Biology

23 pages, 664 KiB

Open AccessArticle

Local Similarity Search to Find Gene Indicators in Mitochondrial Genomes

by Ruby L. V. Moritz^*, Matthias Bernt and Martin Middendorf

Department of Computer Science, University of Leipzig, Postfach 100920, Leipzig D-04009, Germany

Biology 2014, 3(1), 220-242; https://doi.org/10.3390/biology3010220 - 11 Mar 2014

Cited by 1 | Viewed by 7529

Given a set of nucleotide sequences we consider the problem of identifying conserved substrings occurring in homologous genes in a large number of sequences. The problem is solved by identifying certain nodes in a suffix tree containing all substrings occurring in the given [...] Read more.

Given a set of nucleotide sequences we consider the problem of identifying conserved substrings occurring in homologous genes in a large number of sequences. The problem is solved by identifying certain nodes in a suffix tree containing all substrings occurring in the given nucleotide sequences. Due to the large size of the targeted data set, our approach employs a truncated version of suffix trees. Two methods for this task are introduced: (1) The annotation guided marker detection method uses gene annotations which might contain a moderate number of errors; (2) The probability based marker detection method determines sequences that appear significantly more often than expected. The approach is successfully applied to the mitochondrial nucleotide sequences, and the corresponding annotations that are available in RefSeq for 2989 metazoan species. We demonstrate that the approach finds appropriate substrings. Full article

(This article belongs to the Special Issue Developments in Bioinformatic Algorithms)

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15 pages, 602 KiB

Open AccessArticle

Automated Sample Preparation Platform for Mass Spectrometry-Based Plasma Proteomics and Biomarker Discovery

by Vilém Guryča, Daniel Roeder, Paolo Piraino, Jens Lamerz, Axel Ducret

, Hanno Langen and Paul Cutler^*

F. Hoffmann-La Roche Ltd., Pharma Research and Early Development (pRED), Translational Technologies and Bioinformatics, 124 Grenzacherstrasse, Bldg. 93/4.38, 4070 Basel, Switzerland

Biology 2014, 3(1), 205-219; https://doi.org/10.3390/biology3010205 - 11 Mar 2014

Cited by 11 | Viewed by 9197

Abstract

The identification of novel biomarkers from human plasma remains a critical need in order to develop and monitor drug therapies for nearly all disease areas. The discovery of novel plasma biomarkers is, however, significantly hampered by the complexity and dynamic range of proteins [...] Read more.

The identification of novel biomarkers from human plasma remains a critical need in order to develop and monitor drug therapies for nearly all disease areas. The discovery of novel plasma biomarkers is, however, significantly hampered by the complexity and dynamic range of proteins within plasma, as well as the inherent variability in composition from patient to patient. In addition, it is widely accepted that most soluble plasma biomarkers for diseases such as cancer will be represented by tissue leakage products, circulating in plasma at low levels. It is therefore necessary to find approaches with the prerequisite level of sensitivity in such a complex biological matrix. Strategies for fractionating the plasma proteome have been suggested, but improvements in sensitivity are often negated by the resultant process variability. Here we describe an approach using multidimensional chromatography and on-line protein derivatization, which allows for higher sensitivity, whilst minimizing the process variability. In order to evaluate this automated process fully, we demonstrate three levels of processing and compare sensitivity, throughput and reproducibility. We demonstrate that high sensitivity analysis of the human plasma proteome is possible down to the low ng/mL or even high pg/mL level with a high degree of technical reproducibility. Full article

(This article belongs to the Special Issue Advances in Proteomics Methods)

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27 pages, 1137 KiB

Open AccessReview

Dancing to Another Tune—Adhesive Moonlighting Proteins in Bacteria

by Veera Kainulainen^1,2 and Timo K. Korhonen^2,*

¹ Department of Veterinary Biosciences, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland

² General Microbiology, Department of Biosciences, University of Helsinki, P.O. Box 56, FI-00014 Helsinki, Finland

Biology 2014, 3(1), 178-204; https://doi.org/10.3390/biology3010178 - 10 Mar 2014

Cited by 126 | Viewed by 11174

Abstract

Biological moonlighting refers to proteins which express more than one function. Moonlighting proteins occur in pathogenic and commensal as well as in Gram-positive and Gram-negative bacteria. The canonical functions of moonlighting proteins are in essential cellular processes, i.e., glycolysis, protein synthesis, chaperone [...] Read more.

Biological moonlighting refers to proteins which express more than one function. Moonlighting proteins occur in pathogenic and commensal as well as in Gram-positive and Gram-negative bacteria. The canonical functions of moonlighting proteins are in essential cellular processes, i.e., glycolysis, protein synthesis, chaperone activity, and nucleic acid stability, and their moonlighting functions include binding to host epithelial and phagocytic cells, subepithelia, cytoskeleton as well as to mucins and circulating proteins of the immune and hemostatic systems. Sequences of the moonlighting proteins do not contain known motifs for surface export or anchoring, and it has remained open whether bacterial moonlighting proteins are actively secreted to the cell wall or whether they are released from traumatized cells and then rebind onto the bacteria. In lactobacilli, ionic interactions with lipoteichoic acids and with cell division sites are important for surface localization of the proteins. Moonlighting proteins represent an abundant class of bacterial adhesins that are part of bacterial interactions with the environment and in responses to environmental changes. Multifunctionality in bacterial surface proteins appears common: the canonical adhesion proteins fimbriae express also nonadhesive functions, whereas the mobility organelles flagella as well as surface proteases express adhesive functions. Full article

(This article belongs to the Special Issue Bacterial Adhesion)

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2 pages, 39 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Biology in 2013

by Biology Editorial Office

MDPI AG, Klybeckstrasse 64, CH-4057 Basel, Switzerland

Biology 2014, 3(1), 176-177; https://doi.org/10.3390/biology3010176 - 27 Feb 2014

Viewed by 4732

Abstract

The editors of Biology would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2013. [...] Full article

9 pages, 387 KiB

Open AccessArticle

In Vitro High Throughput Screening, What Next? Lessons from the Screening for Aurora Kinase Inhibitors

by Thi-My-Nhung Hoang^1,2, Hong-Lien Vu^1,3, Ly-Thuy-Tram Le^1,4, Chi-Hung Nguyen⁵ and Annie Molla^1,*

¹ INSERM UJF U823 Institut Albert Bonniot, Team 4: Chromatin and Epigenetic, BP 170, 38 042 Grenoble Cedex 9, France

² Faculty of Biology, VNU University of Science, HaNoi 10 000, Vietnam

³ Department of biology, University of Natural Sciences, Ho Chi Minh 70 000, Vietnam

⁴ Department of biology, University of Technology, DaNang 55 000, Vietnam

⁵ UMR 176 CNRS-Institut Curie, Bat 110 Centre Universitaire, Orsay 91405, France

Biology 2014, 3(1), 167-175; https://doi.org/10.3390/biology3010167 - 27 Feb 2014

Cited by 2 | Viewed by 6697

Abstract

Based on in vitro assays, we performed a High Throughput Screening (HTS) to identify kinase inhibitors among 10,000 small chemical compounds. In this didactic paper, we describe step-by-step the approach to validate the hits as well as the major pitfalls encountered in the [...] Read more.

Based on in vitro assays, we performed a High Throughput Screening (HTS) to identify kinase inhibitors among 10,000 small chemical compounds. In this didactic paper, we describe step-by-step the approach to validate the hits as well as the major pitfalls encountered in the development of active molecules. We propose a decision tree that could be adapted to most in vitro HTS. Full article

(This article belongs to the Special Issue Screening for Biologically Active Compounds)

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10 pages, 717 KiB

Open AccessReview

McArdle Disease and Exercise Physiology

by Yu Kitaoka

Department of Sports Sciences, The University of Tokyo, Komaba 3-8-1, Meguro-ku, Tokyo 153-8902, Japan

Biology 2014, 3(1), 157-166; https://doi.org/10.3390/biology3010157 - 25 Feb 2014

Cited by 15 | Viewed by 19360

Abstract

McArdle disease (glycogen storage disease Type V; MD) is a metabolic myopathy caused by a deficiency in muscle glycogen phosphorylase. Since muscle glycogen is an important fuel for muscle during exercise, this inborn error of metabolism provides a model for understanding the role [...] Read more.

McArdle disease (glycogen storage disease Type V; MD) is a metabolic myopathy caused by a deficiency in muscle glycogen phosphorylase. Since muscle glycogen is an important fuel for muscle during exercise, this inborn error of metabolism provides a model for understanding the role of glycogen in muscle function and the compensatory adaptations that occur in response to impaired glycogenolysis. Patients with MD have exercise intolerance with symptoms including premature fatigue, myalgia, and/or muscle cramps. Despite this, MD patients are able to perform prolonged exercise as a result of the “second wind” phenomenon, owing to the improved delivery of extra-muscular fuels during exercise. The present review will cover what this disease can teach us about exercise physiology, and particularly focuses on the compensatory pathways for energy delivery to muscle in the absence of glycogenolysis. Full article

(This article belongs to the Special Issue Muscle Structure and Function)

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18 pages, 543 KiB

Open AccessArticle

Miniaturized Bioaffinity Assessment Coupled to Mass Spectrometry for Guided Purification of Bioactives from Toad and Cone Snail

by Ferry Heus^1,†, Reka A. Otvos^1,2,†, Ruud L. E. G. Aspers³, Rene Van Elk², Jenny I. Halff¹, Andreas W. Ehlers⁴, Sébastien Dutertre⁵, Richard J. Lewis⁵

, Sybren Wijmenga³, August B. Smit², Wilfried M. A. Niessen^1,6 and Jeroen Kool^1,*

¹ AIMMS Division of BioMolecular Analysis, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1081, 1083 HV Amsterdam, The Netherlands

² Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands

³ Department of Biophysical Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands

⁴ AIMMS Division of Organic Chemistry, Faculty of Sciences, VU University Amsterdam, De Boelelaan 1081, 1083 HV Amsterdam, The Netherlands

⁵ The Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia

⁶ MassSpec Consultancy, de Wetstraat 8, 2332 XT Leiden, The Netherlands

^† These authors contributed equally to this work.

Biology 2014, 3(1), 139-156; https://doi.org/10.3390/biology3010139 - 13 Feb 2014

Cited by 19 | Viewed by 8227

Abstract

A nano-flow high-resolution screening platform, featuring a parallel chip-based microfluidic bioassay and mass spectrometry coupled to nano-liquid chromatography, was applied to screen animal venoms for nicotinic acetylcholine receptor like (nAChR) affinity by using the acetylcholine binding protein, a mimic of the nAChR. The [...] Read more.

A nano-flow high-resolution screening platform, featuring a parallel chip-based microfluidic bioassay and mass spectrometry coupled to nano-liquid chromatography, was applied to screen animal venoms for nicotinic acetylcholine receptor like (nAChR) affinity by using the acetylcholine binding protein, a mimic of the nAChR. The potential of this microfluidic platform is demonstrated by profiling the Conus textile venom proteome, consisting of over 1,000 peptides. Within one analysis (<90 min, 500 ng venom injected), ligands are detected and identified. To show applicability for non-peptides, small molecular ligands such as steroidal ligands were identified in skin secretions from two toad species (Bufo alvarius and Bufo marinus). Bioactives from the toad samples were subsequently isolated by MS-guided fractionation. The fractions analyzed by NMR and a radioligand binding assay with α7-nAChR confirmed the identity and bioactivity of several new ligands. Full article

(This article belongs to the Special Issue Screening for Biologically Active Compounds)

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38 pages, 1360 KiB

Open AccessArticle

High-Throughput Screen of Natural Product Libraries for Hsp90 Inhibitors

by Jason Davenport¹, Maurie Balch¹, Lakshmi Galam^1,†, Antwan Girgis², Jessica Hall², Brian S. J. Blagg² and Robert L. Matts^1,*

¹ Department of Biochemistry and Molecular Biology, 246 Noble Research Center, Oklahoma State University, Stillwater, OK 74078, USA

² Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, KS 66045, USA

^† Current address: Department of Internal Medicine, University of South Florida School of Medicine, 12901 Bruce B. Downs Blvd. MDC 19, Tampa, FL 33612, USA.

Biology 2014, 3(1), 101-138; https://doi.org/10.3390/biology3010101 - 10 Feb 2014

Cited by 25 | Viewed by 12489

Abstract

Hsp90 has become the target of intensive investigation, as inhibition of its function has the ability to simultaneously incapacitate proteins that function in pathways that represent the six hallmarks of cancer. While a number of Hsp90 inhibitors have made it into clinical trials, [...] Read more.

Hsp90 has become the target of intensive investigation, as inhibition of its function has the ability to simultaneously incapacitate proteins that function in pathways that represent the six hallmarks of cancer. While a number of Hsp90 inhibitors have made it into clinical trials, a number of short-comings have been noted, such that the search continues for novel Hsp90 inhibitors with superior pharmacological properties. To identify new potential Hsp90 inhibitors, we have utilized a high-throughput assay based on measuring Hsp90-dependent refolding of thermally denatured luciferase to screen natural compound libraries. Over 4,000 compounds were screen with over 100 hits. Data mining of the literature indicated that 51 compounds had physiological effects that Hsp90 inhibitors also exhibit, and/or the ability to downregulate the expression levels of Hsp90-dependent proteins. Of these 51 compounds, seven were previously characterized as Hsp90 inhibitors. Four compounds, anthothecol, garcinol, piplartine, and rottlerin, were further characterized, and the ability of these compounds to inhibit the refolding of luciferase, and reduce the rate of growth of MCF7 breast cancer cells, correlated with their ability to suppress the Hsp90-dependent maturation of the heme-regulated eIF2α kinase, and deplete cultured cells of Hsp90-dependent client proteins. Thus, this screen has identified an additional 44 compounds with known beneficial pharmacological properties, but with unknown mechanisms of action as possible new inhibitors of the Hsp90 chaperone machine. Full article

(This article belongs to the Special Issue Screening for Biologically Active Compounds)

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16 pages, 590 KiB

Open AccessReview

R-Based Software for the Integration of Pathway Data into Bioinformatic Algorithms

by Frank Kramer^*, Michaela Bayerlová and Tim Beißbarth

University Medical Center Göttingen, Department of Medical Statistics, Humboldtallee 32, D-37073 Göttingen, Germany

Biology 2014, 3(1), 85-100; https://doi.org/10.3390/biology3010085 - 7 Feb 2014

Cited by 17 | Viewed by 11825

Abstract

Putting new findings into the context of available literature knowledge is one approach to deal with the surge of high-throughput data results. Furthermore, prior knowledge can increase the performance and stability of bioinformatic algorithms, for example, methods for network reconstruction. In this review, [...] Read more.

Putting new findings into the context of available literature knowledge is one approach to deal with the surge of high-throughput data results. Furthermore, prior knowledge can increase the performance and stability of bioinformatic algorithms, for example, methods for network reconstruction. In this review, we examine software packages for the statistical computing framework R, which enable the integration of pathway data for further bioinformatic analyses. Different approaches to integrate and visualize pathway data are identified and packages are stratified concerning their features according to a number of different aspects: data import strategies, the extent of available data, dependencies on external tools, integration with further analysis steps and visualization options are considered. A total of 12 packages integrating pathway data are reviewed in this manuscript. These are supplemented by five R-specific packages for visualization and six connector packages, which provide access to external tools. Full article

(This article belongs to the Special Issue Developments in Bioinformatic Algorithms)

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4 pages, 133 KiB

Open AccessEditorial

Polar Microbiology: Recent Advances and Future Perspectives

by Pabulo Henrique Rampelotto

Interdisciplinary Center for Biotechnology Research, Federal University of Pampa, AntônioTrilha Avenue, P.O.Box 1847, 97300-000, São Gabriel – RS, Brazil

Biology 2014, 3(1), 81-84; https://doi.org/10.3390/biology3010081 - 3 Feb 2014

Cited by 23 | Viewed by 7719

Abstract

Polar microbiology is a thriving branch of science with the potential to provide new insights into a wide range of basic and applied issues in biology. In this context, it is timely to review and highlight the progress so far and discuss exciting [...] Read more.

Polar microbiology is a thriving branch of science with the potential to provide new insights into a wide range of basic and applied issues in biology. In this context, it is timely to review and highlight the progress so far and discuss exciting future perspectives. In this special issue, some of the leaders in the field have described their work, ideas and findings in a collection of reviews and original research articles with studies ranging from one of the oldest permafrost areas on Earth, located in Siberia, to the accretion ice of Lake Vostok, located in Antarctica. Altogether, these articles provide a comprehensive and reliable source of information on the current advances and future perspectives in this exciting field of research. In this Editorial, I present a brief overview on the theme [...] Full article

(This article belongs to the Special Issue Polar Microbiology: Recent Advances and Future Perspectives)

25 pages, 524 KiB

Open AccessReview

Polar Microalgae: New Approaches towards Understanding Adaptations to an Extreme and Changing Environment

by Barbara R. Lyon and Thomas Mock^*

School of Environmental Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK

Biology 2014, 3(1), 56-80; https://doi.org/10.3390/biology3010056 - 28 Jan 2014

Cited by 108 | Viewed by 14217

Abstract

Polar Regions are unique and highly prolific ecosystems characterized by extreme environmental gradients. Photosynthetic autotrophs, the base of the food web, have had to adapt physiological mechanisms to maintain growth, reproduction and metabolic activity despite environmental conditions that would shut-down cellular processes in [...] Read more.

Polar Regions are unique and highly prolific ecosystems characterized by extreme environmental gradients. Photosynthetic autotrophs, the base of the food web, have had to adapt physiological mechanisms to maintain growth, reproduction and metabolic activity despite environmental conditions that would shut-down cellular processes in most organisms. High latitudes are characterized by temperatures below the freezing point, complete darkness in winter and continuous light and high UV in the summer. Additionally, sea-ice, an ecological niche exploited by microbes during the long winter seasons when the ocean and land freezes over, is characterized by large salinity fluctuations, limited gas exchange, and highly oxic conditions. The last decade has been an exciting period of insights into the molecular mechanisms behind adaptation of microalgae to the cryosphere facilitated by the advancement of new scientific tools, particularly “omics” techniques. We review recent insights derived from genomics, transcriptomics, and proteomics studies. Genes, proteins and pathways identified from these highly adaptable polar microbes have far-reaching biotechnological applications. Furthermore, they may provide insights into life outside this planet, as well as glimpses into the past. High latitude regions also have disproportionately large inputs into global biogeochemical cycles and are the region most sensitive to climate change. Full article

(This article belongs to the Special Issue Polar Microbiology: Recent Advances and Future Perspectives)

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17 pages, 344 KiB

Open AccessArticle

Analysis of T-DNA/Host-Plant DNA Junction Sequences in Single-Copy Transgenic Barley Lines

by Joanne G. Bartlett, Mark A. Smedley and Wendy A. Harwood^*

Department of Crop Genetics, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK

Biology 2014, 3(1), 39-55; https://doi.org/10.3390/biology3010039 - 21 Jan 2014

Cited by 15 | Viewed by 9020

Abstract

Sequencing across the junction between an integrated transfer DNA (T-DNA) and a host plant genome provides two important pieces of information. The junctions themselves provide information regarding the proportion of T-DNA which has integrated into the host plant genome, whilst the transgene flanking [...] Read more.

Sequencing across the junction between an integrated transfer DNA (T-DNA) and a host plant genome provides two important pieces of information. The junctions themselves provide information regarding the proportion of T-DNA which has integrated into the host plant genome, whilst the transgene flanking sequences can be used to study the local genetic environment of the integrated transgene. In addition, this information is important in the safety assessment of GM crops and essential for GM traceability. In this study, a detailed analysis was carried out on the right-border T-DNA junction sequences of single-copy independent transgenic barley lines. T-DNA truncations at the right-border were found to be relatively common and affected 33.3% of the lines. In addition, 14.3% of lines had rearranged construct sequence after the right border break-point. An in depth analysis of the host-plant flanking sequences revealed that a significant proportion of the T-DNAs integrated into or close to known repetitive elements. However, this integration into repetitive DNA did not have a negative effect on transgene expression. Full article

(This article belongs to the Special Issue Insights from Plant Genomes)

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17 pages, 886 KiB

Open AccessReview

Contemporary Network Proteomics and Its Requirements

by Wilson Wen Bin Goh^1,*, Limsoon Wong¹ and Judy Chia Ghee Sng^2,3

¹ School of Computing, National University of Singapore, 13 Computing Drive, Singapore 117417, Singapore

² Department of Physiology, National University of Singapore, 2 Medical Drive, Singapore 117597, Singapore

³ Neuroepigenetics Laboratory, Growth, Development and Metabolism Programme, Singapore Institute for Clinical Sciences, Agency for Science and Technology (A*STAR), Singapore 117609, Singapore

Biology 2014, 3(1), 22-38; https://doi.org/10.3390/biology3010022 - 20 Dec 2013

Cited by 5 | Viewed by 8749

Abstract

The integration of networks with genomics (network genomics) is a familiar field. Conventional network analysis takes advantage of the larger coverage and relative stability of gene expression measurements. Network proteomics on the other hand has to develop further on two critical factors: (1) [...] Read more.

The integration of networks with genomics (network genomics) is a familiar field. Conventional network analysis takes advantage of the larger coverage and relative stability of gene expression measurements. Network proteomics on the other hand has to develop further on two critical factors: (1) expanded data coverage and consistency, and (2) suitable reference network libraries, and data mining from them. Concerning (1) we discuss several contemporary themes that can improve data quality, which in turn will boost the outcome of downstream network analysis. For (2), we focus on network analysis developments, specifically, the need for context-specific networks and essential considerations for localized network analysis. Full article

(This article belongs to the Special Issue Advances in Proteomics Methods)

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21 pages, 361 KiB

Open AccessReview

Algorithmic Perspectives of Network Transitive Reduction Problems and their Applications to Synthesis and Analysis of Biological Networks

by Satabdi Aditya¹, Bhaskar DasGupta^1,* and Marek Karpinski²

¹ Department of Computer Science, University of Illinois at Chicago, Chicago, IL 60607, USA

² Department of Computer Science, University of Bonn, Bonn 53113, Germany

Biology 2014, 3(1), 1-21; https://doi.org/10.3390/biology3010001 - 19 Dec 2013

Cited by 3 | Viewed by 7574

Abstract

In this survey paper, we will present a number of core algorithmic questions concerning several transitive reduction problems on network that have applications in network synthesis and analysis involving cellular processes. Our starting point will be the so-called minimum equivalent digraph problem, a [...] Read more.

In this survey paper, we will present a number of core algorithmic questions concerning several transitive reduction problems on network that have applications in network synthesis and analysis involving cellular processes. Our starting point will be the so-called minimum equivalent digraph problem, a classic computational problem in combinatorial algorithms. We will subsequently consider a few non-trivial extensions or generalizations of this problem motivated by applications in systems biology. We will then discuss the applications of these algorithmic methodologies in the context of three major biological research questions: synthesizing and simplifying signal transduction networks, analyzing disease networks, and measuring redundancy of biological networks. Full article

(This article belongs to the Special Issue Developments in Bioinformatic Algorithms)

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Biology, Volume 3, Issue 1 (March 2014) – 14 articles , Pages 1-242

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