially clinical, but although the signs and symptoms of PD are well known, the rate of diagnostic error is relatively high. It is estimated that 10-30% of patients initially diagnosed with PD are later reclassified. This disease has a high prevalence beyond the age of 60, and one of its biggest problems is that it is diagnosed when the degenerative process is already at a very advanced stage. Therefore, it is necessary to look for other biomarkers that make it possible to carry out an early diagnosis of PD, follow up its development, distinguish it from other related pathologies (parkinsonisms) and help monitor the effect of novel therapies. The fact that there are mutations that lead to PD, as well as polygenetic combinations that can act as risk factors, suggests the possibility of measuring the proteins resulting from the expression of these genes in peripheral tissues. And once their sensitivity and specificity have been proved they could be used as biomarkers for PD, even in the early phases of the disease. The aim of this work is to focus on a detailed review of the main candidate proteomic biomarkers researched to date by discussing the most recent literature.

  15. Dietary biomarkers: advances, limitations and future directions

    Directory of Open Access Journals (Sweden)

    Hedrick Valisa E


    Full Text Available Abstract The subjective nature of self-reported dietary intake assessment methods presents numerous challenges to obtaining accurate dietary intake and nutritional status. This limitation can be overcome by the use of dietary biomarkers, which are able to objectively assess dietary consumption (or exposure without the bias of self-reported dietary intake errors. The need for dietary biomarkers was addressed by the Institute of Medicine, who recognized the lack of nutritional biomarkers as a knowledge gap requiring future research. The purpose of this article is to review existing literature on currently available dietary biomarkers, including novel biomarkers of specific foods and dietary components, and assess the validity, reliability and sensitivity of the markers. This review revealed several biomarkers in need of additional validation research; research is also needed to produce sensitive, specific, cost-effective and noninvasive dietary biomarkers. The emerging field of metabolomics may help to advance the development of food/nutrient biomarkers, yet advances in food metabolome databases are needed. The availability of biomarkers that estimate intake of specific foods and dietary components could greatly enhance nutritional research targeting compliance to national recommendations as well as direct associations with disease outcomes. More research is necessary to refine existing biomarkers by accounting for confounding factors, to establish new indicators of specific food intake, and to develop techniques that are cost-effective, noninvasive, rapid and accurate measures of nutritional status.

  16. Dietary biomarkers: advances, limitations and future directions. (United States)

    Hedrick, Valisa E; Dietrich, Andrea M; Estabrooks, Paul A; Savla, Jyoti; Serrano, Elena; Davy, Brenda M


    The subjective nature of self-reported dietary intake assessment methods presents numerous challenges to obtaining accurate dietary intake and nutritional status. This limitation can be overcome by the use of dietary biomarkers, which are able to objectively assess dietary consumption (or exposure) without the bias of self-reported dietary intake errors. The need for dietary biomarkers was addressed by the Institute of Medicine, who recognized the lack of nutritional biomarkers as a knowledge gap requiring future research. The purpose of this article is to review existing literature on currently available dietary biomarkers, including novel biomarkers of specific foods and dietary components, and assess the validity, reliability and sensitivity of the markers. This review revealed several biomarkers in need of additional validation research; research is also needed to produce sensitive, specific, cost-effective and noninvasive dietary biomarkers. The emerging field of metabolomics may help to advance the development of food/nutrient biomarkers, yet advances in food metabolome databases are needed. The availability of biomarkers that estimate intake of specific foods and dietary components could greatly enhance nutritional research targeting compliance to national recommendations as well as direct associations with disease outcomes. More research is necessary to refine existing biomarkers by accounting for confounding factors, to establish new indicators of specific food intake, and to develop techniques that are cost-effective, noninvasive, rapid and accurate measures of nutritional status.

  17. Interfering with bacterial gossip

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Tolker-Nielsen, Tim; Givskov, Michael


    defense. Antibiotics exhibit a rather limited effect on biofilms. Furthermore, antibiotics have an ‘inherent obsolescence’ because they select for development of resistance. Bacterial infections with origin in bacterial biofilms have become a serious threat in developed countries. Pseudomonas aeruginosa...... that appropriately target bacteria in their relevant habitat with the aim of mitigating their destructive impact on patients. In this review we describe molecular mechanisms involved in “bacterial gossip” (more scientifically referred to as quorum sensing (QS) and c-di-GMP signaling), virulence, biofilm formation......, resistance and QS inhibition as future antimicrobial targets, in particular those that would work to minimize selection pressures for the development of resistant bacteria....

  18. Use of cervicovaginal fluid for the identification of biomarkers for pathologies of the female genital tract

    Directory of Open Access Journals (Sweden)

    Tjalma Wiebren AA


    Full Text Available Abstract Cervicovaginal fluid has an important function in the homeostasis and immunity of the lower female genital tract. Analysis of the cervicovaginal fluid proteome may therefore yield important information about the pathogenesis of numerous gynecological pathologies. Additionally, cervicovaginal fluid has great potential as a source of biomarkers for these conditions. This review provides a detailed discussion about the human cervicovaginal proteome and the proteomics studies performed to characterize this biological fluid. Furthermore, infection-correlated pathological conditions of the female genital tract are discussed for which cervicovaginal fluid has been used in order to identify potential biomarkers. Recent years, numerous studies have analyzed cervicovaginal fluid samples utilizing antibody-based technologies, such as ELISA or Western blotting, to identify biomarkers for preterm birth, premature preterm rupture of membranes, bacterial vaginosis and cervical cancer. The present article will discuss the importance of proteomic technologies as alternative techniques to gain additional meaningful information about these conditions. In addition, the review focuses on recent proteomic studies on cervicovaginal fluid samples for the identification of potential biomarkers. We conclude that the use of proteomic technology for analysis of human cervicovaginal fluid samples is promising and may lead to the discovery of new biomarkers which can improve disease prevention and therapy development.

  19. Bacterial intermediate filaments

    DEFF Research Database (Denmark)

    Charbon, Godefroid; Cabeen, M.; Jacobs-Wagner, C.


    Crescentin, which is the founding member of a rapidly growing family of bacterial cytoskeletal proteins, was previously proposed to resemble eukaryotic intermediate filament (IF) proteins based on structural prediction and in vitro polymerization properties. Here, we demonstrate that crescentin...

  20. Bacterial Wound Culture (United States)

    ... Home Visit Global Sites Search Help? Bacterial Wound Culture Share this page: Was this page helpful? Also known as: Aerobic Wound Culture; Anaerobic Wound Culture Formal name: Culture, wound Related ...

  1. Bacterial surface adaptation (United States)

    Utada, Andrew


    Biofilms are structured multi-cellular communities that are fundamental to the biology and ecology of bacteria. Parasitic bacterial biofilms can cause lethal infections and biofouling, but commensal bacterial biofilms, such as those found in the gut, can break down otherwise indigestible plant polysaccharides and allow us to enjoy vegetables. The first step in biofilm formation, adaptation to life on a surface, requires a working knowledge of low Reynolds number fluid physics, and the coordination of biochemical signaling, polysaccharide production, and molecular motility motors. These crucial early stages of biofilm formation are at present poorly understood. By adapting methods from soft matter physics, we dissect bacterial social behavior at the single cell level for several prototypical bacterial species, including Pseudomonas aeruginosa and Vibrio cholerae.

  2. Bacterial Meningitis in Infants

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


    Full Text Available A retrospective study of 80 infantile patients (ages 30-365 days; 47 male, 33 female with culture-proven bacterial meningitis seen over a 16 year period (1986-2001 is reported from Taiwan.

  3. Bacterial proteases and virulence

    DEFF Research Database (Denmark)

    Frees, Dorte; Brøndsted, Lone; Ingmer, Hanne


    Bacterial pathogens rely on proteolysis for variety of purposes during the infection process. In the cytosol, the main proteolytic players are the conserved Clp and Lon proteases that directly contribute to virulence through the timely degradation of virulence regulators and indirectly by providing....... These extracellular proteases are activated in complex cascades involving auto-processing and proteolytic maturation. Thus, proteolysis has been adopted by bacterial pathogens at multiple levels to ensure the success of the pathogen in contact with the human host....

  4. Circulating Biomarkers for Duchenne Muscular Dystrophy (United States)

    Aartsma-Rus, Annemieke; Spitali, Pietro


    Abstract Duchenne muscular dystrophy is the most common form of muscular dystrophy. Genetic and biochemical research over the years has characterized the cause, pathophysiology and development of the disease providing several potential therapeutic targets and/or biomarkers. High throughput – omic technologies have provided a comprehensive understanding of the changes occurring in dystrophic muscles. Murine and canine animal models have been a valuable source to profile muscles and body fluids, thus providing candidate biomarkers that can be evaluated in patients. This review will illustrate known circulating biomarkers that could track disease progression and response to therapy in patients affected by Duchenne muscular dystrophy. We present an overview of the transcriptomic, proteomic, metabolomics and lipidomic biomarkers described in literature. We show how studies in muscle tissue have led to the identification of serum and urine biomarkers and we highlight the importance of evaluating biomarkers as possible surrogate endpoints to facilitate regulatory processes for new medicinal products. PMID:27858763

  5. Molecular biomarkers for grass pollen immunotherapy. (United States)

    Popescu, Florin-Dan


    Grass pollen allergy represents a significant cause of allergic morbidity worldwide. Component-resolved diagnosis biomarkers are increasingly used in allergy practice in order to evaluate the sensitization to grass pollen allergens, allowing the clinician to confirm genuine sensitization to the corresponding allergen plant sources and supporting an accurate prescription of allergy immunotherapy (AIT), an important approach in many regions of the world with great plant biodiversity and/or where pollen seasons may overlap. The search for candidate predictive biomarkers for grass pollen immunotherapy (tolerogenic dendritic cells and regulatory T cells biomarkers, serum blocking antibodies biomarkers, especially functional ones, immune activation and immune tolerance soluble biomarkers and apoptosis biomarkers) opens new opportunities for the early detection of clinical responders for AIT, for the follow-up of these patients and for the development of new allergy vaccines.

  6. Advances in Biomarker Research in Parkinson's Disease. (United States)

    Mehta, Shyamal H; Adler, Charles H


    Parkinson's disease (PD) is the second most common neurodegenerative disease, and the numbers are projected to double in the next two decades with the increase in the aging population. An important focus of current research is to develop interventions to slow the progression of the disease. However, prerequisites to it include the development of reliable biomarkers for early diagnosis which would identify at-risk groups and disease progression. In this review, we present updated evidence of already known clinical biomarkers (such as hyposmia and rapid eye movement (REM) sleep behavior disorder (RBD)) and neuroimaging biomarkers, as well as newer possible markers in the blood, CSF, and other tissues. While several promising candidates and methods to assess these biomarkers are on the horizon, it is becoming increasingly clear that no one candidate will clearly fulfill all the roles as a single biomarker. A multimodal and combinatorial approach to develop a battery of biomarkers will likely be necessary in the future.

  7. [Diagnosis of bacterial vaginosis]. (United States)

    Djukić, Slobodanka; Ćirković, Ivana; Arsić, Biljana; Garalejić, Eliana


    Bacterial vaginosis is a common, complex clinical syndrome characterized by alterations in the normal vaginal flora. When symptomatic, it is associated with a malodorous vaginal discharge and on occasion vaginal burning or itching. Under normal conditions, lactobacilli constitute 95% of the bacteria in the vagina. Bacterial vaginosis is associated with severe reduction or absence of the normal H2O2-producing lactobacilli and overgrowth of anaerobic bacteria and Gardnerella vaginalis, Atopobium vaginae, Mycoplasma hominis and Mobiluncus species. Most types of infectious disease are diagnosed by culture, by isolating an antigen or RNA/DNA from the microbe, or by serodiagnosis to determine the presence of antibodies to the microbe. Therefore, demonstration of the presence of an infectious agent is often a necessary criterion for the diagnosis of the disease. This is not the case for bacterial vaginosis, since the ultimate cause of the disease is not yet known. There are a variety of methods for the diagnosis of bacterial vaginosis but no method can at present be regarded as the best. Diagnosing bacterial vaginosis has long been based on the clinical criteria of Amsel, whereby three of four defined criteria must be satisfied. Nugent's scoring system has been further developed and includes validation of the categories of observable bacteria structures. Up-to-date molecular tests are introduced, and better understanding of vaginal microbiome, a clear definition for bacterial vaginosis, and short-term and long-term fluctuations in vaginal microflora will help to better define molecular tests within the broader clinical context.

  8. Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization. (United States)

    Amur, S; LaVange, L; Zineh, I; Buckman-Garner, S; Woodcock, J


    The discovery, development, and use of biomarkers for a variety of drug development purposes are areas of tremendous interest and need. Biomarkers can become accepted for use through submission of biomarker data during the drug approval process. Another emerging pathway for acceptance of biomarkers is via the biomarker qualification program developed by the Center for Drug Evaluation and Research (CDER, US Food and Drug Administration). Evidentiary standards are needed to develop and evaluate various types of biomarkers for their intended use and multiple stakeholders, including academia, industry, government, and consortia must work together to help develop this evidence. The article describes various types of biomarkers that can be useful in drug development and evidentiary considerations that are important for qualification. A path forward for coordinating efforts to identify and explore needed biomarkers is proposed for consideration.

  9. Biomarkers of selenium status in dogs


    Van Zelst, Marielle; Hesta, Myriam; Gray, Kerry; Staunton, Ruth; Du Laing, Gijs; Janssens, Geert


    Background: Inadequate dietary selenium (Se) intake in humans and animals can lead to long term health problems, such as cancer. In view of the owner's desire for healthy longevity of companion animals, the impact of dietary Se provision on long term health effects warrants investigation. Little is currently known regards biomarkers, and rate of change of such biomarkers in relation to dietary selenium intake in dogs. In this study, selected biomarkers were assessed for their suitability to d...

  10. Neurophysiological biomarkers for Lewy body dementias


    Cromarty, Ruth A.; Elder, Greg J.; Graziadio, Sara; Baker, Mark; Bonanni, Laura; Onofrj, Marco; O’Brien, John T.; Taylor, John-Paul


    Objective Lewy body dementias (LBD) include both dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD), and the differentiation of LBD from other neurodegenerative dementias can be difficult. Currently, there are few biomarkers which might assist early diagnosis, map onto LBD symptom severity, and provide metrics of treatment response. Traditionally, biomarkers in LBD have focussed on neuroimaging modalities; however, as biomarkers need to be simple, inexpensive and non-...

  11. Current and future biomarkers in allergic asthma. (United States)

    Zissler, U M; Esser-von Bieren, J; Jakwerth, C A; Chaker, A M; Schmidt-Weber, C B


    Diagnosis early in life, sensitization, asthma endotypes, monitoring of disease and treatment progression are key motivations for the exploration of biomarkers for allergic rhinitis and allergic asthma. The number of genes related to allergic rhinitis and allergic asthma increases steadily; however, prognostic genes have not yet entered clinical application. We hypothesize that the combination of multiple genes may generate biomarkers with prognostic potential. The current review attempts to group more than 161 different potential biomarkers involved in respiratory inflammation to pave the way for future classifiers. The potential biomarkers are categorized into either epithelial or infiltrate-derived or mixed origin, epithelial biomarkers. Furthermore, surface markers were grouped into cell-type-specific categories. The current literature provides multiple biomarkers for potential asthma endotypes that are related to T-cell phenotypes such as Th1, Th2, Th9, Th17, Th22 and Tregs and their lead cytokines. Eosinophilic and neutrophilic asthma endotypes are also classified by epithelium-derived CCL-26 and osteopontin, respectively. There are currently about 20 epithelium-derived biomarkers exclusively derived from epithelium, which are likely to innovate biomarker panels as they are easy to sample. This article systematically reviews and categorizes genes and collects current evidence that may promote these biomarkers to become part of allergic rhinitis or allergic asthma classifiers with high prognostic value.

  12. Biomarkers in Parkinson's disease: a funder's perspective. (United States)

    Frasier, Mark; Chowdhury, Sohini; Eberling, Jamie; Sherer, Todd


    Therapeutic development in Parkinson's disease is hampered by the paucity of well-validated biomarkers that can assist with diagnosis and/or tracking the progression of the disease. Since its inception, the Michael J Fox Foundation for Parkinson's Research has invested heavily in biomarker research and continues to prioritize discovery and development efforts. This article summarizes the history and evolution of the Michael J Fox Foundation's role in supporting biomarker research and lays out the current challenges in successfully developing markers that can be used to test therapies, while also providing a vision of future funding efforts in Parkinson's disease biomarkers.

  13. Changes in rhizosphere bacterial gene expression following glyphosate treatment. (United States)

    Newman, Molli M; Lorenz, Nicola; Hoilett, Nigel; Lee, Nathan R; Dick, Richard P; Liles, Mark R; Ramsier, Cliff; Kloepper, Joseph W


    In commercial agriculture, populations and interactions of rhizosphere microflora are potentially affected by the use of specific agrichemicals, possibly by affecting gene expression in these organisms. To investigate this, we examined changes in bacterial gene expression within the rhizosphere of glyphosate-tolerant corn (Zea mays) and soybean (Glycine max) in response to long-term glyphosate (PowerMAX™, Monsanto Company, MO, USA) treatment. A long-term glyphosate application study was carried out using rhizoboxes under greenhouse conditions with soil previously having no history of glyphosate exposure. Rhizosphere soil was collected from the rhizoboxes after four growing periods. Soil microbial community composition was analyzed using microbial phospholipid fatty acid (PLFA) analysis. Total RNA was extracted from rhizosphere soil, and samples were analyzed using RNA-Seq analysis. A total of 20-28 million bacterial sequences were obtained for each sample. Transcript abundance was compared between control and glyphosate-treated samples using edgeR. Overall rhizosphere bacterial metatranscriptomes were dominated by transcripts related to RNA and carbohydrate metabolism. We identified 67 differentially expressed bacterial transcripts from the rhizosphere. Transcripts downregulated following glyphosate treatment involved carbohydrate and amino acid metabolism, and upregulated transcripts involved protein metabolism and respiration. Additionally, bacterial transcripts involving nutrients, including iron, nitrogen, phosphorus, and potassium, were also affected by long-term glyphosate application. Overall, most bacterial and all fungal PLFA biomarkers decreased after glyphosate treatment compared to the control. These results demonstrate that long-term glyphosate use can affect rhizosphere bacterial activities and potentially shift bacterial community composition favoring more glyphosate-tolerant bacteria.

  14. Synthesis of arborane triterpenols by a bacterial oxidosqualene cyclase (United States)

    Banta, Amy B.; Wei, Jeremy H.; Gill, Clare C. C.; Giner, José-Luis; Welander, Paula V.


    Cyclic triterpenoids are a broad class of polycyclic lipids produced by bacteria and eukaryotes. They are biologically relevant for their roles in cellular physiology, including membrane structure and function, and biochemically relevant for their exquisite enzymatic cyclization mechanism. Cyclic triterpenoids are also geobiologically significant as they are readily preserved in sediments and are used as biomarkers for ancient life throughout Earth's history. Isoarborinol is one such triterpenoid whose only known biological sources are certain angiosperms and whose diagenetic derivatives (arboranes) are often used as indicators of terrestrial input into aquatic environments. However, the occurrence of arborane biomarkers in Permian and Triassic sediments, which predates the accepted origin of angiosperms, suggests that microbial sources of these lipids may also exist. In this study, we identify two isoarborinol-like lipids, eudoraenol and adriaticol, produced by the aerobic marine heterotrophic bacterium Eudoraea adriatica. Phylogenetic analysis demonstrates that the E. adriatica eudoraenol synthase is an oxidosqualene cyclase homologous to bacterial lanosterol synthases and distinct from plant triterpenoid synthases. Using an Escherichia coli heterologous sterol expression system, we demonstrate that substitution of four amino acid residues in a bacterial lanosterol synthase enabled synthesis of pentacyclic arborinols in addition to tetracyclic sterols. This variant provides valuable mechanistic insight into triterpenoid synthesis and reveals diagnostic amino acid residues to differentiate between sterol and arborinol synthases in genomic and metagenomic datasets. Our data suggest that there may be additional bacterial arborinol producers in marine and freshwater environments that could expand our understanding of these geologically informative lipids.

  15. The bacterial lipocalins. (United States)

    Bishop, R E


    The lipocalins were once regarded as a eukaryotic protein family, but new members have been recently discovered in bacteria. The first bacterial lipocalin (Blc) was identified in Escherichia coli as an outer membrane lipoprotein expressed under conditions of environmental stress. Blc is distinguished from most lipocalins by the absence of intramolecular disulfide bonds, but the presence of a membrane anchor is shared with two of its closest homologues, apolipoprotein D and lazarillo. Several common features of the membrane-anchored lipocalins suggest that each may play an important role in membrane biogenesis and repair. Additionally, Blc proteins are implicated in the dissemination of antibiotic resistance genes and in the activation of immunity. Recent genome sequencing efforts reveal the existence of at least 20 bacterial lipocalins. The lipocalins appear to have originated in Gram-negative bacteria and were probably transferred horizontally to eukaryotes from the endosymbiotic alpha-proteobacterial ancestor of the mitochondrion. The genome sequences also reveal that some bacterial lipocalins exhibit disulfide bonds and alternative modes of subcellular localization, which include targeting to the periplasmic space, the cytoplasmic membrane, and the cytosol. The relationships between bacterial lipocalin structure and function further illuminate the common biochemistry of bacterial and eukaryotic cells.

  16. Biomarkers of intermediate endpoints in environmental and occupational health

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E; Hansen, Ase M


    aberrations (CA), sister chromatid exchanges and micronuclei (MN). The validation of biomarkers includes measurements of sensitivity and specificity of biomarkers and round robin tests to ensure reproducible protocols within different laboratories. The predictive value of biomarkers with respect to adverse...

  17. Biomarkers of chronic alcohol misuse

    Directory of Open Access Journals (Sweden)

    Gonzalo P


    Full Text Available Philippe Gonzalo,1 Sylvie Radenne,2 Sylvie Gonzalo31Laboratoire de Biochimie, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France; 2Service d'Hépatologie-Gastroentérologie, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France; 3Laboratoire Biomnis, Lyon, FranceAbstract: Biological markers of chronic alcoholism can be divided into two groups: direct and indirect markers. Direct markers (mainly blood or serum and urine ethanol, ethylglucuronide, ethyl sulfate, and phosphatidylethanol directly track the intake of alcohol and vary in their sensitivity and kinetics of appearance and clearance. Indirect markers (mean corpuscular volume,γ-glutamyl transferase, alanine aminotransferase and aspartate aminotransferase, and carbohydrate-deficient transferrin are biological parameters that are influenced by a steady and significant alcohol intake. We discuss the values of these tests and the relevance of their prescriptions for the clinical evaluation of heavy drinking. We indicate, when known, the pathophysiological mechanism of their elevations. We also discuss the amount and time of alcohol consumption required to give a positive result and the duration of abstinence required for the return to normal values. The forensic use of these biomarkers will not be considered in this review.Keywords: alcoholism, biomarker, CDT, relapse, alcohol-induced liver disease

  18. Biomarkers in Pancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Maria Serafeim Theochari


    Full Text Available The aim of biomarkers is to identify patients most likely to benefit from a therapeutic strategy. Pancreatic neuroendocrinetumors are rare neoplasms that arise in the endocrine tissues of the pancreas. Pancreatic neuroendocrine tumors represent3% of primary pancreatic neoplasms and their incidence has risen. The SMAD4 gene is located on chromosome 18q andsomeday the SMAD4 gene status may be useful for prognostic stratification and therapeutic decision. The cells respond toenvironmental signals by modulating the expressions of genes contained within the nucleus, when genes are activated aretranscribed to generate messenger RNA (mRNA. The examination of multiple expressed genes and proteins provides moreuseful information for prognostication of individual tumors. Here we summarize and discuss findings presented at the 2014ASCO Gastrointestinal Cancers Symposium. Anna Karpathakis et al. (Abstract #212 reported data about the role of DNAmethylation in gastrointestinal neuroendocrine tumors. Christina Lynn Roland et al. (Abstract #250 looked the impact OfSMAD4 on oncologic outcomes. Bong Kynn Kang et al. (Abstract #251 investigated prognostic biomarker using microRNAarray technology.

  19. Exploration of new HCC biomarkers

    Directory of Open Access Journals (Sweden)

    Regina M. Santella


    Full Text Available

    Analysis of plasma/serum for levels of viral antigens or antibodies to viral proteins has been used extensively as an early biomarker of potential risk of HCC. In addition, detection of elevated levels of alpha-fetoprotein is commonly used for early identification of HCC. Unfortunately, both of these approaches are not highly sensitive or specific. As a result, there is continuing investigation to identify additional biomarkers that may help in the early identification of cases. The use of DNA isolated from plasma or serum for detection of gene specific methylation has been discussed previously. In addition, tumor DNA isolated from blood has been analyzed for the presence of p53 mutations and found in a subset of cases to be present years prior to diagnosis as for methylated DNA. The general level of DNA present in blood has also been suggested as a potential biomarker of cancer.

    Among the newer methods being tested are the detection of specific mutations in HBV. In many cases of HCC in China and Africa a double mutation, an A to T transversion at nucleotide 1762 and a G to A transition at nucleotide 1764 (1762T/1764A have been found. These mutations have been associated with increased severity of HBV infection and cirrhosis suggesting that they might be a useful biomarker for high risk subjects.

    The field of proteomics also holds promise for the development of new biomarkers. A number of groups are developing mass spectrometry methods for the identification of serum/plasma proteomic patterns that will distinguish bloods of HCC cases from those of controls. While some interesting preliminary data have been developed for several cancers, much additional work needs to be done in this area

  20. Cytokines as Biomarkers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Agata Burska


    Full Text Available RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge’s relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.

  1. Proteomic Biomarkers for Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana


    This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

  2. Bias in emerging biomarkers for bipolar disorder

    DEFF Research Database (Denmark)

    Carvalho, A F; Köhler, C A; Fernandes, B S


    BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed...

  3. DNA Methylation Biomarkers: Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Thomas Mikeska


    Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

  4. Biomarkers in Alzheimer’s disease

    Institute of Scientific and Technical Information of China (English)

    Rajka M Liscic; Yuanhan Yang


    Alzheimer’s disease (AD) so far did not have promising treatment. The accurate and early diagnosis is still the important issue. For these purpose, biomarkers related to diagnosis, clinical course, and other aims have been proposed and reported. Meanwhile, along with the ongoing researches for AD, biomarkers with their own aims are also on the way.

  5. Cytokines as biomarkers in rheumatoid arthritis. (United States)

    Burska, Agata; Boissinot, Marjorie; Ponchel, Frederique


    RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria) and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge's relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.

  6. Consensus on biomarkers for neuroendocrine tumour disease (United States)

    Oberg, Kjell; Modlin, Irvin M; De Herder, Wouter; Pavel, Marianne; Klimstra, David; Frilling, Andrea; Metz, David C; Heaney, Anthony; Kwekkeboom, Dik; Strosberg, Jonathan; Meyer, Timothy; Moss, Steven F; Washington, Kay; Wolin, Edward; Liu, Eric; Goldenring, James


    Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours. PMID:26370353

  7. Current and emerging biomarkers of hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Yang X


    Full Text Available Xi Yang, William F Salminen, Laura K SchnackenbergDivision of Systems Biology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USAAbstract: Drug-induced liver injury (DILI is of great concern to human health. Generally, liver function and injury is evaluated based upon clinical signs, a select group of serum clinical biomarkers, and occasionally liver biopsies. While alanine aminotransferase, the most commonly used biomarker of hepatocellular injury, is a sensitive marker of liver injury, it is not necessarily specific for liver injury. Furthermore, alanine aminotransferase levels may not always correlate with the extent of injury. Therefore, new hepatotoxicity biomarkers are needed that are more predictive and specific indicators of liver injury and altered function. In addition, no current biomarker provides prognostic information about ultimate outcome once injury occurs, and any new biomarker filling this need is desperately needed. The omics technologies, including genomics, proteomics, and metabolomics, are being used in preclinical animal studies as well as clinical studies to evaluate markers of hepatotoxicity in easily obtained biofluids, such as urine and serum. Recently, the evaluation of circulating microRNAs in urine and blood has also shown promise for the identification of novel, sensitive markers of liver injury. This review evaluates the current status of proposed biomarkers of hepatotoxicity from the omics platforms, as well as from analysis of microRNAs. A brief description of the qualification of proposed biomarkers is also given.Keywords: biomarkers, hepatotoxicity, metabolomics, microRNA, proteomics, transcriptomics

  8. Milk fat biomarkers and cardiometabolic disease (United States)

    Risérus, Ulf; Marklund, Matti


    Purpose of review Dairy is a major food group with potential impact on cardiometabolic health. Self-reported dairy intake has limitations that can partly be avoided by using biomarkers. This review aims to summarize the evidence of odd-chain saturated fatty acids (OCFAs), that is, pentadecanoic acid (C15 : 0) and heptadecanoic acid (17 : 0), as biomarkers of dairy fat intake. In addition, the associations of OCFA biomarkers with cardiometabolic disease will be overviewed. Recent findings Adipose tissue 15 : 0 is the preferred biomarker but also circulating 15 : 0, and to a weaker extent 17 : 0, reflects both habitual and changes in dairy intake. Whereas results from studies assessing cardiovascular outcomes are inconsistent, OCFA biomarkers are overall associated with lower diabetes risk. Residual confounding should however be considered until interventional data and mechanisms are available. Although OCFA biomarkers mainly reflect dairy fat intake, recently proposed endogenous synthesis and metabolism do motivate further research. Summary Taking into account the study population diet and limitations of OCFA biomarkers, both adipose and circulating levels of 15 : 0, in particular, are useful for estimating total dairy fat intake. OCFA biomarkers are overall not linked to cardiovascular disease risk, but a possible beneficial role of dairy foods in diabetes prevention warrant further study. PMID:27906713

  9. Novel diagnostic biomarkers for prostate cancer

    Directory of Open Access Journals (Sweden)

    Chikezie O. Madu, Yi Lu


    Full Text Available Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of

  10. Novel diagnostic biomarkers for prostate cancer. (United States)

    Madu, Chikezie O; Lu, Yi


    Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The

  11. Bacterial glycosyltransferase toxins. (United States)

    Jank, Thomas; Belyi, Yury; Aktories, Klaus


    Mono-glycosylation of host proteins is a common mechanism by which bacterial protein toxins manipulate cellular functions of eukaryotic target host cells. Prototypic for this group of glycosyltransferase toxins are Clostridium difficile toxins A and B, which modify guanine nucleotide-binding proteins of the Rho family. However, toxin-induced glycosylation is not restricted to the Clostridia. Various types of bacterial pathogens including Escherichia coli, Yersinia, Photorhabdus and Legionella species produce glycosyltransferase toxins. Recent studies discovered novel unexpected variations in host protein targets and amino acid acceptors of toxin-catalysed glycosylation. These findings open new perspectives in toxin as well as in carbohydrate research.

  12. Diagnostic and prognostic epigenetic biomarkers in cancer. (United States)

    Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen


    Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

  13. Cellular Proteases as Cancer Biomarkers: A Review

    Directory of Open Access Journals (Sweden)

    Sarah R. Röthlisberger


    Full Text Available Over the past few decades a variety of biomolecules have been proposed as diagnostic biomarkers and predictors of severity for transmissible and nontransmissible diseases. Studies in a range of cancers have revealed many biomarkers with great potential in cancer diagnosis, in establishing tumor stage, progression, and response to therapies; such as the Kallikrein and Metalloproteinase families. Traditionally blood (serum and tissue have been the main biological sources of biomarker discovery, but in the past decade urine has emerged as a promising source of cancer biomarkers. In this review we will focus on two large families, the Kallikrein family of serine proteases discovered in serum, and the Metalloproteinase family of zinc proteases discovered in urine, as potential cancer biomarkers.

  14. Diagnostic and Prognostic Biomarkers in Melanoma (United States)

    Leininger, Jennifer; Hamby, Carl; Safai, Bijan


    Melanoma is a lethal melanocytic neoplasm. Unfortunately, the histological diagnosis can be difficult at times. Distinguishing ambiguous melanocytic neoplasms that are benign nevi from those that represent true melanoma is important both for treatment and prognosis. Diagnostic biomarkers currently used to assist in the diagnosis of melanoma are usually specific only for melanocytic neoplasms and not necessarily for their ability to metastasize. Traditional prognostic biomarkers include depth of invasion and mitotic count. Newer diagnostic and prognostic biomarkers utilize immunohistochemical staining as well as ribonucleic acid, micro-ribonucleic acid, and deoxyribonucleic acid assays and fluorescence in situ hybridization. Improved diagnostic and prognostic biomarkers are of increasing importance in the treatment of melanoma with the development of newer and more targeted therapies. Herein, the authors review many of the common as well as newer diagnostic and prognostic biomarkers used in melanoma. PMID:25013535

  15. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy


    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

  16. Bacterial contribution to dissolved organic matter in eutrophic Lake Kasumigaura, Japan. (United States)

    Kawasaki, Nobuyuki; Komatsu, Kazuhiro; Kohzu, Ayato; Tomioka, Noriko; Shinohara, Ryuichiro; Satou, Takayuki; Watanabe, Fumiko Nara; Tada, Yuya; Hamasaki, Koji; Kushairi, M R M; Imai, Akio


    Incubation experiments using filtered waters from Lake Kasumigaura were conducted to examine bacterial contribution to a dissolved organic carbon (DOC) pool. Bacterial abundance, bacterial production, concentrations of DOC, total dissolved amino acids (TDAA), and total dissolved neutral sugars (TDNS) were monitored during the experiments. Bacterial production during the first few days was very high (20 to 35 μg C liter(-1) day(-1)), accounting for 40 to 70% of primary production. The total bacterial production accounted for 34 to 55% of the DOC loss during the experiment, indicating high bacterial activities in Lake Kasumigaura. The DOC degradation was only 12 to 15%, whereas the degradation of TDAA and TDNS ranged from 30 to 50%, suggesting the preferential usage of TDAA and TDNS. The contribution of bacterially derived carbon to a DOC pool in Lake Kasumigaura was estimated using d-amino acids as bacterial biomarkers and accounted for 30 to 50% of the lake DOC. These values were much higher than those estimated for the open ocean (20 to 30%). The ratio of bacterially derived carbon to bulk carbon increased slightly with time, suggesting that the bacterially derived carbon is more resistant to microbial degradation than bulk carbon. This is the first study to estimate the bacterial contribution to a DOC pool in freshwater environments. These results indicate that bacteria play even more important roles in carbon cycles in freshwater environments than in open oceans and also suggests that recent increases in recalcitrant DOC in various lakes could be attributed to bacterially derived carbon. The potential differences in bacterial contributions to dissolved organic matter (DOM) between freshwater and marine environments are discussed.

  17. Seizures Complicating Bacterial Meningitis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap


    Full Text Available The clinical data of 116 patients, 1 month to <5 years of age, admitted for bacterial meningitis, and grouped according to those with and without seizures during hospitalization, were compared in a study at Buddhist Dalin Tzu Chi General Hospital, Chang Gung Memorial Hospital and other centers in Taiwan.

  18. Diversity of cyanobacterial biomarker genes from the stromatolites of Shark Bay, Western Australia. (United States)

    Garby, Tamsyn J; Walter, Malcolm R; Larkum, Anthony W D; Neilan, Brett A


    Families of closely related chemical compounds, which are relatively resistant to degradation, are often used as biomarkers to help trace the evolutionary history of early groups of organisms and the environments in which they lived. Biomarkers derived from hopanoid variations are particularly useful in determining bacterial community compositions. 2-Methylhopananoids have been thought to be diagnostic for cyanobacteria, and 2-methylhopanes in the geological record are taken as evidence for the presence of cyanobacteria-containing communities at the time of sediment deposition. Recently, however, doubt has been cast on the validity of 2-methylhopanes as cyanobacterial biomarkers, since non-cyanobacterial species have been shown to produce significant amounts of 2-methylhopanoids. This study examines the diversity of hpnP, the hopanoid biosynthesis gene coding for the enzyme that methylates hopanoids at the C2 position. Genomic DNA isolated from stromatolite-associated pustular and smooth microbial mat samples from Shark Bay, Western Australia, was analysed for bacterial diversity, and used to construct an hpnP clone library. A total of 117 partial hpnP clones were sequenced, representing 12 operational taxonomic units (OTUs). Phylogenetic analysis showed that 11 of these OTUs, representing 115 sequences, cluster within the cyanobacterial clade. We conclude that the dominant types of microorganisms with the detected capability of producing 2-methylhopanoids within pustular and smooth microbial mats in Shark Bay are cyanobacteria.

  19. Biomarkers in Parkinson's disease (recent update). (United States)

    Sharma, Sushil; Moon, Carolyn Seungyoun; Khogali, Azza; Haidous, Ali; Chabenne, Anthony; Ojo, Comfort; Jelebinkov, Miriana; Kurdi, Yousef; Ebadi, Manuchair


    Parkinson's disease (PD) is the second most common neurodegenerative disorder mostly affecting the aging population over sixty. Cardinal symptoms including, tremors, muscle rigidity, drooping posture, drooling, walking difficulty, and autonomic symptoms appear when a significant number of nigrostriatal dopaminergic neurons are already destroyed. Hence we need early, sensitive, specific, and economical peripheral and/or central biomarker(s) for the differential diagnosis, prognosis, and treatment of PD. These can be classified as clinical, biochemical, genetic, proteomic, and neuroimaging biomarkers. Novel discoveries of genetic as well as nongenetic biomarkers may be utilized for the personalized treatment of PD during preclinical (premotor) and clinical (motor) stages. Premotor biomarkers including hyper-echogenicity of substantia nigra, olfactory and autonomic dysfunction, depression, hyposmia, deafness, REM sleep disorder, and impulsive behavior may be noticed during preclinical stage. Neuroimaging biomarkers (PET, SPECT, MRI), and neuropsychological deficits can facilitate differential diagnosis. Single-cell profiling of dopaminergic neurons has identified pyridoxal kinase and lysosomal ATPase as biomarker genes for PD prognosis. Promising biomarkers include: fluid biomarkers, neuromelanin antibodies, pathological forms of α-Syn, DJ-1, amyloid β and tau in the CSF, patterns of gene expression, metabolomics, urate, as well as protein profiling in the blood and CSF samples. Reduced brain regional N-acetyl-aspartate is a biomarker for the in vivo assessment of neuronal loss using magnetic resonance spectroscopy and T2 relaxation time with MRI. To confirm PD diagnosis, the PET biomarkers include [(18)F]-DOPA for estimating dopaminergic neurotransmission, [(18)F]dG for mitochondrial bioenergetics, [(18)F]BMS for mitochondrial complex-1, [(11)C](R)-PK11195 for microglial activation, SPECT imaging with (123)Iflupane and βCIT for dopamine transporter, and urinary

  20. Dissecting the Syndrome of Schizophrenia: Progress toward Clinically Useful Biomarkers

    Directory of Open Access Journals (Sweden)

    Brian Dean


    Full Text Available The search for clinically useful biomarkers has been one of the holy grails of schizophrenia research. This paper will outline the evolving notion of biomarkers and then outline outcomes from a variety of biomarkers discovery strategies. In particular, the impact of high-throughput screening technologies on biomarker discovery will be highlighted and how new or improved technologies may allow the discovery of either diagnostic biomarkers for schizophrenia or biomarkers that will be useful in determining appropriate treatments for people with the disorder. History tells those involved in biomarker research that the discovery and validation of useful biomarkers is a long process and current progress must always be viewed in that light. However, the approval of the first biomarker screen with some value in predicting responsiveness to antipsychotic drugs suggests that biomarkers can be identified and that these biomarkers that will be useful in diagnosing and treating people with schizophrenia.

  1. Dissecting the Syndrome of Schizophrenia: Progress toward Clinically Useful Biomarkers. (United States)

    Dean, Brian


    The search for clinically useful biomarkers has been one of the holy grails of schizophrenia research. This paper will outline the evolving notion of biomarkers and then outline outcomes from a variety of biomarkers discovery strategies. In particular, the impact of high-throughput screening technologies on biomarker discovery will be highlighted and how new or improved technologies may allow the discovery of either diagnostic biomarkers for schizophrenia or biomarkers that will be useful in determining appropriate treatments for people with the disorder. History tells those involved in biomarker research that the discovery and validation of useful biomarkers is a long process and current progress must always be viewed in that light. However, the approval of the first biomarker screen with some value in predicting responsiveness to antipsychotic drugs suggests that biomarkers can be identified and that these biomarkers that will be useful in diagnosing and treating people with schizophrenia.

  2. Biomarkers in canine parvovirus enteritis. (United States)

    Schoeman, J P; Goddard, A; Leisewitz, A L


    Canine parvovirus (CPV) enteritis has, since its emergence in 1978, remained a common and important cause of morbidity and mortality in young dogs. The continued incidence of parvoviral enteritis is partly due to the virus' capability to evolve into more virulent and resistant variants with significant local gastrointestinal and systemic inflammatory sequelae. This paper reviews current knowledge on historical-, signalment-, and clinical factors as well as several haematological-, biochemical- and endocrine parameters that can be used as diagnostic and prognostic biomarkers in CPV enteritis. These factors include season of presentation, purebred nature, bodyweight, vomiting, leukopaenia, lymphopaenia, thrombocytopaenia, hypercoagulability, hypercortisolaemia, hypothyroxinaemia, hypoalbuminaemia, elevated C-reactive protein and tumour necrosis factor, hypocholesterolaemia and hypocitrullinaemia. Factors contributing to the manifestations of CPV infection are multiple with elements of host, pathogen, secondary infections, underlying stressors and environment affecting severity and outcome. The availability of several prognosticators has made identification of patients at high risk of death and their subsequent targeted management more rewarding.

  3. Biomarkers in chronic adult hydrocephalus

    Directory of Open Access Journals (Sweden)

    Kitchen Neil D


    Full Text Available Abstract Awareness of the importance of chronic adult hydrocephalus has been raised again with the recent emergence of epidemiological studies. It is estimated that between 5 and 10% of patients suffering from dementia might, in fact, have chronic hydrocephalus. Although, surgical diversion of the cerebrospinal fluid (CSF represents the only known procedure able to treat the symptoms of this condition, the selection of surgical patients has always been problematic. In the last 40 years, we have become wiser in using appropriate diagnostic tests for the selection of these patients; however, the area of biological markers has so far been overlooked in this condition, in contrast to that for other neurodegenerative disorders and dementias. Biomarkers are biological substances that may be used to indicate either the onset or the presence, and the progression of a clinical condition, being closely linked to its pathophysiology. In such a setting they might assist in the more appropriate selection of patients for shunt surgery. In this article, we have reviewed research carried out in the last 25 years regarding the identification of serum and CSF biomarkers for chronic hydrocephalus, discussed the potential for each one, and finally discussed the limitations for use, as well as future directions and possibilities in this field. It is concluded that tumour-necrosis factor, tau protein, lactate, sulfatide and neurofilament triple protein are the most promising CSF markers for chronic hydrocephalus. At present however, none of these meet the criteria required to justify a change clinical practice. In the future, collaborative multi-centre projects will be needed to obtain more substantial data that overcome the problems that arise from small individual and uncoordinated studies.

  4. Predicting Clinical Outcomes Using Molecular Biomarkers. (United States)

    Burke, Harry B


    Over the past 20 years, there has been an exponential increase in the number of biomarkers. At the last count, there were 768,259 papers indexed in directly related to biomarkers. Although many of these papers claim to report clinically useful molecular biomarkers, embarrassingly few are currently in clinical use. It is suggested that a failure to properly understand, clinically assess, and utilize molecular biomarkers has prevented their widespread adoption in treatment, in comparative benefit analyses, and their integration into individualized patient outcome predictions for clinical decision-making and therapy. A straightforward, general approach to understanding how to predict clinical outcomes using risk, diagnostic, and prognostic molecular biomarkers is presented. In the future, molecular biomarkers will drive advances in risk, diagnosis, and prognosis, they will be the targets of powerful molecular therapies, and they will individualize and optimize therapy. Furthermore, clinical predictions based on molecular biomarkers will be displayed on the clinician's screen during the physician-patient interaction, they will be an integral part of physician-patient-shared decision-making, and they will improve clinical care and patient outcomes.

  5. Delivery of High-Quality Biomarker Assays

    Directory of Open Access Journals (Sweden)

    Brian N. Swanson


    Full Text Available Biomarker measurements now support key decisions throughout the drug development process, from lead optimization to regulatory approvals. They are essential for documenting exposure-response relationships, specificity and potency toward the molecular target, untoward effects, and therapeutic applications. In a broader sense, biomarkers constitute the basis of clinical pathology and laboratory medicine. The utility of biomarkers is limited by their specificity and sensitivity toward the drug or disease process and by their overall variability. Understanding and controlling sources of variability is not only imperative for delivering high-quality assay results, but ultimately for controlling the size and expense of research studies. Variability in biomarker measurements is affected by: biological and environmental factors (e.g., gender, age, posture, diet and biorhythms, sample collection factors (e.g., preservatives, transport and storage conditions, and collection technique, and analytical factors (e.g., purity of reference material, pipetting precision, and antibody specificity. The quality standards for biomarker assays used in support of nonclinical safety studies fall under GLP (FDA regulations, whereas, those assays used to support human diagnostics and healthcare are established by CLIA (CMS regulations and accrediting organizations such as the College of American Pathologists. While most research applications of biomarkers are not regulated, biomarker laboratories in all settings are adopting similar laboratory practices in order to deliver high-quality data. Because of the escalation in demand for biomarker measurements, the highly-parallel (multi-plexed assay platforms that have fueled the rise of genomics will likely evolve into the analytical engines that drive the biomarker laboratories of tomorrow.

  6. Biomarkers in DILI: one more step forward

    Directory of Open Access Journals (Sweden)

    Mercedes Robles-Díaz


    Full Text Available Despite being relatively rare, drug-induced liver injury (DILI is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in omics technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (for example metabolites, proteins or DNA simultaneously enables the identification of ‘toxicity signatures’, which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review we summarize recent advances in the area of DILI biomarker studies.

  7. Biomarkers in Alzheimer's Disease-Recent Update. (United States)

    Sharma, Sushil; Lipincott, Walter


    Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized by loss of memory and cognitive function. It is the common cause of dementia in elderly and is a global health concern as the population of people aged 85 and older, is growing alarmingly. Although pharmacotherapy for the treatment of AD has improved, lot of work remains to treat this devastating disease. AD pathology begins even before the onset of clinical symptoms. Because therapies could be more effective if implemented early in the disease progression, it is highly prudent to discover reliable biomarkers, to detect its exact pathophysiology during pre-symptomatic stage. Biomarker(s) with high sensitivity and specificity would facilitate AD diagnosis at early stages. Currently, CSF amyloid β 1-42, total tau, and phosphorylated tau181 are used as AD biomarkers. This report describes conventional and potential in-vitro and in-vivo biomarkers of AD. Particularly, in-vitro transcriptomic, proteomic, lipidomic, and metabolomic; body fluid biomarkers (C-reactive proteins, homocysteine, α-sunuclein index, and dehydroepiandrosterone sulphate) from blood, serum, plasma, CSF, and saliva; and neuronal, platelets, and lymphocyte microRNA, mtDNA, and Charnoly body are detected. In-vivo physiological and neurobehavioral biomarkers are evaluated by analyzing computerized EEG, event-related potentials, circadian rhythm, and multimodality fusion imaging including: CT, MRI, SPECT, and PET. More specifically, PET imaging biomarkers representing reduced fronto-temporal 18FdG uptake, increased 11C or 18F-PIB uptake, 11C-PBR28 to measure 18 kDa translocator protein (TSPO), a biomarker for inflammation; and 3-D MRI (ventriculomegaly)/MRS are performed for early and effective clinical management of AD.

  8. Biomarkers in DILI: One More Step Forward (United States)

    Robles-Díaz, Mercedes; Medina-Caliz, Inmaculada; Stephens, Camilla; Andrade, Raúl J.; Lucena, M. Isabel


    Despite being relatively rare, drug-induced liver injury (DILI) is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings, and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis, and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in “omics” technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (e.g., metabolites, proteins, or DNA) simultaneously enables the identification of ‘toxicity signatures,’ which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review, we summarize recent advances in the area of DILI biomarker studies. PMID:27597831

  9. Methane seepage intensities traced by biomarker patterns in authigenic carbonates from the South China Sea (United States)

    Guan, H.; Feng, D.


    Authigenic carbonate rocks from an active seep (Site F) at 1120 m water depth of the South China Sea (SCS) were studied using mineralogical and lipid biomarker analyses. Carbonate mineral compositions, in specific samples, were predominantly aragonite, high-Mg calcite (HMC), or a mixture of both. Abundant 13C-depleted lipid biomarkers (various isoprenoids) diagnostic for archaea provide evidence that anaerobic oxidation of methane (AOM) mediated by anaerobic methane oxidizing archaea (ANME) and their bacterial partners is the major process leading to formation of the carbonates. Nearly a pure suite of AOM biomarkers was preserved in aragonitic carbonate in which predominant consortia were most likely ANME-2/Desulfosarcina & Desulfococcus (DSS) assemblages and a mixture of ANME-2/DSS and ANME-1/DSS consortia in the mixed mineral sample, the predominant consortia are in good accordance with the point that the relative higher methane seepage intensity favors the precipitation of aragonite over HMC. In contrast, the completely different biomarker patterns in HMC sample were mainly composed terrestrial organic matter and marine Thaumarchaea, which most likely originally within sediments accompanied with high organic matter input and low methane supply. This environment is known to be favored for archaea of ANME-1 and precipitation of HMC. High concentrations of 13C-depleted hopanoids, including diplopterol, hopanoic acids and hopanols were observed in the aragonite sample that may be sourced by the intermittent presence of oxic conditions in an overall anoxic condition, which was possibly induced by changing seepage intensities.

  10. Cardiac Biomarkers and Cycling Race

    Directory of Open Access Journals (Sweden)

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier


    Full Text Available In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011, but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac biomarkers: creatin kinase (CK, creating kinase midbrain (CK-MB, myoglobin (MYO, highly sensitive troponin T (hs-TnT and N-terminal brain natriuretic peptide (NT-proBNP. The population studied was a group of young trained cyclists participating in a 177-km cycling race. The group of individuals was selected for maximal homogeneity. Their annual training volume was between 10,000 and 16,000 kilometers. The rhythm of races is comparable and averages 35 km/h, depending on the race’s difficulty. The cardiac frequency was recorded via a heart rate monitor. Three blood tests were taken. The first blood test, T0, was taken approximately 2 hours before the start of the race and was intended to gather values which would act as references for the following tests. The second blood test, T1, was realized within 5 minutes of their arrival. The third and final blood test, T3, was taken 3 hours following their arrival. The CK, CK-MB, MYO, hs-TnT and NT-proBNP were measured on the Roche Diagnostic modular E (Manhein, Germany. For the statistical analysis, an ANOVA and post hoc test of Scheffé were calculated with the Statistica Software version 9.1. We noticed an important significant variation in the cardiac frequency between T0 and T1 (p < 0.0001, T0 and T3 (p < 0.0001, and T1 and T3 (p < 0.01. Table 1 shows the results obtained for the different biomarkers. CK and CK-MB showed significant variation between T0-T1 and T0-T3 (p < 0.0001. Myoglobin increased significantly

  11. Biomarkers of oxidative stress in antioxidant therapy

    Directory of Open Access Journals (Sweden)

    Wilfredo Mañon Rossi


    Full Text Available Biomarkers are used regularly in medical practice to provide objective markers of health status of a person, as well as the physiological response of the body to a pharmacological therapeutic intervention. In the specific case of the use of antioxidant products (antioxidant therapy, it is necessary to measure both biomarkers of oxidative stress level of the person as those that are specific to a physiological or pathological progression of a disease disorder. This paper describes the main biomarkers of oxidative general and specific stress as well as laboratory techniques, which should be taken into account when measuring the effectiveness of antioxidant therapies.

  12. Ready for Prime Time? Biomarkers in Sepsis. (United States)

    Long, Brit; Koyfman, Alex


    Sepsis is a common condition managed in the emergency department. Current diagnosis relies on physiologic criteria and suspicion of a source of infection using history, physical examination, laboratory studies, and imaging studies. The infection triggers a host response with the aim to destroy the pathogen, and this response can be measured. A reliable biomarker for sepsis should assist with earlier diagnosis, improve risk stratification, or improve clinical decision making. Current biomarkers for sepsis include lactate, troponin, and procalcitonin. This article discusses the use of lactate, procalcitonin, troponin, and novel biomarkers for use in sepsis.

  13. Toward Multiplexing Detection of Wound Healing Biomarkers on Porous Silicon Resonant Microcavities (United States)

    Krismastuti, Fransiska Sri Herwahyu; Cavallaro, Alex; Prieto‐Simon, Beatriz


    Bacterial wound infections can cause septicemia and lead to limb amputation or death. Therefore, early detection of bacteria is important in chronic wound management. Here, an optical biosensor based on porous silicon resonant microcavity (pSiRM) structure modified with fluorogenic peptide substrate is demonstrated to detect the presence of Sortase A (SrtA), a bacterial enzyme found in the cell membrane protein of Staphylococcus aureus. The combination of fluorescence enhancement effects of the pSiRM architecture with the incorporation of SrtA fluorogenic peptide substrate within the pSi matrix enables the sensing of SrtA with an outstanding limit of detection of 8 × 10−14 m. Modification of the pSiRM structure with microscale spots of two fluorogenic peptide substrates, one specific for SrtA and the other for matrix metalloproteinases, effectively demonstrates the feasibility to perform multiplexed biomarker analysis. The results in this study highlight the potential of the pSiRM sensing platform as a point‐of‐care diagnostic tool for biomarkers of bacterial wound infection.

  14. Cooperative Bacterial Foraging Optimization

    Directory of Open Access Journals (Sweden)

    Hanning Chen


    Full Text Available Bacterial Foraging Optimization (BFO is a novel optimization algorithm based on the social foraging behavior of E. coli bacteria. This paper presents a variation on the original BFO algorithm, namely, the Cooperative Bacterial Foraging Optimization (CBFO, which significantly improve the original BFO in solving complex optimization problems. This significant improvement is achieved by applying two cooperative approaches to the original BFO, namely, the serial heterogeneous cooperation on the implicit space decomposition level and the serial heterogeneous cooperation on the hybrid space decomposition level. The experiments compare the performance of two CBFO variants with the original BFO, the standard PSO and a real-coded GA on four widely used benchmark functions. The new method shows a marked improvement in performance over the original BFO and appears to be comparable with the PSO and GA.

  15. Bacterial Colony Optimization

    Directory of Open Access Journals (Sweden)

    Ben Niu


    Full Text Available This paper investigates the behaviors at different developmental stages in Escherichia coli (E. coli lifecycle and developing a new biologically inspired optimization algorithm named bacterial colony optimization (BCO. BCO is based on a lifecycle model that simulates some typical behaviors of E. coli bacteria during their whole lifecycle, including chemotaxis, communication, elimination, reproduction, and migration. A newly created chemotaxis strategy combined with communication mechanism is developed to simplify the bacterial optimization, which is spread over the whole optimization process. However, the other behaviors such as elimination, reproduction, and migration are implemented only when the given conditions are satisfied. Two types of interactive communication schemas: individuals exchange schema and group exchange schema are designed to improve the optimization efficiency. In the simulation studies, a set of 12 benchmark functions belonging to three classes (unimodal, multimodal, and rotated problems are performed, and the performances of the proposed algorithms are compared with five recent evolutionary algorithms to demonstrate the superiority of BCO.

  16. Bacterial assays for recombinagens. (United States)

    Hoffmann, G R


    Two principal strategies have been used for studying recombinagenic effects of chemicals and radiation in bacteria: (1) measurement of homologous recombination involving defined alleles in a partially diploid strain, and (2) measurement of the formation and loss of genetic duplications in the bacterial chromosome. In the former category, most methods involve one allele in the bacterial chromosome and another in a plasmid, but it is also possible to detect recombination between two chromosomal alleles or between two extrachromosomal alleles. This review summarizes methods that use each of these approaches for detecting recombination and tabulates data on agents that have been found to be recombinagenic in bacteria. The assays are discussed with respect to their effectiveness in testing for recombinagens and their potential for elucidating mechanisms underlying recombinagenic effects.

  17. Bacterial transformation of terpenoids (United States)

    Grishko, V. V.; Nogovitsina, Y. M.; Ivshina, I. B.


    Data on the bacterial transformation of terpenoids published in the literature in the past decade are analyzed. Possible pathways for chemo-, regio- and stereoselective modifications of terpenoids are discussed. Considerable attention is given to new technological approaches to the synthesis of terpenoid derivatives suitable for the use in the perfume and food industry and promising as drugs and chiral intermediates for fine organic synthesis. The bibliography includes 246 references.

  18. Spontaneous bacterial peritonitis


    Al Amri Saleh


    Spontaneous bacterial peritonitis (SBP) is an infection of the ascitic fluid without obvious intra-abdominal source of sepsis; usually complicates advanced liver disease. The pathogenesis of the disease is multifactorial: low ascitic protein-content, which reflects defi-cient ascitic fluid complement and hence, reduced opsonic activity is thought to be the most important pathogenic factor. Frequent and prolonged bacteremia has been considered as another pertinent cause of SBP. This disease is...

  19. Modelling bacterial speciation



    A central problem in understanding bacterial speciation is how clusters of closely related strains emerge and persist in the face of recombination. We use a neutral Fisher–Wright model in which genotypes, defined by the alleles at 140 house-keeping loci, change in each generation by mutation or recombination, and examine conditions in which an initially uniform population gives rise to resolved clusters. Where recombination occurs at equal frequency between all members of the population, we o...

  20. Markers of bacterial translocation in end-stage liver disease

    Institute of Scientific and Technical Information of China (English)

    Ioannis; Koutsounas; Garyfallia; Kaltsa; Spyros; I; Siakavellas; Giorgos; Bamias


    Bacterial translocation(BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence.BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT.

  1. Adaptive Bacterial Foraging Optimization

    Directory of Open Access Journals (Sweden)

    Hanning Chen


    Full Text Available Bacterial Foraging Optimization (BFO is a recently developed nature-inspired optimization algorithm, which is based on the foraging behavior of E. coli bacteria. Up to now, BFO has been applied successfully to some engineering problems due to its simplicity and ease of implementation. However, BFO possesses a poor convergence behavior over complex optimization problems as compared to other nature-inspired optimization techniques. This paper first analyzes how the run-length unit parameter of BFO controls the exploration of the whole search space and the exploitation of the promising areas. Then it presents a variation on the original BFO, called the adaptive bacterial foraging optimization (ABFO, employing the adaptive foraging strategies to improve the performance of the original BFO. This improvement is achieved by enabling the bacterial foraging algorithm to adjust the run-length unit parameter dynamically during algorithm execution in order to balance the exploration/exploitation tradeoff. The experiments compare the performance of two versions of ABFO with the original BFO, the standard particle swarm optimization (PSO and a real-coded genetic algorithm (GA on four widely-used benchmark functions. The proposed ABFO shows a marked improvement in performance over the original BFO and appears to be comparable with the PSO and GA.

  2. Neglected bacterial zoonoses. (United States)

    Chikeka, I; Dumler, J S


    Bacterial zoonoses comprise a group of diseases in humans or animals acquired by direct contact with or by oral consumption of contaminated animal materials, or via arthropod vectors. Among neglected infections, bacterial zoonoses are among the most neglected given emerging data on incidence and prevalence as causes of acute febrile illness, even in areas where recognized neglected tropical diseases occur frequently. Although many other bacterial infections could also be considered in this neglected category, five distinct infections stand out because they are globally distributed, are acute febrile diseases, have high rates of morbidity and case fatality, and are reported as commonly as malaria, typhoid or dengue virus infections in carefully designed studies in which broad-spectrum diagnoses are actively sought. This review will focus attention on leptospirosis, relapsing fever borreliosis and rickettsioses, including scrub typhus, murine typhus and spotted fever group rickettsiosis. Of greatest interest is the lack of distinguishing clinical features among these infections when in humans, which confounds diagnosis where laboratory confirmation is lacking, and in regions where clinical diagnosis is often attributed to one of several perceived more common threats. As diseases such as malaria come under improved control, the real impact of these common and under-recognized infections will become evident, as will the requirement for the strategies and allocation of resources for their control.

  3. Quantitative imaging as cancer biomarker (United States)

    Mankoff, David A.


    The ability to assay tumor biologic features and the impact of drugs on tumor biology is fundamental to drug development. Advances in our ability to measure genomics, gene expression, protein expression, and cellular biology have led to a host of new targets for anticancer drug therapy. In translating new drugs into clinical trials and clinical practice, these same assays serve to identify patients most likely to benefit from specific anticancer treatments. As cancer therapy becomes more individualized and targeted, there is an increasing need to characterize tumors and identify therapeutic targets to select therapy most likely to be successful in treating the individual patient's cancer. Thus far assays to identify cancer therapeutic targets or anticancer drug pharmacodynamics have been based upon in vitro assay of tissue or blood samples. Advances in molecular imaging, particularly PET, have led to the ability to perform quantitative non-invasive molecular assays. Imaging has traditionally relied on structural and anatomic features to detect cancer and determine its extent. More recently, imaging has expanded to include the ability to image regional biochemistry and molecular biology, often termed molecular imaging. Molecular imaging can be considered an in vivo assay technique, capable of measuring regional tumor biology without perturbing it. This makes molecular imaging a unique tool for cancer drug development, complementary to traditional assay methods, and a potentially powerful method for guiding targeted therapy in clinical trials and clinical practice. The ability to quantify, in absolute measures, regional in vivo biologic parameters strongly supports the use of molecular imaging as a tool to guide therapy. This review summarizes current and future applications of quantitative molecular imaging as a biomarker for cancer therapy, including the use of imaging to (1) identify patients whose tumors express a specific therapeutic target; (2) determine

  4. Development of biomarkers for Huntington's disease. (United States)

    Weir, David W; Sturrock, Aaron; Leavitt, Blair R


    Huntington's disease is an autosomal dominant, progressive neurodegenerative disorder, for which there is no disease-modifying treatment. By use of predictive genetic testing, it is possible to identify individuals who carry the gene defect before the onset of symptoms, providing a window of opportunity for intervention aimed at preventing or delaying disease onset. However, without robust and practical measures of disease progression (ie, biomarkers), the efficacy of therapeutic interventions in this premanifest Huntington's disease population cannot be readily assessed. Current progress in the development of biomarkers might enable evaluation of disease progression in individuals at the premanifest stage of the disease; these biomarkers could be useful in defining endpoints in clinical trials in this population. Clinical, cognitive, neuroimaging, and biochemical biomarkers are being investigated for their potential in clinical use and their value in the development of future treatments for patients with Huntington's disease.

  5. Statistical design and evaluation of biomarker studies. (United States)

    Dobbin, Kevin K


    We review biostatistical aspects of biomarker studies, including design and analysis issues, covering the range of settings required for translational research-from early exploratory studies through clinical trials.

  6. Biomarker monitoring in sports doping control. (United States)

    Pottgiesser, Torben; Schumacher, Yorck Olaf


    Biomarker monitoring can be considered a new era in the effort against doping. Opposed to the old concept in doping control of direct detection of a prohibited substance in a biological sample such as urine or blood, the new paradigm allows a personalized longitudinal monitoring of biomarkers that indicate non-physiological responses independently of the used doping technique or substance, and may cause sanctioning of illicit practices. This review presents the development of biomarker monitoring in sports doping control and focuses on the implementation of the Athlete Biological Passport as the current concept of the World Anti Doping Agency for the detection of blood doping (hematological module). The scope of the article extends to the description of novel biomarkers and future concepts of application.

  7. The development and applications of biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Normandy, J.; Peeters, J. [eds.


    This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community.

  8. Early-Phase Studies of Biomarkers

    DEFF Research Database (Denmark)

    Pepe, Margaret S.; Janes, Holly; Li, Christopher I.;


    BACKGROUND: Many cancer biomarker research studies seek to develop markers that can accurately detect or predict future onset of disease. To design and evaluate these studies, one must specify the levels of accuracy sought. However, justified target levels are rarely available. METHODS: We describe...... a way to calculate target levels of sensitivity and specificity for a biomarker intended to be applied in a defined clinical context. The calculation requires knowledge of the prevalence or incidence of cases in the clinical population and the ratio of benefit associated with the clinical consequences...... of a positive biomarker test in cases (true positive) to cost associated with a positive biomarker test in controls (false positive). Guidance is offered on soliciting the cost/benefit ratio. The calculations are based on the longstanding decision theory concept of providing a net benefit on average...

  9. Cardiorenal biomarkers in acute heart failure

    Institute of Scientific and Technical Information of China (English)

    Rajiv Choudhary; Dipika Gopal; Ben A. Kipper; Alejandro De La Parra Landa; Hermineh Aramin


    Managing patients with heart failure (HF) is a challenging task within itself, but the presence of associated worsening renal function can greatly increase mortality and morbidity. Early diagnosis and treatment is the key to prevent re-hospitalizations and reduce healthcare costs. Biomarkers have long been established as highly sensitive and specific tools in diagnosing and prognosticating patients with HF. Reflecting distinct pathophysiological events and ongoing cellular insult, biomarkers have been proven superior to conventional laboratory tests. Availability of better assays and rapid analysis has allowed the use of biomarkers as point-of-care tests in the emergency department and at the patient's bed-side. Acute HF patients often go on to develop worsening renal function, termed as acute cardiorenal syndrome. The growing breadth of studies has shown the implications of combining multiple biomarkers to better chart outcomes and produce desirable results in such patients.

  10. Clinical Relevance of Biomarkers of Oxidative Stress

    DEFF Research Database (Denmark)

    Frijhoff, Jeroen; Winyard, Paul G; Zarkovic, Neven;


    SIGNIFICANCE: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino...... acids. RECENT ADVANCES: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES: The literature is very heterogeneous....... It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured...

  11. Carbon sources in the Beaufort Sea revealed by molecular lipid biomarkers and compound specific isotope analysis (United States)

    Tolosa, I.; Fiorini, S.; Gasser, B.; Martín, J.; Miquel, J. C.


    Molecular lipid biomarkers (hydrocarbons, alcohols, sterols and fatty acids) and compound specific isotope analysis of suspended particulate organic matter (SPM) and surface sediments of the Mackenzie Shelf and slope (Southeast Beaufort Sea, Arctic Ocean), were studied in summer 2009. The concentrations of the molecular lipid markers, characteristic of known organic matter sources, were grouped and used as proxies to evaluate the relative importance of fresh algal, detrital algal, fossil, C3 terrestrial plants, bacterial and zooplankton material in the sedimentary organic matter (OM). Fossil and detrital algal contributions were the major fractions of the freshwater SPM from the Mackenzie River with ~34% each of the total molecular biomarkers. Fresh algal, C3 terrestrial, bacterial and zooplanktonic components represented much lower percentages, 17, 10, 4 and 80%) with a minor contribution of fossil and C3 terrestrial biomarkers. Characterization of the sediments revealed a major sink of refractory algal material mixed with some fresh algal material, fossil hydrocarbons and a small input of C3 terrestrial sources. In particular, the sediments from the shelf and at the mouth of the Amundsen Gulf presented the highest contribution of detrital algal material (60-75%) whereas those from the slope contained the highest proportion of fossil (40%) and C3 terrestrial plant material (10%). Overall, considering that the detrital algal material is marine derived, autochthonous sources contributed more than allochthonous sources to the OM lipid pool. Using the ratio of an allochthonous biomarker (normalized to total organic carbon, TOC) found in the sediments to those measured at the river mouth water, we estimated that the fraction of terrestrial material preserved in the sediments accounted for 30-40% of the total carbon in the inner shelf sediments, 17% in the outer shelf and Amundsen Gulf and up to 25% in the slope sediments.

  12. Biomarkers in Multiple Sclerosis: Role of Antibodies


    Thomas Berger; Markus Reindl


    The first international workshop on “Biomarkers in Multiple Sclerosis” was organized by B. Bielekova, R. Hohlfeld, R. Martin and U. Utz from April 14–16, 2004, in Washington, DC. The workshop intended to discuss the current status and potential applicability of biological markers for the understanding of the pathogenesis, diagnosis, and therapy of multiple sclerosis. The present review summarizes the presentation on the potential role of antibodies as biomarkers for diagnosis, disease activit...

  13. Biomarkers in aquatic plants: selection and utility. (United States)

    Brain, Richard A; Cedergreen, Nina


    This review emphasizes the predictive ability, sensitivity and specificity of aquatic plant biomarkers as biomonitoring agents of exposure and effect. Biomarkers of exposure are those that provide functional measures of exposure that are characterized at a sub-organism level. Biomarkers of effect require causal linkages between the biomarker and effects, measured at higher levels of biological organization. With the exception of pathway specific metabolites, the biomarkers assessed in this review show variable sensitivity and predictive ability that is often confounded by variations in growth conditions, rendering them unsuitable as stand alone indicators of environmental stress. The use of gene expression for detecting pollution has been, and remains immature; this immaturity derives from inadequate knowledge on predictive ability, sensitivity and specificity. Moreover, the ability to the detect mode of action of unknown toxicants using gene expression is not as clear-cut as initially hypothesized. The principal patterns in gene expression is not as clear-cut as initially hypothesized. The principal patterns in gene expression are generally derived from stress induced genes, rather than on ones that respond to substances with known modes of action (Baerson et al. 2005). Future developments in multivariate statistics and chemometric methods that enhance pattern analyses in ways that could produce a "fingerprint", may improve methods for discovering modes of action of unknown toxicants. Pathway specific metabolites are unambiguous, sensitive, correlate well to growth effects, and are relatively unaffected by growth conditions. These traits make them excellent biomarkers under both field and laboratory conditions. Changes in metabolites precede visible growth effects; therefore, measuring changes in metabolite concentrations (Harring et al. 1998; Shaner et al. 2005). The metabolic phase I enzymes (primarily associated with P-450 activity) are non-specific biomarkers

  14. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael


    Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

  15. Blood biomarker for Parkinson disease: peptoids (United States)

    Yazdani, Umar; Zaman, Sayed; Hynan, Linda S; Brown, L Steven; Dewey, Richard B; Karp, David; German, Dwight C


    Parkinson disease (PD) is the second most common neurodegenerative disease. Because dopaminergic neuronal loss begins years before motor symptoms appear, a biomarker for the early identification of the disease is critical for the study of putative neuroprotective therapies. Brain imaging of the nigrostriatal dopamine system has been used as a biomarker for early disease along with cerebrospinal fluid analysis of α-synuclein, but a less costly and relatively non-invasive biomarker would be optimal. We sought to identify an antibody biomarker in the blood of PD patients using a combinatorial peptoid library approach. We examined serum samples from 75 PD patients, 25 de novo PD patients, and 104 normal control subjects in the NINDS Parkinson’s Disease Biomarker Program. We identified a peptoid, PD2, which binds significantly higher levels of IgG3 antibody in PD versus control subjects (P<0.0001) and is 68% accurate in identifying PD. The PD2 peptoid is 84% accurate in identifying de novo PD. Also, IgG3 levels are significantly higher in PD versus control serum (P<0.001). Finally, PD2 levels are positively correlated with the United Parkinson’s Disease Rating Scale score (r = 0.457, P<0001), a marker of disease severity. The PD2 peptoid may be useful for the early-stage identification of PD, and serve as an indicator of disease severity. Additional studies are needed to validate this PD biomarker. PMID:27812535

  16. Biomarker-based dissection of neurodegenerative diseases. (United States)

    Olsson, Bob; Zetterberg, Henrik; Hampel, Harald; Blennow, Kaj


    The diagnosis of neurodegenerative diseases within neurology and psychiatry are hampered by the difficulty in getting biopsies and thereby validating the diagnosis by pathological findings. Biomarkers for other types of disease have been readily adopted into the clinical practice where for instance troponins are standard tests when myocardial infarction is suspected. However, the use of biomarkers for neurodegeneration has not been fully incorporated into the clinical routine. With the development of cerebrospinal fluid (CSF) biomarkers that reflect pathological events within the central nervous system (CNS), important clinical diagnostic tools are becoming available. This review summarizes the most promising biomarker candidates that may be used to monitor different types of neurodegeneration and protein inclusions, as well as different types of metabolic changes, in living patients in relation to the clinical phenotype and disease progression over time. Our aim is to provide the reader with an updated lexicon on currently available biomarker candidates, how far they have come in development and how well they reflect pathogenic processes in different neurodegenerative diseases. Biomarkers for specific pathogenetic processes would also be valuable tools both to study disease pathogenesis directly in patients and to identify and monitor the effect of novel treatment strategies.

  17. The use of biomarkers in clinical osteoporosis. (United States)

    Cabral, Hebert Wilson Santos; Andolphi, Bruna Ferreira Galone; Ferreira, Brunna Vila Coutinho; Alves, Danielle Cristina Filgueira; Morelato, Renato Lírio; Chambo, Antônio; Borges, Lizânia Spinassé


    Osteoporosis is a disease of ascending character in the world population; in this context, bone biomarkers are being increasingly studied in order to aid in the diagnosis and monitoring of these patients. The main objective of this study was a literature review of articles whose main theme was the use of biomarkers for bone formation and degradation, and to evaluate their possible applicability in clinical practice. Literature review was performed through articles indexed and published in the last five years in the PubMed database. The findings of this study showed that most of the previously selected articles were published in the last two years, and the most cited markers were bone resorption, C-terminal collagen telopeptide (CTX), showing the highest correlation with the dynamics of bone, and the biomarker of bone formation, bone-specific alkaline phosphatase (BAP), which is increased in the event of fracture or may suggest another bone disease. There was an increase in published articles, associating different bone biomarkers and their clinical applicability, especially for treatment control. Our findings suggest that in recent years there has been significant increase in publications evaluating the use of bone turnover biomarkers for bone formation and resorption and their possible clinical applicability, especially in the monitoring of treatment. Still, we believe that further studies need to be conducted to confirm these findings, given the advantages that bone biomarkers can deliver in the clinical management of the disease.

  18. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health

    Directory of Open Access Journals (Sweden)

    Mariya Ivanova Petrova


    Full Text Available The human body is colonized by a vast number of microorganisms collectively referred to as the human microbiota. One of the main microbiota body sites is the female genital tract, commonly dominated by Lactobacillus spp., in approximately 70% of women. Each individual species can constitute approximately 99% of the ribotypes observed in any individual woman. The most frequently isolated species are Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii and Lactobacillus iners. Residing at the port of entry of bacterial and viral pathogens, the vaginal Lactobacillus species can create a barrier against pathogen invasion since mainly products of their metabolism secreted in the cervicovaginal fluid can play an important role in the inhibition of bacterial and viral infections. Therefore, a Lactobacillus-dominated microbiota appears to be a good biomarker for a healthy vaginal ecosystem. This balance can be rapidly altered during processes such as menstruation, sexual activity, pregnancy and various infections. An abnormal vaginal microbiota is characterized by an increased diversity of microbial species, leading to a condition known as bacterial vaginosis. Information on the vaginal microbiota can be gathered from the analysis of cervicovaginal fluid, by using the Nugent scoring or the Amsel’s criteria, or at the molecular level by investigating the number and type of Lactobacillus species. However, when translating this to the clinical setting, it should be noted that the absence of a Lactobacillus-dominated microbiota does not appear to directly imply a diseased condition or dysbiosis. Nevertheless, the widely documented beneficial role of vaginal Lactobacillus species demonstrates the potential of data on the composition and activity of lactobacilli as biomarkers for vaginal health. The substantiation and further validation of such biomarkers will allow the design of better targeted probiotic strategies.

  19. New serological biomarkers of inflammatory bowel disease. (United States)

    Li, Xuhang; Conklin, Laurie; Alex, Philip


    Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and characterization of new serological biomarkers (identified since 2007). These include five new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibodies against chemically synthesized (Sigma) two major oligomannose epitopes, Man alpha-1,3 Man alpha-1,2 Man (SigmaMan3) and Man alpha-1,3 Man alpha-1,2 Man alpha-1,2 Man (SigmaMan4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), ALCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-like receptors (TLR) 2 and 4, and beta-defensin-1. Furthermore, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCL16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and multiplex enzyme-linked immunosorbent assay (ELISA)'s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more

  20. Population-Sequencing as a Biomarker of Burkholderia mallei and Burkholderia pseudomallei Evolution through Microbial Forensic Analysis

    Directory of Open Access Journals (Sweden)

    John P. Jakupciak


    Full Text Available Large-scale genomics projects are identifying biomarkers to detect human disease. B. pseudomallei and B. mallei are two closely related select agents that cause melioidosis and glanders. Accurate characterization of metagenomic samples is dependent on accurate measurements of genetic variation between isolates with resolution down to strain level. Often single biomarker sensitivity is augmented by use of multiple or panels of biomarkers. In parallel with single biomarker validation, advances in DNA sequencing enable analysis of entire genomes in a single run: population-sequencing. Potentially, direct sequencing could be used to analyze an entire genome to serve as the biomarker for genome identification. However, genome variation and population diversity complicate use of direct sequencing, as well as differences caused by sample preparation protocols including sequencing artifacts and mistakes. As part of a Department of Homeland Security program in bacterial forensics, we examined how to implement whole genome sequencing (WGS analysis as a judicially defensible forensic method for attributing microbial sample relatedness; and also to determine the strengths and limitations of whole genome sequence analysis in a forensics context. Herein, we demonstrate use of sequencing to provide genetic characterization of populations: direct sequencing of populations.

  1. Biomarkers in the Molar Tooth (MT)-Bearing Limestones in the Jilin-Liaoning Area of China

    Institute of Scientific and Technical Information of China (English)

    旷红伟; 李艳霞; 曾艳涛; 孟祥化; 葛铭


    The origin of Molar Tooth(MT)carbonates has been argued for more than 100 years, which are a kind of Proterozoic carbonates especially composed of microsparite with ptygmatically folded and sheet-like structures. Biomarkers detected in the microcalcsparite from the Wanlong and Xingmincun formations in the Jilin-Liaoning area showed there are abundant normal alkanes, isoprenoids, hopanes, steranes, alkylmethylcyclohexanes, and alkylcyclohexanes, indicating a diversity of biological source: long-chain isoprenoids, the major components of chlorophyll, such as C-19, C-20, a kind of major biomarkers synthesized early by isoprenoid monomers; hopanes a type of characteristic biomarkers from prokaryote, such as archaebacteria and cyanobacteria; sterane a biomarker for eukaryote; and two kinds of alkanes with C-17, C-18 as the main peaks representing aquatic bacteria and with C-23, C-24 as the main peaks representing fungi, respectively. Biomarker analysis showed that MT is the result of bacterial and algal activities, which is a kind of organisms between aerobic and anaerobic bacteria, reproducing well in normal or slightly saline sea water under weak oxidation-reduction conditions, resulting in rapid deposition of calcite as microsparite due to some mechanisms.

  2. Bacterial chromosome segregation. (United States)

    Possoz, Christophe; Junier, Ivan; Espeli, Olivier


    Dividing cells have mechanisms to ensure that their genomes are faithfully segregated into daughter cells. In bacteria, the description of these mechanisms has been considerably improved in the recent years. This review focuses on the different aspects of bacterial chromosome segregation that can be understood thanks to the studies performed with model organisms: Escherichia coli, Bacillus subtilis, Caulobacter crescentus and Vibrio cholerae. We describe the global positionning of the nucleoid in the cell and the specific localization and dynamics of different chromosomal loci, kinetic and biophysic aspects of chromosome segregation are presented. Finally, a presentation of the key proteins involved in the chromosome segregation is made.

  3. Bacterial Degradation of Pesticides

    DEFF Research Database (Denmark)

    Knudsen, Berith Elkær

    This PhD project was carried out as part of the Microbial Remediation of Contaminated Soil and Water Resources (MIRESOWA) project, funded by the Danish Council for Strategic Research (grant number 2104-08-0012). The environment is contaminated with various xenobiotic compounds e.g. pesticides......D student, to construct fungal-bacterial consortia in order to potentially stimulate pesticide degradation thereby increasing the chance of successful bioaugmentation. The results of the project are reported in three article manuscripts, included in this thesis. In manuscript I, the mineralization of 2...

  4. Spontaneous bacterial peritonitis

    Directory of Open Access Journals (Sweden)

    Al Amri Saleh


    Full Text Available Spontaneous bacterial peritonitis (SBP is an infection of the ascitic fluid without obvious intra-abdominal source of sepsis; usually complicates advanced liver disease. The pathogenesis of the disease is multifactorial: low ascitic protein-content, which reflects defi-cient ascitic fluid complement and hence, reduced opsonic activity is thought to be the most important pathogenic factor. Frequent and prolonged bacteremia has been considered as another pertinent cause of SBP. This disease is associated with high mortality and recurrence. Therefore, orompt recognition and institution of therapy and plan of prophylaxis is vital.

  5. Bacterial mitotic machineries

    DEFF Research Database (Denmark)

    Gerdes, Kenn; Møller-Jensen, Jakob; Ebersbach, Gitte;


    Here, we review recent progress that yields fundamental new insight into the molecular mechanisms behind plasmid and chromosome segregation in prokaryotic cells. In particular, we describe how prokaryotic actin homologs form mitotic machineries that segregate DNA before cell division. Thus, the Par......M protein of plasmid R1 forms F actin-like filaments that separate and move plasmid DNA from mid-cell to the cell poles. Evidence from three different laboratories indicate that the morphogenetic MreB protein may be involved in segregation of the bacterial chromosome....

  6. Quantitative imaging biomarker ontology (QIBO) for knowledge representation of biomedical imaging biomarkers. (United States)

    Buckler, Andrew J; Liu, Tiffany Ting; Savig, Erica; Suzek, Baris E; Ouellette, M; Danagoulian, J; Wernsing, G; Rubin, Daniel L; Paik, David


    A widening array of novel imaging biomarkers is being developed using ever more powerful clinical and preclinical imaging modalities. These biomarkers have demonstrated effectiveness in quantifying biological processes as they occur in vivo and in the early prediction of therapeutic outcomes. However, quantitative imaging biomarker data and knowledge are not standardized, representing a critical barrier to accumulating medical knowledge based on quantitative imaging data. We use an ontology to represent, integrate, and harmonize heterogeneous knowledge across the domain of imaging biomarkers. This advances the goal of developing applications to (1) improve precision and recall of storage and retrieval of quantitative imaging-related data using standardized terminology; (2) streamline the discovery and development of novel imaging biomarkers by normalizing knowledge across heterogeneous resources; (3) effectively annotate imaging experiments thus aiding comprehension, re-use, and reproducibility; and (4) provide validation frameworks through rigorous specification as a basis for testable hypotheses and compliance tests. We have developed the Quantitative Imaging Biomarker Ontology (QIBO), which currently consists of 488 terms spanning the following upper classes: experimental subject, biological intervention, imaging agent, imaging instrument, image post-processing algorithm, biological target, indicated biology, and biomarker application. We have demonstrated that QIBO can be used to annotate imaging experiments with standardized terms in the ontology and to generate hypotheses for novel imaging biomarker-disease associations. Our results established the utility of QIBO in enabling integrated analysis of quantitative imaging data.

  7. Extremely high frequency electromagnetic radiation enforces bacterial effects of inhibitors and antibiotics. (United States)

    Tadevosyan, Hasmik; Kalantaryan, Vitaly; Trchounian, Armen


    The coherent electromagnetic radiation (EMR) of the frequency of 51.8 and 53 GHz with low intensity (the power flux density of 0.06 mW/cm(2)) affected the growth of Escherichia coli K12(lambda) under fermentation conditions: the lowering of the growth specific rate was considerably (approximately 2-fold) increased with exposure duration of 30-60 min; a significant decrease in the number of viable cells was also shown. Moreover, the enforced effects of the N,N'-dicyclohexylcarbodiimide (DCCD), inhibitor of H(+)-transporting F(0)F(1)-ATPase, on energy-dependent H(+) efflux by whole cells and of antibiotics like tetracycline and chloramphenicol on the following bacterial growth and survival were also determined after radiation. In addition, the lowering in DCCD-inhibited ATPase activity of membrane vesicles from exposed cells was defined. The results confirmed the input of membranous changes in bacterial action of low intensity extremely high frequency EMR, when the F(0)F(1)-ATPase is probably playing a key role. The radiation of bacteria might lead to changed metabolic pathways and to antibiotic resistance. It may also give bacteria with a specific role in biosphere.

  8. Biomarkers for osteoarthritis: investigation, identification, and prognosis

    Directory of Open Access Journals (Sweden)

    Zhai G


    Full Text Available Guangju Zhai,1,2 Erfan Aref Eshghi11Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada; 2Department of Twin Research and Genetic Epidemiology, King's College London, London, UKAbstract: Osteoarthritis (OA is the most common form of arthritis and results in substantial morbidity and disability in the elderly, imposing a great economic burden on society. While there are drugs available on the market that mitigate pain and improve function, there are no disease-modifying osteoarthritis drugs, partly because there is no reliable method that can be used to identify early OA changes. There is a pressing need to develop reliable biomarkers that can inform on the process of joint destruction in OA. Such biomarkers could aid in drug development by identifying fast progressors and detecting early response to therapy, thus reducing patient numbers and time required for clinical trials. Over the last several years, dramatic advances in our understanding of the biochemistry of cartilage have led to a cascade of studies testing proteins as biomarkers of OA. Investigation of single-nucleotide polymorphisms as genetic biomarkers and the application of technologies such as metabolomics to OA are generating potentially additional biomarkers that could help detect early OA changes. This review summarizes the data on the investigation of biochemical and genetic markers in OA and highlights the new biomarkers that are recently reported and their application and limitation in the management of OA. However, despite the dramatic growth of knowledge concerning the discovery of a number of useful biomarkers, the real breakthrough in this area is still not achieved.Keywords: osteoarthritis, biochemical markers, metabolomics, genetics, epigenetics

  9. Spontaneous bacterial peritonitis

    Institute of Scientific and Technical Information of China (English)

    Anastasios Koulaouzidis; Shivaram Bhat; Athar A Saeed


    Since its initial description in 1964, research has transformed spontaneous bacterial peritonitis (SBP) from a feared disease (with reported mortality of 90%) to a treatable complication of decompensated cirrhosis,albeit with steady prevalence and a high recurrence rate. Bacterial translocation, the key mechanism in the pathogenesis of SBP, is only possible because of the concurrent failure of defensive mechanisms in cirrhosis.Variants of SBP should be treated. Leucocyte esterase reagent strips have managed to shorten the 'tap-toshot' time, while future studies should look into their combined use with ascitic fluid pH. Third generation cephalosporins are the antibiotic of choice because they have a number of advantages. Renal dysfunction has been shown to be an independent predictor of mortality in patients with SBP. Albumin is felt to reduce the risk of renal impairment by improving effective intravascular volume, and by helping to bind proinflammatory molecules. Following a single episode of SBP, patients should have long-term antibiotic prophylaxis and be considered for liver transplantation.

  10. Antimicrobials for bacterial bioterrorism agents. (United States)

    Sarkar-Tyson, Mitali; Atkins, Helen S


    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future.

  11. New serological biomarkers of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Xuhang Li; Laurie Conldin; Philip Alex


    Serological biomarkers in inflammatory bowel disease(IBD)are a rapidty expanding list of non-invasive tests for objective assessments of disease activity,early diagnosis,prognosis evaluation and surveillance.This review summarizes both old and new biomarkers in IBD,but focuses on the development and characterization of new serological iomarkers(identified since 2007).These include five new anti-glycan antibodies,anti-chitobioside IgA(ACCA),anti-laminaribioside IgG(ALCA),anti-manobioside IgG(AMCA),and antibodies against chemically synthesized(∑)two major oligomannose epitopes,Man α-1,3 Man α-1,2 Man(∑Man3)and Man α-1,3 Man α-1,2 Man α-1,2 Man(∑Man4).These new biomarkers erve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease(CD),ulcerative colitis(UC),normal and other non-IBD gut diseases,but also in predicting disease involvement(ileum vs colon),IBD risk(as subclinical biomarkers),and disease course(risk of complication and surgery).Interestingly,the prevalence of he antiglycan antibodies,including anti-Saccharomyces cerevisiae antibodies(ASCA),ALCA and AMCA,was found to be associated with single nucleotide polymorphisms(SNPs)of IBD susceptible genes such as NOD2/CARDl5,NOD1/CARD4,toll-like receptors(TLR)2 and 4,and β-defensin-1.Further more,a gene dosage effect was observed:anti-glycan positivity became more requent as the number of NOD2/CARDl5 SNPS increased.Other new serum/plasma IBD biomarkers reviewed include ubiquitination factor E4A(UBE4A),CXCL16(a chemokine),resistin,and apolipoprotein A-Ⅳ.This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics,fourier transform near-infrared spectroscopy,and multiplex enzyme-linked immunosorbent assay(ELISA)'s(with an emphasis on cytokine/chemokine profiling).Finally,the prospects of developing more clinically useful novel diagnostic algorithms by incorporating new technologies in

  12. Methodological and analytic considerations for blood biomarkers. (United States)

    Christenson, Robert H; Duh, Show-Hong


    Biomarkers typically evolve from a research setting to use in clinical care as evidence for their independent contribution to patient management accumulates. This evidence relies heavily on knowledge of the preanalytical, analytical, and postanalytical characteristics of the biomarker's measurement. For the preanalytical phase, considerations such specimen type, acceptable anticoagulants for blood samples, biologic variation and stability of the biomarker under various conditions are key. The analytical phase entails critical details for development and maintenance of assays having performance characteristics that are "fit for service" for the clinical application at hand. Often, these characteristics describe the ability to measure minute quantities in the biologic matrix used for measurement. Although techniques such as mass spectrometry are used effectively for biomarker discovery, routine quantification often relies on use of immunoassays; early in development, the most common immunoassay used is the enzyme-linked immunosorbent assay format. As biomarkers evolve successfully, they will be adapted to large main laboratory platforms or, depending on the need for speed, point-of-care devices. Users must pay particular attention to performance parameters of assays they are considering for clinical implementation. These parameters include the limit of blank, a term used to describe the limit of analytical noise for an assay; limit of detection, which describes the lowest concentration that can reliably be discriminated from analytical noise; and perhaps most importantly, the limit of quantitation, which is the lowest concentration at which a biomarker can be reliably measured within some predefined specifications for total analytical error that is based on clinical requirements of the test. The postanalytical phase involves reporting biomarker values, which includes reporting units, any normalization factors, and interpretation. Standardization, a process that

  13. Biomarkers of Parkinson's disease: present and future. (United States)

    Miller, Diane B; O'Callaghan, James P


    Sporadic or idiopathic Parkinson's disease (PD) is an age-related neurodegenerative disorder of unknown origin that ranks only second behind Alzheimer's disease (AD) in prevalence and its consequent social and economic burden. PD neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta; however, more widespread involvement of other CNS structures and peripheral tissues now is widely documented. The onset of molecular and cellular neuropathology of PD likely occurs decades before the onset of the motor symptoms characteristic of PD. The hallmark symptoms of PD, resting tremors, rigidity and postural disabilities, are related to dopamine (DA) deficiency. Current therapies treat these symptoms by replacing or boosting existing DA. All current interventions have limited therapeutic benefit for disease progression because damage likely has progressed over an estimated period of ~5 to 15years to a loss of 60%-80% of the nigral DA neurons, before symptoms emerge. There is no accepted definitive biomarker of PD. An urgent need exists to develop early diagnostic biomarkers for two reasons: (1) to intervene at the onset of disease and (2) to monitor the progress of therapeutic interventions that may slow or stop the course of the disease. In the context of disease development, one of the promises of personalized medicine is the ability to predict, on an individual basis, factors contributing to the susceptibility for the development of a given disease. Recent advances in our understanding of genetic factors underlying or contributing to PD offer the potential for monitoring susceptibility biomarkers that can be used to identify at-risk individuals and possibly prevent the onset of disease through treatment. Finally, the exposome concept is new in the biomarker discovery arena and it is suggested as a way to move forward in identifying biomarkers of neurological diseases. It is a two-stage scheme involving a first stage

  14. Biomarkers for wound healing and their evaluation. (United States)

    Patel, S; Maheshwari, A; Chandra, A


    A biological marker (biomarker) is a substance used as an indicator of biological state. Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Research has identified several cellular events and mediators associated with wound healing that can serve as biomarkers. Macrophages, neutrophils, fibroblasts and platelets release cytokines molecules including TNF-α, interleukins (ILs) and growth factors, of which platelet-derived growth factor (PDGF) holds the greatest importance. As a result, various white cells and connective tissue cells release both matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). Studies have demonstrated that IL-1, IL-6, and MMPs, levels above normal, and an abnormally high MMP/TIMP ratio are often present in non-healing wounds. Clinical examination of wounds for these mediators could predict which wounds will heal and which will not, suggesting use of these chemicals as biomarkers of wound healing. There is also evidence that the application of growth factors like PDGF will alleviate the recuperating process of chronic, non-healing wounds. Finding a specific biomarker for wound healing status would be a breakthrough in this field and helping treat impaired wound healing.

  15. Biomarkers in the Management of Difficult Asthma. (United States)

    Schleich, Florence; Demarche, Sophie; Louis, Renaud


    Difficult asthma is a heterogeneous disease of the airways including various types of bronchial inflammation and various degrees of airway remodeling. Therapeutic response of severe asthmatics can be predicted by the use of biomarkers of Type2-high or Type2-low inflammation. Based on sputum cell analysis, four inflammatory phenotypes have been described. As induced sputum is timeconsuming and expensive technique, surrogate biomarkers are useful in clinical practice. Eosinophilic phenotype is likely to reflect ongoing adaptive immunity in response to allergen. Several biomarkers of eosinophilic asthma are easily available in clinical practice (blood eosinophils, serum IgE, exhaled nitric oxyde, serum periostin). Neutrophilic asthma is thought to reflect innate immune system activation in response to pollutants or infectious agents while paucigranulocytic asthma is thought to be not inflammatory and characterized by smooth muscle dysfunction. We currently lack of user-friendly biomarkers of neutrophilic asthma and airway remodeling. In this review, we summarize the biomarkers available for the management of difficult asthma.

  16. Fish metalloproteins as biomarkers of environmental contamination. (United States)

    Hauser-Davis, Rachel Ann; de Campos, Reinaldo Calixto; Ziolli, Roberta Lourenço


    Fish are well-recognized bioindicators of environmental contamination. Several recent proteomic studies have demonstrated the validity and value of using fish in the search and discovery of new biomarkers. Certain analytical tools, such as comparative protein expression analyses, both in field and lab exposure studies, have been used to improve the understanding of the potential for chemical pollutants to cause harmful effects. The metallomic approach is in its early stages of development, but has already shown great potential for use in ecological and environmental monitoring contexts. Besides discovering new metalloproteins that may be used as biomarkers for environmental contamination, metallomics can be used to more comprehensively elucidate existing biomarkers, which may enhance their effectiveness. Unfortunately, metallomic profiling for fish has not been explored, because only a few fish metalloproteins have thus far been discovered and studied. Of those that have, some have shown ecological importance, and are now successfully used as biomarkers of environmental contamination. These biomarkers have been shown to respond to several types of environmental contamination, such as cyanotoxins, metals, and sewage effluents, although many do not yet possess any known function. Examples of successes include MMPs, superoxide dismutases, selenoproteins, and iron-bound proteins. Unfortunately, none of these have, as yet, been extensively studied. As data are developed for them, valuable new information on their roles in fish physiology and in inducing environmental effects should become available.

  17. Proteome-based biomarkers in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Chen Sun; Ann H Rosendahl; Daniel Ansari; Roland Andersson


    Pancreatic cancer, as a highly malignant cancer and the fourth cause of cancer-related death in world, is characterized by dismal prognosis, due to rapid disease progression, highly invasive tumour phenotype, and resistance to chemotherapy. Despite significant advances in treatment of the disease during the past decade,the survival rate is little improved. A contributory factor to the poor outcome is the lack of appropriate sensitive and specific biomarkers for early diagnosis. Furthermore, biomarkers for targeting, directing and assessing therapeutic intervention, as well as for detection of residual or recurrent cancer are also needed. Thus, the identification of adequate biomarkers in pancreatic cancer is of extreme importance. Recently, accompanying the development of proteomic technology and devices, more and more potential biomarkers have appeared and are being reported. In this review, we provide an overview of the role of proteome-based biomarkers in pancreatic cancer, including tissue, serum, juice, urine and cell lines. We also discuss the possible mechanism and prospects in the future. That information hopefully might be helpful for further research in the field.

  18. Biomarkers of teratogenesis: suggestions from animal studies. (United States)

    Giavini, Erminio; Menegola, Elena


    Biomarkers of effect are measurable biochemical, physiological or other alterations within an organism that can be recognized as causing an established or potential impairment of embryo-fetal development. They may be identified studying the mechanisms of action of teratogens. Hyperacetylation of histones, oxidative stress, cholesterol and retinoic acid unbalance are some of the identified mechanisms of action of some known teratogens. Nevertheless, their use is not currently applicable in human pregnancy because of the difficulty of the choice of biological material, the time when the material must be obtained, and the invasivity of methods. Furthermore, before using them in human pregnancy studies, biomarkers should be validated in experimental animals and in epidemiologic studies. On the contrary, some biomarkers could be useful in the screening of developmental toxicity of chemicals and drugs, comparing molecules of the same chemical class or with the similar pharmacologic activity, and using adequate in vitro tests, in order to reduce the use of experimental animals.

  19. Urinary biomarkers for prostate cancer: a review

    Institute of Scientific and Technical Information of China (English)

    Daphne Hessels; Jack A Schalken


    Although the routine use of serum prostate-specific antigen (PSA) testing has undoubtedly increased prostate cancer (PCa) detection,one of its main drawbacks is its lack of specificity.As a consequence,many men undergo unnecessary biopsies or treatments for indolent tumours.PCa-specific markers are needed for the early detection of the disease and the prediction of aggressiveness of a prostate tumour.Since PCa is a heterogeneous disease,a panel of tumour markers is fundamental for a more precise diagnosis.Several biomarkers are promising due to their specificity for the disease in tissue.However,tissue is unsuitable as a possible screening tool.Since urine can be easily obtained in a non-invasive manner,it is a promising substrate for biomarker testing.This article reviews the biomarkers for the non-invasive testing of PCa in urine.

  20. Advances in biomarkers of major depressive disorder. (United States)

    Huang, Tiao-Lai; Lin, Chin-Chuen


    Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Biomarkers are measurable indicators that could help diagnosing MDD or predicting treatment response. In this chapter, lipid profiles, immune/inflammation, and neurotrophic factor pathways that have long been implicated in the pathogenesis of MDD are discussed. Then, pharmacogenetics and epigenetics of serotonin transport and its metabolism pathway, brain-derived neurotrophic factor, and abnormality of hypothalamo-pituitary-adrenocortical axis also revealed new biomarkers. Lastly, new techniques, such as proteomics and metabolomics, which allow researchers to approach the studying of MDD with new directions and make new discoveries are addressed. In the future, more data are needed regarding pathophysiology of MDD, including protein levels, single nucleotide polymorphism, epigenetic regulation, and clinical data in order to better identify reliable and consistent biomarkers for diagnosis, treatment choice, and outcome prediction.

  1. Using Aptamers for Cancer Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Yun Min Chang


    Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.


    Directory of Open Access Journals (Sweden)

    Lei Zhang


    Full Text Available Early detection of cancer biomarkers with high precision is critically important for cancer therapy. A variety of sensors based on different nanostructured materials have attracted intensive research interest due to their potential for highly sensitive and selective detection of cancer biomarkers. This review covers the use of a variety of nanostructured materials, including carbon nanotubes, silicon nanowires, gold nanoparticles and quantum dots, in the fabrication of sensors. Emphases are placed on how the detection systems work and what detection limits can be achieved. Some assays described in this review outperform established methods for cancer biomarker detection. It is highly promising that these sensors would soon move into commercial-scale production and find routine use in hospitals.

  3. Current early diagnostic biomarkers of prostate cancer

    Directory of Open Access Journals (Sweden)

    Min Qu


    Full Text Available Prostate cancer (PCa has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers.

  4. Use of cardiac biomarkers in neonatology. (United States)

    Vijlbrief, Daniel C; Benders, Manon J N L; Kemperman, Hans; van Bel, Frank; de Vries, Willem B


    Cardiac biomarkers are used to identify cardiac disease in term and preterm infants. This review discusses the roles of natriuretic peptides and cardiac troponins. Natriuretic peptide levels are elevated during atrial strain (atrial natriuretic peptide (ANP)) or ventricular strain (B-type natriuretic peptide (BNP)). These markers correspond well with cardiac function and can be used to identify cardiac disease. Cardiac troponins are used to assess cardiomyocyte compromise. Affected cardiomyocytes release troponin into the bloodstream, resulting in elevated levels of cardiac troponin. Cardiac biomarkers are being increasingly incorporated into clinical trials as indicators of myocardial strain. Furthermore, cardiac biomarkers can possibly be used to guide therapy and improve outcome. Natriuretic peptides and cardiac troponins are potential tools in the diagnosis and treatment of neonatal disease that is complicated by circulatory compromise. However, clear reference ranges need to be set and validation needs to be carried out in a population of interest.

  5. Flavonoids as fruit and vegetable intake biomarkers

    DEFF Research Database (Denmark)

    Krogholm, Kirstine Suszkiewicz

    correlation coefficients between total fruit, juice, tea and vegetable intake estimated by FFQ and each of the biomarkers. This finding, of a statistically significant correlation between the Inter99 FFQ and two independent biomarkers indicates that the Inter99 FFQ provides a useful estimate of the overall...... dietary intake of fruits, juices, tea and vegetables in the Inter99 cohort. VCs for the FFQ ranged from 0.43-0.68 using 24h urine and from 0.35-0.64 using morning spot urine, indicating that the intake of fruits, juice, tea and vegetables was reflected by flavonoids both in morning spot and 24h urine...... of fruit and vegetable intake (Nielsen et al. 2002). The overall aim of the present Ph.D. thesis was to further develop and validate this potentially new fruit and vegetable biomarker and furthermore use it for the validation of self-reported dietary intake of fruits and vegetables in intervention...

  6. Reappraisal of hydrocarbon biomarkers in Archean rocks (United States)

    French, Katherine L.; Hallmann, Christian; Hope, Janet M.; Schoon, Petra L.; Zumberge, J. Alex; Hoshino, Yosuke; Peters, Carl A.; George, Simon C.; Love, Gordon D.; Brocks, Jochen J.; Buick, Roger; Summons, Roger E.


    Hopanes and steranes found in Archean rocks have been presented as key evidence supporting the early rise of oxygenic photosynthesis and eukaryotes, but the syngeneity of these hydrocarbon biomarkers is controversial. To resolve this debate, we performed a multilaboratory study of new cores from the Pilbara Craton, Australia, that were drilled and sampled using unprecedented hydrocarbon-clean protocols. Hopanes and steranes in rock extracts and hydropyrolysates from these new cores were typically at or below our femtogram detection limit, but when they were detectable, they had total hopane (oxygenic photosynthesis and eukaryotes by ∼2.7 billion years ago. Although suitable Proterozoic rocks exist, no currently known Archean strata lie within the appropriate thermal maturity window for syngenetic hydrocarbon biomarker preservation, so future exploration for Archean biomarkers should screen for rocks with milder thermal histories.

  7. Fluid biomarkers in multiple system atrophy: A review of the MSA Biomarker Initiative. (United States)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy; Gerhard, Alexander; Jellinger, Kurt; Jeromin, Andreas; Krismer, Florian; Mollenhauer, Brit; Schlossmacher, Michael G; Shaw, Leslie M; Verbeek, Marcel M; Wenning, Gregor K; Winge, Kristian; Zhang, Jing; Meissner, Wassilios G


    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results suggest that combining several CSF fluid biomarkers may be more successful than using single markers, at least for the diagnosis. Currently, the clinically most useful markers may comprise a combination of the light chain of neurofilament (which is consistently elevated in MSA compared to controls and Parkinson's disease), metabolites of the catecholamine pathway and proteins such as α-synuclein, DJ-1 and total-tau. Beyond future efforts in biomarker discovery, the harmonization of standard operating procedures will be crucial for future success.

  8. Epigenetics and bacterial infections. (United States)

    Bierne, Hélène; Hamon, Mélanie; Cossart, Pascale


    Epigenetic mechanisms regulate expression of the genome to generate various cell types during development or orchestrate cellular responses to external stimuli. Recent studies highlight that bacteria can affect the chromatin structure and transcriptional program of host cells by influencing diverse epigenetic factors (i.e., histone modifications, DNA methylation, chromatin-associated complexes, noncoding RNAs, and RNA splicing factors). In this article, we first review the molecular bases of the epigenetic language and then describe the current state of research regarding how bacteria can alter epigenetic marks and machineries. Bacterial-induced epigenetic deregulations may affect host cell function either to promote host defense or to allow pathogen persistence. Thus, pathogenic bacteria can be considered as potential epimutagens able to reshape the epigenome. Their effects might generate specific, long-lasting imprints on host cells, leading to a memory of infection that influences immunity and might be at the origin of unexplained diseases.

  9. Bacterial polyhydroxyalkanoates: Still fabulous? (United States)

    Możejko-Ciesielska, Justyna; Kiewisz, Robert


    Bacterial polyhydroxyalkanoates (PHA) are polyesters accumulated as carbon and energy storage materials under limited growth conditions in the presence of excess carbon sources. They have been developed as biomaterials with unique properties for the past many years being considered as a potential substitute for conventional non-degradable plastics. Due to the increasing concern towards global climate change, depleting petroleum resource and problems with an utilization of a growing number of synthetic plastics, PHAs have gained much more attention from industry and research. These environmentally friendly microbial polymers have great potential in biomedical, agricultural, and industrial applications. However, their production on a large scale is still limited. This paper describes the backgrounds of PHAs and discussed the current state of knowledge on the polyhydroxyalkanoates. Ability of bacteria to convert different carbon sources to PHAs, the opportunities and challenges of their introduction to global market as valuable renewable products have been also discussed.

  10. Next-Generation Biomarkers of Health. (United States)

    van Ommen, Ben; Wopereis, Suzan


    Current biomarkers used in health care and in nutrition and health research are based on quantifying disease onset and its progress. Yet, both health care and nutrition should focus on maintaining optimal health, where the related biology is essentially differing from biomedical science. Health is characterized by the ability to continuously adapt in varying circumstances where multiple mechanisms of systems flexibility are involved. A new generation of biomarkers is needed that quantifies all aspects of systems flexibility, opening the door to real lifestyle-related health optimization, self-empowerment, and related products and services.

  11. Stable Feature Selection for Biomarker Discovery

    CERN Document Server

    He, Zengyou


    Feature selection techniques have been used as the workhorse in biomarker discovery applications for a long time. Surprisingly, the stability of feature selection with respect to sampling variations has long been under-considered. It is only until recently that this issue has received more and more attention. In this article, we review existing stable feature selection methods for biomarker discovery using a generic hierarchal framework. We have two objectives: (1) providing an overview on this new yet fast growing topic for a convenient reference; (2) categorizing existing methods under an expandable framework for future research and development.

  12. Early succession of bacterial biofilms in paper machines. (United States)

    Tiirola, Marja; Lahtinen, Tomi; Vuento, Matti; Oker-Blom, Christian


    Formation of biofilms causes severe problems in paper machines, and hence financial costs. It would be preferable to prevent attachment of the primary-colonizing bacteria than to control the growth of secondary communities, which are sheltered by exopolysaccharide slime layers. We have therefore investigated the early succession of paper-machine biofilms by incubating stainless-steel test coupons in the process water-flow lines in two paper machines operating in slightly alkaline conditions in temperatures (45 and 49 degrees C) supporting thermophilic microbes. Microbial succession was profiled using length heterogeneity analysis of PCR-amplified 16S rRNA genes (LH-PCR) and linking the sequence data of the created 16S rRNA gene libraries to the dominant LH-PCR peaks. Although the bacterial fingerprints obtained from the attached surface communities varied slightly in different samples, the biomarker signals of the dominating primary-colonizing bacterial groups remained high over time in each paper machine. Most of the 16S rRNA gene copies in the early biofilms were assigned to the genera Rhodobacter, Tepidimonas, and Cloacibacterium. The dominance of these sequence types decreased in the developing biofilms. Finally, as phylogenetically identical primary-colonizers were detected in the two different paper mills, the machines evidently had similar environmental conditions for bacterial growth and potentially a common source of contamination.

  13. Recent Advances on Lipid Biomarkers in Marine Sediments

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-lin


    This paper reviews the recent advances of marine biomarker. Biomarkers of marine microorganisms are also included. It is important to the origin of marine biological and the monitor and evaluation of marine environment.

  14. Tau/Amyloid Beta 42 Peptide Test (Alzheimer Biomarkers) (United States)

    ... Was this page helpful? Also known as: Alzheimer Biomarkers Formal name: Tau Protein and Amyloid Beta 42 ... being researched for their potential use as AD biomarkers. If someone has symptoms of dementia , a health ...

  15. A systematic review of biomarkers in the diagnosis of infective endocarditis. (United States)

    Snipsøyr, Magnus G; Ludvigsen, Maja; Petersen, Eskild; Wiggers, Henrik; Honoré, Bent


    Timely diagnosis of bacterial infective endocarditis (IE) is crucial, as mortality remains high in this severe bacterial infection, currently without any distinct biological markers. Our goal was to evaluate potential diagnostic biomarkers by reviewing current literature. The MEDLINE, Embase and Scopus databases were searched for articles published from 1980 through June 2015 restricted to English, Norwegian, Danish and Swedish. Eighteen studies qualified, providing a review of the most promising candidates for future studies. Several studies are inconclusive, since they are characterized by using improper control groups. Patients with IE have bacteremia, and control groups should therefore be patients with bacteremia without IE. Based on current research, N-terminal-pro-B-type natriuretic peptide (NT-proBNP) alone or in combination with Cystatin C (Cys C), lipopolysaccharide-binding protein (LBP), troponins, aquaporin-9 (AQP9), S100 calcium binding protein A11 (S100A11), E-selectin (CD62E) and VCAM-1 (CD54) and interleukin-6 (IL-6) are potential biomarkers for future studies.

  16. Conventional, molecular methods and biomarkers molecules in detection of septicemia

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Arabestani


    Full Text Available Sepsis is a leading cause of morbidity and mortality in hospitalized patients worldwide and based on studies, 30-40% of all cases of severe sepsis and septic shock results from the blood stream infections (BSIs. Identifying of the disease, performing laboratory tests, and consequently treatment are factors that required for optimum management of BSIs. In addition, applying precise and immediate identification of the etiologic agent is a prerequisite for specific antibiotic therapy of pathogen and thereby decreasing mortality rates. The diagnosis of sepsis is difficult because clinical signs of sepsis often overlap with other noninfectious cases of systemic inflammation. BSIs are usually diagnosed by performing a series of techniques such as blood cultures, polymerase chain reaction-based methods, and biomarkers of sepsis. Extremely time-consuming even to take up to several days is a major limitation of conventional methods. In addition, yielding false-negative results due to fastidious and slow-growing microorganisms and also in case of antibiotic pretreated samples are other limitations. In comparison, molecular methods are capable of examining a blood sample obtained from suspicious patient with BSI and gave the all required information to prescribing antimicrobial therapy for detected bacterial or fungal infections immediately. Because of an emergency of sepsis, new methods are being developed. In this review, we discussed about the most important sepsis diagnostic methods and numbered the advantage and disadvantage of the methods in detail.

  17. Evaluation of Innate Immune Biomarkers in Saliva for Diagnostic Potential of Bacterial and Viral Respiratory Infection (United States)


    Neonatology 101 :55- 60. 7. Streckfus C, Bigler L. 2002. Saliva as a Diagnostic Fluid. Oral Diseases 8:69- 76. 8. Jain V, Armah H, Tongren J, Ned R, Wilson...oropharyngeal candidiasis . J Acquir Immune Defic Syndr Hum Retrovirol 19:373-380. 21. Zhang Y, Lin M, Zhang S, Wang Z, Jiang L, Shen J, Bai J, Gao F...Zhou M, Chen Q. 2008. NF-kappaB-dependent cytokines in saliva and serum from patients with oral lichen planus: a study in an ethnic Chinese population

  18. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Cristina Gluhovschi


    Full Text Available Diabetic nephropathy (DN is a frequent and severe complication of diabetes mellitus (DM. Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.


    Serum biomarkers to identify susceptibility to disease in aged humans are well researched. On the other hand, our understanding of biomarkers in animal models of aging is limited. Hence, we applied a commercially available panel of 58 serum analytes to screen for possible biomark...

  20. Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease.

    Directory of Open Access Journals (Sweden)

    Shigeo Hanada

    Full Text Available Invasive pneumococcal disease (IPD causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.In a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.Overall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7-12.8, p < .001; age ≥80 years (OR, 6.5; 95% CI, 2.0-21.6, p = .002; serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5-8.1, p < .001; underlying liver disease (OR, 3.5; 95% CI, 1.6-7.8, p = .002; mechanical ventilation (OR, 3.0; 95% CI, 1.7-5.6, p < .001; and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4-4.0, p = .001. Pneumococcal serotype and drug resistance were not associated with poor outcomes.Host factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.

  1. Variation of Geochemical Signatures and Correlation of Biomarkers in Icelandic Mars Analogue Environments (United States)

    Gentry, D.; Amador, E. S.; Cable, M. L.; Cantrell, T.; Chaudry, N.; Cullen, T.; Duca, Z. A.; Jacobsen, M. B.; McCaig, H. C.; Murukesan, G.; Rennie, V.; Schwieterman, E. W.; Stevens, A. H.; Tan, G.; Yin, C.; Stockton, A.; Cullen, D.; Geppert, W.


    Exploration missions to Mars rely on rovers to perform deep analyses over small sampling areas; however, landing site selection is done using large-scale but low-resolution remote sensing data. Using Earth analogue environments to estimate the small-scale spatial and temporal distributions of key geochemical signatures and (for habitability studies) biomarkers helps ensure that the chosen sampling strategies meet mission science goals. We conducted two rounds of analogue expeditions to recent Icelandic lava fields. In July 2013, we tested correlation between three common biomarker assays: cell quantification via fluorescence microscopy, ATP quantification via bioluminescence, and quantitative PCR with universal primer sets. Sample sites were nested at four spatial scales (1 m, 10 m, 100 m, and > 1 km) and homogeneous at 'remote imaging' resolution (overall temperature, apparent moisture content, and regolith grain size). All spatial scales were highly diverse in ATP, bacterial 16S, and archaeal 16S DNA content; nearly half of sites were statistically different in ATP content at α = 0.05. Cell counts showed significant variation at the 10 m and 100 m scale; at the > 1 km scale, the mean counts were not distinguishable, but the median counts were, indicating differences in underlying distribution. Fungal 18S DNA content similarly varied at 1 m, 10 m, and 100 m scales only. Cell counts were not correlated with ATP or DNA content at any scale. ATP concentration and DNA content for all three primer sets were positively correlated. Bacterial DNA content was positively correlated with archaeal and fungal DNA content, though archaeal correlation was weak. Fungal and archaeal correlation was borderline. In July 2015, we repeated the sampling strategy, with the addition of a smaller-scale sampling grid of 10 cm and a third > 1 km location. This expedition also measured reflectance of the tephra cover and preserved mineral samples for future Raman spectroscopy in order to

  2. Protein biomarker enrichment by biomarker antibody complex elution for immunoassay biosensing. (United States)

    Sabatte, Gwenola; Feitsma, Harma; Evers, Toon H; Prins, Menno W J


    It is very challenging to perform sample enrichment for protein biomarkers because proteins can easily change conformation and denature. In this paper we demonstrate protein enrichment suited for high-sensitivity integrated immuno-biosensing. The method enhances the concentration of the biomarkers and simultaneously removes matrix components that could interfere with the immunoassay. Biomarkers are captured using antibody coated magnetic particles and the biomarker antibody complexes are released by enzymatic elution. The eluted complexes are subsequently detected in a sandwich immunoassay biosensor. A scaling study of the enrichment process demonstrates an enrichment factor of 15 in buffer and plasma. We analyze the enrichment factor in terms of the three basic steps of the assay (capture, concentration, elution) and we quantify their respective efficiencies. The process is suited for integration into bio-analytical tools.

  3. Isorenieratene: Biomarker for Photic Layer Anoxia? (United States)

    Casford, J.


    The use of biomarkers is a relatively new and growing field and while these novel proxies hold the potential to revolutionise our understanding of past environments it is important that we fully understand the assumptions that underlie their use and the systems in which they operate. The use of the biomarker, isorenieratene to identify photic layer anoxia, particularly in marine systems is increasing. However recent papers have identified this carotenoid in settings that also show evidence of deep ventilation. This synthesis will assess the history and evidence for the use of this biomarker, focusing on the diagenesis of isorenieratene and the habitat of the Chlorobiaceae species that are its main producers. While it is clear this biomarker can be produced under euxinic condition in the photic layer I highlight evidence that: 1) The most common occurrence of these Chlorobiaceae species is photolithotropic and that even in marine systems it preferentially occurs at the sediment water interface rather than in pelagic conditions; 2) That these species are not the only source of this pigment and its products; and 3) These species can also operate in common micro - niches within more oxic environments.

  4. Imaging biomarkers in primary brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)


    We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

  5. Biomarkers for Major Depressive Disorder: Economic Considerations. (United States)

    Bogavac-Stanojevic, Natasa; Lakic, Dragana


    Preclinical Research Major depressive disorder (MDD) is a major psychiatric illness and it is predicted to be the second leading cause of disability by 2020 with a lifetime prevalence of about 13%. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used therapeutic class for MDD. However, response to SSRI treatment varies considerably between patients. Biomarkers of treatment response may enable clinicians to target the appropriate drug for each patient. Biomarkers need to have accuracy in real life, sensitivity, specificity, and relevance to depression. Introduction of MDD biomarkers into the health care system can increase the overall cost of clinical diagnosis of patients. Because of that, decisions to allocate health research funding must be based on drug effectiveness and cost-effectiveness. The assessment of MDD biomarkers should include reliable evidence of associated drug effectiveness, adverse events and consequences (reduced productivity and quality of life, disability) and effectiveness of alternative approaches, other drug classes or behavioral or alternative therapies. In addition, all the variables included in an economic model (probabilities, outcomes, and costs) should be based on reliable evidence gained from the literature-ideally meta-analyses-and the evidence should also be determined by informed and specific expert opinion. Early assessment can guide decisions about whether or not to continue test development, and ideally to optimize the process. Drug Dev Res 77 : 374-378, 2016. © 2016 Wiley Periodicals, Inc.

  6. Biomarkers in Pediatric ARDS: Future Directions

    Directory of Open Access Journals (Sweden)

    Benjamin E Orwoll


    Full Text Available Acute respiratory distress syndrome (ARDS is common among mechanically ventilated children, and accompanies up to 30% of all PICU deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids such as brochoalveolar lavage have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pediatric ARDS (pARDS provides additional impetus for measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.

  7. Lung cancer biomarkers in exhaled breath. (United States)

    Amann, Anton; Corradi, Massimo; Mazzone, Peter; Mutti, Antonio


    Lung cancer is the leading cause of cancer-related mortality worldwide. Methods for early detection of lung cancer, such as computerized tomography scanning technology, often discover a large number of small lung nodules, posing a new problem to radiologists and chest physicians. The vast majority of these nodules will be benign, but there is currently no easy way to determine which nodules represent very early lung cancer. Adjuvant testing with PET imaging and nonsurgical biopsies has a low yield for these small indeterminate nodules, carries potential morbidity and is costly. Indeed, purely morphological criteria seem to be insufficient for distinguishing lung cancer from benign nodules at early stages with sufficient confidence, therefore false positives undergoing surgical resection frequently occur. A molecular approach to the diagnosis of lung cancer through the analysis of exhaled breath could greatly improve the specificity of imaging procedures. A biomarker-driven approach to signs or symptoms possibly due to lung cancer would represent a complementary tool aimed at ruling out (with known error probability) rather than diagnosing lung cancer. Volatile and nonvolatile components of the breath are being studied as biomarkers of lung cancer. Breath testing is noninvasive and potentially inexpensive. There is promise that an accurate lung cancer breath biomarker, capable of being applied clinically, will be developed in the near future. In this article, we summarize some of the rationale for breath biomarker development, review the published literature in this field and provide thoughts regarding future directions.

  8. Quantitative multiplex detection of pathogen biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Mukundan, Harshini; Xie, Hongzhi; Swanson, Basil I.; Martinez, Jennifer; Grace, Wynne K.


    The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.

  9. Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar


    Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

  10. Pulmonary biomarkers in chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Barnes, Peter J.; Chowdhury, Badrul; Kharitonov, Sergei A.; Magnussen, Helgo; Page, Clive P.; Postma, Dirkje; Saetta, Marina


    There has been increasing interest in using pulmonary biomarkers to understand and monitor the inflammation in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD). In this Pulmonary Perspective we discuss the merits of the various approaches by reviewing the current l

  11. Potential Serological Biomarkers of Cerebral Malaria

    Directory of Open Access Journals (Sweden)

    Naomi W. Lucchi


    Full Text Available Biomarkers have been used to diagnose and prognosticate the progress and outcome of many chronic diseases such as neoplastic and non communicable diseases. However, only recently did the field of malaria research move in the direction of actively identifying biomarkers that can accurately discriminate the severe forms of malaria. Malaria continues to be a deadly disease, killing close to a million people (mostly children every year. One life-threatening complication of malaria is cerebral malaria (CM. Studies carried out in Africa have demonstrated that even with the best treatment, as high as 15–30% of CM patients die and about 10–24% of CM survivors suffer short-or long-term neurological impairment. The transition from mild malaria to CM can be sudden and requires immediate intervention. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify CM patients and potential risk for adverse outcomes would greatly enhance better intervention and clinical management to improve the outcomes. We review here what is currently known regarding biomarkers for CM outcomes.

  12. Functional MRI and CT biomarkers in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Winfield, J.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom); Institute of Cancer Research and Royal Marsden Hospital, MRI Unit, Sutton (United Kingdom); Payne, G.S.; DeSouza, N.M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, CRUK Imaging Centre at the Institute of Cancer Research, Sutton (United Kingdom)


    Imaging biomarkers derived from MRI or CT describe functional properties of tumours and normal tissues. They are finding increasing numbers of applications in diagnosis, monitoring of response to treatment and assessment of progression or recurrence. Imaging biomarkers also provide scope for assessment of heterogeneity within and between lesions. A wide variety of functional parameters have been investigated for use as biomarkers in oncology. Some imaging techniques are used routinely in clinical applications while others are currently restricted to clinical trials or preclinical studies. Apparent diffusion coefficient, magnetization transfer ratio and native T{sub 1} relaxation time provide information about structure and organization of tissues. Vascular properties may be described using parameters derived from dynamic contrast-enhanced MRI, dynamic contrast-enhanced CT, transverse relaxation rate (R{sub 2}*), vessel size index and relative blood volume, while magnetic resonance spectroscopy may be used to probe the metabolic profile of tumours. This review describes the mechanisms of contrast underpinning each technique and the technical requirements for robust and reproducible imaging. The current status of each biomarker is described in terms of its validation, qualification and clinical applications, followed by a discussion of the current limitations and future perspectives. (orig.)

  13. Biomarker Use in Tailored Combat Casualty Care (United States)


    468 Brown, Safford, Caraman ica & Elster In the following sections, we describe our efforts ro define rhe role of biomarkers :moci- ated wich...Salroraf;u GH, Peru ~ G: Principle• of ’"u 12 Bently R, Nuccin P, Wolfe E tr a/.: 250(6), 1002-1007 (2009). M11gcry: cu rrtnt cunccpt~ n nd fn ru rc

  14. Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity. (United States)

    Redman, Christopher W G; Staff, Anne Cathrine


    The maternal syndrome of preeclampsia is mediated by dysfunctional syncytiotrophoblast (STB). When this is stressed by uteroplacental malperfusion, its signaling to the mother changes, as part of a highly coordinated stress response. The STB signals are both proinflammatory and dysangiogenic such that the preeclamptic mother has a stronger vascular inflammatory response than normal, with an antiangiogenic bias. Angiogenic factors have limitations as preeclampsia biomarkers, especially for prediction and diagnosis of preeclampsia at term. However, if they are recognized as markers of STB stress, their physiological changes at term demonstrate that STB stress develops in all pregnancies. The biomarkers reveal that the duration of pregnancies is restricted by placental capacity, such that there is increasing placental dysfunction, at and beyond term. This capacity includes limitations imposed by the size of the uterus, the capacity of the uteroplacental circulation and, possibly, the supply of villous progenitor trophoblast cells. Limited placental capacity explains the increasing risks of postmaturity, including preeclampsia. Early-onset preeclampsia is predictable because STB stress and changes in its biomarkers are intrinsic to poor placentation, an early pregnancy pathology. Prediction of preeclampsia at term is not good because there is no early STB pathology. Moreover, biomarkers cannot accurately diagnose term preeclampsia against a background of universal STB dysfunction, which may or may not be clinically revealed before spontaneous or induced delivery. In this sense, postterm pregnancy is, at best, a pseudonormal state. However, the markers may prove useful in screening for women with more severe problems of postmaturity.


    Directory of Open Access Journals (Sweden)

    Ernest Marshall Graham


    Full Text Available Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the liquid brain biopsy. A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

  16. Biomarkers of necrotising soft tissue infections

    DEFF Research Database (Denmark)

    Hansen, Marco Bo; Simonsen, Ulf; Garred, Peter


    INTRODUCTION: The mortality and amputation rates are still high in patients with necrotising soft tissue infections (NSTIs). It would be ideal to have a set of biomarkers that enables the clinician to identify high-risk patients with NSTI on admission. The objectives of this study are to evaluate...

  17. Quantitative multiplex detection of pathogen biomarkers (United States)

    Mukundan, Harshini; Xie, Hongzhi; Swanson, Basil I; Martinez, Jennifer; Grace, Wynne K


    The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.

  18. Huntington's disease : functional and structural biomarkers

    NARCIS (Netherlands)

    Dumas, Eve Marie


    The aims of this thesis were to gain insight into specific disease processes in Huntington’s Disease (HD) and to identify biomarkers. To achieve these aims, cognitive functioning, structural brain characteristics and intrinstic functional brain connectivity of premanifest and early HD subjects were

  19. Biomarkers in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Sin, Don D; Vestbo, Jørgen


    Currently, with exception of lung function tests, there are no well validated biomarkers or surrogate endpoints that can be used to establish efficacy of novel drugs for chronic obstructive pulmonary disease (COPD). However, the lung function test is not an ideal surrogate for short-term drug...

  20. Cerebrospinal fluid biomarkers for Parkinson's disease

    DEFF Research Database (Denmark)

    Dammann Andersen, Andreas; Binzer, Michael; Stenager, Egon;


    Diagnosticering af Parkinson's sygdom (PD) er baseret på den kliniske udvikling af sygdommen samt en fysisk undersøgelse af patienten, men fejldiagnosticering sker hyppigt; specielt i tidlige stadier. Biomarkører for PD kan muliggøre en tidligere og mere præcis diagnosticering samt monitorering af...

  1. Cerebrospinal fluid biomarker candidates for parkinsonian disorders

    Directory of Open Access Journals (Sweden)

    Radu eConstantinescu


    Full Text Available The parkinsonian disorders are a large group of neurodegenerative diseases including idiopathic Parkinson's disease (PD and atypical parkinsonian disorders, such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The etiology of these disorders is not known although it is considered to be a combination of genetic and environmental factors. One of the greatest obstacles for developing efficacious disease-modifying treatment strategies is the lack of biomarkers. Reliable biomarkers are needed for early and accurate diagnosis, to measure disease progression and response to therapy. In this review several of the most promising cerebrospinal biomarker candidates are discussed. Alpha synuclein seems to be intimately involved in the pathogenesis of synucleinopathies and its levels can be measured in the cerebrospinal fluid and in plasma. In a similar way, tau protein accumulation seems to be involved in the pathogenesis of tauopathies. Urate, a potent antioxidant, seems to be associated to the risk of developing PD and with its progression. Neurofilament light chain levels are increased in atypical parkinsonian disorders compared with PD and healthy controls. The new "omics" techniques are potent tools offering new insights in the patho-etiology of these disorders. Some of the difficulties encountered in developing biomarkers are discussed together with future perspectives.

  2. Biomarkers in Parkinson's disease: Advances and strategies. (United States)

    Delenclos, Marion; Jones, Daryl R; McLean, Pamela J; Uitti, Ryan J


    Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor disturbances and affects more than 1% of the worldwide population. Despite considerable progress in understanding PD pathophysiology, including genetic and biochemical causes, diagnostic approaches lack accuracy and interventions are restricted to symptomatic treatments. PD is a complex syndrome with different clinical subtypes and a wide variability in disorder course. In order to deliver better clinical management of PD patients and discovery of novel therapies, there is an urgent need to find sensitive, specific, and reliable biomarkers. The development of biomarkers will not only help the scientific community to identify populations at risk, but also facilitate clinical diagnosis. Furthermore, these tools could monitor progression, which could ultimately deliver personalized therapeutic strategies. The field of biomarker discovery in PD has attracted significant attention and there have been numerous contributions in recent years. Although none of the parameters have been validated for clinical practice, some candidates hold promise. This review summarizes recent advances in the development of PD biomarkers and discusses new strategies for their utilization.

  3. Biomarkers of fever: from bench to bedside

    NARCIS (Netherlands)

    M. Limper (Maarten)


    markdownabstract__Abstract__ This thesis aims to study biomarkers in inflammation and infection, with a special focus on the distinction between infectious and non-infectious fever. The thesis consists of three parts, part I being this introduction, in which the concept of fever in infectious and n

  4. Novel biomarkers for cancer detection and prognostication

    NARCIS (Netherlands)

    Mehra, N.


    In this thesis we used a variety of approaches for biomarker discovery; in Part I we assessed whether we could identify a non-invasive surrogate markers of angiogenesis, as new vessel formation plays critical roles in the growth and metastatic spread of tumors. Moreover, many agents targeting the va

  5. A Comparative Analysis of Biomarker Selection Techniques

    Directory of Open Access Journals (Sweden)

    Nicoletta Dessì


    Full Text Available Feature selection has become the essential step in biomarker discovery from high-dimensional genomics data. It is recognized that different feature selection techniques may result in different set of biomarkers, that is, different groups of genes highly correlated to a given pathological condition, but few direct comparisons exist which quantify these differences in a systematic way. In this paper, we propose a general methodology for comparing the outcomes of different selection techniques in the context of biomarker discovery. The comparison is carried out along two dimensions: (i measuring the similarity/dissimilarity of selected gene sets; (ii evaluating the implications of these differences in terms of both predictive performance and stability of selected gene sets. As a case study, we considered three benchmarks deriving from DNA microarray experiments and conducted a comparative analysis among eight selection methods, representatives of different classes of feature selection techniques. Our results show that the proposed approach can provide useful insight about the pattern of agreement of biomarker discovery techniques.

  6. Hypermethylated DNA, a Biomarker for colorectal cancer

    DEFF Research Database (Denmark)

    Rasmussen, Simon Ladefoged; Krarup, Henrik Bygum; Sunesen, Kåre Gotschalck;


    and specific for CRC have been proposed. Articles describing the use of hypermethylated promoter regions in blood or stool as biomarkers for CRC were systematically reviewed. METHOD: The Medline, Web of Science, and Embase databases were used in a systematic literature search. Studies were included...


    Many marine eukaryotic algae have been shown to possess characteristic chemotaxonomic lipid biomarkers. Dinoflagellates in particular are often characterized by the presence of sterols and pigments that are rarely found in other classes of algae. To evaluate the utility of chemic...

  8. Rapid culture-independent microbial analysis aboard the international space station (ISS) stage two: quantifying three microbial biomarkers. (United States)

    Morris, Heather C; Damon, Michael; Maule, Jake; Monaco, Lisa A; Wainwright, Norm


    Abstract A portable, rapid, microbial detection unit, the Lab-On-a-Chip Application Development Portable Test System (LOCAD-PTS), was launched to the International Space Station (ISS) as a technology demonstration unit in December 2006. Results from the first series of experiments designed to detect Gram-negative bacteria on ISS surfaces by quantifying a single microbial biomarker lipopolysaccharide (LPS) were reported in a previous article. Herein, we report additional technology demonstration experiments expanding the on-orbit capabilities of the LOCAD-PTS to detecting three different microbial biomarkers on ISS surfaces. Six different astronauts on more than 20 occasions participated in these experiments, which were designed to test the new beta-glucan (fungal cell wall molecule) and lipoteichoic acid (LTA; Gram-positive bacterial cell wall component) cartridges individually and in tandem with the existing Limulus Amebocyte Lysate (LAL; Gram-negative bacterial LPS detection) cartridges. Additionally, we conducted the sampling side by side with the standard culture-based detection method currently used on the ISS. Therefore, we present data on the distribution of three microbial biomarkers collected from various surfaces in every module present on the ISS at the time of sampling. In accordance with our previous experiments, we determined that spacecraft surfaces known to be frequently in contact with crew members demonstrated higher values of all three microbial molecules. Key Words: Planetary protection-Spaceflight-Microbiology-Biosensor. Astrobiology 12, 830-840.

  9. Bacterial degradation of aminopyrine. (United States)

    Blecher, H; Blecher, R; Wegst, W; Eberspaecher, J; Lingens, F


    1. Four strains of bacteria growing with aminopyrine as sole source of carbon were isolated from soil and were identified as strains of Phenylobacterium immobilis. 2. Strain M13 and strain E, the type species of Phenylobacterium immobilis (DSM 1986), which had been isolated by enrichment with chloridazon (5-amino-4-chloro-2-phenyl-2H-pyridazin-3-one) were used to investigate the bacterial degradation of aminopyrine. 3. Three metabolites were isolated and identified as: 4-(dimethylamino)-1,2-dihydro-1,5-dimethyl-2-(2,3-dihydro-2,3-dihydroxy-4,6-cyc lohexadien-1-yl)-3H-pyrazol-3-one, 4-(dimethylamino)-1,2-dihydro-1,5-dimethyl-2-(2,3-dihydroxyphenyl)-3H-pyrazol-3 -one and 4-(dimethylamino)-1,2-dihydro-1,5-dimethyl-3H-pyrazol-3-one. 4. An enzyme extract from cells of strain m13 was shown to further metabolize the catechol derivative of aminopyrine, with the formation of 2-pyrone-6-carboxylic acid. 5. Results indicate that the benzene ring of aminopyrine is the principal site of microbial metabolism.

  10. Electromagnetism of Bacterial Growth (United States)

    Ainiwaer, Ailiyasi


    There has been increasing concern from the public about personal health due to the significant rise in the daily use of electrical devices such as cell phones, radios, computers, GPS, video games and television. All of these devices create electromagnetic (EM) fields, which are simply magnetic and electric fields surrounding the appliances that simultaneously affect the human bio-system. Although these can affect the human system, obstacles can easily shield or weaken the electrical fields; however, magnetic fields cannot be weakened and can pass through walls, human bodies and most other objects. The present study was conducted to examine the possible effects of bacteria when exposed to magnetic fields. The results indicate that a strong causal relationship is not clear, since different magnetic fields affect the bacteria differently, with some causing an increase in bacterial cells, and others causing a decrease in the same cells. This phenomenon has yet to be explained, but the current study attempts to offer a mathematical explanation for this occurrence. The researchers added cultures to the magnetic fields to examine any effects to ion transportation. Researchers discovered ions such as potassium and sodium are affected by the magnetic field. A formula is presented in the analysis section to explain this effect.

  11. Evolution of Bacterial Suicide (United States)

    Tchernookov, Martin; Nemenman, Ilya


    While active, controlled cellular suicide (autolysis) in bacteria is commonly observed, it has been hard to argue that autolysis can be beneficial to an individual who commits it. We propose a theoretical model that predicts that bacterial autolysis is evolutionarily advantageous to an individualand would fixate in physically structured environments for stationary phase colonies. We perform spatially resolved agent-based simulations of the model, which predict that lower mixing in the environment results in fixation of a higher autolysis rate from a single mutated cell, regardless of the colony's genetic diversity. We argue that quorum sensing will fixate as well, even if initially rare, if it is coupled to controlling the autolysis rate. The model does not predict a strong additional competitive advantage for cells where autolysis is controlled by quorum sensing systems that distinguish self from nonself. These predictions are broadly supported by recent experimental results in B. subtilisand S. pneumoniae. Research partially supported by the James S McDonnell Foundation grant No. 220020321 and by HFSP grant No. RGY0084/2011.

  12. Bacterial endocarditis prophylaxis. (United States)

    Blanco-Carrión, Andrés


    Bacterial endocarditis (BE) is a disease resulting from the association of morphological alterations of the heart and bacteraemia originating from different sources that at times can be indiscernible (infectious endocarditis). It is classified on the basis of the morphological alteration involved, depending on the clinical manifestations and course of illness, which varies according to the causative microorganism and host conditions (for example, it is characteristic in I.V. drug users). The most common microorganisms involved are: Streptococcus viridans (55%), Staphylococcus aureus (30%), Enterococcus (6%) and HACEK bacteria (corresponding to the initials: Haemophilus, Actinobacillus, Cardiobacterium, Eikenella and Kingella), although on occasions it can also be caused by fungi. The oral microbiological flora plays a very important role in the aetiopathogenesis of BE, given that the condition may be of oral or dental origin. This paper will deal with the prevention of said bacteraemia. Prophylaxis will be undertaken using amoxicillin or clindamycin according to action protocols, with special emphasis placed on oral hygiene in patients with structural defects of the heart.

  13. Chiral Biomarkers and Microfossils in Carbonaceous Meteorites (United States)

    Hoover, Richard B.


    Homochirality of the biomolecules (D-sugars of DNA and RNA and L-amino acids of proteins) is a fundamental property of all life on Earth. Abiotic mechanisms yield racemic mixtures (D/L=1) of chiral molecules and after the death of an organism, the enantiopure chiral biomolecules slowly racemize. Several independent investigators have now established that the amino acids present in CI1 and CM2 carbonaceous meteorites have a moderate to strong excess of the L-enantiomer. Stable isotope data have established that these amino acids are both indigenous and extraterrestrial. Carbonaceous meteorites also contain many other strong chemical biomarkers including purines and pyrimidines (nitrogen heterocycles of nucleic acids); pristine and phytane (components of the chlorophyll pigment) and morphological biomarkers (microfossils of filamentous cyanobacteria). Energy dispersive X-ray Spectroscopy (EDS) analysis reveals that nitrogen is below the detectability level in most of the meteorite filaments as well as in Cambrian Trilobites and filaments of 2.7 Gya Archaean cyanobacteria from Karelia. The deficiency of nitrogen in the filaments and the total absence of sugars, of twelve of the life-critical protein amino acids, and two of the nucleobases of DNA and RNA provide clear and convincing evidence that these filaments are not modern biological contaminants. This paper reviews the chiral, chemical biomarkers morphological biomarkers and microfossils in carbonaceous meteorites. This paper reviews chiral and morphological biomarkers and discusses the missing nitrogen, sugars, protein amino acids, and nucleobases as ?bio-discriminators? that exclude modern biological contaminants as a possible explanation for the permineralized cyanobacterial filaments found in the meteorites.

  14. Circulating Biomarker Panels in Alzheimer's Disease. (United States)

    Zafari, Sachli; Backes, Christina; Meese, Eckart; Keller, Andreas


    The early diagnosis of diseases frequently represents an important unmet clinical need supporting in-time treatment of pathologies. This also applies to neurodegenerative diseases such as Alzheimer's disease (AD), the most common form of dementia, estimated to affect millions of individuals worldwide. The respective diagnostic and prognostic markers, especially for the preclinical stages of AD, are expected to improve patients' outcome significantly. In the last decades, many approaches to detecting AD have been developed, including markers to discover changes in amyloid-β levels [from cerebrospinal fluid (CSF) or using positron emission tomography] or other brain imaging technologies such as structural magnetic resonance imaging (MRI), functional-connectivity MRI or task-related functional MRI. A major challenge is the detection of AD using minimally or even noninvasive biomarkers from body fluids such as plasma or serum. Circulating biomarker candidates based on mRNAs or proteins measured from blood cells, plasma or serum have been proposed for various pathologies including AD. As for other diseases, there is a tendency to use marker signatures obtained by high-throughput approaches, which allow the generation of profiles of hundreds to thousands of biomarkers simultaneously [microarrays, mass spectrometry or next-generation sequencing (NGS)]. Beyond mRNAs and proteins, recent approaches have measured small noncoding RNA (so-called microRNA) profiles in AD patients' blood samples using NGS or array-based technologies. Generally, the development of marker panels is in its early stages and requires further, substantial clinical validation. In this review, we provide an overview of different circulating AD biomarkers, starting with a brief summary of CSF markers and focusing on novel biomarker signatures such as small noncoding RNA profiles.

  15. Biomarkers: how detect life on mineral matrix (United States)

    Fornaro, Teresa; Brucato, John Robert; Pucci, Amaranta; Baratta, Giuseppe; Branciamore, Sergio


    Life Marker Chip (LMC) is a bioanalytical instrument on board of the ESA Exomars mission to detect specific organic molecules that may be associated with life on Mars. Observation of possible biomarkers is critical for the understanding of prebiotic evolution and to detect signature of past and/or present life on other extraterrestrial body. Biomarkers usually are associated with mineral matrix, so it is necessary to investigate the nature of the interaction of organic molecules with minerals. Our approach is to combine physical-chemical analisys (adsorption isotherm, adsorption kinetics, surface area measurement, etc.) with FTIR and Raman spectroscopy in order to clarify the kind of interaction at molecular level between biomarkers and minerals. In particular we focus our attention on nucleobases that are the precursor of genetic material (DNA, RNA) with several minerals (MgO, forsterite, TiO2, hydroxylapatite, olivine) that mimic extraterrestrial materials. A second objective was to investigate the desorption processes in order to optimize the experimental procedure for the detection of biomarkers in the contest of LMC. In this study we have evaluated the effect of several parameters such as sonication and temperature on the extraction efficiency. Moreover because the desorption process strongly depends on the chemical nature of organics and minerals and on their own interaction, we have also evaluated the capability of different solvent mixtures (water, methanol, etc.) with different polarity and the use of surfactant (Tween 80) to extract previously adsorbed biomolecules. The results obtained could contribute to improve the biomarker extraction procedure in the LMC experiment.

  16. The Process Chain for Peptidomic Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Michael Schrader


    Full Text Available Over the last few years the interest in diagnostic markers for specific diseases has increased continuously. It is expected that they not only improve a patient's medical treatment but also contribute to accelerating the process of drug development. This demand for new biomarkers is caused by a lack of specific and sensitive diagnosis in many diseases. Moreover, diseases usually occur in different types or stages which may need different diagnostic and therapeutic measures. Their differentiation has to be considered in clinical studies as well. Therefore, it is important to translate a macroscopic pathological or physiological finding into a microscopic view of molecular processes and vice versa, though it is a difficult and tedious task. Peptides play a central role in many physiological processes and are of importance in several areas of drug research. Exploration of endogenous peptides in biologically relevant sources may directly lead to new drug substances, serve as key information on a new target and can as well result in relevant biomarker candidates. A comprehensive analysis of peptides and small proteins of a biological system corresponding to the respective genomic information (peptidomics®methods was a missing link in proteomics. A new peptidomic technology platform addressing peptides was recently presented, developed by adaptation of the striving proteomic technologies. Here, concepts of using peptidomics technologies for biomarker discovery are presented and illustrated with examples. It is discussed how the biological hypothesis and sample quality determine the result of the study. A detailed study design, appropriate choice and application of technology as well as thorough data interpretation can lead to significant results which have to be interpreted in the context of the underlying disease. The identified biomarker candidates will be characterised in validation studies before use. This approach for discovery of peptide

  17. Bacterial diversity in sediments of core MD05-2902 from the Xisha Trough, the South China Sea

    Institute of Scientific and Technical Information of China (English)

    LI Tao; WANG Peng


    A sediment core MD05-2902 was collected from the deep-sea basin of the Xisha Trough. The vertical dis-tribution and diversity of bacteria in the core was investigated through ten sub-sampling with an interval of 1 m using bacterial 16S rRNA gene as a phylogenetic bio-marker. Eighteen phylogenetic groups were identified from 16S rRNA gene clone libraries. The dominant bacterial groups were JS1, Planctomycetes and Chloroflexi, which accounted for 30.6%, 16.6%, and 15.6%of bacterial clones in the libraries, respectively. In order to reveal the relationship between biotic and abiotic data, a nonmetric multidimensional scaling analysis was performed. The result revealed that theδ15N,δ13C, total organic carbon and total organic ni-trogen possibly influenced the bacterial community structure. This study expanded our knowledge of the biogeochemical cycling in the Xisha Trough sediment.

  18. Influences of floral composition and environment on plant biomarkers across a Cretaceous landscape (Big Cedar Ridge) (United States)

    Bush, R. T.; Diefendorf, A. F.; Wing, S. L.; McInerney, F. A.


    The Late Cretaceous fossil site at Big Cedar Ridge (BCR; late Campanian, 72.7 Ma), located in the Bighorn Basin, Wyoming, USA, contains a flora preserved in situ in a volcanic ash tuff over an organic-rich paleosol. The BCR flora is irregularly but extensively exposed along a ~4 km north-south transect and records a lowland flora that grew on a coastal delta on the western shore of the Cretaceous Interior Seaway (Meeteetse Formation). The transect spans a diverse landscape and a range of environmental gradients from very carbon-rich, swampy soils in the southern portion to less carbon-rich in the north; the landscape is also intersected by multiple inactive channel cuts that were filling with sediment and organic matter at the time of ash deposition. Recently Wing and others (2012, Ecological Monographs) described the composition of the local plant community at high resolution across the entire landscape, including identification and quantification of cover and richness for >122 taxonomic morphotypes, for each of 100 sites along the transect. Big Cedar Ridge captures an important time in the ecological development of plant communities: the site preserves ferns, gymnosperms, and angiosperms in 'fern thicket' floral assemblages, which are rare today, as well as disturbed habitats with abundant herbaceous 'dicot' angiosperms. During the Late Cretaceous angiosperms were globally increasing in abundance, displacing other plant groups as vegetational dominants. This setting allows for a novel analysis of plant biomarkers in the context of floral diversity, abundance, and landscape heterogeneity. We quantified leaf waxes (n-alkyl lipids), plant-derived terpenoids, bacterial hopanes, carbon isotope values (including bulk and compound-specific), and percent total organic carbon of the underlying paleosol for 36 sites along the transect in order to assess the influence of floral composition and soil environment on biomarker distributions and preservation. We compare lipid

  19. Biomarkers for Primary Sjo¨ gren’s Syndrome

    Institute of Scientific and Technical Information of China (English)

    Weiqian Chen; Heng Cao; Jin Lin; Nancy Olsen; Song Guo Zheng


    Primary Sjogren’s syndrome (pSS) is a systemic autoimmune disease with exocrine gland dysfunction and multi-organ involvement. Recent progress in understanding the pathogenesis of pSS offers an opportunity to find new biomarkers for the diagnosis and assessment of disease activity. Screening noninvasive biomarkers from the saliva and tears has significant potential. The need for specific and sensitive biomarker candidates in pSS is significant. This review aims to summarize recent advances in the identification of biomarkers of Sjogren syndrome, trying to identify reliable, sensitive, and specific biomarkers that can be used to guide treatment decisions.

  20. Projection 0f Labor Needs and Productivity to Reduce Unemployment

    Directory of Open Access Journals (Sweden)

    Lestari Agusalim


    Full Text Available The purpose of this study is to estimate the amount of labor needs and productivity in Banten Province from 2016 until 2020. By estimating the needs and productivity of the labor, the government can use this information to create the appropriate policies in order to reduce the open unemployment rate (OUR in Banten Province. According to BPS data in 2014, OUR of Banten Province was the highest among other provinces in Java and second highest in Indonesia after Maluku. This study used the quantitative method, which are the exponential and geometric methods to project the labor needs. Other than that, this study used the descriptive method to interpret the quantitative data. The result showed that (1 from 2016 until 2020 there will be an increasing condition of employment, (2 from 2010 until 2014, the highest labor productivity were from electricity, gas and water sector. However from 2016 – 2020, the highest labor productivity will be from financing, insurance, real estate, land, and business services. (3 The number of OUR is expected to decrease annually. Meanwhile OUR in 2016 which is 7.39 percent will decrease to 3.94 percent in 2020.

  1. The Vegetation Red Edge Spectroscopic Feature as a Surface Biomarker

    CERN Document Server

    Seager, S


    The search for Earth-like extrasolar planets is in part motivated by the potential detection of spectroscopic biomarkers. Spectroscopic biomarkers are spectral features that are either consistent with life, indicative of habitability, or provide clues to a planet's habitability. Most attention so far has been given to atmospheric biomarkers, gases such as O2, O3, H2O, CO, and CH4. Here we discuss surface biomarkers. Surface biomarkers that have large, distinct, abrupt changes in their spectra may be detectable in an extrasolar planet's spectrum at wavelengths that penetrate to the planetary surface. Earth has such a surface biomarker: the vegetation "red edge" spectroscopic feature. Recent interest in Earth's surface biomarker has motivated Earthshine observations of the spatially unresolved Earth and two recent studies may have detected the vegetation red edge feature in Earth's hemispherically integrated spectrum. A photometric time series in different colors should help in detecting unusual surface feature...

  2. Meningitis bacteriana Bacterial meningitis

    Directory of Open Access Journals (Sweden)

    Ana Teresa Alvarado Guevara


    causales son virales lo cual conlleva a las diferentes sub-clasificaciones. También en ciertos casos puede ser ocasionada por hongos, bacterias atípicas, micobacterias y parásitos.In Costa Rica the bacterial meningitis had turn into a high-priority subject in which to monitoring epidemiologist. It had been talked about in the last months, to dice an increase in the attention is published of this subject, due to this phenomenon it becomes necessary to make a revision of topic. Meningitis is an inflammation of leptomeninges and colonization of the subarachnoid cerebrospinal fluid (LCR due to different agents, which produces meningeal symptoms (ex. migraine, neck rigidity, and photophobia and pleocytosis in LCR. De pending on the variables to take into account is possible to group it in different classifications, taking into account the time of evolution are possible to be divided in acute or chronic, to first with few hours or days of beginning of the symptoms, whereas the chronicle also presents a silence course but of the disease of approximately 4 weeks of instauration. There is a difference according to its etiologic agent; they can be infectious and non-infectious. Examples of common non-infectious causes include medications (ex, nonsteroidal anti-inflammatory drugs, and antibiotics and carcinomatosis. A classification exists as well according to the causal agent. The acute bacterial meningitis remarks a bacterial origin of the syndrome, which characterizes by the by an acute onset of meningeal symptoms and neutrophilic pleocytosis. Each one of the bacteriological agents, parasitic or fungus finishes by characterizing the different presentations of the clinical features (ex, meningocóccica meningitis, Cryptococcus meningitis. Finally, there is also the aseptic meningitis, denominated in this form because it’s nonpyogenic cellular response caused by many types of agents. The patients show an acute beginning of symptoms, fever and lymphocytic pleocytosis. After

  3. Bacterial Communities: Interactions to Scale

    Directory of Open Access Journals (Sweden)

    Reed M. Stubbendieck


    Full Text Available In the environment, bacteria live in complex multispecies communities. These communities span in scale from small, multicellular aggregates to billions or trillions of cells within the gastrointestinal tract of animals. The dynamics of bacterial communities are determined by pairwise interactions that occur between different species in the community. Though interactions occur between a few cells at a time, the outcomes of these interchanges have ramifications that ripple through many orders of magnitude, and ultimately affect the macroscopic world including the health of host organisms. In this review we cover how bacterial competition influences the structures of bacterial communities. We also emphasize methods and insights garnered from culture-dependent pairwise interaction studies, metagenomic analyses, and modeling experiments. Finally, we argue that the integration of multiple approaches will be instrumental to future understanding of the underlying dynamics of bacterial communities.

  4. Bacterial Chromosome Organization and Segregation


    Toro, Esteban; Shapiro, Lucy


    Bacterial chromosomes are generally ∼1000 times longer than the cells in which they reside, and concurrent replication, segregation, and transcription/translation of this crowded mass of DNA poses a challenging organizational problem. Recent advances in cell-imaging technology with subdiffraction resolution have revealed that the bacterial nucleoid is reliably oriented and highly organized within the cell. Such organization is transmitted from one generation to the next by progressive segrega...

  5. Bacterial Protein-Tyrosine Kinases

    DEFF Research Database (Denmark)

    Shi, Lei; Kobir, Ahasanul; Jers, Carsten


    phosphorylation. Protein-tyrosine phosphorylation in bacteria is particular with respect to very low occupancy of phosphorylation sites in vivo; this has represented a major challenge for detection techniques. Only the recent breakthroughs in gel-free high resolution mass spectrometry allowed the systematic...... and highlighted their importance in bacterial physiology. Having no orthologues in Eukarya, BY-kinases are receiving a growing attention from the biomedical field, since they represent a particularly promising target for anti-bacterial drug design....

  6. Surface micropattern limits bacterial contamination


    Mann, Ethan E.; Manna, Dipankar; Mettetal, Michael R; May, Rhea M.; Dannemiller, Elisa M; Chung, Kenneth K.; Brennan, Anthony B; Reddy, Shravanthi T


    Background Bacterial surface contamination contributes to transmission of nosocomial infections. Chemical cleansers used to control surface contamination are often toxic and incorrectly implemented. Additional non-toxic strategies should be combined with regular cleanings to mitigate risks of human error and further decrease rates of nosocomial infections. The Sharklet micropattern (MP), inspired by shark skin, is an effective tool for reducing bacterial load on surfaces without toxic additiv...

  7. Bacterial cellulose/boehmite composites

    Energy Technology Data Exchange (ETDEWEB)

    Salvi, Denise T.B. de; Barud, Hernane S.; Messaddeq, Younes; Ribeiro, Sidney J.L. [Universidade Estadual Paulista Julio de Mesquita Filho. UNESP. Instituto de Quimica de Araraquara, SP (Brazil); Caiut, Jose Mauricio A. [Universidade de Sao Paulo. Departamento de Quimica - FFCLRP/USP, Ribeirao Preto, SP (Brazil)


    Composites based on bacterial cellulose membranes and boehmite were obtained. SEM results indicate that the bacterial cellulose (BC) membranes are totally covered by boehmite and obtained XRD patterns suggest structural changes due to this boehmite addition. Thermal stability is accessed through TG curves and is dependent on boehmite content. Transparency is high comparing to pure BC as can be seen through UV-vis absorption spectroscopy. (author)

  8. Inconvenient truth: cancer biomarker development by using proteomics. (United States)

    Kondo, Tadashi


    A biomarker is a crucial tool for measuring the progress of disease and the effects of treatment for better clinical outcomes in cancer patients. Diagnostic, predictive, and prognostic biomarkers are required in various clinical settings. The proteome, a functional translation of the genome, is considered a rich source of biomarkers; therefore, sizable time and funding have been spent in proteomics to develop biomarkers. Although significant progress has been made in technologies toward comprehensive protein expression profiling, and many biomarker candidates published, none of the reported biomarkers have proven to be beneficial for cancer patients. The present deceleration in biomarker research can be attributed to technical limitations. Additional efforts are required to further technical progress; however, there are many examples demonstrating that problems in biomarker research are not so much with the technology but in the study design. In the study of biomarkers for early diagnosis, candidates are screened and validated by comparing cases and controls of similar sample size, and the low prevalence of disease is often ignored. Although it is reasonable to take advantage of multiple rather than single biomarkers when studying diverse disease mechanisms, the annotation of individual components of reported multiple biomarkers does not often explain the variety of molecular events underlying the clinical observations. In tissue biomarker studies, the heterogeneity of disease tissues and pathological observations are often not considered, and tissues are homogenized as a whole for protein extraction. In addition to the challenge of technical limitations, the fundamental aspects of biomarker development in a disease study need to be addressed. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.

  9. Methylated genes as new cancer biomarkers.

    LENUS (Irish Health Repository)

    Duffy, M J


    Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.

  10. Microparticles as Potential Biomarkers of Cardiovascular Disease

    Energy Technology Data Exchange (ETDEWEB)

    França, Carolina Nunes, E-mail: [Universidade Federal de São Paulo - UNIFESP - UNISA, SP, São Paulo (Brazil); Universidade de Santo Amaro - UNISA, SP, São Paulo (Brazil); Izar, Maria Cristina de Oliveira; Amaral, Jônatas Bussador do; Tegani, Daniela Melo; Fonseca, Francisco Antonio Helfenstein [Universidade Federal de São Paulo - UNIFESP - UNISA, SP, São Paulo (Brazil)


    Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice.

  11. MicroRNA biomarkers in glioblastoma

    DEFF Research Database (Denmark)

    Hermansen, Simon Kjær; Kristensen, Bjarne Winther


    Recent research suggests that deregulation of microRNAs (miRNAs) is involved in initiation and progression of many cancers, including gliomas and that miRNAs hold great potential as future diagnostic and therapeutic tools in cancer. MiRNAs are a class of short non-coding RNA sequences (18......-24 nucleotides), which base-pair to target messenger RNA (mRNA) and thereby cause translational repression or mRNA degradation based on the level of complementarity between strands. Profiling miRNAs in clinical glioblastoma samples has shown aberrant expression of numerous miRNAs when compared to normal brain...... tissues. Understanding these alterations is key to developing new biomarkers and intelligent treatment strategies. This review presents an overview of current knowledge about miRNA alterations in glioblastoma while focusing on the clinical future of miRNAs as biomarkers and discussing the strengths...

  12. HCC Biomarkers in China and Taiwan

    Directory of Open Access Journals (Sweden)

    Regina M. Santella


    Full Text Available

    A number of different types of biomarkers have been used to understand the etiology and progression of hepatocellular cancer (HCC. Perhaps the most well known are the serum/ plasma markers of HBV or HCV infection. These markers include analysis of viral DNA or proteins or antibodies produced against the viral proteins. HBV surface antigen (HBsAg is most frequently used to determine chronic infection with high or low viral replication, while HBeAg is a measure of chronic infection with high viral replication. Analysis of antibodies includes measurement of anti-HBV core antigen, anti-HBV e antigen and anti-HBsAg. The response to immunization can be monitored by analysis of anti-HBsAg. The other major classes of biomarkers used in studies of HCC are biomarkers of exposure to environmental, lifestyle or dietary carcinogens, biomarkers of oxidative stress and early biologic response. In addition, studies of genetic susceptibility have studied polymorphisms in a number of pathways and their role in HCC risk. The biomarkers of exposure include the measurement of carcinogens in urine and carcinogen-DNA and protein adducts. Examples are measurement of aflatoxin and polycyclic aromatic hydrocarbon metabolites, and DNA and protein adducts.

    Biomarkers of oxidative stress include urinary isoprostanes and 8-oxodeoxyguanosine and oxidized plasma proteins. Most of these assays are immunologic although the use of high performance liquid chromatograph (HPLC as well as gas chromatography/mass spectroscopy (GC/MS have been utilized. In nested case-control studies, many of these markers are associated with elevated risk. For example, elevated aflatoxin and polycyclic aromatic hydrocarbon-albumin adducts, aflatoxin metabolites in urine and urinary isoprostanes were observed in baseline samples from

  13. Current Status of Biomarkers for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Vicki M. Velonas


    Full Text Available Prostate cancer (PCa is a leading cause of cancer-related death of men globally. Since its introduction, there has been intense debate as to the effectiveness of the prostate specific antigen (PSA test as a screening tool for PCa. It is now evident that the PSA test produces unacceptably high rates of false positive results and is not prognostic. Here we review the current status of molecular biomarkers that promise to be prognostic and that might inform individual patient management. It highlights current efforts to identify biomarkers obtained by minimally invasive methods and discusses current knowledge with regard to gene fusions, mRNA and microRNAs, immunology, and cancer-associated microparticles.

  14. Biomarkers for Lupus Nephritis: A Critical Appraisal

    Directory of Open Access Journals (Sweden)

    Chi Chiu Mok


    Full Text Available Kidney disease is one of the most serious manifestations of systemic lupus erythematosus (SLE. Despite the improvement in the medical care of SLE in the past two decades, the prognosis of lupus nephritis remains unsatisfactory. Besides exploring more effective but less toxic treatment modalities that will further improve the remission rate, early detection and treatment of renal activity may spare patients from intensive immunosuppressive therapies and reduce renal damage. Conventional clinical parameters such as creatinine clearance, proteinuria, urine sediments, anti-dsDNA, and complement levels are not sensitive or specific enough for detecting ongoing disease activity in the lupus kidneys and early relapse of nephritis. Thus, novel biomarkers are necessary to enhance the diagnostic accuracy and sensitivity of lupus renal disease, prognostic stratification, monitoring of treatment response, and detection of early renal flares. This paper reviews promising biomarkers that have recently been evaluated in longitudinal studies of lupus nephritis.

  15. Metrology Standards for Quantitative Imaging Biomarkers. (United States)

    Sullivan, Daniel C; Obuchowski, Nancy A; Kessler, Larry G; Raunig, David L; Gatsonis, Constantine; Huang, Erich P; Kondratovich, Marina; McShane, Lisa M; Reeves, Anthony P; Barboriak, Daniel P; Guimaraes, Alexander R; Wahl, Richard L


    Although investigators in the imaging community have been active in developing and evaluating quantitative imaging biomarkers (QIBs), the development and implementation of QIBs have been hampered by the inconsistent or incorrect use of terminology or methods for technical performance and statistical concepts. Technical performance is an assessment of how a test performs in reference objects or subjects under controlled conditions. In this article, some of the relevant statistical concepts are reviewed, methods that can be used for evaluating and comparing QIBs are described, and some of the technical performance issues related to imaging biomarkers are discussed. More consistent and correct use of terminology and study design principles will improve clinical research, advance regulatory science, and foster better care for patients who undergo imaging studies.

  16. Biomarkers of Barrett’s esophagus

    Institute of Scientific and Technical Information of China (English)

    Yasser; Mahrous; Fouad; Ibrahim; Mostafa; Reem; Yehia; Hisham; El-Khayat


    Barrett’s esophagus is the strongest risk for esophageal adenocarcinoma(EAC). Metaplasia in patients with BE may progress to dysplasia and then invasive carcinoma. Well-defined diagnostic, progressive, predictive, and prognostic biomarkers are needed to identify the presence of the disease, estimate the risk of malignant transformation, and predict the therapeutic outcome and survival of EAC patients. There are many predictive and prognostic markers that lack substantial validation, and do not allow stratification of patients with gastroesophageal reflux disease in clinical practice for outcome and effectiveness of therapy. In this short review we summarize the current knowledge regarding possible biomarkers, focusing on the pathophysiologic mechanisms to improve prognostic and therapeutic approaches.

  17. Biomarkers of cognitive decline in Parkinson's disease. (United States)

    Lin, Chin-Hsien; Wu, Ruey-Meei


    Cognitive impairment is a frequent and devastating non-motor symptom of Parkinson's disease (PD). Impaired cognition has a major impact on either quality of life or mortality in patients with PD. Notably, the rate of cognitive decline and pattern of early cognitive deficits in PD are highly variable between individuals. Given that the underlying mechanisms of cognitive decline or dementia associated with PD remain unclear, there is currently no mechanism-based treatment available. Identification of biological markers, including neuroimaging, biofluids and common genetic variants, that account for the heterogeneity of PD related cognitive decline could provide important insights into the pathological processes that underlie cognitive impairment in PD. These combined biomarker approaches will enable early diagnosis and provide indicators of cognitive progression in PD patients. This review summarizes recent advances in the development of biomarkers for cognitive impairments in PD.

  18. Biomarkers for rheumatoid and psoriatic arthritis. (United States)

    Verheul, M K; Fearon, U; Trouw, L A; Veale, D J


    Rheumatic diseases, such as rheumatoid and psoriatic arthritis are systemic inflammatory conditions characterized by a chronic form of arthritis, often leading to irreversible joint damage. Early treatment for patients with rheumatic diseases is required to reduce or prevent joint injury. However, early diagnosis can be difficult and currently it is not possible to predict which individual patient will develop progressive erosive disease or who may benefit from a specific treatment according to their clinical features at presentation. Biomarkers are therefore required to enable earlier diagnosis and predict prognosis in both rheumatoid arthritis and psoriatic arthritis. In this review we will examine the evidence and current status of established and experimental biomarkers in rheumatoid and psoriatic arthritis for three important purposes; disease diagnosis, prognosis and prediction of response to therapy.

  19. Biomarker Records Associated with Mass Extinction Events (United States)

    Whiteside, Jessica H.; Grice, Kliti


    The history of life on Earth is punctuated by a series of mass extinction episodes that vary widely in their magnitude, duration, and cause. Biomarkers are a powerful tool for the reconstruction of historical environmental conditions and can therefore provide insights into the cause and responses to ancient extinction events. In examining the five largest mass extinctions in the geological record, investigators have used biomarkers to elucidate key processes such as eutrophy, euxinia, ocean acidification, changes in hydrological balance, and changes in atmospheric CO2. By using these molecular fossils to understand how Earth and its ecosystems have responded to unusual environmental activity during these extinctions, models can be made to predict how Earth will respond to future changes in its climate.

  20. Current and emerging breast cancer biomarkers

    Directory of Open Access Journals (Sweden)

    Maryam Sana


    Full Text Available Breast cancer treatment has experienced several advancements in the past few decades with the discovery of specific predictive and prognostic biomarkers that make possible the application of individualized therapies. In addition to traditional prognostic factors of breast carcinoma, molecular biomarkers have played a significant role in tumor prediction and treatment. The most frequent genetic alterations of breast cancer are gained along chromosome 1q, 8q, 17q, 20q, and 11q and losses along 8p, 13q, 16q, 18q, and 11q. Interestingly, many of these chromosomal fragments harbor known proto oncogenes or tumor suppressor genes such as BRCA1, BRCA2, p53, HER2-neu, cyclin D1, and cyclin E, which are briefly described in this review.

  1. Biomarker in der Osteologie: Aktueller Stand

    Directory of Open Access Journals (Sweden)

    Bieglmayer C


    Full Text Available Laboruntersuchungen helfen Ursachen von Osteopathien aufzudecken und Geschwindigkeit und Bilanz des Knochenumbaus zu beurteilen. Diese Faktoren können durch Resorptions- und Anbaumarker erfaßt werden. Für einige Marker haben wir geschlechtsspezifische Referenzbereiche evaluiert. Die Konzentrationsveränderungen zirkulierender Biomarker zeigen Erfolg oder Mißerfolg von osteoprotektiven Therapien erheblich rascher an als densitometrische Messungen. Die zur Interpretation von Verlaufsbeobachtungen wichtigen kleinsten signifikanten Änderungen der Markerspiegel liegen zwischen 15 % und 60%.

  2. Network-based drugs and biomarkers

    DEFF Research Database (Denmark)

    Erler, Janine Terra; Linding, Rune


    The structure and dynamics of protein signalling networks governs cell decision processes and the formation of tissue boundaries. Complex diseases such as cancer and diabetes are diseases of such networks. Therefore approaches that can give insight into how these networks change during disease pr...... associated technologies. We then focus on the multivariate nature of cellular networks and how this has implications for biomarker and drug discovery using cancer metastasis as an example....

  3. New serum biomarkers for prostate cancer diagnosis (United States)

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie


    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  4. New serum biomarkers for prostate cancer diagnosis

    Directory of Open Access Journals (Sweden)

    Kailash C Chadha


    Full Text Available Background: Prostate-specific antigen (PSA is currently used as a biomarker for diagnosis and management of prostate cancer (CaP. However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective: The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods: Concurrent measurements of circulating interleukin-8 (IL-8, Tumor necrosis factor-α (TNF-α and soluble tumor necrosis factor-α receptors 1 (sTNFR1 were obtained from four groups of men: (1 Controls (2 with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx (3 with clinically localized CaP and (4 with castration resistant prostate cancer. Results: TNF-α Area under the receiver operating characteristic curve (AUC = 0.93 and sTNFR1 (AUC = 0.97 were strong predictors of elPSA_negBx (vs. CaP. The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997. The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992 and PSA (AUC = 0.963 levels. Conclusions: The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted.

  5. Sleep electroencephalography as a biomarker in depression


    Steiger A; Pawlowski M.; Kimura M


    Axel Steiger, Marcel Pawlowski, Mayumi Kimura Max Planck Institute of Psychiatry, Munich, Germany Abstract: The sleep electroencephalogram (EEG) provides biomarkers of depression, which may help with diagnosis, prediction of therapy response, and prognosis in the treatment of depression. In patients with depression, characteristic sleep EEG changes include impaired sleep continuity, disinhibition of rapid-eye-movement (REM) sleep, and impaired non-REM sleep. Most antidepressants suppress REM...

  6. Cancer and molecular biomarkers of phase 2

    DEFF Research Database (Denmark)

    Dalhoff, Kim; Enghusen Poulsen, Henrik


    as molecular genetic biomarkers of risk. GSTM(my)1 has been associated with an increased risk of colorectal cancer, lung cancer, and bladder cancer and GSTP(pi)1 with prostate cancer. UGT1A1*28 and *37 are both associated with an increased risk of breast cancer as is SULT1A1*2. The presence of UGT1A1...

  7. Biomarkers for Basal-like Breast Cancer


    Choo, Jennifer R.; Torsten O. Nielsen


    Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of breast cancer through identification of subtype-specific biomarkers. This review aims to present an in depth summary and analysis of the current status of basal...

  8. Recent developments in biomarkers in Parkinson disease


    Schapira, Anthony H.V.


    Purpose of review Parkinson disease is the second most common neurodegenerative disease after Alzheimer disease, and current demographic trends indicate a life-time risk approaching 4% and predict a doubling of prevalence by 2030. Strategies are being developed to apply recent advances in our understanding of the cause of Parkinson disease to the development of biomarkers that will enable the identification of at-risk individuals, enable early diagnosis and reflect the progression of disease....

  9. Saliva: A diagnostic biomarker of periodontal diseases. (United States)

    Patil, Priti Basgauda; Patil, Basgauda Ramesh


    Early detection of disease plays a crucial role in successful therapy. Early diagnosis and management reduces the severity and possible complications of the disease process. To overcome this challenge, medical researchers are devoted to finding molecular disease biomarkers that reveal a hidden lethal threat before the disease becomes complicated. Saliva, an important physiologic fluid, containing a highly complex mixture of substances, is rapidly gaining popularity as a diagnostic tool. Periodontal disease is a chronic disease of the oral cavity comprising a group of inflammatory conditions affecting the supporting structures of the dentition. In the field of periodontology, traditional clinical criteria are often insufficient for determining sites of active disease, for monitoring the response to therapy, or for measuring the degree of susceptibility to future disease progression. Saliva, as a mirror of oral and systemic health, is a valuable source for clinically relevant information because it contains biomarkers specific for the unique physiologic aspects of periodontal diseases. This review highlights the various potentials of saliva as a diagnostic biomarker for periodontal diseases.

  10. Biomarkers for Gastroesophageal Reflux in Respiratory Diseases

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    Össur Ingi Emilsson


    Full Text Available Gastroesophageal reflux (GER is commonly associated with respiratory symptoms, either through a vagal bronchoconstrictive reflex or through microaspiration of gastric contents. No diagnostic test is available, however, to diagnose when respiratory illnesses are caused by GER and when not, but research in this field has been moving forward. Various biomarkers in different types of biosamples have been studied in this context. The aim of this review is to summarize the present knowledge in this field. GER patients with respiratory diseases seem to have a different biochemical profile from similar patients without GER. Inflammatory biomarkers differ in asthmatics based on GER status, tachykinins are elevated in patients with GER-related cough, and bile acids are elevated in lung transplant patients with GER. However, studies on these biomarkers are often limited by their small size, methods of analysis, and case selections. The two pathogenesis mechanisms are associated with different respiratory illnesses and biochemical profiles. A reliable test to identify GER-induced respiratory disorders needs to be developed. Bronchoalveolar lavage is too invasive to be of use in most patients. Exhaled breath condensate samples need further evaluation and standardization. The newly developed particles in exhaled air measurements remain to be studied further.

  11. Lung cancer biomarkers: State of the art

    Directory of Open Access Journals (Sweden)

    Sangeetha Subramaniam


    Full Text Available Lung cancer is one of the deadliest cancers worldwide, with the highest incidence and mortality amongst all cancers. While the prognosis of lung cancer is generally grim, with 5-year survival rates of only 15%, there is hope, and evidence, that early detection of lung cancer can reduce mortality. Today, only computed tomography screening has shown to lead to early detection and reduction in mortality, but is limited by being anatomic in nature, unable to differentiate between inflammatory and neoplastic pathways, and therefore, susceptible to false positives. There is increasing interest in biomarkers for lung cancer, especially those that predict metastatic risk. Some biomarkers like DNA mutations and epigenetic changes potentially require tissue from the at-risk site; some like serum proteins and miRNAs are minimally invasive, but may not be specific to the lung. In comparison, emerging biomarkers from exhaled breath, like volatile organic compounds (VOC, and exhaled breath condensate, e.g., small molecules and nucleic acids, have the potential to combine the best of both. This mini review is intended to provide an overview of the field, briefly discussing the potential of what is known and highlighting the exciting recent developments, particularly with miRNAs and VOCs.

  12. Biomarkers for early detection of Alzheimer disease. (United States)

    Barber, Robert C


    The existence of an effective biomarker for early detection of Alzheimer disease would facilitate improved diagnosis and stimulate therapeutic trials. Multidisciplinary clinical diagnosis of Alzheimer disease is time consuming and expensive and relies on experts who are rarely available outside of specialty clinics. Thus, many patients do not receive proper diagnosis until the disease has progressed beyond stages in which treatments are maximally effective. In the clinical trial setting, rapid, cost-effective screening of patients for Alzheimer disease is of paramount importance for the development of new treatments. Neuroimaging of cortical amyloid burden and volumetric changes in the brain and assessment of protein concentrations (eg, β-amyloid 1-42, total tau, phosphorylated tau) in cerebrospinal fluid are diagnostic tools that are not widely available. Known genetic markers do not provide sufficient discriminatory power between different forms of dementia to be useful in isolation. Recent studies using panels of biomarkers for diagnosis of Alzheimer disease or mild cognitive impairment have been promising, though no such studies have been cross-validated in independent samples of subjects. The ideal biomarker enabling early detection of Alzheimer disease has not yet been identified.

  13. Nanostructured optical microchips for cancer biomarker detection. (United States)

    Zhang, Tianhua; He, Yuan; Wei, Jianjun; Que, Long


    Herein we report the label-free detection of a cancer biomarker using newly developed arrayed nanostructured Fabry-Perot interferometer (FPI) microchips. Specifically, the prostate cancer biomarker free prostate-specific antigen (f-PSA) has been detected with a mouse anti-human PSA monoclonal antibody (mAb) as the receptor. Experiments found that the limit-of-detection of current nanostructured FPI microchip for f-PSA is about 10 pg/mL and the upper detection range for f-PSA can be dynamically changed by varying the amount of the PSA mAb immobilized on the sensing surface. The control experiments have also demonstrated that the immunoassay protocol used in the experiments shows excellent specificity and selectivity, suggesting the great potential to detect the cancer biomarkers at trace levels in complex biofluids. In addition, given its nature of low cost, simple-to-operation and batch fabrication capability, the arrayed nanostructured FPI microchip-based platform could provide an ideal technical tool for point-of-care diagnostics application and anticancer drug screen and discovery.

  14. Biological features and biomarkers in hepatocellularcarcinoma

    Institute of Scientific and Technical Information of China (English)


    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.

  15. Biomarkers and Pharmacogenetics in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Xunhai Xu


    Full Text Available Appropriate identification and validation of biomarkers as well as pharmacogenetics are important in formulating patient-oriented, individualized chemotherapy or biological therapy in cancer patients. These markers can be especially valuable in pancreatic cancer, where high mortality and complex disease biology are frequently encountered. Recently, several advances have been made to further our knowledge in this specific area of pancreatic cancer. In the 2011 American Society of Clinical Oncology (ASCO Annual Meeting, researchers have presented several interesting results in biomarkers development: the identifications of 9 single nucleotide polymorphisms (SNPs that is associated with positive efficacy of gemcitabine (Abstract #4022; the introduction of circulating tumor cells as a prognostic markers in pancreatic adenocarcinoma (Abstract #e14657; the re-affirmation of plasma cytidine deaminase (CDA as a positive predictive markers for gemcitabine efficacy, as well as the postulations that CDA*3 as a potential genotype marker to predict gemcitabine responses (Abstract #e14645; and finally the retrospective tumor tissues analysis in the Arbeitsgemeinschaft Internistische Onkologie (AIO trial in an attempt for epidermal growth factor receptor (EGFR pathway biomarker identifications (Abstract #4047

  16. Biomarkers of cardiovascular disease risk in women. (United States)

    Manson, JoAnn E; Bassuk, Shari S


    Cardiovascular disease (CVD), including coronary heart disease and stroke, is the leading cause of death among U.S. women and men. Established cardiovascular risk factors such as smoking, diabetes, hypertension, and elevated total cholesterol, and risk prediction models based on such factors, perform well but do not perfectly predict future risk of CVD. Thus, there has been much recent interest among cardiovascular researchers in identifying novel biomarkers to aid in risk prediction. Such markers include alternative lipids, B-type natriuretic peptides, high-sensitivity troponin, coronary artery calcium, and genetic markers. This article reviews the role of traditional cardiovascular risk factors, risk prediction tools, and selected novel biomarkers and other exposures in predicting risk of developing CVD in women. The predictive role of novel cardiovascular biomarkers for women in primary prevention settings requires additional study, as does the diagnostic and prognostic utility of cardiac troponins for acute coronary syndromes in clinical settings. Sex differences in the clinical expression and physiology of metabolic syndrome may have implications for cardiovascular outcomes. Consideration of exposures that are unique to, or more prevalent in, women may also help to refine cardiovascular risk estimates in this group.

  17. Parkinson's disease biomarkers program brain imaging repository. (United States)

    Ofori, Edward; Du, Guangwei; Babcock, Debra; Huang, Xuemei; Vaillancourt, David E


    The Parkinson's Disease Biomarkers Program (PDBP) is a multi-site study designed to identify Parkinson's disease (PD) biomarkers that can be used to improve the understanding of PD pathophysiology and to develop tools that provide novel measures to evaluate PD clinical trials. The PDBP consortium comprises numerous individual projects of which two are specifically geared to the development of brain imaging markers for diagnosis, progression, and prognosis of PD or related disorders. All study data from PD patients, atypical Parkinsonian patients, patients with essential tremor, and healthy controls collected from the sites are integrated in the PDBP database and will be publically available. All subjects are asked to submit blood samples, and undergo a battery of clinical evaluations that cover motor, cognitive, and other background information. In addition, a subset of subjects contributed cerebrospinal fluid samples. A restricted access, web-based Data Management Resource facilitates rapid sharing of data and biosamples across the entire PD research community. The PDBP consortium is a useful resource for research and collaboration aimed at the discovery of biomarkers and their use in understanding the pathophysiology of PD.

  18. Imaging biomarker roadmap for cancer studies (United States)

    O’Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; deSouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, John R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.


    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing ‘translational gaps’ through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored ‘roadmap’. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use. PMID:27725679

  19. Biomarkers for cardiac cachexia: reality or utopia. (United States)

    Martins, Telma; Vitorino, Rui; Amado, Francisco; Duarte, José Alberto; Ferreira, Rita


    Cardiac cachexia is a serious complication of chronic heart failure, characterized by significant weight loss and body wasting. Chronic heart failure-related muscle wasting results from a chronic imbalance in the activation of anabolic or catabolic pathways, caused by a series of immunological, metabolic, and neurohormonal processes. In spite of the high morbidity and mortality associated to this condition, there is no universally accepted definition or specific biomarkers for cardiac cachexia, which makes its diagnosis and treatment difficult. Several hormonal, inflammatory and oxidative stress molecules have been proposed as serological markers of prognosis in cardiac cachexia but with doubtful success. As individual biomarkers may have limited sensitivity and specificity, multimarker strategies involving mediators of the biological processes modulated by cardiac cachexia will strongly contribute for the diagnosis and management of the disease, as well as for the establishment of new therapeutic targets. An integrated analysis of the biomarkers proposed so far for cardiac cachexia is made in the present review, highlighting the biological processes to which they are related.

  20. Salivary pH: A diagnostic biomarker

    Directory of Open Access Journals (Sweden)

    Sharmila Baliga


    Full Text Available Objectives: Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. Study Design: The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. Results: The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001 whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001. Conclusion: These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

  1. Biological hypotheses and biomarkers of bipolar disorder. (United States)

    Sigitova, Ekaterina; Fišar, Zdeněk; Hroudová, Jana; Cikánková, Tereza; Raboch, Jiří


    The most common mood disorders are major depressive disorders and bipolar disorders (BD). The pathophysiology of BD is complex, multifactorial, and not fully understood. Creation of new hypotheses in the field gives impetus for studies and for finding new biomarkers for BD. Conversely, new biomarkers facilitate not only diagnosis of a disorder and monitoring of biological effects of treatment, but also formulation of new hypotheses about the causes and pathophysiology of the BD. BD is characterized by multiple associations between disturbed brain development, neuroplasticity, and chronobiology, caused by: genetic and environmental factors; defects in apoptotic, immune-inflammatory, neurotransmitter, neurotrophin, and calcium-signaling pathways; oxidative and nitrosative stress; cellular bioenergetics; and membrane or vesicular transport. Current biological hypotheses of BD are summarized, including related pathophysiological processes and key biomarkers, which have been associated with changes in genetics, systems of neurotransmitter and neurotrophic factors, neuroinflammation, autoimmunity, cytokines, stress axis activity, chronobiology, oxidative stress, and mitochondrial dysfunctions. Here we also discuss the therapeutic hypotheses and mechanisms of the switch between depressive and manic state.

  2. Lipids and Molecular Tools as Biomarkers in Monitoring Air Sparging Bioremediation Processes (United States)

    Heipieper, Hermann J.; Fischer, Janett


    The fluctuation of membrane lipids offers a promising tool as biomarkers for the analysis of microbial population changes as well as for the physiological status of micro-organisms. The investigation of changes in lipid composition is of common use for the assessment of physiological conditions in pure cultures. However, as lipid composition does not show drastic diversity among living organisms the use of lipids as biomarkers in mixed cultures and environmental samples has certain limitations. Therefore, special marker phospholipid fatty acids as well as modern statistical analysis of the results are necessary to receive certain information about the qualitative and quantitative changes of e.g. a soil microflora due to a contamination with organic compounds and its bioremediation. The use of lipids as biomarker in monitoring bioremediation are shown at the Hradčany site, a former Russian air force base in the Czech Republic that operated until 1990. In this time in an area of 32 ha soil and groundwater were contaminated with kerosene and BTEX compounds in an amount of 7,150 tons. This highly contaminated site is treated with the so-called air sparging method to clean-up the contamination by aerobic biodegradation. The results of PLFA analysis demonstrated a community shift to a gram-negative bacterial biomass with time. The results, including a principal component analysis (PCA) of the obtained fatty acid profiles, showed that the air sparging leads to substantial differences in microbial communities depending on the contamination levels and length of treatment, respectively. Obviously, the length of air sparging treatment controlling the BTEX concentration in soils causes temporal changes of bacterial community and adaptations of its respective members. This work was supported by the project BIOTOOL (Contract No. 003998) of the European Commission within its Sixth Framework Programme. Kabelitz N., Machackova J., Imfeld G., Brennerova M., Pieper D.H., Heipieper H

  3. The Human Vaginal Bacterial Biota and Bacterial Vaginosis

    Directory of Open Access Journals (Sweden)

    Sujatha Srinivasan


    Full Text Available The bacterial biota of the human vagina can have a profound impact on the health of women and their neonates. Changes in the vaginal microbiota have been associated with several adverse health outcomes including premature birth, pelvic inflammatory disease, and acquisition of HIV infection. Cultivation-independent molecular methods have provided new insights regarding bacterial diversity in this important niche, particularly in women with the common condition bacterial vaginosis (BV. PCR methods have shown that women with BV have complex communities of vaginal bacteria that include many fastidious species, particularly from the phyla Bacteroidetes and Actinobacteria. Healthy women are mostly colonized with lactobacilli such as Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus iners, though a variety of other bacteria may be present. The microbiology of BV is heterogeneous. The presence of Gardnerella vaginalis and Atopobium vaginae coating the vaginal epithelium in some subjects with BV suggests that biofilms may contribute to this condition.

  4. Biomarker evidence for Archean oxygen fluxes (Invited) (United States)

    Hallmann, C.; Waldbauer, J.; Sherman, L. S.; Summons, R. E.


    Knowledge of deep-time organismic diversity may be gained from the study of preserved sedimentary lipids with taxonomic specificity, i.e. biomarker hydrocarbons (e.g. Brocks and Summons, 2003; Waldbauer et al., 2009). As a consequence of long residence times and high thermal maturities however, biomarker concentrations are extremely low in most ancient (Precambrian) sediment samples, making them exceptionally prone to contamination during drilling, sampling and laboratory workup (e.g. Brocks et al., 2008). Outcrop samples most always carry a modern overprint and deep-time biogeochemistry thus relies on drilling operations to retrieve ‘clean’ sediment cores. One such effort was initiated by NASA’s Astrobiology Institute (NAI): the Archean biosphere drilling project (ABDP). We here report on the lipids retrieved from sediment samples in drill hole ABDP-9. Strong heterogeneities of extractable organic matter - both on a spatial scale and in free- vs. mineral-occluded bitumen - provide us with an opportunity to distinguish indigenous lipids from contaminants introduced during drilling. Stratigraphic trends in biomarker data for mineral-occluded bitumens are complementary to previously reported data (e.g. S- and N-isotopes, molybdenum enrichments) from ABDP-9 sediments (Anbar et al., 2007; Kaufman et al., 2007; Garvin et al., 2009) and suggest periodic fluxes of oxygen before the great oxidation event. Anbar et al. A whiff of oxygen before the great oxidation event. Science 317 (2007), 1903-1906. Brocks & Summons. Sedimentary hydrocarbons, biomarkers for early life. In: Schlesinger (Ed.) Treatise on Geochemistry, Vol. 8 (2003), 63-115. Brocks et al. Assessing biomarker syngeneity using branched alkanes with quaternary carbon (BAQCs) and other plastic contaminants. Geochimica et Cosmochimica Acta 72 (2008), 871-888. Garvin et al. Isotopic evidence for a aerobic nitrogen cycle in the latest Archean. Science 323 (2009), 1045-1048. Kaufman et al. Late Archean

  5. New Treatments for Bacterial Keratitis

    Directory of Open Access Journals (Sweden)

    Raymond L. M. Wong


    Full Text Available Purpose. To review the newer treatments for bacterial keratitis. Data Sources. PubMed literature search up to April 2012. Study Selection. Key words used for literature search: “infectious keratitis”, “microbial keratitis”, “infective keratitis”, “new treatments for infectious keratitis”, “fourth generation fluoroquinolones”, “moxifloxacin”, “gatifloxacin”, “collagen cross-linking”, and “photodynamic therapy”. Data Extraction. Over 2400 articles were retrieved. Large scale studies or publications at more recent dates were selected. Data Synthesis. Broad spectrum antibiotics have been the main stay of treatment for bacterial keratitis but with the emergence of bacterial resistance; there is a need for newer antimicrobial agents and treatment methods. Fourth-generation fluoroquinolones and corneal collagen cross-linking are amongst the new treatments. In vitro studies and prospective clinical trials have shown that fourth-generation fluoroquinolones are better than the older generation fluoroquinolones and are as potent as combined fortified antibiotics against common pathogens that cause bacterial keratitis. Collagen cross-linking was shown to improve healing of infectious corneal ulcer in treatment-resistant cases or as an adjunct to antibiotics treatment. Conclusion. Fourth-generation fluoroquinolones are good alternatives to standard treatment of bacterial keratitis using combined fortified topical antibiotics. Collagen cross-linking may be considered in treatment-resistant infectious keratitis or as an adjunct to antibiotics therapy.

  6. Bacterial carbonatogenesis; La carbonatogenese bacterienne

    Energy Technology Data Exchange (ETDEWEB)

    Castanier, S. [Angers Univ., 49 (France). Faculte des Sciences; Le Metayer-Levrel, G.; Perthuisot, J.P. [Nantes Univ., 44 (France). Laboratoire de Biogeologie, Faculte des Sciences et des Techniques


    Several series of experiments in the laboratory as well as in natural conditions teach that the production of carbonate particles by heterotrophic bacteria follows different ways. The `passive` carbonatogenesis is generated by modifications of the medium that lead to the accumulation of carbonate and bicarbonate ions and to the precipitation of solid particles. The `active` carbonatogenesis is independent of the metabolic pathways. The carbonate particles are produced by ionic exchanges through the cell membrane following still poorly known mechanisms. Carbonatogenesis appears to be the response of heterotrophic bacterial communities to an enrichment of the milieu in organic matter. The active carbonatogenesis seems to start first. It is followed by the passive one which induces the growth of initially produced particles. The yield of heterotrophic bacterial carbonatogenesis and the amounts of solid carbonates production by bacteria are potentially very high as compared to autotrophic or chemical sedimentation from marine, paralic or continental waters. Furthermore, the bacterial processes are environmentally very ubiquitous; they just require organic matter enrichment. Thus, apart from purely evaporite and autotrophic ones, all Ca and/or Mg carbonates must be considered as from heterotrophic bacterial origin. By the way, the carbon of carbonates comes from primary organic matter. Such considerations ask questions about some interpretations from isotopic data on carbonates. Finally, bacterial heterotrophic carbonatogenesis appears as a fundamental phase in the relationships between atmosphere and lithosphere and in the geo-biological evolution of Earth. (author) 43 refs.

  7. Cocktail effects on biomarker responses in fish

    Energy Technology Data Exchange (ETDEWEB)

    Celander, Malin C., E-mail: [University of Gothenburg, Department of Zoology, Box 463, SE-405 30 Gothenburg (Sweden)


    One of today's greatest challenges in environmental toxicology is to understand effects of mixture toxicity, commonly referred to as cocktail effects, in humans and in wildlife. Biomarker responses in fish are routinely used to assess exposure of anthropogenic chemicals in the aquatic environment. However, little is known about how cocktail effects affect these biomarker responses. For this reason, there is an obvious risk for misinterpretation of biomarker-data and this can have profound negative effects on stakeholder's decisions and actions, as well as on legislations and remediation-plans initiated in order to reduce exposure to certain chemicals. Besides, chemical safety-levels are traditionally based on experiences from lab-studies with single chemicals, which is unfortunate as a chemical can be more toxic when it is mixed with other chemicals, because of the cocktail effect. This review focuses on pharmacokinetic interactions between different classes of pollutants on detoxification mechanisms and how that affects two commonly used biomarkers in the aquatic environment: (1) induction of cytochrome P450 1A (CYP1A) that is mediated via activation of the arylhydrocarbon receptor (AhR), used to assess exposure to aromatic hydrocarbons; (2) induction of vitellogenin (VTG) that is mediated via activation of the estrogen receptor (ER), used to assess exposure to estrogenic chemicals. These responses can be either directly or indirectly affected by the presence of other classes of pollutants as a result of cocktail effects. For example, chemicals that inhibit the function of key metabolic enzymes and transporter pumps that are involved in elimination of AhR- and ER agonists, can result in bioaccumulation of aromatic hydrocarbons and estrogenic chemicals resulting in increased biomarker responses. This cocktail effect can lead to overestimation of the actual exposure pressure. On the contrary, induction of expression of key metabolic enzymes and transporter

  8. Investigation of Hopanoid Biomarkers in Lake Sediments by GC-MS and RP-HPLC-APCI-MS

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    Gamze Kavran Belin


    Full Text Available Hopanoids are mainly derived from bacteriohopanpolyols that occur especially in bacteria, show the importance of bacterial lipid contributions in geological materials. In this work, GC-MS and RP-HPLC-APCI-MS analyses of hopanoid biomarkers in oxic and anoxic sediment samples from Lake Cadagno (Swiss Alps and Lake Voua de la Motte (Haute Savoie, France are presented and discussed. Samples were ultrasonically extracted, fractionated by flush chromatography on silica gel and derivatised before the analyses. Periodic acid/ sodium borohydride cleavage was used to identify highly functionalised hopanoids

  9. Proteomic biomarkers of preterm birth risk in women with polycystic ovary syndrome (PCOS: a systematic review and biomarker database integration.

    Directory of Open Access Journals (Sweden)

    Nicolas Galazis

    Full Text Available BACKGROUND: Preterm Birth (PTB is a major cause of neonatal mortality and morbidity. Women with Polycystic Ovary Syndrome (PCOS are at high risk of PTB. There is a need for research studies to investigate the mechanisms linking PCOS and PTB, to facilitate screening, and develop novel preventative strategies. OBJECTIVE: To list all the proteomic biomarkers of PTB and integrate this list with the PCOS biomarker database to identify commonly expressed biomarkers of the two conditions. SEARCH STRATEGY: A systematic review of PTB biomarkers and update of PCOS biomarker database. All eligible published studies on proteomic biomarkers for PTB and PCOS identified through various databases were evaluated. SELECTION CRITERIA: For the identification of the relevant studies, the following search terms were used: "proteomics", "proteomic", "preterm birth", "preterm labour", "proteomic biomarker" and "polycystic ovary syndrome". This search was restricted to humans only DATA COLLECTION AND ANALYSIS: A database on proteomic biomarkers for PTB was created while an already existing PCOS biomarker database was updated. The two databases were integrated and biomarkers that were co-expressed in both women with PCOS and PTB were identified and investigated. RESULTS: A panel of six proteomic biomarkers was similarly differentially expressed in women with PTB and women with PCOS compared to their respective controls (normal age-matched women in the case of PCOS studies and women with term pregnancy in the case of PTB studies. These biomarkers include Pyruvate kinase M1/M2, Vimentin, Fructose bisphosphonate aldolase A, Heat shock protein beta-1, Peroxiredoxin-1 and Transferrin. CONCLUSIONS: These proteomic biomarkers (Pyruvate kinase M1/M2, Vimentin, Fructose bisphosphonate aldolase A, Heat shock protein beta-1, Peroxiredoxin-1 and Transferrin can be potentially used to better understand the pathophysiological mechanisms linking PCOS and PTB. This would help to

  10. A proteomic approach for the diagnosis of bacterial meningitis.

    Directory of Open Access Journals (Sweden)

    Sarah Jesse

    Full Text Available BACKGROUND: The discrimination of bacterial meningitis (BM versus viral meningitis (VM shapes up as a problem, when laboratory data are not equivocal, in particular, when Gram stain is negative. METHODOLOGY/PRINCIPAL FINDINGS: With the aim to determine reliable marker for bacterial or viral meningitis, we subjected cerebrospinal fluid (CSF to a quantitative proteomic screening. By using a recently established 2D-DIGE protocol which was adapted to the individual CSF flow, we compared a small set of patients with proven BM and VM. Thereby, we identified six potential biomarkers out of which Prostaglandin-H2 D-isomerase was already described in BM, showing proof of concept. In the subsequent validation phase on a more comprehensive collective of 80 patients, we could validate that in BM high levels of glial fibrillary acidic protein (GFAP and low levels of soluble amyloid precursor protein alpha/beta (sAPPalpha/beta are present as possible binding partner of Fibulin-1. CONCLUSIONS/SIGNIFICANCE: We conclude that our CSF flow-adapted 2D-DIGE protocol is valid especially in comparing samples with high differences in total protein and suppose that GFAP and sAPPalpha/beta have a high potential as additional diagnostic markers for differentiation of BM from VM. In the clinical setting, this might lead to an improved early diagnosis and to an individual therapy.

  11. Ecology and distribution of a new biomarker linked to 1,2-dichloropropane dechlorination in subsurface environments (United States)

    Padilla-Crespo, E.; Loeffler, F. E.


    Reductive dechlorination plays a major role in the transformation and detoxification of chlorinated solvents, including chlorinated ethenes. Molecular biological tools are being applied at contaminated sites in order to assess the process-specific biomarkers that impact site performance, and to monitor the progress of bioremediation approaches. The few current biomarker genes in use provide an incomplete picture of the reductively dechlorinating bacterial community; this is a limitation for implementing enhanced bioremediation and monitored natural attenuation as cleanup strategies at chlorinated solvent contaminated sites. Reductively dehalogenating organisms, particularly Dehalococcoides (Dhc) strains, possess multiple reductive dehalogenase (RDase) genes, which are promising targets to specifically monitor dehalogenation processes of interest. Dehalococcoides populations in two highly enriched cultures (RC and KS) have been implicated in the reductive dechlorination of dechlorination of 1,2-dichloropropane (1,2-D), a widespread halogenated organic pollutant, to the non-toxic propene. Using a combined approach of transcription, expression and molecular analysis a new biomarker linked to 1,2-dichloropropane has been identified in Dhc strains RC and KS providing for the first time, convincing evidence of a specific RDase implicated in 1,2-D dechlorination to propene. Further analyses imply that new biomarker is in a "mobile DNA segment", a genomic island (GI) of horizontal gene transfer origin. A valid quantitative PCR approach was designed to detect and enumerate this gene in cultures and environmental samples; this will be a useful to bioremediation practitioners to more efficiently implement reductive dechlorination as a remediation tool. The new biomarker has been identified in fresh water sediment samples from different geographical locations in Europe, North and South America. Further research aims to shed light on RDase gene dissemination and the adaptation

  12. A review on airway biomarkers: exposure, effect and susceptibility. (United States)

    Corradi, Massimo; Goldoni, Matteo; Mutti, Antonio


    Current research in pulmonology requires the use of biomarkers to investigate airway exposure and diseases, for both diagnostic and prognostic purposes. The traditional approach based on invasive approaches (lung lavages and biopsies) can now be replaced, at least in part, through the use of non invasively collected specimens (sputum and breath), in which biomarkers of exposure, effect and susceptibility can be searched. The discovery of specific lung-related proteins, which can spill over in blood or excreted in urine, further enhanced the spectrum of airway specific biomarkers to be studied. The recent introduction of high-performance 'omic' technologies - genomics, proteomics and metabolomics, and the rate at which biomarker candidates are being discovered, will permit the use of a combination of biomarkers for a more precise selection of patient with different outcomes and responses to therapies. The aim of this review is to critically evaluate the use of airway biomarkers in the context of research and clinical practice.

  13. Biomarkers of Aging: From Function to Molecular Biology. (United States)

    Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard


    Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  14. The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Nielsen, Katja Maretty; Keller, Johnny;


    OBJECTIVE: Certain biomarkers such as the C-reactive protein, serum albumin, and the neutrophils to lymphocyte ratio are of prognostic significance regarding survival in different types of cancers. Data from sarcoma patients are sparse and mainly derived from soft tissue sarcoma and/or metastatic...... cases. Adjusting for confounders such as comorbidity and age is an essential safeguard against erroneous conclusions regarding the possible prognostic value of these biomarkers. The aim of this study was to assess the prognostic value of a battery of pretreatment biomarkers in the serum of patients......, lymphocytes, and sodium were collected from the patient records. The prognostic values of overall and disease-specific mortality were tested for each individual biomarker as well as for the Glasgow prognostic score (GPS) and for a new composite score incorporating five biomarkers (Aarhus composite biomarker...

  15. Bacterial Degradation of Aromatic Compounds

    Directory of Open Access Journals (Sweden)

    Qing X. Li


    Full Text Available Aromatic compounds are among the most prevalent and persistent pollutants in the environment. Petroleum-contaminated soil and sediment commonly contain a mixture of polycyclic aromatic hydrocarbons (PAHs and heterocyclic aromatics. Aromatics derived from industrial activities often have functional groups such as alkyls, halogens and nitro groups. Biodegradation is a major mechanism of removal of organic pollutants from a contaminated site. This review focuses on bacterial degradation pathways of selected aromatic compounds. Catabolic pathways of naphthalene, fluorene, phenanthrene, fluoranthene, pyrene, and benzo[a]pyrene are described in detail. Bacterial catabolism of the heterocycles dibenzofuran, carbazole, dibenzothiophene, and dibenzodioxin is discussed. Bacterial catabolism of alkylated PAHs is summarized, followed by a brief discussion of proteomics and metabolomics as powerful tools for elucidation of biodegradation mechanisms.

  16. Pupillometry and Saccades as Objective mTBI Biomark (United States)


    1 AWARD NUMBER: W81XWH-14-C-0048 TITLE: Pupillometry and Saccades as Objective mTBI Biomark PRINCIPAL INVESTIGATOR: LTC Jose E. Capo-Aponte...Pupillometry and Saccades as Objective mTBI Biomark 5a. CONTRACT NUMBER W81XWH-14-C-0048 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) LTC... objective biomarkers 14. ABSTRACT The objective of the study is to validate pupillary light reflex (PLR), saccadic and convergence eye movements as

  17. Validation of Biomarker-based risk prediction models


    Taylor, Jeremy M.G.; Ankerst, Donna P.; Andridge, Rebecca R.


    The increasing availability and use of predictive models to facilitate informed decision making highlights the need for careful assessment of the validity of these models. In particular, models involving biomarkers require careful validation for two reasons: issues with overfitting when complex models involve a large number of biomarkers, and inter-laboratory variation in assays used to measure biomarkers. In this paper we distinguish between internal and external statistical validation. Inte...

  18. Sparse discriminant analysis for breast cancer biomarker identification and classification

    Institute of Scientific and Technical Information of China (English)

    Yu Shi; Daoqing Dai; Chaochun Liu; Hong Yan


    Biomarker identification and cancer classification are two important procedures in microarray data analysis. We propose a novel uni-fied method to carry out both tasks. We first preselect biomarker candidates by eliminating unrelated genes through the BSS/WSS ratio filter to reduce computational cost, and then use a sparse discriminant analysis method for simultaneous biomarker identification and cancer classification. Moreover, we give a mathematical justification about automatic biomarker identification. Experimental results show that the proposed method can identify key genes that have been verified in biochemical or biomedical research and classify the breast cancer type correctly.

  19. Cerebrospinal fluid biomarkers in neurological diseases in children. (United States)

    Shahim, Pashtun; Månsson, Jan-Eric; Darin, Niklas; Zetterberg, Henrik; Mattsson, Niklas


    Analysis of cerebrospinal fluid (CSF) biomarkers is an integral part of neurology. Basic CSF biomarkers, such as CSF/serum albumin ratio and CSF cell counts, have been used to diagnose inflammatory and infectious CNS disorders in adults and children for decades. During recent years, however, numerous biomarkers for neuronal and astroglial injury, as well as disease-specific protein inclusions, have been developed for neurodegenerative disorders in adults. The overall aim of this paper is to give an updated overview of some of these biomarkers with special focus on their possible relevance to neurological disorders in children and adolescents.

  20. The economics of cardiac biomarker testing in suspected myocardial infarction. (United States)

    Goodacre, Steve; Thokala, Praveen


    Suspected myocardial infarction (MI) is a common reason for emergency hospital attendance and admission. Cardiac biomarker measurement is an essential element of diagnostic assessment of suspected MI. Although the cost of a routinely available biomarker may be small, the large patient population and consequences in terms of hospital admission and investigation mean that the economic impact of cardiac biomarker testing is substantial. Economic evaluation involves comparing the estimated costs and effectiveness (outcomes) of two or more interventions or care alternatives. This process creates some difficulties with respect to cardiac biomarkers. Estimating the effectiveness of cardiac biomarkers involves identifying how they help to improve health and how we can measure this improvement. Comparison to an appropriate alternative is also problematic. New biomarkers may be promoted on the basis of reducing hospital admission or length of stay, but hospital admission for low risk patients may incur significant costs while providing very little benefit, making it an inappropriate comparator. Finally, economic evaluation may conclude that a more sensitive biomarker strategy is more effective but, by detecting and treating more cases, is also more expensive. In these circumstances it is unclear whether we should use the more effective or the cheaper option. This article provides an introduction to health economics and addresses the specific issues relevant to cardiac biomarkers. It describes the key concepts relevant to economic evaluation of cardiac biomarkers in suspected MI and highlights key areas of uncertainty and controversy.

  1. Coherent pipeline for biomarker discovery using mass spectrometry and bioinformatics

    Directory of Open Access Journals (Sweden)

    Al-Shahib Ali


    Full Text Available Abstract Background Robust biomarkers are needed to improve microbial identification and diagnostics. Proteomics methods based on mass spectrometry can be used for the discovery of novel biomarkers through their high sensitivity and specificity. However, there has been a lack of a coherent pipeline connecting biomarker discovery with established approaches for evaluation and validation. We propose such a pipeline that uses in silico methods for refined biomarker discovery and confirmation. Results The pipeline has four main stages: Sample preparation, mass spectrometry analysis, database searching and biomarker validation. Using the pathogen Clostridium botulinum as a model, we show that the robustness of candidate biomarkers increases with each stage of the pipeline. This is enhanced by the concordance shown between various database search algorithms for peptide identification. Further validation was done by focusing on the peptides that are unique to C. botulinum strains and absent in phylogenetically related Clostridium species. From a list of 143 peptides, 8 candidate biomarkers were reliably identified as conserved across C. botulinum strains. To avoid discarding other unique peptides, a confidence scale has been implemented in the pipeline giving priority to unique peptides that are identified by a union of algorithms. Conclusions This study demonstrates that implementing a coherent pipeline which includes intensive bioinformatics validation steps is vital for discovery of robust biomarkers. It also emphasises the importance of proteomics based methods in biomarker discovery.

  2. Acute kidney injury in children: Enhancing diagnosis with novel biomarkers

    Directory of Open Access Journals (Sweden)

    Samuel Nkachukwu Uwaezuoke


    Full Text Available This narrative review aims to appraise the sensitivity and specificity of novel biomarkers in identifying acute kidney injury (AKI in children. Serum creatinine represents a poor traditional biomarker for AKI due to some limitations. Although alternative reliable biomarkers that would better identify individuals at high risk for developing AKI, identify AKI early enough, monitor its progression and patients' recovery, as well as identify those patients at higher risk for poor outcomes are not yet available in renal care, the search-light has recently been focused on various novel biomarkers, some of which could provide this information in time ahead. Several studies have established their predictive value. However, none of them could solely fulfill all the criteria of the ideal biomarker. Therefore, to increase their sensitivity and specificity and enhance the diagnosis of AKI, constellations of different biomarkers with specific features are probably required. In future, the diagnostic evaluation of AKI in intensive care units will have to undergo a paradigm shift from serum creatinine as the traditional biomarker to tissue-specific injury biomarkers. A panel of these novel biomarkers employed at the bedside setting will ultimately revolutionize the diagnosis and prognostication of AKI in children.

  3. YKL-40: a new biomarker in cardiovascular disease?

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Henningsen, Kristoffer Mads Aaris; Harutyunyan, Marina Jurjevna;


    . But in spite of improved treatments, many patients are still plagued by a high frequency of angina symptoms, hospitalizations and a poor prognosis. There is a need for new independent or supplementary biomarkers that can help to predict cardiovascular disease and cardiovascular events earlier and more...... precisely, and thus accompany existing biomarkers in both primary and secondary cardiovascular prevention. One such potential new biomarker is the protein YKL-40. As an independent biomarker in both cardiovascular diseases and noncardiovascular diseases, current evidence suggests YKL-40 to be most useful...

  4. The Search for Biomarkers in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Anna Meiliana


    Full Text Available BACKGROUND: As population demographic shift and the number of individuals with Alzheimer Disease (AD continue to increase, the challenge is to develop targeted, effective treatments and our ability to recognize early symptoms. In view of this, the need for specific AD biomarker is crucial. CONTENT: In recent years it has become evident that CSF concentrations of some brain-specific proteins are related to underlying disease pathogenesis and may therefore aid clinical investigation. Among several, we have focused on three candidates that have been suggested to fulfil the requirements for biomarkers of AD: β-amyloid 42 (Aβ42, total Tau (T-tau and tau phosphorylated at various epitopes (P-tau. An increasing number of studies suggest that supplementary use of these CSF markers, preferably in combination, adds to the accuracy of an AD diagnosis. More recently visinin-like protein (VLP-1, a marker for neuronal cell injury has been studied. CSF VLP-1 concentrations were 50% higher in AD patients than in the control population. SUMMARY: The number of studies aimed at the identification of new biomarkers for AD is expected to increase rapidly, not only because of the increasing insights into the pathological mechanisms underlying this disease, but also because new therapies have been developed or are under consideration now, which warrant an early and specific diagnosis for effective treatment of the patients. KEYWORDS: dementia, amyloid plaque, neurofibrillary tangels, amyloid β-peptide 42 (Aβ42, total tau (T-tau, phosphorylated tau (P-tau, visinin–like protein 1 (VLP-1.

  5. Salivary biomarkers for detection of systemic diseases.

    Directory of Open Access Journals (Sweden)

    Nilminie Rathnayake

    Full Text Available BACKGROUND AND OBJECTIVE: Analysis of inflammatory biomarkers in saliva could offer an attractive opportunity for the diagnosis of different systemic conditions specifically in epidemiological surveys. The aim of this study was to investigate if certain salivary biomarkers could be used for detection of common systemic diseases. MATERIALS AND METHODS: A randomly selected sample of 1000 adults living in Skåne, a county in the southern part of Sweden, was invited to participate in a clinical study of oral health. 451 individuals were enrolled in this investigation, 51% women. All participants were asked to fill out a questionnaire, history was taken, a clinical examination was made and stimulated saliva samples were collected. Salivary concentrations of IL-1β, -6, -8, TNF-α, lysozyme, MMP-8 and TIMP-1 were determined using ELISA, IFMA or Luminex assays. RESULTS: Salivary IL-8 concentration was found to be twice as high in subjects who had experience of tumour diseases. In addition, IL-8 levels were also elevated in patients with bowel disease. MMP-8 levels were elevated in saliva from patients after cardiac surgery or suffering from diabetes, and muscle and joint diseases. The levels of IL-1β, IL-8 and MMP-8, as well as the MMP-8/TIMP-1 ratio were higher in subjects with muscle and joint diseases. CONCLUSION: Biomarkers in saliva have the potential to be used for screening purposes in epidemiological studies. The relatively unspecific inflammatory markers used in this study can not be used for diagnosis of specific diseases but can be seen as markers for increased systemic inflammation.

  6. Cerebrospinal Fluid Biomarkers of Simian Immunodeficiency Virus Encephalitis : CSF Biomarkers of SIV Encephalitis. (United States)

    Bissel, Stephanie J; Kofler, Julia; Nyaundi, Julia; Murphey-Corb, Michael; Wisniewski, Stephen R; Wiley, Clayton A


    Antiretroviral therapy has led to increased survival of HIV-infected patients but also increased prevalence of HIV-associated neurocognitive disorders. We previously identified YKL40 as a potential cerebrospinal fluid (CSF) biomarker of lentiviral central nervous system (CNS) disease in HIV-infected patients and in the macaque model of HIV encephalitis. The aim of this study was to define the specificity and sensitivity along with the predictive value of YKL40 as a biomarker of encephalitis and to assess its relationship to CSF viral load. CSF YKL40 and SIV RNA concentrations were analyzed over the course of infection in 19 SIV-infected pigtailed macaques and statistical analyses were performed to evaluate the relationship to encephalitis. Using these relationships, CSF alterations of 31 neuroimmune markers were studied pre-infection, during acute and asymptomatic infection, at the onset of encephalitis, and at necropsy. YKL40 CSF concentrations above 1122 ng/ml were found to be a specific and sensitive biomarker for the presence of encephalitis and were highly correlated with CSF viral load. Macaques that developed encephalitis had evidence of chronic CNS immune activation during early, asymptomatic, and end stages of infection. At the onset of encephalitis, CSF demonstrated a rise of neuroimmune markers associated with macrophage recruitment, activation and interferon response. CSF YKL40 concentration and viral load are valuable biomarkers to define the onset of encephalitis. Chronic CNS immune activation precedes the development of encephalitis while some responses suggest protection from CNS lentiviral disease.

  7. BIOMARKERS New biomarker for Sjogren's syndrome-time to treat patients

    NARCIS (Netherlands)

    Kroese, Frans G. M.; Bootsma, Hendrika


    Recent progress in our understanding of the pathogenesis of primary Sjgren's syndrome (pSS) and the development of indices to measure disease activity in patients with this condition, offer us ample possibilities for treatment with biologic DMARDs. New biomarkers further aid selection of patients wi

  8. Exhaled Breath Condensate for Proteomic Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Sean W. Harshman


    Full Text Available Exhaled breath condensate (EBC has been established as a potential source of respiratory biomarkers. Compared to the numerous small molecules identified, the protein content of EBC has remained relatively unstudied due to the methodological and technical difficulties surrounding EBC analysis. In this review, we discuss the proteins identified in EBC, by mass spectrometry, focusing on the significance of those proteins identified. We will also review the limitations surrounding mass spectral EBC protein analysis emphasizing recommendations to enhance EBC protein identifications by mass spectrometry. Finally, we will provide insight into the future directions of the EBC proteomics field.

  9. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D


    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  10. T lymphocyte surface expression of exhaustion markers as biomarkers of the efficacy of chemotherapy for tuberculosis (United States)

    Henao-Tamayo, Marcela; Irwin, Scott M.; Shang, Shaobin; Ordway, Diane; Orme, Ian M.


    Summary Predictive biomarkers illustrating the effectiveness of chemotherapeutic regimens for tuberculosis still remain elusive. To date, most are predicated on assays using sputum or serum; as a result, if not predictive, treatment failure in patients may not be evident for some time. We report here the results of a simple screening study in which T cell surface markers were examined in mice infected with Mycobacterium tuberculosis and then treated with drugs. These studies identified certain markers, the exhaustion markers PD-1 and TIM-3, as well as the marker KLRG-1, particularly on CD8 T cells, that changed in concert with reduction of the bacterial load in the lungs. While there is no guarantee these changes would also be seen on T cells in the blood, this approach should be further investigated. PMID:21530406

  11. Molecular mechanisms underlying bacterial persisters

    DEFF Research Database (Denmark)

    Maisonneuve, Etienne; Gerdes, Kenn


    All bacteria form persisters, cells that are multidrug tolerant and therefore able to survive antibiotic treatment. Due to the low frequencies of persisters in growing bacterial cultures and the complex underlying molecular mechanisms, the phenomenon has been challenging to study. However, recent...

  12. Bacterial Cytotoxins Target Rho GTPases (United States)

    Schmidt, Gudula; Aktories, Klaus


    Low molecular mass GTPases of the Rho family, which are involved in the regulation of the actin cytoskeleton and in various signal transduction processes, are the eukaryotic targets of bacterial protein toxins. The toxins covalently modify Rho proteins by ADP ribosylation, glucosylation, and deamidation, thereby inactivating and activating the GTPases.

  13. Disease notes - Bacterial root rot (United States)

    Bacterial root rot initiated by lactic acid bacteria, particularly Leuconostoc, occurs every year in Idaho sugarbeet fields. Hot fall weather seems to make the problem worse. Although Leuconostoc initiates the rot, other bacteria and yeast frequently invade the tissue as well. The acetic acid bac...

  14. Bacterial canker resistance in tomato

    NARCIS (Netherlands)

    Sen, Y.


    Clavibacter michiganensis subsp. michiganensis (Cmm) is the pathogen causing bacterial  canker in tomato. The disease was described for the first time in 1910 in Michigan, USA. Cmmis considered the most harmful bacteria threatening tomato. Disease transmission occurs via seed and symptoms becom

  15. Biotechnological applications of bacterial cellulases

    Directory of Open Access Journals (Sweden)

    Esther Menendez


    Full Text Available Cellulases have numerous applications in several industries, including biofuel production, food and feed industry, brewing, pulp and paper, textile, laundry, and agriculture.Cellulose-degrading bacteria are widely spread in nature, being isolated from quite different environments. Cellulose degradation is the result of a synergic process between an endoglucanase, an exoglucanase and a,β-glucosidase. Bacterial endoglucanases degrade ß-1,4-glucan linkages of cellulose amorphous zones, meanwhile exoglucanases cleave the remaining oligosaccharide chains, originating cellobiose, which is hydrolyzed by ß-glucanases. Bacterial cellulases (EC are comprised in fourteen Glycosil Hydrolase families. Several advantages, such as higher growth rates and genetic versatility, emphasize the suitability and advantages of bacterial cellulases over other sources for this group of enzymes. This review summarizes the main known cellulolytic bacteria and the best strategies to optimize their cellulase production, focusing on endoglucanases, as well as it reviews the main biotechnological applications of bacterial cellulases in several industries, medicine and agriculture.

  16. Food irradiation and bacterial toxins

    Energy Technology Data Exchange (ETDEWEB)

    Tranter, H.S.; Modi, N.K.; Hambleton, P.; Melling, J.; Rose, S.; Stringer, M.F.


    The authors' findings indicate that irradiation confers no advantage over heat processing in respect of bacterial toxins (clostridium botulinum, neurotoxin A and staphylococcal enterotoxin A). It follows that irradiation at doses less than the ACINF recommended upper limit of 10 kGy could not be used to improve the ambient temperature shelf life on non-acid foods.

  17. Extracardiac manifestations of bacterial endocarditis. (United States)

    Heffner, J E


    Bacterial endocarditis is an elusive disease that challenges clinicians' diagnostic capabilities. Because it can present with various combinations of extravalvular signs and symptoms, the underlying primary disease can go unnoticed.A review of the various extracardiac manifestations of bacterial endocarditis suggests three main patterns by which the valvular infection can be obscured. (1) A major clinical event may be so dramatic that subtle evidence of endocarditis is overlooked. The rupture of a mycotic aneurysm may simulate a subarachnoid hemorrhage from a congenital aneurysm. (2) The symptoms of bacterial endocarditis may be constitutional complaints easily attributable to a routine, trivial illness. Symptoms of low-grade fever, myalgias, back pain and anorexia may mimic a viral syndrome. (3) Endocarditis poses a difficult diagnostic dilemma when it generates constellations of findings that are classic for other disorders. Complaints of arthritis and arthralgias accompanied by hematuria and antinuclear antibody may suggest systemic lupus erythematosus; a renal biopsy study showing diffuse proliferative glomerulonephritis may support this diagnosis. The combination of fever, petechiae, altered mental status, thrombocytopenia, azotemia and anemia may promote the diagnosis of thrombotic thrombocytopenic purpura. When the protean guises of bacterial endocarditis create these clinical difficulties, errors in diagnosis occur and appropriate therapy is delayed. Keen awareness of the varied disease presentations will improve success in managing endocarditis by fostering rapid diagnosis and prompt therapy.

  18. High-resolution taxonomic profiling of the subgingival microbiome for biomarker discovery and periodontitis diagnosis. (United States)

    Szafranski, Szymon P; Wos-Oxley, Melissa L; Vilchez-Vargas, Ramiro; Jáuregui, Ruy; Plumeier, Iris; Klawonn, Frank; Tomasch, Jürgen; Meisinger, Christa; Kühnisch, Jan; Sztajer, Helena; Pieper, Dietmar H; Wagner-Döbler, Irene


    The oral microbiome plays a key role for caries, periodontitis, and systemic diseases. A method for rapid, high-resolution, robust taxonomic profiling of subgingival bacterial communities for early detection of periodontitis biomarkers would therefore be a useful tool for individualized medicine. Here, we used Illumina sequencing of the V1-V2 and V5-V6 hypervariable regions of the 16S rRNA gene. A sample stratification pipeline was developed in a pilot study of 19 individuals, 9 of whom had been diagnosed with chronic periodontitis. Five hundred twenty-three operational taxonomic units (OTUs) were obtained from the V1-V2 region and 432 from the V5-V6 region. Key periodontal pathogens like Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia could be identified at the species level with both primer sets. Principal coordinate analysis identified two outliers that were consistently independent of the hypervariable region and method of DNA extraction used. The linear discriminant analysis (LDA) effect size algorithm (LEfSe) identified 80 OTU-level biomarkers of periodontitis and 17 of health. Health- and periodontitis-related clusters of OTUs were identified using a connectivity analysis, and the results confirmed previous studies with several thousands of samples. A machine learning algorithm was developed which was trained on all but one sample and then predicted the diagnosis of the left-out sample (jackknife method). Using a combination of the 10 best biomarkers, 15 of 17 samples were correctly diagnosed. Training the algorithm on time-resolved community profiles might provide a highly sensitive tool to detect the onset of periodontitis.

  19. Biomarkers in sedimentary sequences: Indicators to track sediment sources over decadal timescales (United States)

    Chen, F. X.; Fang, N. F.; Wang, Y. X.; Tong, L. S.; Shi, Z. H.


    Long-term sedimentary sequence research can reveal how human activities and climate interact to affect catchment vegetation, flooding, soil erosion, and sediment sources. In this study, a biomarker sediment fingerprinting technique based on n-alkanes was used to identify long timescale (decadal) sediment sources in a small agricultural catchment. However, the highly saline carbonate environment and bacterial and algal activities elevated the levels of even-chain n-alkanes in the sediments, leading to an obvious even-over-odd predominance of short and middle components (C15-C26). Therefore, by analyzing three odd, long-chain n-alkanes (C27, C29 and C31) in 27 source samples from cropland, gully, and steep slope areas and one sediment sequence (one cultivated horizon and 47 flood couplets), a composite fingerprinting method and genetic algorithm optimization were applied to find the optimal source contributions to sediments. The biomarker fingerprinting results demonstrated that the primary sediment source is gullies, followed by cropland and steep slope areas. The average median source contributions associated with 47 flood couples collected from sediment core samples ranged from 0 ± 0.1% to 91.9 ± 0.4% with an average of 45.0% for gullies, 0 ± 0.4% to 95.6 ± 1.6% with an average of 38.2% for cropland, and 0 ± 2.1% to 60.7 ± 0.4% with an average of 16.8% for steep slopes. However, because farmers were highly motivated to manage the cropland after the 1980s, over half the sediments were derived from cropland in the 1980s. Biomarkers have significant advantages in the identification of sediments derived from different landscape units (e.g., gully and steep slope areas), and n-alkanes have considerable potential in high-resolution research of environmental change based on soil erosion in the hilly Loess Plateau region.

  20. Charting a roadmap for heart failure biomarker studies. (United States)

    Ahmad, Tariq; Fiuzat, Mona; Pencina, Michael J; Geller, Nancy L; Zannad, Faiez; Cleland, John G F; Snider, James V; Blankenberg, Stephan; Adams, Kirkwood F; Redberg, Rita F; Kim, Jae B; Mascette, Alice; Mentz, Robert J; O'Connor, Christopher M; Felker, G Michael; Januzzi, James L


    Heart failure is a syndrome with a pathophysiological basis that can be traced to dysfunction in several interconnected molecular pathways. Identification of biomarkers of heart failure that allow measurement of the disease on a molecular level has resulted in enthusiasm for their use in prognostication and selection of appropriate therapies. However, despite considerable amounts of information available on numerous biomarkers, inconsistent research methodologies and lack of clinical correlations have made bench-to-bedside translations rare and left the literature with countless publications of varied quality. There is a need for a systematic and collaborative approach aimed at definitively studying the clinical benefits of novel biomarkers. In this review, on the basis of input from academia, industry, and governmental agencies, we propose a systematized approach based on adherence to specific quality measures for studies looking to augment current prediction model or use biomarkers to tailor therapeutics. We suggest that study quality, rather than results, should determine publication and propose a system for grading biomarker studies. We outline the need for collaboration between clinical investigators and statisticians to introduce more advanced statistical methodologies into the field of biomarkers that would allow for data from a large number of variables to be distilled into clinically actionable information. Lastly, we propose the creation of a heart failure biomarker consortium that would allow for a comprehensive list of biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and hypotheses to be generated for testing in biomarker-guided trials. Such a consortium could collaborate in sharing samples to identify biomarkers, undertake meta-analyses on completed trials, and spearhead clinical trials to test the clinical utility of new biomarkers.

  1. Current immunological and molecular tools for leptospirosis: diagnostics, vaccine design, and biomarkers for predicting severity. (United States)

    Rajapakse, Senaka; Rodrigo, Chaturaka; Handunnetti, Shiroma M; Fernando, Sumadhya Deepika


    Leptospirosis is a zoonotic spirochaetal illness that is endemic in many tropical countries. The research base on leptospirosis is not as strong as other tropical infections such as malaria. However, it is a lethal infection that can attack many vital organs in its severe form, leading to multi-organ dysfunction syndrome and death. There are many gaps in knowledge regarding the pathophysiology of leptospirosis and the role of host immunity in causing symptoms. This hinders essential steps in combating disease, such as developing a potential vaccine. Another major problem with leptospirosis is the lack of an easy to perform, accurate diagnostic tests. Many clinicians in resource limited settings resort to clinical judgment in diagnosing leptospirosis. This is unfortunate, as many other diseases such as dengue, hanta virus, rickettsial infections, and even severe bacterial sepsis, can mimic leptospirosis. Another interesting problem is the prediction of disease severity at the onset of the illness. The majority of patients recover from leptospirosis with only a mild febrile illness, while a few others have severe illness with multi-organ failure. Clinical features are poor predictors of potential severity of infection, and therefore the search is on for potential biomarkers that can serve as early warnings for severe disease. This review concentrates on these three important aspects of this neglected tropical disease: diagnostics, developing a vaccine, and potential biomarkers to predict disease severity.

  2. Sleep electroencephalography as a biomarker in depression

    Directory of Open Access Journals (Sweden)

    Steiger A


    Full Text Available Axel Steiger, Marcel Pawlowski, Mayumi Kimura Max Planck Institute of Psychiatry, Munich, Germany Abstract: The sleep electroencephalogram (EEG provides biomarkers of depression, which may help with diagnosis, prediction of therapy response, and prognosis in the treatment of depression. In patients with depression, characteristic sleep EEG changes include impaired sleep continuity, disinhibition of rapid-eye-movement (REM sleep, and impaired non-REM sleep. Most antidepressants suppress REM sleep in depressed patients, healthy volunteers, and in animal models. REM suppression appears to be an important, but not an absolute requirement, for antidepressive effects of a substance. Enhanced REM density, a measure for frequency of REM, characterizes high-risk probands for affective disorders. REM-sleep changes were also found in animal models of depression. Sleep-EEG variables were shown to predict the response to treatment with antidepressants. Furthermore, certain clusters of sleep EEG variables predicted the course of the disorder for several years. Some of the predicted sleep EEG markers appear to be related to hypothalamic–pituitary–adrenal system activity. Keywords: biomarkers, depression, sleep EEG, antidepressants, prediction, animal models

  3. Sarcopenia--The search for emerging biomarkers. (United States)

    Kalinkovich, Alexander; Livshits, Gregory


    Sarcopenia, an age-related decline in skeletal muscle mass and function, dramatically affects the life quality of elder people. In view of increasing life expectancy, sarcopenia renders a heavy burden on the health care system. However, although there is a consensus that sarcopenia is a multifactorial syndrome, its etiology, underlying mechanisms, and even definition remain poorly delineated, thus, preventing development of a precise treatment strategy. The main aim of our review is to critically analyze potential sarcopenia biomarkers in light of the molecular mechanisms of their involvement in sarcopenia pathogenesis. Normal muscle mass and function maintenance are proposed to be dependent on the dynamic balance between the positive regulators of muscle growth such as bone morphogenetic proteins (BMPs), brain-derived neurotrophic factor (BDNF), follistatin (FST) and irisin, and negative regulators including TGFβ, myostatin, activins A and B, and growth and differentiation factor-15 (GDF-15). We hypothesize that the shift in this balance to muscle growth inhibitors, along with increased expression of the C- terminal agrin fragment (CAF) associated with age-dependent neuromuscular junction (NMJ) dysfunction, as well as skeletal muscle-specific troponin T (sTnT), a key component of contractile machinery, is a main mechanism underlying sarcopenia pathogenesis. Thus, this review proposes and emphasizes that these molecules are the emerging sarcopenia biomarkers.

  4. [Biomarkers for neoplasmas in digestive organs]. (United States)

    Iwasaki, Yoshiaki; Arai, Kuniyoshi; Katayanagi, Soh; Takahashi, Keiichi; Yamaguchi, Tatsurou; Matsumoto, Hiroshi; Miyamoto, Hidenori


    This review is concerned with the usefulness and the problem of biomarkers for cancer of digestive organs. Carcinoembryonic antigen (CEA) is a most popular and useful tumor marker for cancer of digestive organs. Squamous cell carcinoma (SCC) antigen and CYFRA have been reported as a useful tumor marker for esophageal cancer. CEA and CA 19-9 are a good prognostic factor in gastric cancer patients. The post-operative increase of serum CEA can be a predictive marker for the patients of colorectal cancer. Development of a radioimmunoassay for highly sensitive detection of tumor markers, they are considered to be useful for monitoring after treatment. But are not useful for the early diagnosis. The diagnosis of hepatocellular carcinoma (HCC) is based mainly on serological markers, such as alpha-fetoprotein and PIVKA-II. The two are useful complementary markers of HCC because they do not correlate with each other. But the problem of the false-positive rate for the patients with chronic hepatitis or liver cirrhosis is still remained. A typical marker of pancreatic and bile duct cancer is carbohydrate antigen, but the sensitivity of these markers is only 50%. Recent molecular biological analysis may be used as effective biomarkers in the diagnosis, prognosis, therapy, and risk assessment of digestive cancer.

  5. Biomarkers of extrasolar planets and their observability (United States)

    Selsis, Franck; Paillet, Jimmy; Allard, France

    The first space-borne instruments able to detect and characterize extrasolar terrestrial planets, Darwin (ESA) and TPF-C (Terrestrial Planet Finder-Coronograph, NASA), should be launched at the end of the next decade. Beyond the challenge of planet detection itself, the ability to measure mid-infrared (Darwin) and visible (TPF-C) spectra at low resolution will allow us to characterize the exoplanets discovered. The spectral analysis of these planets will extend the field of planetary science beyond the Solar System to the nearby Universe: It will give access to certain planetary properties (albedo, brightness temperature, radius) and reveal the presence of atmospheric compounds, which, together with the radiative budget of the planet, will provide the keys to understanding how the climate system works on these worlds. If terrestrial planets are sufficiently abundant, these missions will collect data for numerous planetary systems of different ages and orbiting different types of stars. Theories for the formation, evolution and habitability of the terrestrial planets will at last face the test observation. The most fascinating perspective offered by these space observatories is the ability to detect spectral signatures indicating biological activity. In this chapter, we review and discuss the concept of extrasolar biosignatures or biomarkers. We focus mainly on the identification of oxygen-rich atmospheres through the detection of O2 and O3 features, addressing also the case of other possible biomarkers and indicators of habitability.

  6. Diagnosis of Periodontal Diseases by Biomarkers (United States)

    Kido, Jun-Ichi; Hino, Mami; Bando, Mika; Hiroshima, Yuka

    Many middle aged and old persons take periodontal diseases that mainly cause teeth loss and result in some systemic diseases. The prevention of periodontal diseases is very important for oral and systemic health, but the present diagnostic examination is not fully objective and suitable. To diagnose periodontal diseases exactly, some biomarkers shown inflammation, tissue degradation and bone resorption, in gingival crevicular fluid (GCF) and saliva are known. We demonstrated that GCF levels of calprotectin, inflammation-related protein, and carboxy-terminal propeptide of type I procollagen, bone metabolism-related protein, were associated with clinical condition of periodontal diseases, and suggested that these proteins may be useful biomarkers for periodontal diseases. Recently, determinations of genes and proteins by using microdevices are studied for diagnosis of some diseases. We detected calprotectin protein by chemiluminescent immunoassay on a microchip and showed the possibility of specific and quantitative detection of calprotectin in a very small amount of GCF. To determine plural markers in GCF by using microdevices contributes to develop accurate, objective diagnostic system of periodontal diseases.

  7. Chemokine Receptors as Biomarkers in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Robert J. Fox


    Full Text Available Leukocyte infiltrates characterize tissue inflammation and are thought to be integral in the pathogenesis of multiple sclerosis (MS. This attribute underlines the importance of understanding mechanisms of leukocyte migration. Chemokines are secreted proteins which govern leukocyte trafficking into targeted organs. Chemokine receptors (CKR are differentially expressed on leukocytes and their modulation is a potential target for MS disease modifying therapies. Chemokines and their receptors are also potential biomarkers of both disease activity and response to treatment. We describe the fluctuations in CKR expression on peripheral leukocytes in a group of MS patients followed longitudinally for up to 36 months. We observed little fluctuation in CKR expression within each patient over time, despite considerable variability in CKR expression between patients. These observations suggest that individual patients have a CKR set point, and this set point varies from one patient to another. Evaluation of chemokines or chemokine receptors as biomarkers in MS will need to account for this individual variability in CKR expression.

  8. Biomarkers and Mechanisms of FANCD2 Function

    Directory of Open Access Journals (Sweden)

    Henning Willers


    Full Text Available Genetic or epigenetic inactivation of the pathway formed by the Fanconi anemia (FA and BRCA1 proteins occurs in several cancer types, making the affected tumors potentially hypersensitive to DNA cross-linkers and other chemotherapeutic agents. It has been proposed that the inability of FA/BRCA-defective cells to form subnuclear foci of effector proteins, such as FANCD2, can be used as a biomarker to aid individualization of chemotherapy. We show that FANCD2 inactivation not only renders cells sensitive to cross-links, but also oxidative stress, a common effect of cancer therapeutics. Oxidative stress sensitivity does not correlate with FANCD2 or RAD51 foci formation, but associates with increased γH2AX foci levels and apoptosis. Therefore, FANCD2 may protect cells against cross-links and oxidative stress through distinct mechanisms, consistent with the growing notion that the pathway is not linear. Our data emphasize the need for multiple biomarkers, such as γH2AX, FANCD2, and RAD51, to capture all pathway activities.

  9. Prostatitis-bacterial - self-care (United States)

    ... this page: // Prostatitis- bacterial - self-care To use the sharing features ... enable JavaScript. You have been diagnosed with bacterial prostatitis . This is an infection of the prostate gland. ...

  10. Cognitive outcome in adults after bacterial meningitis.

    NARCIS (Netherlands)

    Hoogman, M.; Beek, D. van de; Weisfelt, M.; Gans, J. de; Schmand, B.


    OBJECTIVE: To evaluate cognitive outcome in adult survivors of bacterial meningitis. METHODS: Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy c

  11. DNA methylation based biomarkers: Practical considerations and applications

    DEFF Research Database (Denmark)

    Nielsen, Helene Myrtue; How Kit, Alexandre; Tost, Jorg


    A biomarker is a molecular target analyzed in a qualitative or quantitative manner to detect and diagnose the presence of a disease, to predict the outcome and the response to a specific treatment allowing personalized tailoring of patient management. Biomarkers can belong to different types of b...

  12. Improving Biomarker Development and Assessment: Standards for Study Design

    Institute of Scientific and Technical Information of China (English)

    Ziding FENG


    Background: The Early Detection Research Network (EDRN), NCI funded and investigator driven, has the mission to evaluate biomarkers for their clinical utilities in cancer risk prediction, diagnosis, early detection, and prognosis. Abundant cancer biomarkers reported in literature yet few are used in clinics. Therefore, the emphasis of the EDRN is biomarker validation. Although schema for a phased approach to development exists and guidelines are available for study reporting, a coherent and comprehensive set of guideline for a definitive biomarker validation study design have not been delineated.Methods: We proposed PROBE study design, Prospective specimen collec-tion and Retrospective Blinded Evaluation, for pivotal definitive evaluation of the accuracy of a classification biomarker. A detailed formulation of all aspects of the design is provided. Four tables itemize aspects that relate to (i) the Clinical Context; (ii) Performance Criteria; (iii) the Biomarker test; and (iv) Study power and termination. Alternative designs and strategies were contrasted to illustrate the merit of PROBE design.Results: The ideas are applied to studies of biomarkers the intended use of which is for disease diagnosis, screening, or prognosis. Two EDRN valida-tion studies (breast cancer and prostate cancer) were used as examples to elucidate PROBE design.Conclusion: Common biases that pervade the biomarker research literaturewould be eliminated if these rigorous standards were followed closely. We urge the adoption of the design as standard of practice for pivotal evaluation of the classification accuracy ofbiomarkers.

  13. Current technological challenges in biomarker discovery and validation

    NARCIS (Netherlands)

    Horvatovich, Peter L.; Bischoff, Rainer


    In this review we will give an overview of the issues related to biomarker discovery studies with a focus on liquid chromatography-mass spectrometry (LC-MS) methods. Biomarker discovery is based on a close collaboration between clinicians, analytical scientists and chemometritians/statisticians. It

  14. State of the Art : Newer biomarkers in heart failure

    NARCIS (Netherlands)

    de Boer, Rudolf A.; Daniels, Lori B.; Maisel, Alan S.; Januzzi, James L.


    Since natriuretic peptides were successfully integrated into the clinical practice of heart failure (HF), the possibility of using new biomarkers to advance the management of affected patients has been explored. While a huge number of candidate HF biomarkers have been described recently, very few ha

  15. Urinary Sugars--A Biomarker of Total Sugars Intake. (United States)

    Tasevska, Natasha


    Measurement error in self-reported sugars intake may explain the lack of consistency in the epidemiologic evidence on the association between sugars and disease risk. This review describes the development and applications of a biomarker of sugars intake, informs its future use and recommends directions for future research. Recently, 24 h urinary sucrose and fructose were suggested as a predictive biomarker for total sugars intake, based on findings from three highly controlled feeding studies conducted in the United Kingdom. From this work, a calibration equation for the biomarker that provides an unbiased measure of sugars intake was generated that has since been used in two US-based studies with free-living individuals to assess measurement error in dietary self-reports and to develop regression calibration equations that could be used in future diet-disease analyses. Further applications of the biomarker include its use as a surrogate measure of intake in diet-disease association studies. Although this biomarker has great potential and exhibits favorable characteristics, available data come from a few controlled studies with limited sample sizes conducted in the UK. Larger feeding studies conducted in different populations are needed to further explore biomarker characteristics and stability of its biases, compare its performance, and generate a unique, or population-specific biomarker calibration equations to be applied in future studies. A validated sugars biomarker is critical for informed interpretation of sugars-disease association studies.

  16. Identifying module biomarkers from gastric cancer by differential correlation network

    Directory of Open Access Journals (Sweden)

    Liu X


    Full Text Available Xiaoping Liu,1–3,* Xiao Chang1,3,* 1College of Statistics and Applied Mathematics, Anhui University of Finance and Economics, Bengbu, Anhui Province, People’s Republic of China; 2Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 3Collaborative Research Center for Innovative Mathematical Modeling, Institute of Industrial Science, University of Tokyo, Tokyo, Japan *These authors contributed equally to this work Abstract: Gastric cancer (stomach cancer is a severe disease caused by dysregulation of many functionally correlated genes or pathways instead of the mutation of individual genes. Systematic identification of gastric cancer biomarkers can provide insights into the mechanisms underlying this deadly disease and help in the development of new drugs. In this paper, we present a novel network-based approach to predict module biomarkers of gastric cancer that can effectively distinguish the disease from normal samples. Specifically, by assuming that gastric cancer has mainly resulted from dysfunction of biomolecular networks rather than individual genes in an organism, the genes in the module biomarkers are potentially related to gastric cancer. Finally, we identified a module biomarker with 27 genes, and by comparing the module biomarker with known gastric cancer biomarkers, we found that our module biomarker exhibited a greater ability to diagnose the samples with gastric cancer. Keywords: biomarkers, gastric cancer, stomach cancer, differential network

  17. Optimal allocation of resources in a biomarker setting. (United States)

    Rosner, Bernard; Hendrickson, Sara; Willett, Walter


    Nutrient intake is often measured with substantial error both in commonly used surrogate instruments such as a food frequency questionnaire (FFQ) and in gold standard-type instruments such as a diet record (DR). If there is a correlated error between the FFQ and DR, then standard measurement error correction methods based on regression calibration can produce biased estimates of the regression coefficient (λ) of true intake on surrogate intake. However, if a biomarker exists and the error in the biomarker is independent of the error in the FFQ and DR, then the method of triads can be used to obtain unbiased estimates of λ, provided that there are replicate biomarker data on at least a subsample of validation study subjects. Because biomarker measurements are expensive, for a fixed budget, one can use a either design where a large number of subjects have one biomarker measure and only a small subsample is replicated or a design that has a smaller number of subjects and has most or all subjects validated. The purpose of this paper is to optimize the proportion of subjects with replicated biomarker measures, where optimization is with respect to minimizing the variance of ln(λ̂). The methodology is illustrated using vitamin C intake data from the European Prospective Investigation into Cancer and Nutrition study where plasma vitamin C is the biomarker. In this example, the optimal validation study design is to have 21% of subjects with replicated biomarker measures.

  18. Biomarkers for predicting complete debulking in ovarian cancer

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten Lindberg; Ottesen, Bent; Christensen, Ib Jarle;


    Aim: We aimed to construct and validate a model based on biomarkers to predict complete primary debulking surgery for ovarian cancer patients.......Aim: We aimed to construct and validate a model based on biomarkers to predict complete primary debulking surgery for ovarian cancer patients....

  19. Sleep Spindles as Biomarker for Early Detection of Neurodegenerative Disorders

    DEFF Research Database (Denmark)


    The present invention relates to the use of sleep spindles as a novel biomarker for early diagnosis of synucleinopathies, in particular Parkinson's disease (PD). The method is based on automatic detection of sleep spindles. The method may be combined with measurements of one or more further...... biomarkers derived from polysomnographic recordings....

  20. Biomarkers of Parkinson's disease: current status and future perspectives. (United States)

    Wang, Jian; Hoekstra, Jake G; Zuo, Chuantao; Cook, Travis J; Zhang, Jing


    This review summarizes major advances in biomarker discovery for diagnosis, differential diagnosis and progression of Parkinson's disease (PD), with emphasis on neuroimaging and biochemical markers. Potential strategies to develop biomarkers capable of predicting PD in the prodromal stage before the appearance of motor symptoms or correlating with nonmotor symptoms, an active area of research, are also discussed.

  1. Asymptomatic cattle naturally infected with Mycobacterium bovis present exacerbated tissue pathology and bacterial dissemination.

    Directory of Open Access Journals (Sweden)

    Álvaro Menin

    Full Text Available Rational discovery of novel immunodiagnostic and vaccine candidate antigens to control bovine tuberculosis (bTB requires knowledge of disease immunopathogenesis. However, there remains a paucity of information on the Mycobacterium bovis-host immune interactions during the natural infection. Analysis of 247 naturally PPD+ M. bovis-infected cattle revealed that 92% (n = 228 of these animals were found to display no clinical signs, but presented severe as well as disseminated bTB-lesions at post-mortem examination. Moreover, dissemination of bTB-lesions positively correlated with both pathology severity score (Spearman r = 0.48; p<0.0001 and viable tissue bacterial loads (Spearman r = 0.58; p = 0.0001. Additionally, granuloma encapsulation negatively correlated with M. bovis growth as well as pathology severity, suggesting that encapsulation is an effective mechanism to control bacterial proliferation during natural infection. Moreover, multinucleated giant cell numbers were found to negatively correlate with bacterial counts (Spearman r = 0.25; p = 0.03 in lung granulomas. In contrast, neutrophil numbers in the granuloma were associated with increased M. bovis proliferation (Spearman r = 0.27; p = 0.021. Together, our findings suggest that encapsulation and multinucleated giant cells control M. bovis viability, whereas neutrophils may serve as a cellular biomarker of bacterial proliferation during natural infection. These data integrate host granuloma responses with mycobacterial dissemination and could provide useful immunopathological-based biomarkers of disease severity in natural infection with M. bovis, an important cattle pathogen.

  2. The bacterial lux reporter system: applications in bacterial localisation studies. (United States)

    Gahan, Cormac G M


    Bacterial production of visible light is a natural phenomenon occurring in marine (Vibrio and Photobacterium) and terrestrial (Photorhabdus) species. The mechanism underpinning light production in these organisms is similar and involves the oxidation of an aldehyde substrate in a reaction catalysed by the bacterial luciferase enzyme. The genes encoding the luciferase and a fatty acid reductase complex which synthesizes the substrate are contained in a single operon (the lux operon). This provides a useful reporter system as cloning the operon into a recipient host bacterium will generate visible light without the requirement to add exogenous substrate. The light can be detected in vivo in the living animal using a sensitive detection system and is therefore ideally suited to bioluminescence imaging protocols. The system has therefore been widely used to track bacteria during infection or colonisation of the host. As bacteria are currently being examined as bactofection vectors for gene delivery, particularly to tumour tissue, the use of bioluminescence imaging offers a powerful means to investigate vector amplification in situ. The implications of this technology for bacterial localization, tumour targeting and gene transfer (bactofection) studies are discussed.

  3. Emerging Biomarkers in Heart Failure and Cardiac Cachexia

    Directory of Open Access Journals (Sweden)

    Goran Loncar


    Full Text Available Biomarkers are objective tools with an important role for diagnosis, prognosis and therapy optimization in patients with heart failure (HF. To date, natriuretic peptides are closest to optimal biomarker standards for clinical implications in HF. Therefore, the efforts to identify and test new biomarkers in HF are reasonable and justified. Along the natural history of HF, cardiac cachexia may develop, and once at this stage, patient performance and prognosis is particularly poor. For these reasons, numerous biomarkers reflecting hormonal, inflammatory and oxidative stress pathways have been investigated, but only a few convey relevant information. The complex pathophysiology of HF appears far too complex to be embraced by a single biomarker; thus, a combined approach appears reasonable. With these considerations, we have reviewed the recent developments in the field to highlight key candidates with diagnostic, prognostic and therapy optimization properties, either alone or in combination.

  4. Biomarkers of acute lung injury: worth their salt?

    Directory of Open Access Journals (Sweden)

    Proudfoot Alastair G


    Full Text Available Abstract The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.

  5. Potential Peripheral Biomarkers for the Diagnosis of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Seema Patel


    Full Text Available Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer's would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker.

  6. 2-Furoylglycine as a Candidate Biomarker of Coffee Consumption. (United States)

    Heinzmann, Silke S; Holmes, Elaine; Kochhar, Sunil; Nicholson, Jeremy K; Schmitt-Kopplin, Philippe


    Specific and sensitive food biomarkers are necessary to support dietary intake assessment and link nutritional habits to potential impact on human health. A multistep nutritional intervention study was conducted to suggest novel biomarkers for coffee consumption. (1)H NMR metabolic profiling combined with multivariate data analysis resolved 2-furoylglycine (2-FG) as a novel putative biomarker for coffee consumption. We relatively quantified 2-FG in the urine of coffee drinkers and investigated its origin, metabolism, and excretion kinetics. When searching for its potential precursors, we found different furan derivatives in coffee products, which are known to get metabolized to 2-FG. Maximal urinary excretion of 2-FG occurred 2 h after consumption (p = 0.0002) and returned to baseline after 24 h (p = 0.74). The biomarker was not excreted after consumption of coffee substitutes such as tea and chicory coffee and might therefore be a promising acute biomarker for the detection of coffee consumption in human urine.

  7. Biomarkers in neonatology: the next generation of tests. (United States)

    Ng, Pak C; Lam, Hugh S


    Over the past two decades, neonatal clinicians have commonly used host response biomarkers to diagnose and assess the severity of systemic infection. Most of these biomarkers, such as acute-phase proteins or cytokines, are non-specific immunomodulating mediators of the inflammatory cascade. With advances in biochemical/genetic research, it is anticipated that future biomarkers will be 'organ and/or disease specific'. There is also the quest for discovery of 'novel' biomarkers to assist diagnosis and prognosis of neonatal diseases using powerful mass-screening techniques, e.g. the next-generation sequencing, proteomics and arrays. This article aims to introduce the concept of the next generation of biomarkers to practising neonatal clinicians, and, hopefully, to integrate basic science research into day-to-day clinical practice in the future.

  8. Oral biomarkers in exercise-induced neuroplasticity in Parkinson's disease. (United States)

    Mougeot, J-Lc; Hirsch, M A; Stevens, C B; Mougeot, Fkb


    In this article, we review candidate biomarkers for Parkinson's disease (PD) in oral cavity, potential of oral biomarkers as markers of neuroplasticity, and literature on the effects of exercise on oral cavity biomarkers in PD. We first describe how pathophysiological pathways of PD may be transduced from brain stem and ganglia to oral cavity through the autonomic nervous system or transduced by a reverse path. Next we describe the effects of exercise in PD and potential impact on oral cavity. We propose that biomarkers in oral cavity may be useful targets for describing exercise-induced brain neuroplasticity in PD. Nevertheless, much research remains to be carried out before applying these biomarkers for the determination of disease state and therapeutic response to develop strategies to mitigate motor or non-motor symptoms in PD.

  9. Use of biomarkers in pediatric sepsis: literature review (United States)

    Lanziotti, Vanessa Soares; Póvoa, Pedro; Soares, Márcio; Silva, José Roberto Lapa e; Barbosa, Arnaldo Prata; Salluh, Jorge Ibrain Figueira


    Despite advances in recent years, sepsis is still a leading cause of hospitalization and mortality in infants and children. The presence of biomarkers during the response to an infectious insult makes it possible to use such biomarkers in screening, diagnosis, prognosis (risk stratification), monitoring of therapeutic response, and rational use of antibiotics (for example, the determination of adequate treatment length). Studies of biomarkers in sepsis in children are still relatively scarce. This review addresses the use of biomarkers in sepsis in pediatric patients with emphasis on C-reactive protein, procalcitonin, interleukins 6, 8, and 18, human neutrophil gelatinase, and proadrenomedullin. Assessment of these biomarkers may be useful in the management of pediatric sepsis. PMID:28099644

  10. Biomarkers for the detection of prenatal alcohol exposure (PAE)

    DEFF Research Database (Denmark)

    Bjerregaard, Lene Berit Skov; Bager, Heidi; Husby, Steffen


    Alcohol exposure during pregnancy can cause adverse effects to the fetus, because it interferes with fetal development, leading to later physical and mental impairment. The most common clinical tool to determine fetal alcohol exposure is maternal self-reporting. However, a more objective and useful...... method is based on the use of biomarkers in biological specimens alone or in combination with maternal self-reporting. This review reports on clinically relevant biomarkers for detection of prenatal alcohol exposure (PAE). A systematic search was performed to ensure a proper overview in existing...... literature. Studies were selected to give an overview on clinically relevant neonatal and maternal biomarkers. The direct biomarkers fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulfate, and phosphatidylethanol (PEth) were found to be the most appropriate biomarkers in relation...

  11. Distribution of Triplet Separators in Bacterial Genomes

    Institute of Scientific and Technical Information of China (English)

    HU Rui; ZHENG Wei-Mou


    Distributions of triplet separator lengths for two bacterial complete genomes are analyzed. The theoretical distributions for the independent random sequence and the first-order Markov chain are derived and compared with the distributions of the bacterial genomes. A prominent double band structure, which does not exist in the theoretical distributions, is observed in the bacterial distributions for most triplets.``

  12. Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma. (United States)

    Shah, Alok K; Cao, Kim-Anh Lê; Choi, Eunju; Chen, David; Gautier, Benoît; Nancarrow, Derek; Whiteman, David C; Saunders, Nicholas A; Barbour, Andrew P; Joshi, Virendra; Hill, Michelle M


    We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector ( The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (, for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (NPL)-reactive Apolipoprotein B-100 (p value = 0.0231; AUROC = 0.71); BE versus EAC, Aleuria aurantia lectin (AAL)-reactive complement component C9 (p value = 0.0001; AUROC = 0.85); healthy versus EAC, Erythroagglutinin Phaseolus vulgaris (EPHA)-reactive gelsolin (p value = 0.0014; AUROC = 0.80). A panel of 8 glycoforms showed an improved AUROC of 0.94 to discriminate EAC from BE. Two biomarker candidates

  13. Early biomarkers of joint damage in rheumatoid and psoriatic arthritis. (United States)

    Mc Ardle, Angela; Flatley, Brian; Pennington, Stephen R; FitzGerald, Oliver


    Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate

  14. Early biomarkers of joint damage in rheumatoid and psoriatic arthritis.

    LENUS (Irish Health Repository)

    Mc Ardle, Angela


    Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate

  15. Antibiotic drugs targeting bacterial RNAs

    Directory of Open Access Journals (Sweden)

    Weiling Hong


    Full Text Available RNAs have diverse structures that include bulges and internal loops able to form tertiary contacts or serve as ligand binding sites. The recent increase in structural and functional information related to RNAs has put them in the limelight as a drug target for small molecule therapy. In addition, the recognition of the marked difference between prokaryotic and eukaryotic rRNA has led to the development of antibiotics that specifically target bacterial rRNA, reduce protein translation and thereby inhibit bacterial growth. To facilitate the development of new antibiotics targeting RNA, we here review the literature concerning such antibiotics, mRNA, riboswitch and tRNA and the key methodologies used for their screening.

  16. Electromagnetic Signals from Bacterial DNA

    CERN Document Server

    Widom, A; Srivastava, Y N; Sivasubramanian, S


    Chemical reactions can be induced at a distance due to the propagation of electromagnetic signals during intermediate chemical stages. Although is is well known at optical frequencies, e.g. photosynthetic reactions, electromagnetic signals hold true for muck lower frequencies. In E. coli bacteria such electromagnetic signals can be generated by electric transitions between energy levels describing electrons moving around DNA loops. The electromagnetic signals between different bacteria within a community is a "wireless" version of intercellular communication found in bacterial communities connected by "nanowires". The wireless broadcasts can in principle be of both the AM and FM variety due to the magnetic flux periodicity in electron energy spectra in bacterial DNA orbital motions.

  17. Bacterial survival in Martian conditions

    CERN Document Server

    D'Alessandro, Giuseppe Galletta; Giulio Bertoloni; Maurizio


    We shortly discuss the observable consequences of the two hypotheses about the origin of life on Earth and Mars: the Lithopanspermia (Mars to Earth or viceversa) and the origin from a unique progenitor, that for Earth is called LUCA (the LUCA hypothesis). To test the possibility that some lifeforms similar to the terrestrial ones may survive on Mars, we designed and built two simulators of Martian environments where to perform experiments with different bacterial strains: LISA and mini-LISA. Our LISA environmental chambers can reproduce the conditions of many Martian locations near the surface trough changes of temperature, pressure, UV fluence and atmospheric composition. Both simulators are open to collaboration with other laboratories interested in performing experiments on many kind of samples (biological, minerals, electronic) in situations similar to that of the red planet. Inside LISA we have studied the survival of several bacterial strains and endospores. We verified that the UV light is the major re...

  18. Bacterial streamers in curved microchannels (United States)

    Rusconi, Roberto; Lecuyer, Sigolene; Guglielmini, Laura; Stone, Howard


    Biofilms, generally identified as microbial communities embedded in a self-produced matrix of extracellular polymeric substances, are involved in a wide variety of health-related problems ranging from implant-associated infections to disease transmissions and dental plaque. The usual picture of these bacterial films is that they grow and develop on surfaces. However, suspended biofilm structures, or streamers, have been found in natural environments (e.g., rivers, acid mines, hydrothermal hot springs) and are always suggested to stem from a turbulent flow. We report the formation of bacterial streamers in curved microfluidic channels. By using confocal laser microscopy we are able to directly image and characterize the spatial and temporal evolution of these filamentous structures. Such streamers, which always connect the inner corners of opposite sides of the channel, are always located in the middle plane. Numerical simulations of the flow provide evidences for an underlying hydrodynamic mechanism behind the formation of the streamers.

  19. Bacterial chromosome organization and segregation. (United States)

    Badrinarayanan, Anjana; Le, Tung B K; Laub, Michael T


    If fully stretched out, a typical bacterial chromosome would be nearly 1 mm long, approximately 1,000 times the length of a cell. Not only must cells massively compact their genetic material, but they must also organize their DNA in a manner that is compatible with a range of cellular processes, including DNA replication, DNA repair, homologous recombination, and horizontal gene transfer. Recent work, driven in part by technological advances, has begun to reveal the general principles of chromosome organization in bacteria. Here, drawing on studies of many different organisms, we review the emerging picture of how bacterial chromosomes are structured at multiple length scales, highlighting the functions of various DNA-binding proteins and the impact of physical forces. Additionally, we discuss the spatial dynamics of chromosomes, particularly during their segregation to daughter cells. Although there has been tremendous progress, we also highlight gaps that remain in understanding chromosome organization and segregation.

  20. Dynamics of bacterial gene regulation (United States)

    Narang, Atul


    The phenomenon of diauxic growth is a classical problem of bacterial gene regulation. The most well studied example of this phenomenon is the glucose-lactose diauxie, which occurs because the expression of the lac operon is strongly repressed in the presence of glucose. This repression is often explained by appealing to molecular mechanisms such as cAMP activation and inducer exclusion. I will begin by analyzing data showing that these molecular mechanisms cannot explain the strong lac repression because they exert a relatively weak effect. I will then present a minimal model accounting only for enzyme induction and dilution, which yields strong repression despite the absence of catabolite repression and inducer exclusion. The model also explains the growth patterns observed in batch and continuous cultures of various bacterial strains and substrate mixtures. The talk will conclude with a discussion of the experimental evidence regarding positive feedback, the key component of the minimal model.

  1. Collective Functionality through Bacterial Individuality (United States)

    Ackermann, Martin

    According to the conventional view, the properties of an organism are a product of nature and nurture - of its genes and the environment it lives in. Recent experiments with unicellular organisms have challenged this view: several molecular mechanisms generate phenotypic variation independently of environmental signals, leading to variation in clonal groups. My presentation will focus on the causes and consequences of this microbial individuality. Using examples from bacterial genetic model systems, I will first discuss different molecular and cellular mechanisms that give rise to bacterial individuality. Then, I will discuss the consequences of individuality, and focus on how phenotypic variation in clonal populations of bacteria can promote interactions between individuals, lead to the division of labor, and allow clonal groups of bacteria to cope with environmental uncertainty. Variation between individuals thus provides clonal groups with collective functionality.

  2. Biomarkers in translational research of Alzheimer's disease. (United States)

    Tarawneh, Rawan; Holtzman, David M


    The identification and characterization of amyloid-beta (Abeta) and tau as the main pathological substrates of Alzheimer's disease (AD) have driven many efforts in search for suitable biomarkers for AD. In the last decade, research in this area has focused on developing a better understanding of the principles that govern protein deposition, mechanisms that link aggregation to toxicity and neuronal death, and a better understanding of protein dynamics in brain tissue, interstitial fluid and CSF. While Abeta and tau represent the two key pathological mediators of disease, other aspects of this multifaceted disease (e.g. oxidative stress, calcium-mediated toxicity, and neuroinflammation) are being unraveled, with the hope to develop a more comprehensive approach in exploring disease mechanisms. This has not only expanded possible areas for disease-modifying therapies, but has also allowed the introduction of novel, and potentially useful, fluid and radiological markers for the presence and progression of AD pathology. There is no doubt that the identification of several fluid and imaging biomarkers that can reliably detect the early stages of AD will have great implications in the design of clinical trials, in the selection of homogenous research populations, and in the assessment of disease outcomes. Markers with good diagnostic specificity will aid researchers in differentiating individuals with preclinical and probable AD from individuals who do not have AD pathology or have other dementing disorders. Markers that change with disease progression may offer utility in assessing the rates of disease progression and the efficacy of potential therapeutic agents on AD pathology. For both of these purposes, CSF Abeta42, amyloid imaging, and CSF tau appear to be very good markers of the presence of AD pathology as well as predictive of who will progress from MCI to AD. Volumetric MRI is also good at separating individuals with MCI and AD from controls and is predictive of

  3. Bacterial Interstitial Nephritis in Children


    Bobadilla Chang, Fernando; Departamento de Ciencias Dinámicas Facultad de Medicina Universidad Nacional Mayor de San Marcos Lima, Perú; Villanueva, Dolores; Departamento de Ciencias Dinámicas Facultad de Medicina Universidad Nacional Mayor de San Marcos Lima, Perú


    OBJECTIVE: To assess the diagnosis approach to urinary tract infections in children. MATERIAL AND METHODS: Medical records from 103 children with diagnosis of interstitial bacterial nephritis were retrospectively reviewed. Diagnosis was supported by the dramatic involvement of renal parenquima, which is not addressed as "urinary tract infection". RESULTS: From all 103 patients, 49 were 2-years-old or younger, 33 were between 2 and 5-years-old, and 21 were between 6 to 10. Clinical picture inc...

  4. Bacterial canker resistance in tomato


    Sen, Y.


    Clavibacter michiganensis subsp. michiganensis (Cmm) is the pathogen causing bacterial  canker in tomato. The disease was described for the first time in 1910 in Michigan, USA. Cmmis considered the most harmful bacteria threatening tomato. Disease transmission occurs via seed and symptoms become visible at least 20 days after infection. Due to its complex strategy and transmission, Cmm is under quarantine regulation in EU and other countries. There is no method to stop disease progress i...

  5. Small intestinal bacterial overgrowth syndrome

    Institute of Scientific and Technical Information of China (English)

    Jan; Bures; Jiri; Cyrany; Darina; Kohoutova; Miroslav; Frstl; Stanislav; Rejchrt; Jaroslav; Kvetina; Viktor; Vorisek; Marcela; Kopacova


    Human intestinal microbiota create a complex polymi-crobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO).SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastro-intestinal tract. There...

  6. Biotechnological applications of bacterial cellulases


    Esther Menendez; Paula Garcia-Fraile; Raul Rivas


    Cellulases have numerous applications in several industries, including biofuel production, food and feed industry, brewing, pulp and paper, textile, laundry, and agriculture.Cellulose-degrading bacteria are widely spread in nature, being isolated from quite different environments. Cellulose degradation is the result of a synergic process between an endoglucanase, an exoglucanase and a,β-glucosidase. Bacterial endoglucanases degrade ß-1,4-glucan linkages of cellulose amorphous zones, mean...

  7. Bacterial motility on abiotic surfaces


    Gibiansky, Maxsim


    Bacterial biofilms are structured microbial communities which are widespread both in nature and in clinical settings. When organized into a biofilm, bacteria are extremely resistant to many forms of stress, including a greatly heightened antibiotic resistance. In the early stages of biofilm formation on an abiotic surface, many bacteria make use of their motility to explore the surface, finding areas of high nutrition or other bacteria to form microcolonies. They use motility appendages, incl...

  8. Cytochemical Differences in Bacterial Glycocalyx (United States)

    Krautgartner, Wolf Dietrich; Vitkov, Ljubomir; Hannig, Matthias; Pelz, Klaus; Stoiber, Walter


    To examine new cytochemical aspects of the bacterial adhesion, a strain 41452/01 of the oral commensal Streptococcus sanguis and a wild strain of Staphylococcus aureus were grown with and without sucrose supplementation for 6 days. Osmiumtetraoxyde (OsO4), uranyl acetate (UA), ruthenium red (RR), cupromeronic blue (CB) staining with critical electrolytic concentrations (CECs), and the tannic acid-metal salt technique (TAMST) were applied for electron microscopy. Cytochemically, only RR-positive fimbriae in S. sanguis were visualized. By contrast, some types of fimbriae staining were observed in S. aureus glycocalyx: RR-positive, OsO4-positive, tannophilic and CB-positive with ceasing point at 0.3 M MgCl2. The CB staining with CEC, used for the first time for visualization of glycoproteins of bacterial glycocalyx, also reveals intacellular CB-positive substances-probably the monomeric molecules, that is, subunits forming the fimbriae via extracellular assembly. Thus, glycosylated components of the biofilm matrix can be reliably related to single cells. The visualization of intracellular components by CB with CEC enables clear distinction between S. aureus and other bacteria, which do not produce CB-positive substances. The small quantities of tannophilic substances found in S. aureus makes the use of TAMST for the same purpose difficult. The present work protocol enables, for the first time, a partial cytochemical differentiation of the bacterial glycocalyx.


    Directory of Open Access Journals (Sweden)

    Vinicius Orso


    Full Text Available Objective : To analyze aspects related to the diagnostic difficulty in patients with bacterial spondylodiscitis. Methods : Cross-sectional observational study with retrospective data collected in the period from March 2004 to January 2014.Twenty-one patients diagnosed with bacterial spondylodiscitis were analyzed. Results : Women were the most affected, as well as older individuals. Pain in the affected region was the initial symptom in 52% of patients, and 45.5% of the patients had low back pain, and those with dorsal discitis had back pain as the main complaint; the patients with thoracolumbar discitis had pain in that region, and only one patient had sacroiliac discitis. The average time between onset of symptoms and treatment was five months. The lumbar segment was the most affected with 11 cases (52%, followed by thoracolumbar in 24%, dorsal in 19% of cases and a case in the sacroiliac segment. Only seven patients had fever. Pain in the affected level was coincidentally the most common symptom. Conclusions : Early diagnosis of bacterial spondylodiscitis remains a challenge due to the nonspecific signs and symptoms reported by the patient and the wide variability of laboratory results and imaging. The basis for early diagnosis remains the clinical suspicion at the time of initial treatment.

  10. Detergent-compatible bacterial amylases. (United States)

    Niyonzima, Francois N; More, Sunil S


    Proteases, lipases, amylases, and cellulases are enzymes used in detergent formulation to improve the detergency. The amylases are specifically supplemented to the detergent to digest starchy stains. Most of the solid and liquid detergents that are currently manufactured contain alkaline enzymes. The advantages of using alkaline enzymes in the detergent formulation are that they aid in removing tough stains and the process is environmentally friendly since they reduce the use of toxic detergent ingredients. Amylases active at low temperature are preferred as the energy consumption gets reduced, and the whole process becomes cost-effective. Most microbial alkaline amylases are used as detergent ingredients. Various reviews report on the production, purification, characterization, and application of amylases in different industry sectors, but there is no specific review on bacterial or fungal alkaline amylases or detergent-compatible amylases. In this mini-review, an overview on the production and property studies of the detergent bacterial amylases is given, and the stability and compatibility of the alkaline bacterial amylases in the presence of the detergents and the detergent components are highlighted.

  11. The COPD Biomarker Qualification Consortium (CBQC)

    DEFF Research Database (Denmark)

    Casaburi, Richard; Celli, Bartolome; Crapo, James


    Abstract Knowledge about the pathogenesis and pathophysiology of chronic obstructive pulmonary disease (COPD) has advanced dramatically over the last 30 years. Unfortunately, this has had little impact in terms of new treatments. Over the same time frame, only one new class of medication for COPD......, and no interested party has been in a position to undertake such a process. In order to facilitate the development of novel tools to assess new treatments, the Food and Drug Administration, in collaboration with the COPD Foundation, the National Heart Lung and Blood Institute and scientists from the pharmaceutical...... industry and academia conducted a workshop to survey the available information that could contribute to new tools. Based on this, a collaborative project, the COPD Biomarkers Qualification Consortium, was initiated. The Consortium in now actively preparing integrated data sets from existing resources...

  12. Apolipoprotein M - a new biomarker in sepsis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo


    Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship...... to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence...... on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation....

  13. Symptoms and biomarkers associated with celiac disease

    DEFF Research Database (Denmark)

    Kårhus, Line L; Thuesen, Betina H; Rumessen, Jüri J


    OBJECTIVES: To identify possible early predictors (symptoms and biomarkers) of celiac disease, compare symptoms before and after screening, and evaluate the diagnostic efficacy of serologic screening for celiac disease in an adult Danish population. METHODS: This cross-sectional population......-based study was based on the 5-year follow-up of the Health2006 cohort, where 2297 individuals were screened for celiac disease; 56 were antibody positive and thus invited to clinical evaluation. Eight were diagnosed with biopsy-verified celiac disease. A follow-up questionnaire was sent to antibody......-positive individuals 19 months after the clinical evaluation to obtain information on their symptoms and their experience with participation in the screening. RESULTS: Before screening, participants subsequently diagnosed with celiac disease did not differ from the rest of the population with respect to symptoms...

  14. Diagnostic and therapeutic biomarkers in pancreaticobiliarymalignancy

    Institute of Scientific and Technical Information of China (English)


    Pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma(CCA) are two malignancies that carry significantmorbidity and mortality. The poor prognoses ofthese cancers are strongly related to lack of effectivescreening modalities as well as few therapeutic options.In this review, we highlight novel biomarkers that havethe potential to be used as diagnostic, prognostic andpredictive markers. The focus of this review is biomarkersthat can be evaluated on endoscopically-obtained biopsiesor brush specimens in the pre-operative setting.We also provide an overview of novel serum basedmarkers in the early diagnosis of both PDAC and CCA. Inpancreatic cancer, the emphasis is placed on prognosticand theranostic markers, whereas in CCA the utilityof molecular markers in diagnosis and prognosis arehighlighted.

  15. Adipokines as Potential Biomarkers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Annalisa Del Prete


    Full Text Available Rheumatoid arthritis (RA is a chronic systemic inflammatory autoimmune disease characterized by severe joint injury. Recently, research has been focusing on the possible identification of predictor markers of disease onset and/or progression, of joint damage, and of therapeutic response. Recent findings have uncovered the role of white adipose tissue as a pleiotropic organ not only specialized in endocrine functions but also able to control multiple physiopathological processes, including inflammation. Adipokines are a family of soluble mediators secreted by white adipose tissue endowed with a wide spectrum of actions. This review will focus on the recent advances on the role of the adipokine network in the pathogenesis of RA. A particular attention will be devoted to the action of these proteins on RA effector cells, and on the possibility to use circulating levels of adipokines as potential biomarkers of disease activity and therapeutic response.

  16. Pneumoproteins and inflammatory biomarkers in asphalt pavers. (United States)

    Ellingsen, Dag G; Ulvestad, Bente; Andersson, Lena; Barregard, Lars


    Pneumoproteins, biomarkers of systemic inflammation and endothelial activation were studied across a season in 72 asphalt pavers, 32 asphalt plant operators and 19 asphalt engineers. Smokers had lower concentrations of Clara cell protein (CC-16) and surfactant protein A, but higher concentrations of surfactant protein D, interleukin 6, C-reactive protein, fibrinogen and intercellular adhesion molecule (ICAM)-1 than non-smokers. Smokers reporting wheezing had lower mean CC-16 concentration than smokers not reporting wheezing (5.7 vs 8.6 microg l(-1); p = 0.05). Cholesterol, P-selectin and ICAM-1 were lower in pavers and operators at the end compared with the start of the season. This may be related to increased physical activity during the season.

  17. Biomarkers of postoperative delirium and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Ganna eAndrosova


    Full Text Available Elderly surgical patients frequently experience postoperative delirium (POD and the subsequent development of postoperative cognitive dysfunction (POCD. Clinical features include deterioration in cognition, disturbance in attention and reduced awareness of the environment and result in higher morbidity, mortality and greater utilization of social financial assistance. The aging Western societies can expect an increase in the incidence of POD and POCD. The underlying pathophysiological mechanisms have been studied on the molecular level albeit with unsatisfying small research efforts given their societal burden. Here, we review the known physiological and immunological changes and genetic risk factors, identify candidates for further studies and integrate the information into a draft network for exploration on a systems level. The pathogenesis of these postoperative cognitive impairments is multifactorial; application of integrated systems biology has the potential to reconstruct the underlying network of molecular mechanisms and help in the identification of prognostic and diagnostic biomarkers.

  18. [Micronucleus test: cytome assay and health biomarker]. (United States)

    García Sagredo, José Miguel


    Micronuclei are structures similar to a nucleus but small size and localized in the cytoplasm. A micronucleus contents chromosome fragments or whole chromosomes. The micronucleus test is considered a biomarker for early induced genetic damage. Micronucleus test with cytochalasin B (CBMN test) is used to evaluate genotoxic effects induced by physical and chemical environmental agents, and to estimate the genetic damage induced in population groups exposed to such agents. After the study of large groups of control population, it is estimated that CBMN test can be used as a marker of health status with ability to establish a cancer risk. Finally, recent studies about the onset of cancer, based on single catastrophic events able to originate a cancer, such as chromothripsis or chromoanagenesis, are going to understand through an anomalous replication of DNA within the micronucleus.

  19. Adiponectin as a routine clinical biomarker. (United States)

    Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro


    Adiponectin is a protein synthesized and secreted predominantly by adipocytes into the peripheral blood. However, circulating adiponectin level is inversely related with body weight, especially visceral fat accumulation. The mechanism of this paradoxical relation remains obscure. Low circulating adiponectin concentrations (hypoadiponectinemia; metabolic syndrome, hyperuricemia), atherosclerosis (coronary artery disease, stroke, peripheral artery disease), sleep apnea, non-alcoholic fatty liver disease, gastritis and gastro-esophageal reflux disease, inflammatory bowel diseases, pancreatitis, osteoporosis, and cancer (endometrial cancer, postmenopausal breast cancer, leukemia, colon cancer, gastric cancer, prostate cancer). On the other hand, hyperadiponectinemia is associated with cardiac, renal and pulmonary diseases. This review article focuses on the significance of adiponectin as a clinical biomarker of obesity-related diseases. Routine measurement of adiponectin in patients with lifestyle-related diseases is highly recommended.

  20. Network-based drugs and biomarkers. (United States)

    Erler, Janine T; Linding, Rune


    The structure and dynamics of protein signalling networks governs cell decision processes and the formation of tissue boundaries. Complex diseases such as cancer and diabetes are diseases of such networks. Therefore approaches that can give insight into how these networks change during disease progression are crucial for better understanding, detection and intervention. The era of network medicine has begun; however, there are fundamental principles associated with molecular networks that are essential to consider for this field to succeed. Here, we introduce network biology and some of its associated technologies. We then focus on the multivariate nature of cellular networks and how this has implications for biomarker and drug discovery using cancer metastasis as an example.

  1. Infectious Disease Proteome Biomarkers: Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, Charles L.


    Research for the DOE Infectious Disease Proteome Biomarkers focused on Rift Valley fever virus (RVFV) and Venezuelan Equine Encephalitis Virus (VEEV). RVFV and VEEV are Category A and B pathogens respectively. Among the priority threats, RVFV and VEEV rank high in their potential for being weaponized and introduced to the United States, spreading quickly, and having a large health and economic impact. In addition, they both have live attenuated vaccine, which allows work to be performed at BSL-2. While the molecular biology of RVFV and VEEV are increasingly well-characterized, little is known about its host-pathogen interactions. Our research is aimed at determining critical alterations in host signaling pathways to identify therapeutics targeted against the host.

  2. Volatile emissions from Mycobacterium avium subsp. paratuberculosis mirror bacterial growth and enable distinction of different strains.

    Directory of Open Access Journals (Sweden)

    Phillip Trefz

    Full Text Available Control of paratuberculosis in livestock is hampered by the low sensitivity of established direct and indirect diagnostic methods. Like other bacteria, Mycobacterium avium subsp. paratuberculosis (MAP emits volatile organic compounds (VOCs. Differences of VOC patterns in breath and feces of infected and not infected animals were described in first pilot experiments but detailed information on potential marker substances is missing. This study was intended to look for characteristic volatile substances in the headspace of cultures of different MAP strains and to find out how the emission of VOCs was affected by density of bacterial growth. One laboratory adapted and four field strains, three of MAP C-type and one MAP S-type were cultivated on Herrold's egg yolk medium in dilutions of 10(-0, 10(-2, 10(-4 and 10(-6. Volatile substances were pre-concentrated from the headspace over the MAP cultures by means of Solid Phase Micro Extraction (SPME, thermally desorbed from the SPME fibers and separated and identified by means of GC-MS. Out of the large number of compounds found in the headspace over MAP cultures, 34 volatile marker substances could be identified as potential biomarkers for growth and metabolic activity. All five MAP strains could clearly be distinguished from blank culture media by means of emission patterns based on these 34 substances. In addition, patterns of volatiles emitted by the reference strain were significantly different from the field strains. Headspace concentrations of 2-ethylfuran, 2-methylfuran, 3-methylfuran, 2-pentylfuran, ethyl acetate, 1-methyl-1-H-pyrrole and dimethyldisulfide varied with density of bacterial growth. Analysis of VOCs emitted from mycobacterial cultures can be used to identify bacterial growth and, in addition, to differentiate between different bacterial strains. VOC emission patterns may be used to approximate bacterial growth density. In a perspective volatile marker substances could be used to

  3. A Lipid Biomarker Stratigraphic Record through the Late Ordovician Mass Extinction (United States)

    Rohrssen, M.; Love, G. D.; Fike, D. A.; Finnegan, S.; Fischer, W. W.; Jones, D. S.


    The Late Ordovician (~450-440 Ma) was a period of major environmental change, as indicated by evidence for short-duration (history of strata on the island, lack signs of petroleum-derived contamination (e.g. zero oleanane signal from angiosperms and other self-checks), and yield the C29 sterane predominance and low C28/C29 sterane ratios typical of the Early Paleozoic. These sediments, which bear marine fossils, lack the marine marker 24-n-propylcholestane, and have high 3β-methylhopane (4-11% of C30 αβ-hopane) and moderate 2α-methylhopane (2-4% C30 αβ-hopane) indices, most commonly associated with methanotrophs and cyanobacteria, respectively. Gammacerane is present only in trace amounts. Hopane/sterane ratios range from 1.8 to 11.2 (average = 4.7), with most values significantly above the Phanerozoic marine average values of 0.5-2.0, indicating a high contribution of bacterial input to sedimentary organic matter. Lower hopane/sterane values (average = 2.2) are generally found coincident with the carbon isotope excursion. Taken together, the lipid biomarker data suggest a stressed oligotrophic marine ecosystem in which N2-fixing bacterial communities dominate over eukaryotic algae, possibly as a response to nitrate-limitation in the low-sulfate Paleozoic ocean.

  4. DNA Methylation as a Biomarker for Preeclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Cindy M.; Ralph, Jody L.; Wright, Michelle L.; Linggi, Bryan E.; Ohm, Joyce E.


    Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.

  5. Biomarkers of peripheral muscle fatigue during exercise

    Directory of Open Access Journals (Sweden)

    Finsterer Josef


    Full Text Available Abstract Background Biomarkers of peripheral muscle fatigue (BPMFs are used to offer insights into mechanisms of exhaustion during exercise in order to detect abnormal fatigue or to detect defective metabolic pathways. This review aims at describing recent advances and future perspectives concerning the most important biomarkers of muscle fatigue during exercise. Results BPMFs are classified according to the mechanism of fatigue related to adenosine-triphosphate-metabolism, acidosis, or oxidative-metabolism. Muscle fatigue is also related to an immunological response. impaired calcium handling, disturbances in bioenergetic pathways, and genetic responses. The immunological and genetic response may make the muscle susceptible to fatigue but may not directly cause muscle fatigue. Production of BPMFs is predominantly dependent on the type of exercise. BPMFs need to change as a function of the process being monitored, be stable without appreciable diurnal variations, correlate well with exercise intensity, and be present in detectable amounts in easily accessible biological fluids. The most well-known BPMFs are serum lactate and interleukin-6. The most widely applied clinical application is screening for defective oxidative metabolism in mitochondrial disorders by means of the lactate stress test. The clinical relevance of most other BPMFs, however, is under debate, since they often depend on age, gender, physical fitness, the energy supply during exercise, the type of exercise needed to produce the BPMF, and whether healthy or diseased subjects are investigated. Conclusions Though the role of BPMFs during fatigue is poorly understood, measuring BPMFs under specific, standardised conditions appears to be helpful for assessing biological states or processes during exercise and fatigue.

  6. Bacterial adhesion and biofilms on surfaces

    Institute of Scientific and Technical Information of China (English)

    Trevor Roger Garrett; Manmohan Bhakoo; Zhibing Zhang


    Bacterial adhesion has become a significant problem in industry and in the domicile,and much research has been done for deeper understanding of the processes involved.A generic biological model of bacterial adhesion and population growth called the bacterial biofilm growth cycle,has been described and modified many times.The biofilm growth cycle encompasses bacterial adhesion at all levels,starting with the initial physical attraction of bacteria to a substrate,and ending with the eventual liberation of cell dusters from the biofilm matrix.When describing bacterial adhesion one is simply describing one or more stages of biofilm development,neglecting the fact that the population may not reach maturity.This article provides an overview of bacterial adhesion.cites examples of how bac-terial adhesion affects industry and summarises methods and instrumentation used to improve our understanding of the adhesive prop-erties of bacteria.

  7. Assessment of biomarkers for contaminants of emerging concern on aquatic organisms downstream of a municipal wastewater discharge. (United States)

    Jasinska, Edyta J; Goss, Greg G; Gillis, Patricia L; Van Der Kraak, Glen J; Matsumoto, Jacqueline; de Souza Machado, Anderson A; Giacomin, Marina; Moon, Thomas W; Massarsky, Andrey; Gagné, Francois; Servos, Mark R; Wilson, Joanna; Sultana, Tamanna; Metcalfe, Chris D


    Contaminants of emerging concern (CECs), including pharmaceuticals, personal care products and estrogens, are detected in wastewater treatment plant (WWTP) discharges. However, analytical monitoring of wastewater and surface water does not indicate whether CECs are affecting the organisms downstream. In this study, fathead minnows (Pimephales promelas) and freshwater mussels Pyganodon grandis Say, 1829 (synonym: Anodonta grandis Say, 1829) were caged for 4 weeks in the North Saskatchewan River, upstream and downstream of the discharge from the WWTP that serves the Edmonton, AB, Canada. Passive samplers deployed indicated that concentrations of pharmaceuticals, personal care products, an estrogen (estrone) and an androgen (androstenedione) were elevated at sites downstream of the WWTP discharge. Several biomarkers of exposure were significantly altered in the tissues of caged fathead minnows and freshwater mussels relative to the upstream reference sites. Biomarkers altered in fish included induction of CYP3A metabolism, an increase in vitellogenin (Vtg) gene expression in male minnows, elevated ratios of oxidized to total glutathione (i.e. GSSG/TGSH), and an increase in the activity of antioxidant enzymes (i.e. glutathione reductase, glutathione-S-transferase). In mussels, there were no significant changes in biomarkers of oxidative stress and the levels of Vtg-like proteins were reduced, not elevated, indicating a generalized stress response. Immune function was altered in mussels, as indicated by elevated lysosomal activity per hemocyte in P. grandis caged closest to the wastewater discharge. This immune response may be due to exposure to bacterial pathogens in the wastewater. Multivariate analysis indicated a response to the CECs Carbamazepine (CBZ) and Trimethoprim (TPM). Overall, these data indicate that there is a 1 km zone of impact for aquatic organisms downstream of WWTP discharge. However, multiple stressors in municipal wastewater make measurement and

  8. Far Beyond the Usual Biomarkers in Breast Cancer: A Review (United States)

    dos Anjos Pultz, Brunna; da Luz, Felipe Andrés Cordero; de Faria, Paulo Rogério; Oliveira, Ana Paula Lima; de Araújo, Rogério Agenor; Silva, Marcelo José Barbosa


    Research investigating biomarkers for early detection, prognosis and the prediction of treatment responses in breast cancer is rapidly expanding. However, no validated biomarker currently exists for use in routine clinical practice, and breast cancer detection and management remains dependent on invasive procedures. Histological examination remains the standard for diagnosis, whereas immunohistochemical and genetic tests are utilized for treatment decisions and prognosis determinations. Therefore, we conducted a comprehensive review of literature published in PubMed on breast cancer biomarkers between 2009 and 2013. The keywords that were used together were breast cancer, biomarkers, diagnosis, prognosis and drug response. The cited references of the manuscripts included in this review were also screened. We have comprehensively summarized the performance of several biomarkers for diagnosis, prognosis and predicted drug responses of breast cancer. Finally, we have identified 15 biomarkers that have demonstrated promise in initial studies and several miRNAs. At this point, such biomarkers must be rigorously validated in the clinical setting to be translated into clinically useful tests for the diagnosis, prognosis and prediction of drug responses of breast cancer. PMID:25057307

  9. Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable! (United States)

    Pinho, Rosa T.; Waghabi, Mariana C.; Cardillo, Fabíola; Mengel, José; Antas, Paulo R. Z.


    Biomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management-related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials. PMID:27563302

  10. Biomarkers in the management of ulcerative colitis: a brief review

    Directory of Open Access Journals (Sweden)

    Hussain, Shabnum


    Full Text Available Several attempts have been made in the last two decades to investigate ulcerative colitis (UC patients during the natural course of the disease so as to identify appropriate surrogate markers of disease activity. Most patients with quiescent inflammatory bowel disease have low grade inflammation and it is possible that relapse occurs only once the inflammatory process crosses a critical intensity. Since inflammation is a continuous process, its direct assessment may provide us a quantitative pre-symptomatic measure of imminent relapse. If substantial, it may allow targeted treatment early, to avert relapse or formulate newer therapeutic strategies to maintain symptomatic remission. It is clinically very important to identify these patients at a subclinical stage, noninvasively, by various biomarkers. Biomarkers help to gain an objective measurement of disease activity as symptoms are often subjective. Biomarkers also help to avoid invasive procedures which are often a burden to the patient and the health care system. If an ideal biomarker existed for UC, it would greatly facilitate the work of the gastroenterologist treating these patients. Both “classical” and “emerging” biomarkers of relevance for UC have been studied, but the quest for an ideal biomarker still continues. In this brief review we describe various biomarkers of clinical importance.

  11. Significant biomarkers for the management of hepatocellular carcinoma. (United States)

    Kondo, Yasuteru; Kimura, Osamu; Shimosegawa, Tooru


    Surveillance of hepatocellular carcinoma (HCC) is important for early detection. Imaging tests including computed tomography, magnetic resonance imaging and ultrasonography with or without various kinds of contrast medium are important options for detecting HCC. In addition to the imaging tests, various kinds of biomarkers including alpha-fetoprotein (AFP), lectin-bound AFP (AFP-L3) and protein induced by vitamin K absence or antagonist II (PIVKA-II) have been widely used to detect HCC and analyze treatment response. Recently, various kinds of novel biomarkers (proteins and miRNA) have been found to predict the malignancy potential of HCC and treatment response to specific therapies. Moreover, various combinations of well-established biomarkers and novel biomarkers have been tested to improve sensitivity and specificity. In practical terms, biomarkers that can be analyzed using peripheral blood samples might be more useful than immunohistochemical techniques. It has been reported that quantification of cytokines in peripheral blood and the analysis of peripheral immune subsets could be good biomarkers for managing HCC. Here, we describe the usefulness of and update well-established and novel biomarkers for the management of HCC.

  12. The role of metabolic biomarkers in drug toxicity studies. (United States)

    Schnackenberg, Laura K; Beger, Richard D


    ABSTRACT Metabolic profiling is a technique that can potentially provide more sensitive and specific biomarkers of toxicity than the current clinical measures benefiting preclinical and clinical drug studies. Both nuclear magnetic resonance (NMR) and mass spectrometry (MS) platforms have been used for metabolic profiling studies of drug toxicity. Not only can both techniques provide novel biomarker(s) of toxicity but the combination of both techniques gives a broader range of metabolites evaluated. Changes in metabolic patterns can provide insight into mechanism(s) of toxicity and help to eliminate a potentially toxic new chemical entity earlier in the developmental process. Metabolic profiling offers numerous advantages in toxicological research and screening as sample collection and preparation are relatively simple. Further, sample throughput, reproducibility, and accuracy are high. The area of drug toxicity of therapeutic compounds has already been impacted by metabolic profiling studies and will continue to be impacted as new, more specific biomarker(s) are found. In order for a biomarker or pattern of biomarkers to be accepted, it must be shown that they originate from the target tissue of interest. Metabolic profiling studies are amenable to any biofluid or tissue sample making it possible to link the changes noted in urine for instance as originating from renal injury. Additionally, the ease of sample collection makes it possible to follow a single animal or subject over time in order to determine whether and when the toxicity resolves itself. This review focuses on the advantages of metabolic profiling for drug toxicity studies.

  13. Bacterial meningitis and diseases caused by bacterial toxins. (United States)

    Rings, D M


    Bacterial meningitis most commonly occurs in young calves secondary to septicemia. Clinical signs of hyperirritability are usually seen. Meningitis can be confirmed by cerebrospinal fluid analysis and culture or by necropsy. Intoxications by the exotoxins of Clostridium perfringens types C and D, C. botulinum, and C. tetani are difficult to confirm. The clinical signs of these intoxications vary from flaccid paralysis (botulism) to muscular rigidity (tetanus). Treatment of affected cattle has been unrewarding in botulism and enterotoxemia, whereas early aggressive treatment of tetanus cases can often be successfully resolved. Botulism and enterotoxemia can be proved using mouse inoculation tests, whereas tetanus is diagnosed largely by ruling out other diseases.

  14. Mapping ethical and social aspects of cancer biomarkers. (United States)

    Blanchard, Anne


    Cancer biomarkers represent a revolutionary advance toward personalised cancer treatment, promising therapies that are tailored to subgroups of patients sharing similar generic traits. Notwithstanding the optimism driving this development, biomarkers also present an array of social and ethical questions, as witnessed in sporadic debates across different literatures. This review article seeks to consolidate these debates in a mapping of the complex terrain of ethical and social aspects of cancer biomarker research. This mapping was undertaken from the vantage point offered by a working cancer biomarker research centre called the Centre for Cancer Biomarkers (CCBIO) in Norway, according to a dialectic move between the literature and discussions with researchers and practitioners in the laboratory. Starting in the lab, we found that, with the exception of some classical bioethical dilemmas, researchers regarded many issues relative to the ethos of the biomarker community; how the complexity and uncertainty characterising biomarker research influence their scientific norms of quality. Such challenges to the ethos of cancer research remain largely implicit, outside the scope of formal bioethical enquiry, yet form the basis for other social and ethical issues. Indeed, looking out from the lab we see how questions of complexity, uncertainty and quality contribute to debates around social and global justice; undermining policies for the prioritisation of care, framing the stratification of those patients worthy of treatment, and limiting global access to this highly sophisticated research. We go on to discuss biomarker research within the culturally-constructed 'war on cancer' and highlight an important tension between the expectations of 'magic bullets' and the complexity and uncertainty faced in the lab. We conclude by arguing, with researchers in the CCBIO, for greater reflexivity and humility in cancer biomarker research and policy.

  15. Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis


    Muriel eAldunate; Daniela eSrbinovski; Anna C Hearps; Latham, Catherine F.; Paul A Ramsland; Raffi eGugasyan; Cone, Richard A.; Gilda eTachedjian


    Lactic acid and short chain fatty acids (SCFAs) produced by vaginal microbiota have reported antimicrobial and immune modulatory activities indicating their potential as biomarkers of disease and/or disease susceptibility. In asymptomatic women of reproductive-age the vaginal microbiota is comprised of lactic acid-producing bacteria that are primarily responsible for the production of lactic acid present at ~110 mM and acidifying the vaginal milieu to pH ~3.5. In contrast, bacterial vaginosis...

  16. Metabolomics in the identification of biomarkers of dietary intake. (United States)

    O'Gorman, Aoife; Gibbons, Helena; Brennan, Lorraine


    Traditional methods for assessing dietary exposure can be unreliable, with under reporting one of the main problems. In an attempt to overcome such problems there is increasing interest in identifying biomarkers of dietary intake to provide a more accurate measurement. Metabolomics is an analytical technique that aims to identify and quantify small metabolites. Recently, there has been an increased interest in the application of metabolomics coupled with statistical analysis for the identification of dietary biomarkers, with a number of putative biomarkers identified. This minireview focuses on metabolomics based approaches and highlights some of the key successes.

  17. Cerebrospinal fluid biomarkers of neurodegeneration in chronic neurological diseases. (United States)

    Tumani, Hayrettin; Teunissen, Charlotte; Süssmuth, Sigurd; Otto, Markus; Ludolph, Albert C; Brettschneider, Johannes


    Chronic neurological diseases (CND) like amyotrophic lateral sclerosis (ALS), dementia or multiple sclerosis (MS) share a chronic progressive course of disease that frequently leads to the common pathological pathway of neurodegeneration, including neuroaxonal damage, apoptosis and gliosis. There is an ongoing search for biomarkers that could support early diagnosis of CND and help to identify responders to interventions in therapeutic treatment trials. Cerebrospinal fluid (CSF) is a promising source of biomarkers in CND, since the CSF compartment is in close anatomical contact with the brain interstitial fluid, where biochemical changes related to CND are reflected. We review recent advances in CSF biomarkers research in CND and thereby focus on markers associated with neurodegeneration.

  18. Circulating micrornas as potential biomarkers of muscle atrophy (United States)

    Wang, Fei


    Noninvasive biomarkers with diagnostic value and prognostic applications have long been desired to replace muscle biopsy for muscle atrophy patients. Growing evidence indicates that circulating microRNAs are biomarkers to assess pathophysiological status. Here, we show that the medium levels of six muscle-specific miRNAs (miR-1/23a/206/133/499/208b, also known as myomiRs) were all elevated in the medium of starved C2C12 cell (P atrophy patients, indicating that they might represent the degree of muscle atrophy. Collectively, our data indicated that circulating myomiRs could serve as promising biomarkers for muscle atrophy.

  19. Endometrial cancer risk prediction including serum-based biomarkers

    DEFF Research Database (Denmark)

    Fortner, Renée T; Hüsing, Anika; Kühn, Tilman;


    Endometrial cancer risk prediction models including lifestyle, anthropometric, and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case......-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum...... concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines, and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at pdiscrimination was assessed using...

  20. Clinical states model for biomarkers in bladder cancer. (United States)

    Apolo, Andrea B; Milowsky, Matthew; Bajorin, Dean F


    Bladder cancer is a significant healthcare problem in the USA, with a high recurrence rate, the need for expensive continuous surveillance and limited treatment options for patients with advanced disease. Research has contributed to an understanding of the molecular pathways involved in the development and progression of bladder cancer, and that understanding has led to the discovery of potentially diagnostic, predictive and prognostic biomarkers. In this review, a clinical states model of bladder cancer is introduced and integrated into a paradigm for biomarker development. Biomarkers are systematically incorporated with predefined end points to aid in clinical management.

  1. Identification of cancer protein biomarkers using proteomic techniques

    Energy Technology Data Exchange (ETDEWEB)

    Mor, Gil G; Ward, David C; Bray-Ward, Patricia


    The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.

  2. Identification of cancer protein biomarkers using proteomic techniques

    Energy Technology Data Exchange (ETDEWEB)

    Mor, Gil G. (Cheshire, CT); Ward, David C. (Las Vegas, NV); Bray-Ward, Patricia (Las Vegas, NV)


    The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.

  3. Pre-analytic variability in cardiovascular biomarker testing. (United States)

    Cemin, Roberto; Daves, Massimo


    The impact of laboratory medicine on clinical cardiology has dramatically increased over the years and a lot of cardiovascular biomarkers have been recently proposed. In order to avoid clinical mistakes, physicians should be well aware of all the aspects, which could affect the quality of laboratory results, remembering that pre-analytic variability is an often overlooked significant source of bias, determining the vast majority of laboratory errors. This review addresses the determinants of pre-analitycal variability in cardiovascular biomarker testing, focusing on the most widespread biomarkers, which are cardiac troponins and natriuretic peptides.

  4. The potential biomarkers of drug addiction: proteomic and metabolomics challenges. (United States)

    Wang, Lv; Wu, Ning; Zhao, Tai-Yun; Li, Jin


    Drug addiction places a significant burden on society and individuals. Proteomics and metabolomics approaches pave the road for searching potential biomarkers to assist the diagnosis and treatment. This review summarized putative drug addiction-related biomarkers in proteomics and metabolomics studies and discussed challenges and prospects in future studies. Alterations of several hundred proteins and metabolites were reported when exposure to abused drug, which enriched in energy metabolism, oxidative stress response, protein modification and degradation, synaptic function and neurotrasmission, etc. Hsp70, peroxiredoxin-6 and α- and β-synuclein, as well as n-methylserotonin and purine metabolites, were promising as potential biomarker for drug addiction.

  5. Glycomics as an innovative technology to identify biomarkers of aging


    Borelli, Vincenzo


    Introduction. Glycomic analysis allows investigating on the global glycome within body fluids (as serum/plasma), this could eventually lead to identify new types of disease biomarkers, or as in this study, biomarkers of human aging studying specific aging models. Recent studies demonstrated that the plasma N-glycome is modified during human aging, suggesting that measurements of log-ratio of two serum/plasma N-glycans (NGA2F and NA2F), named GlycoAge test could provide a non-invasive biomarke...

  6. Peripheral Biomarkers of Parkinson's Disease Progression and Pioglitazone Effects. (United States)

    Simon, David K; Simuni, Tanya; Elm, Jordan; Clark-Matott, Joanne; Graebner, Allison K; Baker, Liana; Dunlop, Susan R; Emborg, Marina; Kamp, Cornelia; Morgan, John C; Ross, G Webster; Sharma, Saloni; Ravina, Bernard


    Pioglitazone, an oral hypoglycemic agent, recently failed to show promise as a disease-modifying agent in a 44-week phase 2 placebo-controlled study in 210 Parkinson's disease (PD) subjects. We analyzed peripheral biomarkers, including leukocyte PGC-1α and target gene expression, plasma interleukin 6 (IL-6) as a marker of inflammation, and urine 8-hydroxydeoxyguanosine (8OHdG) as a marker of oxidative DNA damage. Baseline or changes from baseline in biomarker levels were not associated with the rate of progression of PD. Pioglitazone did not significantly alter biomarker levels. Other agents that more effectively target these mechanisms remain of potential interest as disease modifying therapies in PD.

  7. Problems associated with fluid biomarkers for Parkinson's disease. (United States)

    Nyhlén, Jakob; Constantinescu, Radu; Zetterberg, Henrik


    This article focuses on biochemical markers that may be used in the diagnostics of Parkinson's disease and associated disorders, and to identify early cases and stratify patients into subgroups. We present an updated account of some currently available candidate fluid biomarkers, and discuss their diagnostic performance and limitations. We also discuss some of the general problems with Parkinson's disease biomarkers and possible ways of moving forward. It may be concluded that a diagnostically useful fluid biomarker for Parkinson's disease is yet to be identified. However, some interesting candidates exist and may prove useful in the future, alone or when analyzed together in patterns.

  8. Biomarkers of Alzheimer’s disease in body fluids

    Institute of Scientific and Technical Information of China (English)


    Various innovative diagnostic methods for Alzheimer’s disease (AD) have been developed in view of the increasing preva-lence and consequences of later-life dementia. Biomarkers in cerebrospinal fluid (CSF) and blood for AD are primarily based on the detection of components derived from amyloid plaques and neurofibrillary tangles (NFTs). Published reports on CSF and blood biomarkers in AD indicate that although biomarkers in body fluids may be utilized in the clinical diagnosis of AD, there are no specific markers that permit accurate and reliable diagnosis of early-stage AD or the monitoring of disease pro-gression.

  9. The ongoing quest for biomarkers in Ankylosing Spondylitis. (United States)

    Danve, Abhijeet; O'Dell, James


    Ankylosing Spondylitis poses significant challenges in terms of early diagnosis, assessment of disease activity, predicting response to the treatment and monitoring radiographic progression. With better understanding of underlying immunopathogenesis, effective targeted therapies are available which improve symptoms, quality of life and possibly slow the radiographic progression. There has been a growing interest in the discovery of biomarkers for defining various aspects of disease assessment and management in Ankylosing Spondylitis. The C-reactive protein and HLA-B27 are most commonly used biomarkers. This review describes many other newer biomarkers which have potential clinical applications in this chronic inflammatory disease.

  10. Translational biomarkers of acetaminophen-induced acute liver injury. (United States)

    Beger, Richard D; Bhattacharyya, Sudeepa; Yang, Xi; Gill, Pritmohinder S; Schnackenberg, Laura K; Sun, Jinchun; James, Laura P


    Acetaminophen (APAP) is a commonly used analgesic drug that can cause liver injury, liver necrosis and liver failure. APAP-induced liver injury is associated with glutathione depletion, the formation of APAP protein adducts, the generation of reactive oxygen and nitrogen species and mitochondrial injury. The systems biology omics technologies (transcriptomics, proteomics and metabolomics) have been used to discover potential translational biomarkers of liver injury. The following review provides a summary of the systems biology discovery process, analytical validation of biomarkers and translation of omics biomarkers from the nonclinical to clinical setting in APAP-induced liver injury.

  11. Identification of cancer protein biomarkers using proteomic techniques

    Energy Technology Data Exchange (ETDEWEB)

    Mor, Gil G.; Ward, David C.; Bray-Ward, Patricia


    The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.

  12. Predictive value of liver enzymes and inflammatory biomarkers for the severity of liver fibrosis stage in HIV/HCV co-infected patients.

    Directory of Open Access Journals (Sweden)

    Charlotte Charpentier

    Full Text Available OBJECTIVE: The aim of our study was to assess a possible association between plasma inflammatory biomarkers (CRP, IL-6, soluble CD14 and the extent of fibrosis or cirrhosis using a FibroScan® in HIV/HCV co-infected patients. METHODS: This cross-sectional study assessed 60 HIV/HCV co-infected patients who had paired plasma samples and FibroScan® values available. All included patients were controlled for HIV infection (HIV-1 RNA <50 copies/mL and had detectable HCV RNA levels. Levels of three biomarkers were measured in all samples using commercial ELISA kits. Multivariate logistic regression models identified factors associated with the METAVIR stages of fibrosis (F0-F2 vs. F3-F4. RESULTS: In univariate logistic regression analyses, in addition to sCD14 (odds ratio [OR] = 3.23, 95% confidence interval [95%CI] = 1.30-7.97, P = 0.01, aspartate aminotransferase (AST, alanine aminotransferase, platelet counts, and CD4 cell counts were associated with the stage of liver fibrosis and, thus, were introduced into the model. However, only AST (OR = 1.06, 95%CI = 1.02-1.10, P = 0.0009 was independently associated with F3-F4 stage liver fibrosis. CONCLUSIONS: In our study of HIV/HCV co-infected patients, sCD14 plasma level, a biomarker of monocyte activation, was not independently associated with the F3-F4 stage of liver fibrosis. We hypothesize that the higher levels of inflammation markers observed in HIV/HCV co-infected patients, compared to HCV mono-infected patients, prevent this association being observed within this population.

  13. Detection of serological biomarkers by proximity extension assay for detection of colorectal neoplasias in symptomatic individuals

    DEFF Research Database (Denmark)

    Buch Thorsen, Stine; Lundberg, Martin; Villablanca, Andrea;


    of biomarkers from the bench to clinical practice we initiated a biomarker study focusing on a novel technique, the proximity extension assay, with multiplexing capability and the possible additive effect obtained from biomarker panels. We performed a screening of 74 different biomarkers in plasma derived from...

  14. The Combined Detection of Morphological and Molecular Biomarkers: Implications for Astrobiology (United States)

    Toporski, J.; Steele, A.; Westall, F.; McKay, D. S.


    Experience gathered by previous researchers during their hunt for evidence of early Earth life has shown the complexity in interpreting observations of possible microfossils and to establish the evidence to be positive. Similarly, the stillsimmering controversy on the nature of the nano-structures in Martian meteorite ALH84001 described by McKay et al. (1996) emphasizes the difficulties of conclusively identifying those structures as (a) fossilized bacterial cells and (b) establish their indigeneity. A better understanding of biological signatures in rocks is needed in order to identify traces of microbial life, which include morphological, mineralogical and chemical traces. It is thus considered crucial to tackle the problems emerging in the search for evidence of early life on Earth and in exopaleontological research with a multidisciplinary approach. With this is mind we applied surface sensitive Time of Flight-Secondary Ion Mass Spectroscopy (ToF-SIMS) to a previously described 25 m.y. old fossil bacterial biofilm. This technique allows in situ analysis with high mass resolution as well as molecular imaging of micron sized structures. As no extraction or derivatisation of the sample is required for ToF-SIMS analysis, electron microscopical investigation of the same samples subsequent to analysis is possible, thus allowing the combination of molecular and morphological biomarkers. The analysed fossil bacterial biofilms were associated with macrofossils from volcanoclastic lacustrine sediments from the Upper Oligocene Enspel formation (Germany). Preliminary scanning electron microscopy (SEM) studies have shown that a fossil structure interpreted as a coprolite purely consisted of fossilized bacterial biofilm. For ToF-SIMS investigation small particles were taken from the fossil biofilm and mounted onto Au-coated In-foil and analysed in a Phi Evans T-2000 TRIFT system. The ToF-SIMS analysed samples were Au/Pd-sputter coated and imaged using a Philips XL40 Field

  15. Quantitative network measures as biomarkers for classifying prostate cancer disease states: a systems approach to diagnostic biomarkers.

    Directory of Open Access Journals (Sweden)

    Matthias Dehmer

    Full Text Available Identifying diagnostic biomarkers based on genomic features for an accurate disease classification is a problem of great importance for both, basic medical research and clinical practice. In this paper, we introduce quantitative network measures as structural biomarkers and investigate their ability for classifying disease states inferred from gene expression data from prostate cancer. We demonstrate the utility of our approach by using eigenvalue and entropy-based graph invariants and compare the results with a conventional biomarker analysis of the underlying gene expression data.

  16. Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus (United States)

    Limbrick, David D.; Baksh, Brandon; Morgan, Clinton D.; Habiyaremye, Gakwaya; McAllister, James P.; Inder, Terrie E.; Mercer, Deanna; Holtzman, David M.; Strahle, Jennifer; Wallendorf, Michael J.; Morales, Diego M.


    Introduction Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value. Methods CSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPPα, sAPPβ, Aβ42), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC. Results CSF levels of APP, sAPPα, sAPPβ, Aβ42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age (p<0.0001 and AUC = 0.99), followed by normalized sAPPβ (p = 0.0001, AUC = 0.95), tau, APP, and L1CAM. Among subjects ≤12 months, a normalized CSF sAPPα cut-point of 0.41 provided the best prediction of CHC (odds ratio = 528, sensitivity = 0.94, specificity = 0.97); these infants were 32 times more likely to have CHC. Conclusions CSF proteins such as s

  17. Glioblastoma extracellular vesicles: reservoirs of potential biomarkers

    Directory of Open Access Journals (Sweden)

    Redzic JS


    Full Text Available Jasmina S Redzic,1 Timothy H Ung,2 Michael W Graner2 1Skaggs School of Pharmacy and Pharmaceutical Sciences, 2Department of Neurosurgery, School of Medicine, University of Colorado Denver, Aurora, CO, USA Abstract: Glioblastoma multiforme (GBM is the most frequent and most devastating of the primary central nervous system tumors, with few patients living beyond 2 years postdiagnosis. The damage caused by the disease and our treatments for the patients often leave them physically and cognitively debilitated. Generally, GBMs appear after very short clinical histories and are discovered by imaging (using magnetic resonance imaging [MRI], and the diagnosis is validated by pathology, following surgical resection. The treatment response and diagnosis of tumor recurrence are also tracked by MRI, but there are numerous problems encountered with these monitoring modalities, such as ambiguous interpretation and forms of pseudoprogression. Diagnostic, prognostic, and predictive biomarkers would be an immense boon in following treatment schemes and in determining recurrence, which often requires an invasive intracranial biopsy to verify imaging data. Extracellular vesicles (EVs are stable, membrane-enclosed, virus-sized particles released from either the cell surface or from endosomal pathways that lead to the systemic release of EVs into accessible biofluids, such as serum/plasma, urine, cerebrospinal fluid, and saliva. EVs carry a wide variety of proteins, nucleic acids, lipids, and other metabolites, with many common features but with enough individuality to be able to identify the cell of origin of the vesicles. These components, if properly interrogated, could allow for the identification of tumor-derived EVs in biofluids, indicating tumor progression, relapse, or treatment failure. That knowledge would allow clinicians to continue with treatment regimens that were actually effective or to change course if the therapies were failing. Here, we review


    Biomarkers of exposure to chemical contamination, benzo(a)pyrene (BAP) and naphthalene (NAPH) type metabolites were measured in brown bullhead from a heavily polycyclic aromatic hydrocarbon (PAH) contaminated section of the Black River, Ohio during and immediately after remedial ...

  19. Plasma proteomics to identify biomarkers - Application to cardiovascular diseases

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Overgaard, Martin; Melholt Rasmussen, Lars


    , this technology may therefore identify new biomarkers that previously have not been associated with cardiovascular diseases. In this review, we summarize the key challenges and considerations, including strategies, recent discoveries and clinical applications in cardiovascular proteomics that may lead...

  20. Telomere Length – a New Biomarker in Medicine

    Directory of Open Access Journals (Sweden)

    Agnieszka Kozłowska


    Full Text Available A number of xenobiotics in the environment and workplace influences on our health and life. Biomarkers are tools for measuring such exposures and their effects in the organism. Nowadays, telomere length, epigenetic changes, mutations and changes in gene expression pattern have become new molecular biomarkers. Telomeres play the role of molecular clock, which influences on expectancy of cell life and thus aging, the formation of damages, development diseases and carcinogenesis. The telomere length depends on mechanisms of replication and the activity of telomerase. Telomere length is currently used as a biomarker of susceptibility and/or exposure. This paper describes the role of telomere length as a biomarker of aging cells, oxidative stress, a marker of many diseases including cancer, and as a marker of environmental and occupational exposure.

  1. MicroRNA as potential biomarkers in Glioblastoma. (United States)

    Areeb, Zammam; Stylli, Stanley S; Koldej, Rachel; Ritchie, David S; Siegal, Tali; Morokoff, Andrew P; Kaye, Andrew H; Luwor, Rodney B


    Glioblastoma is the most aggressive and lethal tumour of the central nervous system and as such the identification of reliable prognostic and predictive biomarkers for patient survival and tumour recurrence is paramount. MicroRNA detection has rapidly emerged as potential biomarkers, in patients with glioblastoma. Over the last decade, analysis of miRNA in laboratory based studies have yielded several candidates as potential biomarkers however, the accepted use of these candidates in the clinic is yet to be validated. Here we will examine the use of miRNA signatures to improve glioblastoma stratification into subgroups and summarise recent advances made in miRNA examination as potential biomarkers for glioblastoma progression and recurrence.

  2. Natural variation in biomarkers indicating mastitis in healthy cows

    DEFF Research Database (Denmark)

    Åkerstedt, Maria; Forsbäck, Linda; Larsen, Torben


    Dairy herds are expanding and, with increasing numbers of animals in each herd, there is a need for automatic recording of indicators in milk in order to detect mastitis, inflammation of the udder. A number of biomarkers for mastitis have been suggested over the years. Mastitis usually occurs...... in one of the four udder quarters and since it is now possible to milk each udder quarter separately in automated milking systems, it is important to evaluate the normal variation in the biomarkers at udder quarter level. This study evaluated the normal variations between milkings for some biomarkers...... in clinically healthy cows, determined by repeated somatic cell count and bacteriological analysis. The biomarkers studied were serum amyloid A (SAA), haptoglobin (Hp), lactate dehydrogenase (LDH), N-acetyl-β-d-glucosaminidase (NAGase) and alkaline phosphatase (AP), parameters that have been suggested...

  3. Tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Winther, Ole;


    Background: The majority of genetic biomarkers for human cancers are defined by statistical screening of high-throughput genomics data. While a large number of genetic biomarkers have been proposed for diagnostic and prognostic applications, only a small number have been applied in the clinic....... Similarly, the use of proteomics methods for the discovery of cancer biomarkers is increasing. The emerging field of proteogenomics seeks to enrich the value of genomics and proteomics approaches by studying the intersection of genomics and proteomics data. This task is challenging due to the complex nature...... of transcriptional and translation regulatory mechanisms and the disparities between genomic and proteomic data from the same samples. In this study, we have examined tumor antigens as potential biomarkers for breast cancer using genomics and proteomics data from previously reported laser capture microdissected ER...

  4. Functional, Structural, and Neurotoxicity Biomarkers in Integrative Assessment of Concussions

    Directory of Open Access Journals (Sweden)

    Svetlana A Dambinova


    Full Text Available Concussion is a complex, heterogenous process affecting the brain. Accurate assessment and diagnosis and appropriate management of concussion are essential to ensure athletes do not prematurely return to play or others to work or active military duty, risking re-injury. To date, clinical diagnosis relies primarily on evaluating subjects for functional impairment using instruments that include neurocognitive testing, subjective symptom report, and neurobehavioral assessments, such as balance and vestibular-ocular reflex testing. Structural biomarkers, defined as advanced neuroimaging techniques and biomarkers assessing neurotoxicity and immunoexcitotoxicity may complement the use of functional biomarkers. We hypothesize that neurotoxicity AMPA, NMDA, and kainite receptor biomarkers might be utilized as a part of comprehensive approach to concussion evaluations, with the goal of increasing diagnostic accuracy and facilitating treatment planning and prognostic assessment.

  5. Using biomarkers to improve detection of Alzheimer’s disease (United States)

    Biagioni, Milton C; Galvin, James E


    SUMMARY Disease-modifying approaches for Alzheimer’s disease (AD) might be most effective when initiated very early in the course, before the pathologic burden and neuronal and synaptic degeneration make it unlikely that halting disease progression would have a significant impact on patient outcomes. Biomarkers of disease may provide important avenues of research to enhance the diagnosis of individuals with early AD and could assist in the identification of those individuals at risk for developing AD. However, for such biomarkers to become clinically useful, long-term follow-up studies are necessary to evaluate the relevance of cross-sectional biomarker changes to the longitudinal course of the disease. The objective of this article is to review recent progress in AD biomarkers for the early diagnosis, classification, progression and prediction of AD and their usefulness in new treatment trials. PMID:22076127

  6. Computational and Experimental Approaches to Cancer Biomarker Discovery

    DEFF Research Database (Denmark)

    Krzystanek, Marcin

    with a purely biological, experimental approach where the effects of treatment with cytotoxic agents or defects in DNA repair mechanisms can be individually quantified and turned into mutational signatures.In the second part of the thesis I present work towards identification and improvement of the current......Effective cancer treatment requires good biomarkers: measurable indicators of some biological state or condition that constitute the cornerstone of personalized medicine. Prognostic biomarkers provide information about the likely course of the disease, while predictive biomarkers enable prediction...... of a patient’s response to a particular treatment, thus helping to avoid unnecessary treatment and unwanted side effects in non-responding individuals.Currently biomarker discovery is facilitated by recent advances in high-throughput technologies when association between a given biological phenotype...

  7. The Present and Future of Prostate Cancer Urine Biomarkers

    Directory of Open Access Journals (Sweden)

    Jeremy Clark


    Full Text Available In order to successfully cure patients with prostate cancer (PCa, it is important to detect the disease at an early stage. The existing clinical biomarkers for PCa are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid over-treatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two thirds of the biopsies performed are still unnecessary. Thus the discovery of non-invasive PCa biomarkers remains urgent. In recent years, the utilization of urine has emerged as an attractive option for the non-invasive detection of PCa. Moreover, a great improvement in high-throughput “omic” techniques has presented considerable opportunities for the identification of new biomarkers. Herein, we will review the most significant urine biomarkers described in recent years, as well as some future prospects in that field.

  8. Retracing Circulating Tumour Cells for Biomarker Characterization after Enumeration

    Directory of Open Access Journals (Sweden)

    Anders S. Frandsen


    Mapping and retracing of CTCs enables downstream analysis of individual CTCs for existing and future cancer genotypic and phenotypic biomarkers. Future studies will uncover this potential of the novel retracing technology.

  9. Protein Biomarkers for the Early Detection of Breast Cancer

    Directory of Open Access Journals (Sweden)

    David E. Misek


    Full Text Available Advances in breast cancer control will be greatly aided by early detection so as to diagnose and treat breast cancer in its preinvasive state prior to metastasis. For breast cancer, the second leading cause of cancer-related death among women in the United States, early detection does allow for increased treatment options, including surgical resection, with a corresponding better patient response. Unfortunately, however, many patients' tumors are diagnosed following metastasis, thus making it more difficult to successfully treat the malignancy. There are, at present, no existing validated plasma/serum biomarkers for breast cancer. Only a few biomarkers (such as HER-2/neu, estrogen receptor, and progesterone receptor have utility for diagnosis and prognosis. Thus, there is a great need for new biomarkers for breast cancer. This paper will focus on the identification of new serum protein biomarkers with utility for the early detection of breast cancer.

  10. Using biomarkers to improve detection of Alzheimer's disease. (United States)

    Biagioni, Milton C; Galvin, James E


    Disease-modifying approaches for Alzheimer's disease (AD) might be most effective when initiated very early in the course, before the pathologic burden and neuronal and synaptic degeneration make it unlikely that halting disease progression would have a significant impact on patient outcomes. Biomarkers of disease may provide important avenues of research to enhance the diagnosis of individuals with early AD and could assist in the identification of those individuals at risk for developing AD. However, for such biomarkers to become clinically useful, long-term follow-up studies are necessary to evaluate the relevance of cross-sectional biomarker changes to the longitudinal course of the disease. The objective of this article is to review recent progress in AD biomarkers for the early diagnosis, classification, progression and prediction of AD and their usefulness in new treatment trials.

  11. Biomarkers in the diagnosis of ADHD--promising directions. (United States)

    Faraone, Stephen V; Bonvicini, Cristian; Scassellati, Catia


    The etiology and pathogenesis of attention-deficit/hyperactivity disorder (ADHD) are unclear and a more valid diagnosis would certainly be welcomed. Starting from the literature, we built an hypothetical pyramid representing a putative set of biomarkers where, at the top, variants in DAT1 and DRD4 genes are the best candidates for their associations to neuropsychological tasks, activation in specific brain areas, methylphenidate response and gene expression levels. Interesting data come from the noradrenergic system (norepinephrine transporter, norepinephrine, 3-methoxy-4-hydroxyphenylglycol, monoamine oxidase, neuropeptide Y) for their altered peripheral levels, their association with neuropsychological tasks, symptomatology, drugs effect and brain function. Other minor putative genetic biomarkers could be dopamine beta hydroxylase and catechol-O-methyltransferase. In the bottom, we placed endophenotype biomarkers. A more deep integration of "omics" sciences along with more accurate clinical profiles and new high-throughput computational methods will allow us to identify a better list of biomarkers useful for diagnosis and therapies.

  12. Neurotoxicity and Biomarkers of Lead Exposure:a Review

    Institute of Scientific and Technical Information of China (English)

    Kang-sheng Liu; Jia-hu Hao; Yu Zeng; Fan-chun Dai; Ping-qing Gu


    Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups:biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone;the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer’s disease, Parkinson’s disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

  13. Renal Cancer Biomarkers | NCI Technology Transfer Center | TTC (United States)

    The National Cancer Institute's Laboratory of Proteomics and Analytical Technologies is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic, therapeutic and prognostic cancer biomarkers from clinical specimens.


    Directory of Open Access Journals (Sweden)

    Ivančica Strunjak-Perović


    Full Text Available With development of the fish culturing in the sea, the interest in their health also increased. The reason for this are diseases or rather mortality that occur in such controlled cultures and cause great economic losses. By growing large quantities of fish in rather small species, natural conditions are changed, so fish is more sensitive and prone to infection agents (viruses, bacteria, parasites. Besides, a large fish density in the cultural process accelerates spreading if the diseases, but also enables a better perception of them. In wild populations sick specimen very quickly become predator’s prey, witch makes it difficult to note any pathological changes in such fish. There are lots of articles on viral, bacterial and parasitic diseases nowdays, but this work deals exclusively with bacterial deseases that occur in the controlled sea cultures (vibriosis, furunculosis, pastherelosis, nocardiosis, mycobaceriosis, edwardsielosis, yersiniosis, deseases caused by bacteria of genera Flexibacter, Pseudomonas, Aeromonas, Streptococus and bacteria nephryithis. Yet, the knowledge of these deseases vary, depending on wether a fish species is being cultured for a longer period of time or is only being introduced in the controlled culture.

  15. Bacterial Culture of Neonatal Sepsis

    Directory of Open Access Journals (Sweden)

    AH Movahedian


    Full Text Available Neonatal bacterial sepsis is one of the major cause of morbidity and mortality in neonates. This retrospective study was performed to determine the incidence of bacterial sepsis with focus on Gram negative organisms in neonates admitted at Beheshti Hospital in Kashan, during a 3-yr period, from September 2002 to September 2005. Blood culture was performed on all neonates with risk factors or signs of suggestive sepsis. Blood samples were cultured using brain heart infusion (BHI broth according to standard method. From the 1680 neonates 36% had positive blood culture for Pseudomans aeruginosa, 20.7% for Coagulase negative Staphylococci, and 17% for Klebsiella spp. Gram-negative organisms accounted for 72.1% of all positive cultures. The overall mortality rate was 19.8% (22 /111 of whom 63.6% (14 /22 were preterm. Pseudomona aeruginosa and Klebsiella spp. showed a high degree of resistance to commonly used antibiotics (ampicillin, gentamicin as well as third generation cephalosporins. Continued local surveillance studies are urged to monitor emerging antimicrobial resistance and to guide interventions to minimize its occurrence.

  16. Periodontal diseases as bacterial infection

    Directory of Open Access Journals (Sweden)

    A. Bascones Martínez

    Full Text Available The periodontal disease is conformed by a group of illnesses affecting the gums and dental support structures. They are caused by certain bacteria found in the bacterial plaque. These bacteria are essential to the onset of illness; however, there are predisposing factors in both the host and the microorganisms that will have an effect on the pathogenesis of the illness. Periodontopathogenic bacterial microbiota is needed, but by itself, it is not enough to cause the illness, requiring the presence of a susceptible host. These diseases have been classified as gingivitis, when limited to the gums, and periodontitis, when they spread to deeper tissues. Classification of periodontal disease has varied over the years.The one used in this work was approved at the International Workshop for a Classification of Periodontal Diseases and Conditions, held in 1999. This study is an overview of the different periodontal disease syndromes. Later, the systematic use of antibiotic treatment consisting of amoxicillin, amoxicillinclavulanic acid, and metronidazole as first line coadjuvant treatment of these illnesses will be reviewed.

  17. Bioinformatic Comparison of Bacterial Secretomes

    Institute of Scientific and Technical Information of China (English)

    Catharine Song; Aseem Kumar; Mazen Saleh


    The rapid increasing number of completed bacterial genomes provides a good op-portunity to compare their proteomes. This study was undertaken to specifically compare and contrast their secretomes-the fraction of the proteome with pre-dicted N-terminal signal sequences, both type Ⅰ and type Ⅱ. A total of 176 theoreti-cal bacterial proteomes were examined using the ExProt program. Compared with the Gram-positives, the Gram-negative bacteria were found, on average, to con-tain a larger number of potential Sec-dependent sequences. In the Gram-negative bacteria but not in the others, there was a positive correlation between proteome size and secretome size, while there was no correlation between secretome size and pathogenicity. Within the Gram-negative bacteria, intracellular pathogens were found to have the smallest secretomes. However, the secretomes of certain bacte-ria did not fit into the observed pattern. Specifically, the secretome of Borrelia burgdoferi has an unusually large number of putative lipoproteins, and the signal peptides of mycoplasmas show closer sequence similarity to those of the Gram-negative bacteria. Our analysis also suggests that even for a theoretical minimal genome of 300 open reading frames, a fraction of this gene pool (up to a maximum of 20%) may code for proteins with Sec-dependent signal sequences.

  18. Bacterial pericarditis in a cat

    Directory of Open Access Journals (Sweden)

    Nicole LeBlanc


    Full Text Available Case summary A 4-year-old male neutered domestic shorthair cat was presented to the Oregon State University cardiology service for suspected pericardial effusion. Cardiac tamponade was documented and pericardiocentesis yielded purulent fluid with cytologic results supportive of bacterial pericarditis. The microbial population consisted of Pasteurella multocida, Actinomyces canis, Fusobacterium and Bacteroides species. Conservative management was elected consisting of intravenous antibiotic therapy with ampicillin sodium/sulbactam sodium and metronidazole for 48 h followed by 4 weeks of oral antibiotics. Re-examination 3 months after the initial incident indicated no recurrence of effusion and the cat remained free of clinical signs 2 years after presentation. Relevance and novel information Bacterial pericarditis is a rare cause of pericardial effusion in cats. Growth of P multocida, A canis, Fusobacterium and Bacteroides species has not previously been documented in feline septic pericarditis. Conservative management with broad-spectrum antibiotics may be considered when further diagnostic imaging or exploratory surgery to search for a primary nidus of infection is not feasible or elected.

  19. The "Alzheimer's disease signature": potential perspectives for novel biomarkers


    Zella Davide; Di Costanzo Alfonso; Russo Claudio; Intrieri Mariano; Davinelli Sergio; Bosco Paolo; Scapagnini Giovanni


    Abstract Alzheimer's disease is a progressive and neurodegenerative disorder which involves multiple molecular mechanisms. Intense research during the last years has accumulated a large body of data and the search for sensitive and specific biomarkers has undergone a rapid evolution. However, the diagnosis remains problematic and the current tests do not accurately detect the process leading to neurodegeneration. Biomarkers discovery and validation are considered the key aspects to support cl...

  20. Pathological Fingerprints, Systems Biology and Biomarkers of Blast Brain Injury (United States)


    Patho- genesis of pulmonary edema caused by blast waves]. Vojno- sanit. Pregl. 48, 507–514. Cernak, I., Savic, J., Zunic, G., Pejnovic, N., Jovanikic...Cernak I, Savic J, Mrsulja B, Duricic B. [Pathogenesis of pulmonary edema caused by blast waves]. Vojnosanit Pregl. 1991;48:507–514 [in Serbian]. 37...generally accepted definition, a biomarker has the characteristic that it can be objectively measured 1Center of Innovative Research, Banyan Biomarkers, Inc