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    Cellular origin of the viral capsid-like bacterial microcompartments.
    Biol Direct 2017 Nov 13;12(1):25. Epub 2017 Nov 13.
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
    ᅟ: Bacterial microcompartments (BMC) are proteinaceous organelles that structurally resemble viral capsids, but encapsulate enzymes that perform various specialized biochemical reactions in the cell cytoplasm. The BMC are constructed from two major shell proteins, BMC-H and BMC-P, which form the facets and vertices of the icosahedral assembly, and are functionally equivalent to the major and minor capsid proteins of viruses, respectively. This equivalence notwithstanding, neither of the BMC proteins displays structural similarity to known capsid proteins, rendering the origins of the BMC enigmatic. Read More

    ASXL gain-of-function truncation mutants: defective and dysregulated forms of a natural ribosomal frameshifting product?
    Biol Direct 2017 Oct 16;12(1):24. Epub 2017 Oct 16.
    Department of Pathology, Division of Virology, University of Cambridge, Cambridge, CB2 1QP, UK.
    Background: Programmed ribosomal frameshifting (PRF) is a gene expression mechanism which enables the translation of two N-terminally coincident, C-terminally distinct protein products from a single mRNA. Many viruses utilize PRF to control or regulate gene expression, but very few phylogenetically conserved examples are known in vertebrate genes. Additional sex combs-like (ASXL) genes 1 and 2 encode important epigenetic and transcriptional regulatory proteins that control the expression of homeotic genes during key developmental stages. Read More

    Why we don't want another "Synthesis".
    Biol Direct 2017 Oct 2;12(1):23. Epub 2017 Oct 2.
    IBBR, 9600 Gudelsky Drive, Rockville, 20850, MD, USA.
    High-level debates in evolutionary biology often treat the Modern Synthesis as a framework of population genetics, or as an intellectual lineage with a changing distribution of beliefs. Unfortunately, these flexible notions, used to negotiate decades of innovations, are now thoroughly detached from their historical roots in the original Modern Synthesis (OMS), a falsifiable scientific theory. The OMS held that evolution can be adequately understood as a process of smooth adaptive change by shifting the frequencies of small-effect alleles at many loci simultaneously, without the direct involvement of new mutations. Read More

    Differential signal sensitivities can contribute to the stability of multispecies bacterial communities.
    Biol Direct 2017 Sep 15;12(1):22. Epub 2017 Sep 15.
    Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter Street 50/A, Budapest, H-1085, Hungary.
    Background: Bacterial species present in multispecies microbial communities often react to the same chemical signal but at vastly different concentrations. The existence of different response thresholds with respect to the same signal molecule has been well documented in quorum sensing which is one of the best studied inter-cellular signalling mechanisms in bacteria. The biological significance of this phenomenon is still poorly understood, and cannot be easily studied in nature or in laboratory models. Read More

    Evidence-based gene models for structural and functional annotations of the oil palm genome.
    Biol Direct 2017 Sep 8;12(1):21. Epub 2017 Sep 8.
    Advanced Biotechnology and Breeding Centre, Malaysian Palm Oil Board, No. 6, Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia.
    Background: Oil palm is an important source of edible oil. The importance of the crop, as well as its long breeding cycle (10-12 years) has led to the sequencing of its genome in 2013 to pave the way for genomics-guided breeding. Nevertheless, the first set of gene predictions, although useful, had many fragmented genes. Read More

    On the global CRISPR array behavior in class I systems.
    Biol Direct 2017 Aug 29;12(1):20. Epub 2017 Aug 29.
    Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, 400 Dan Allen Drive, Schaub Hall, Campus box 7624, Raleigh, NC, 27695-7624, USA.
    Background: Much effort is underway to build and upgrade databases and tools related to occurrence, diversity, and characterization of CRISPR-Cas systems. As microbial communities and their genome complements are unearthed, much emphasis has been placed on details of individual strains and model systems within the CRISPR-Cas classification, and that collection of information as a whole affords the opportunity to analyze CRISPR-Cas systems from a quantitative perspective to gain insight into distribution of CRISPR array sizes across the different classes, types and subtypes. CRISPR diversity, nomenclature, occurrence, and biological functions have generated a plethora of data that created a need to understand the size and distribution of these various systems to appreciate their features and complexity. Read More

    Breath-giving cooperation: critical review of origin of mitochondria hypotheses : Major unanswered questions point to the importance of early ecology.
    Biol Direct 2017 Aug 14;12(1):19. Epub 2017 Aug 14.
    Eötvös Loránd University, Department of Plant Systematics, Ecology and Theoretical Biology, Pázmány P. sétány 1/C, Budapest, 1117, Hungary.
    The origin of mitochondria is a unique and hard evolutionary problem, embedded within the origin of eukaryotes. The puzzle is challenging due to the egalitarian nature of the transition where lower-level units took over energy metabolism. Contending theories widely disagree on ancestral partners, initial conditions and unfolding of events. Read More

    Cell adhesion heterogeneity reinforces tumour cell dissemination: novel insights from a mathematical model.
    Biol Direct 2017 Aug 11;12(1):18. Epub 2017 Aug 11.
    Center for Information Services and High Performance Computing, Technische Universität Dresden, Nöthnitzer Str. 46, Dresden, 01062, Germany.
    Background: Cancer cell invasion, dissemination, and metastasis have been linked to an epithelial-mesenchymal transition (EMT) of individual tumour cells. During EMT, adhesion molecules like E-cadherin are downregulated and the decrease of cell-cell adhesion allows tumour cells to dissociate from the primary tumour mass. This complex process depends on intracellular cues that are subject to genetic and epigenetic variability, as well as extrinsic cues from the local environment resulting in a spatial heterogeneity in the adhesive phenotype of individual tumour cells. Read More

    EMQIT: a machine learning approach for energy based PWM matrix quality improvement.
    Biol Direct 2017 Aug 1;12(1):17. Epub 2017 Aug 1.
    Institute of Automatic Control, Silesian University of Technology, Akademicka 16, 44-100, Gliwice, Poland.
    Background: Transcription factor binding affinities to DNA play a key role for the gene regulation. Learning the specificity of the mechanisms of binding TFs to DNA is important both to experimentalists and theoreticians. With the development of high-throughput methods such as, e. Read More

    Bacterial tail anchors can target to the mitochondrial outer membrane.
    Biol Direct 2017 Jul 24;12(1):16. Epub 2017 Jul 24.
    Department of Molecular Biology and Genetics, Koç University, 34450 Sarıyer, İstanbul, Turkey.
    Background: During the generation and evolution of the eukaryotic cell, a proteobacterial endosymbiont was re-fashioned into the mitochondrion, an organelle that appears to have been present in the ancestor of all present-day eukaryotes. Mitochondria harbor proteomes derived from coding information located both inside and outside the organelle, and the rate-limiting step toward the formation of eukaryotic cells may have been development of an import apparatus allowing protein entry to mitochondria. Currently, a widely conserved translocon allows proteins to pass from the cytosol into mitochondria, but how proteins encoded outside of mitochondria were first directed to these organelles at the dawn of eukaryogenesis is not clear. Read More

    Computational prediction of lncRNA-mRNA interactionsby integrating tissue specificity in human transcriptome.
    Biol Direct 2017 Jun 8;12(1):15. Epub 2017 Jun 8.
    Department of Electrical Engineering and Bioscience, Faculty of Science and Engineering, Waseda University, 55N-06-10, 3-4-1 Okubo Shinjuku-ku, Tokyo, 169-8555, Japan.
    Long noncoding RNAs (lncRNAs) play a key role in normal tissue differentiation and cancer development through their tissue-specific expression in the human transcriptome. Recent investigations of macromolecular interactions have shown that tissue-specific lncRNAs form base-pairing interactions with various mRNAs associated with tissue-differentiation, suggesting that tissue specificity is an important factor controlling human lncRNA-mRNA interactions.Here, we report investigations of the tissue specificities of lncRNAs and mRNAs by using RNA-seq data across various human tissues as well as computational predictions of tissue-specific lncRNA-mRNA interactions inferred by integrating the tissue specificity of lncRNAs and mRNAs into our comprehensive prediction of human lncRNA-RNA interactions. Read More

    Rotational restriction of nascent peptides as an essential element of co-translational protein folding: possible molecular players and structural consequences.
    Biol Direct 2017 May 31;12(1):14. Epub 2017 May 31.
    McLean, Virginia, USA.
    Background: A basic tenet of protein science is that all information about the spatial structure of proteins is present in their sequences. Nonetheless, many proteins fail to attain native structure upon experimental denaturation and refolding in vitro, raising the question of the specific role of cellular machinery in protein folding in vivo. Recently, we hypothesized that energy-dependent twisting of the protein backbone is an unappreciated essential factor guiding the protein folding process in vivo. Read More

    The complex domain architecture of SAMD9 family proteins, predicted STAND-like NTPases, suggests new links to inflammation and apoptosis.
    Biol Direct 2017 May 25;12(1):13. Epub 2017 May 25.
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.
    We report a comprehensive computational dissection of the domain architecture of the SAMD9 family proteins that are involved in antivirus and antitumor response in humans. We show that the SAMD9 protein family is represented in most animals and also, unexpectedly, in bacteria, in particular actinomycetes. From the N to C terminus, the core SAMD9 family architecture includes DNA/RNA-binding AlbA domain, a variant Sir2-like domain, a STAND-like P-loop NTPase, an array of TPR repeats and an OB-fold domain with predicted RNA-binding properties. Read More

    Recognition of a structural domain (RWDBD) in Gcn1 proteins that interacts with the RWD domain containing proteins.
    Biol Direct 2017 May 19;12(1):12. Epub 2017 May 19.
    Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.
    The protein Gcn1 (General control non-derepressible 1) is found in virtually all eukaryotes, and is a key component of the general amino acid control signal transduction pathway. This pathway is best known for its importance for cells to sense and overcome amino acid starvation. Gcn1 directly binds to the RWD (RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases) domain of the protein kinase Gcn2, and this is essential for delivering the starvation signal to Gcn2. Read More

    Demystification of animal symmetry: symmetry is a response to mechanical forces.
    Biol Direct 2017 May 17;12(1):11. Epub 2017 May 17.
    Institute of Psychology, University of Debrecen, H-4002, Debrecen, P.O. Box 400, Hungary.
    ᅟ: Symmetry is an eye-catching feature of animal body plans, yet its causes are not well enough understood. The evolution of animal form is mainly due to changes in gene regulatory networks (GRNs). Based on theoretical considerations regarding fundamental GRN properties, it has recently been proposed that the animal genome, on large time scales, should be regarded as a system which can construct both the main symmetries - radial and bilateral - simultaneously; and that the expression of any of these depends on functional constraints. Read More

    Biochemical and proteomics analyses of antioxidant enzymes reveal the potential stress tolerance in Rhododendron chrysanthum Pall.
    Biol Direct 2017 May 3;12(1):10. Epub 2017 May 3.
    Jilin Provincial Key Laboratory of Plant Resource Science and Green Production, Jilin Normal University, Siping, 136000, China.
    Background: Rhododendron chrysanthum Pall., an endangered species with significant ornamental and medicinal value, is endemic to the Changbai Mountain of China and can also serve as a significant plant resource for investigating the stress tolerance in plants. Proteomics is an effective analytical tool that provides significant information about plant metabolism and gene expression. Read More

    Integrative modelling of TIR domain-containing adaptor molecule inducing interferon-β (TRIF) provides insights into its autoinhibited state.
    Biol Direct 2017 Apr 20;12(1). Epub 2017 Apr 20.
    National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bellary Road, Bangalore, 560065, India.
    Background: TRIF is a key protein in antiviral innate immunity, operating downstream of TLRs. TRIF activation leads to the production of interferon-β and pro-inflammatory cytokines. There is evidence from experiments to suggest that the N-terminal domain of TRIF binds to its TIR domain to avoid constitutive activation. Read More

    TFAP2A is a component of the ZEB1/2 network that regulates TGFB1-induced epithelial to mesenchymal transition.
    Biol Direct 2017 Apr 17;12(1). Epub 2017 Apr 17.
    Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH-4056, Basel, Switzerland.
    Background: The transition between epithelial and mesenchymal phenotypes (EMT) occurs in a variety of contexts. It is critical for mammalian development and it is also involved in tumor initiation and progression. Master transcription factor (TF) regulators of this process are conserved between mouse and human. Read More

    Adaptive multiscapes: an up-to-date metaphor to visualize molecular adaptation.
    Biol Direct 2017 Feb 28;12(1). Epub 2017 Feb 28.
    Grupo Interdisciplinar de Sistemas Complejos (GISC), Madrid, Spain.
    Background: Wright's metaphor of the fitness landscape has shaped and conditioned our view of the adaptation of populations for almost a century. Since its inception, and including criticism raised by Wright himself, the concept has been surrounded by controversy. Among others, the debate stems from the intrinsic difficulty to capture important features of the space of genotypes, such as its high dimensionality or the existence of abundant ridges, in a visually appealing two-dimensional picture. Read More

    Post translational modification of Parkin.
    Biol Direct 2017 Feb 21;12(1). Epub 2017 Feb 21.
    Department of Biology, University of Padova, Via Ugo Bassi 58b, 35131, Padova, Italy.
    Mutations in the gene encoding for the E3 ubiquitin ligase Parkin are associated to a rare form of familiar autosomal recessive Parkinsonism. Despite decades of research on the Parkin protein, whose structure has been recently solved, little is known about the specific signalling pathways that lead to Parkin activation. Parkin activity spans from mitochondria quality control to tumor suppression and stress protection; it is thus tempting to hypothesize that the broad impact of Parkin on cellular physiology might be the result of different post translational modifications that can be controlled by balanced opposing events. Read More

    Evolution of RNA- and DNA-guided antivirus defense systems in prokaryotes and eukaryotes: common ancestry vs convergence.
    Biol Direct 2017 Feb 10;12(1). Epub 2017 Feb 10.
    National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD, 20894, USA.
    Complementarity between nucleic acid molecules is central to biological information transfer processes. Apart from the basal processes of replication, transcription and translation, complementarity is also employed by multiple defense and regulatory systems. All cellular life forms possess defense systems against viruses and mobile genetic elements, and in most of them some of the defense mechanisms involve small guide RNAs or DNAs that recognize parasite genomes and trigger their inactivation. Read More

    Consistent metagenomic biomarker detection via robust PCA.
    Biol Direct 2017 Jan 31;12(1). Epub 2017 Jan 31.
    College of Veterinary Medicine and Biomedical Sciences, Gastrointestinal Laboratory, Texas A&M University, College Station, 77843-3128, TX, USA.
    Background: Recent developments of high throughput sequencing technologies allow the characterization of the microbial communities inhabiting our world. Various metagenomic studies have suggested using microbial taxa as potential biomarkers for certain diseases. In practice, the number of available samples varies from experiment to experiment. Read More

    Of yeast, mice and men: MAMs come in two flavors.
    Biol Direct 2017 Jan 25;12(1). Epub 2017 Jan 25.
    Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G2H7, Canada.
    The past decade has seen dramatic progress in our understanding of membrane contact sites (MCS). Important examples of these are endoplasmic reticulum (ER)-mitochondria contact sites. ER-mitochondria contacts have originally been discovered in mammalian tissue, where they have been designated as mitochondria-associated membranes (MAMs). Read More

    Thermodynamic and kinetic stability of the Josephin Domain closed arrangement: evidences from replica exchange molecular dynamics.
    Biol Direct 2017 Jan 19;12(1). Epub 2017 Jan 19.
    Istituto Dalle Molle di studi sull'Intelligenza Artificiale (IDSIA), Scuola universitaria professionale della Svizzera italiana (SUPSI), Università della Svizzera italiana (USI), Centro Galleria 2, Manno, CH-6928, Switzerland.
    Background: Molecular phenomena driving pathological aggregation in neurodegenerative diseases are not completely understood yet. Peculiar is the case of Spinocerebellar Ataxia 3 (SCA3) where the conformational properties of the AT-3 N-terminal region, also called Josephin Domain (JD), play a key role in the first step of aggregation, having the JD an amyloidogenic propensity itself. For this reason, unraveling the intimate relationship between JD structural features and aggregation tendency may lead to a step forward in understanding the pathology and rationally design a cure. Read More

    Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models.
    Biol Direct 2017 Jan 17;12(1). Epub 2017 Jan 17.
    Division of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, 98109, WA, USA.
    Background: Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection.

    Results: I describe a new approach that uses a null model based on experimental measurements of a gene's site-specific amino-acid preferences generated by deep mutational scanning in the lab. Read More

    Expansion of the molecular and morphological diversity of Acanthamoebidae (Centramoebida, Amoebozoa) and identification of a novel life cycle type within the group.
    Biol Direct 2016 Dec 28;11(1):69. Epub 2016 Dec 28.
    Department of Biological Sciences, Mississippi State University, PO BOX GY, Mississippi State, MS, 39762, USA.
    Background: Acanthamoebidae is a "family" level amoebozoan group composed of the genera Acanthamoeba, Protacanthamoeba, and very recently Luapeleamoeba. This clade of amoebozoans has received considerable attention from the broader scientific community as Acanthamoeba spp. represent both model organisms and human pathogens. Read More

    Prognostic value of cross-omics screening for kidney clear cell renal cancer survival.
    Biol Direct 2016 Dec 20;11(1):68. Epub 2016 Dec 20.
    Functional Genomics Center Zurich, ETH Zurich and University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland.
    Background: Kidney renal clear cell carcinoma (KIRC) is a type of cancer that is resistant to chemotherapy and radiotherapy and has limited treatment possibilities. Large-scale molecular profiling of KIRC tumors offers a great potential to uncover the genetic and epigenetic changes underlying this disease and to improve the clinical management of KIRC patients. However, in practice the clinicians and researchers typically focus on single-platform molecular data or on a small set of genes. Read More

    Inter-platform concordance of gene expression data for the prediction of chemical mode of action.
    Biol Direct 2016 Dec 20;11(1):67. Epub 2016 Dec 20.
    Department of Biostatistics, University of Florida, Gainesville, 32603, FL, USA.
    Background: It is interesting to study the consistency of outcomes arising from two genomic platforms: Microarray and RNAseq, which are established on fundamentally different technologies. This topic has been frequently discussed from the prospect of comparing differentially expressed genes (DEGs). In this study, we explore the inter-platform concordance between microarray and RNASeq in their ability to classify samples based on genomic information. Read More

    Sensitivity, specificity, and reproducibility of RNA-Seq differential expression calls.
    Biol Direct 2016 Dec 20;11(1):66. Epub 2016 Dec 20.
    Chair of Bioinformatics Research Group, Boku University, Vienna, Austria.
    Background: The MAQC/SEQC consortium has recently compiled a key benchmark that can serve for testing the latest developments in analysis tools for microarray and RNA-seq expression profiling. Such objective benchmarks are required for basic and applied research, and can be critical for clinical and regulatory outcomes. Going beyond the first comparisons presented in the original SEQC study, we here present extended benchmarks including effect strengths typical of common experiments. Read More

    Exploring the importance of cancer pathways by meta-analysis of differential protein expression networks in three different cancers.
    Biol Direct 2016 Dec 20;11(1):65. Epub 2016 Dec 20.
    Department of Biostatistics, University of Florida, Gainesville, FL, 32611, USA.
    Background: It is believed that all cancers occur due to the mutation or change in one or more genes. In order to investigate the significance of the biological pathways which are interrupted by these genetic mutations, we pursue an integrated analysis using multiple cancer datasets released by the International Cancer Genome Consortium (ICGC). This dataset consists of expression profiles for genes/proteins of patients receiving treatment, for three types of cancer - Head and Neck Squamous Cell Carcinoma (HNSC), Lung Adenocarcinoma (LUAD) and Kidney Renal Clear Cell Carcinoma (KIRC). Read More

    The role of the backbone torsion in protein folding.
    Biol Direct 2016 Dec 1;11(1):64. Epub 2016 Dec 1.
    , McLean, Virginia, USA.
    Background: The set of forces and sequence of events that govern the transition from an unfolded polypeptide chain to a functional protein with correct spatial structure remain incompletely known, despite the importance of the problem and decades of theory development, computer simulations, and laboratory experiments. Information about the correctly folded state of most proteins is likely to be present in their sequences, and yet many proteins fail to attain native structure after overexpression in a non-native environment or upon experimental denaturation and refolding.

    Presentation Of The Hypothesis: We hypothesize that correct protein folding in vivo is an active, energy-dependent process that most likely applies torque force co-translationally to all proteins and possibly also post-translationally to many proteins in every cell. Read More

    xHMMER3x2: Utilizing HMMER3's speed and HMMER2's sensitivity and specificity in the glocal alignment mode for improved large-scale protein domain annotation.
    Biol Direct 2016 Nov 29;11(1):63. Epub 2016 Nov 29.
    Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, #07-01, Matrix, Singapore, 138671, Singapore.
    Background: While the local-mode HMMER3 is notable for its massive speed improvement, the slower glocal-mode HMMER2 is more exact for domain annotation by enforcing full domain-to-sequence alignments. Since a unit of domain necessarily implies a unit of function, local-mode HMMER3 alone remains insufficient for precise function annotation tasks. In addition, the incomparable E-values for the same domain model by different HMMER builds create difficulty when checking for domain annotation consistency on a large-scale basis. Read More

    ZFAS1: a long noncoding RNA associated with ribosomes in breast cancer cells.
    Biol Direct 2016 Nov 21;11(1):62. Epub 2016 Nov 21.
    Auckland Cancer Society Research Centre, University of Auckland, 85 Park Rd, Grafton, Auckland, 1023, New Zealand.
    Background: Most of the eukaryotic genome is transcribed, yielding a complex network of transcripts including thousands of lncRNAs that generally lack protein coding potential. However, only a small percentage of these molecules has been functionally characterised, and discoveries of specific functions demonstrate layers of complexity. A large percentage of lncRNAs is located in the cytoplasm, associated with ribosomes but the function of the majority of these transcripts is unclear. Read More

    Importins promote high-frequency NF-κB oscillations increasing information channel capacity.
    Biol Direct 2016 Nov 11;11(1):61. Epub 2016 Nov 11.
    Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland.
    Background: Importins and exportins influence gene expression by enabling nucleocytoplasmic shuttling of transcription factors. A key transcription factor of innate immunity, NF-κB, is sequestered in the cytoplasm by its inhibitor, IκBα, which masks nuclear localization sequence of NF-κB. In response to TNFα or LPS, IκBα is degraded, which allows importins to bind NF-κB and shepherd it across nuclear pores. Read More

    Neurogenomics and the role of a large mutational target on rapid behavioral change.
    Biol Direct 2016 Nov 8;11(1):60. Epub 2016 Nov 8.
    Department of Biology, Temple University, Philadelphia, PA, 19122, USA.
    Background: Behavior, while complex and dynamic, is among the most diverse, derived, and rapidly evolving traits in animals. The highly labile nature of heritable behavioral change is observed in such evolutionary phenomena as the emergence of converged behaviors in domesticated animals, the rapid evolution of preferences, and the routine development of ethological isolation between diverging populations and species. In fact, it is believed that nervous system development and its potential to evolve a seemingly infinite array of behavioral innovations played a major role in the successful diversification of metazoans, including our own human lineage. Read More

    Identification of microRNAs regulating Escherichia coli F18 infection in Meishan weaned piglets.
    Biol Direct 2016 Nov 3;11(1):59. Epub 2016 Nov 3.
    Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, People's Republic of China.
    Background: Escherichia coli F18 is mainly responsible for post-weaning diarrhea (PWD) in piglets. The molecular regulation of E. coli F18 resistance in Chinese domestic weaned piglets is still obscure. Read More

    The struggle by Caenorhabditis elegans to maintain proteostasis during aging and disease.
    Biol Direct 2016 Nov 3;11(1):58. Epub 2016 Nov 3.
    Biology Department, The University of the South, 735 University Avenue, Sewanee, TN, 37383, USA.
    The presence of only small amounts of misfolded protein is an indication of a healthy proteome. Maintaining proteome health, or more specifically, "proteostasis," is the purview of the "proteostasis network." This network must respond to constant fluctuations in the amount of destabilized proteins caused by errors in protein synthesis and exposure to acute proteotoxic conditions. Read More

    CLIP-GENE: a web service of the condition specific context-laid integrative analysis for gene prioritization in mouse TF knockout experiments.
    Biol Direct 2016 Oct 24;11(1):57. Epub 2016 Oct 24.
    Interdisciplinary Program in Bioinformatics, Seoul National University, Daehak-dong, Seoul, 151-742, Korea.
    Motivation: Transcriptome data from the gene knockout experiment in mouse is widely used to investigate functions of genes and relationship to phenotypes. When a gene is knocked out, it is important to identify which genes are affected by the knockout gene. Existing methods, including differentially expressed gene (DEG) methods, can be used for the analysis. Read More

    Long range personalized cancer treatment strategies incorporating evolutionary dynamics.
    Biol Direct 2016 Oct 22;11(1):56. Epub 2016 Oct 22.
    Departments of Oncology and of Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center and Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, USA.
    Background: Current cancer precision medicine strategies match therapies to static consensus molecular properties of an individual's cancer, thus determining the next therapeutic maneuver. These strategies typically maintain a constant treatment while the cancer is not worsening. However, cancers feature complicated sub-clonal structure and dynamic evolution. Read More

    IPC - Isoelectric Point Calculator.
    Biol Direct 2016 Oct 21;11(1):55. Epub 2016 Oct 21.
    , Kielce, 25-430, Poland.
    Background: Accurate estimation of the isoelectric point (pI) based on the amino acid sequence is useful for many analytical biochemistry and proteomics techniques such as 2-D polyacrylamide gel electrophoresis, or capillary isoelectric focusing used in combination with high-throughput mass spectrometry. Additionally, pI estimation can be helpful during protein crystallization trials.

    Results: Here, I present the Isoelectric Point Calculator (IPC), a web service and a standalone program for the accurate estimation of protein and peptide pI using different sets of dissociation constant (pKa) values, including two new computationally optimized pKa sets. Read More

    Evolution of the Tim17 protein family.
    Biol Direct 2016 Oct 19;11(1):54. Epub 2016 Oct 19.
    Department of Parasitology, Faculty of Science, Charles University in Prague, Prumyslova 595, 252 42, Vestec, Czech Republic.
    Background: The Tim17 family of proteins plays a fundamental role in the biogenesis of mitochondria. Three Tim17 family proteins, Tim17, Tim22, and Tim23, are the central components of the widely conserved multi-subunit protein translocases, TIM23 and TIM22, which mediate protein transport across and into the inner mitochondrial membrane, respectively. In addition, several Tim17 family proteins occupy the inner and outer membranes of plastids. Read More

    Cancer heterogeneity and multilayer spatial evolutionary games.
    Biol Direct 2016 Oct 13;11(1):53. Epub 2016 Oct 13.
    Department of Automatic Control, Silesian University of Technology, ul. Akademicka 16, 44-100, Gliwice, Poland.
    Background: Evolutionary game theory (EGT) has been widely used to simulate tumour processes. In almost all studies on EGT models analysis is limited to two or three phenotypes. Our model contains four main phenotypes. Read More

    Unexpected links reflect the noise in networks.
    Biol Direct 2016 Oct 13;11(1):52. Epub 2016 Oct 13.
    College of Pharmacy, Oregon State University, Corvallis, OR, USA.
    Background: Gene covariation networks are commonly used to study biological processes. The inference of gene covariation networks from observational data can be challenging, especially considering the large number of players involved and the small number of biological replicates available for analysis.

    Results: We propose a new statistical method for estimating the number of erroneous edges in reconstructed networks that strongly enhances commonly used inference approaches. Read More

    Emergence of heterogeneity in acute leukemias.
    Biol Direct 2016 Oct 12;11(1):51. Epub 2016 Oct 12.
    Institute of Applied Mathematics, Heidelberg University, Im Neuenheimer Feld 205, Heidelberg, 69120, Germany.
    Background: Leukemias are malignant proliferative disorders of the blood forming system. Sequencing studies demonstrate that the leukemic cell population consists of multiple clones. The genetic relationship between the different clones, referred to as the clonal hierarchy, shows high interindividual variability. Read More

    Weighted-SAMGSR: combining significance analysis of microarray-gene set reduction algorithm with pathway topology-based weights to select relevant genes.
    Biol Direct 2016 Sep 29;11(1):50. Epub 2016 Sep 29.
    Department of Biostatistics, Markey Cancer Center, The University of Kentucky, 800 Rose St., Lexington, KY, 40536, USA.
    Background: It has been demonstrated that a pathway-based feature selection method that incorporates biological information within pathways during the process of feature selection usually outperforms a gene-based feature selection algorithm in terms of predictive accuracy and stability. Significance analysis of microarray-gene set reduction algorithm (SAMGSR), an extension to a gene set analysis method with further reduction of the selected pathways to their respective core subsets, can be regarded as a pathway-based feature selection method.

    Methods: In SAMGSR, whether a gene is selected is mainly determined by its expression difference between the phenotypes, and partially by the number of pathways to which this gene belongs. Read More

    The essence of life.
    Biol Direct 2016 Sep 26;11(1):49. Epub 2016 Sep 26.
    College of Life Sciences, Wuhan University, Wuhan, 430072, People's Republic of China.
    Although biology has achieved great successes in recent years, we have not got a clear idea on "what is life?" Actually, as explained here, the main reason for this situation is that there are two completely distinct aspects for "life", which are usually talked about together. Indeed, in respect to these two aspects: Darwinian evolution and self-sustaining, we must split the concept of life correspondingly, for example, by defining "life form" and "living entity", separately. For life's implementation (related to the two aspects) in nature, three mechanisms are crucial: the replication of DNA/RNA-like polymers by residue-pairing, the sequence-dependent folding of RNA/protein-like polymers engendering special functions, and the assembly of phospholipid-like amphiphiles forming vesicles. Read More

    modPDZpep: a web resource for structure based analysis of human PDZ-mediated interaction networks.
    Biol Direct 2016 Sep 21;11(1):48. Epub 2016 Sep 21.
    Bioinformatics Center, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.
    Background: PDZ domains recognize short sequence stretches usually present in C-terminal of their interaction partners. Because of the involvement of PDZ domains in many important biological processes, several attempts have been made for developing bioinformatics tools for genome-wide identification of PDZ interaction networks. Currently available tools for prediction of interaction partners of PDZ domains utilize machine learning approach. Read More

    Computational inference of a genomic pluripotency signature in human and mouse stem cells.
    Biol Direct 2016 Sep 17;11:47. Epub 2016 Sep 17.
    The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT, 06032, USA.
    Unlabelled: Recent analyses of next-generation sequencing datasets have shown that cell-specific regulatory elements in stem cells are marked with distinguishable patterns of transcription factor (TF) binding and epigenetic marks. For example, we recently demonstrated that promoters of cell-specific genes are covered with expanded trimethylation of histone H3 at lysine 4 (H3K4me3) marks (i.e. Read More

    Cpf1 nucleases demonstrate robust activity to induce DNA modification by exploiting homology directed repair pathways in mammalian cells.
    Biol Direct 2016 Sep 14;11:46. Epub 2016 Sep 14.
    Institute of Enzymology, Research Centre for Natural Sciences of the Hungarian Academy of Sciences, 2 Magyar Tudósok krt., Budapest, H-1117, Hungary.
    Background: Cpf1 nucleases have recently been repurposed for site-specific genome modification. Two members of the Cpf1 family, the AsCpf1 from Acidaminococcus sp. and the LbCpf1 from Lachnospiraceae bacterium were shown to induce higher indel frequencies than SpCas9 when examining four randomly-selected target sequences for each type of nuclease. Read More

    Essential functions linked with structural disorder in organisms of minimal genome.
    Biol Direct 2016 Sep 8;11:45. Epub 2016 Sep 8.
    Structural Biology Research Center (SBRC), Flanders Institute for Biotechnology (VIB), Vrije Universiteit Brussel (VUB), 1050 Pleinlaan 2, Brussels, Belgium.
    Unlabelled: Intrinsically disordered regions (IDRs) of proteins fulfill important regulatory roles in most organisms. However, the proteins of certain endosymbiont and intracellular pathogenic bacteria with extremely reduced genomes contain disproportionately small amounts of IDRs, consisting almost entirely of folded domains. As their genomes co-evolving with their hosts have been reduced in unrelated lineages, the proteomes of these bacteria represent independently evolved minimal protein sets. Read More

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