scholarly journals Algorithmic biosynthesis of eukaryotic glycans

2018 ◽  
Author(s):  
Anjali Jaiman ◽  
Mukund Thattai
Keyword(s):  
Self Assembly ◽  
Surface Proteins ◽  
Biological Processes ◽  
Runaway Reactions ◽  
Early Exit ◽  
Single Input ◽  
Cellular Identity ◽  
Organismal Development ◽  
Species Specific ◽  
Target Output

AbstractAn algorithm converts inputs to corresponding unique outputs through a sequence of actions. Algorithms are used as metaphors for complex biological processes such as organismal development. Here we make this metaphor rigorous for glycan biosynthesis. Glycans are branched sugar oligomers that are attached to cell-surface proteins and convey cellular identity. Eukaryotic O-glycans are synthesized by collections of enzymes in Golgi compartments. A compartment can stochastically convert a single input oligomer to a heterogeneous set of possible output oligomers; yet a given type of protein is invariably associated with a narrow and reproducible glycan oligomer profile. Here we resolve this paradox by borrowing from the theory of algorithmic self-assembly. We rigorously enumerate the sources of glycan microheterogeneity: incomplete oligomers via early exit from the reaction compartment; tandem repeat oligomers via runaway reactions; and competing oligomer fates via divergent reactions. We demonstrate how to diagnose and eliminate each of these, thereby obtaining “algorithmic compartments” that convert inputs to corresponding unique outputs. Given an input and a target output we either prove that the output cannot be algorithmically synthesized from the input, or explicitly construct an ordered series of algorithmic compartments that achieves this synthesis. Our theoretical analysis allows us to infer the causes of non-algorithmic microheterogeneity and species-specific diversity in real glycan datasets.

scholarly journals Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances

Sensors ◽  
2018 ◽  
Vol 18 (10) ◽  
pp. 3249 ◽  
Author(s):  
Hao Huang
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Surface Proteins ◽  
Biological Processes ◽  
Ecm Remodeling ◽  
Plasma Surface ◽  
Ecm Proteins ◽  
Recent Advances ◽  
Metalloproteinase 9

As one of the most widely investigated matrix metalloproteinases (MMPs), MMP-9 is a significant protease which plays vital roles in many biological processes. MMP-9 can cleave many extracellular matrix (ECM) proteins to regulate ECM remodeling. It can also cleave many plasma surface proteins to release them from the cell surface. MMP-9 has been widely found to relate to the pathology of cancers, including but not limited to invasion, metastasis and angiogenesis. Some recent research evaluated the value of MMP-9 as biomarkers to various specific cancers. Besides, recent research of MMP-9 biosensors discovered various novel MMP-9 biosensors to detect this enzyme. In this review, some recent advances in exploring MMP-9 as a biomarker in different cancers are summarized, and recent discoveries of novel MMP-9 biosensors are also presented.

scholarly journals The Diverse Contributions of Fucose Linkages in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1241 ◽  
Author(s):  
Tyler S. Keeley ◽  
Shengyu Yang ◽  
Eric Lau
Keyword(s):  
Cell Surface ◽  
Signaling Pathways ◽  
Cancer Biology ◽  
Surface Proteins ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Therapeutic Approaches ◽  
Cell Surface Proteins ◽  
Clinical Diagnostic

Fucosylation is a post-translational modification of glycans, proteins, and lipids that is responsible for many biological processes. Fucose conjugation via α(1,2), α(1,3), α(1,4), α(1,6), and O’- linkages to glycans, and variations in fucosylation linkages, has important implications for cancer biology. This review focuses on the roles that fucosylation plays in cancer, specifically through modulation of cell surface proteins and signaling pathways. How L-fucose and serum fucosylation patterns might be used for future clinical diagnostic, prognostic, and therapeutic approaches will be discussed.

scholarly journals Cross-linking reveals laminin coiled-coil architecture

2016 ◽  
Vol 113 (47) ◽  
pp. 13384-13389 ◽  
Author(s):  
Gad Armony ◽  
Etai Jacob ◽  
Toot Moran ◽  
Yishai Levin ◽  
Tevie Mehlman ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Self Assembly ◽  
Quaternary Structure ◽  
Coiled Coil ◽  
Surface Proteins ◽  
Cross Linking ◽  
Single Particle Reconstruction ◽  
Cross Links ◽  
Particle Reconstruction ◽  
Key Questions

Laminin, an ∼800-kDa heterotrimeric protein, is a major functional component of the extracellular matrix, contributing to tissue development and maintenance. The unique architecture of laminin is not currently amenable to determination at high resolution, as its flexible and narrow segments complicate both crystallization and single-particle reconstruction by electron microscopy. Therefore, we used cross-linking and MS, evaluated using computational methods, to address key questions regarding laminin quaternary structure. This approach was particularly well suited to the ∼750-Å coiled coil that mediates trimer assembly, and our results support revision of the subunit order typically presented in laminin schematics. Furthermore, information on the subunit register in the coiled coil and cross-links to downstream domains provide insights into the self-assembly required for interaction with other extracellular matrix and cell surface proteins.

scholarly journals Post-translational modifications of PRC2: signals directing its activity

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yiqi Yang ◽  
Gang Li
Keyword(s):  
Catalytic Activity ◽  
Transcriptional Repression ◽  
Essential Role ◽  
Histone H3 ◽  
Post Translational Modifications ◽  
Polycomb Repressive Complex 2 ◽  
Cellular Identity ◽  
Organismal Development ◽  
Biochemical Signals ◽  
Insight Into

Abstract Polycomb repressive complex 2 (PRC2) is a chromatin-modifying enzyme that catalyses the methylation of histone H3 at lysine 27 (H3K27me1/2/3). This complex maintains gene transcriptional repression and plays an essential role in the maintenance of cellular identity as well as normal organismal development. The activity of PRC2, including its genomic targeting and catalytic activity, is controlled by various signals. Recent studies have revealed that these signals involve cis chromatin features, PRC2 facultative subunits and post-translational modifications (PTMs) of PRC2 subunits. Overall, these findings have provided insight into the biochemical signals directing PRC2 function, although many mysteries remain.

scholarly journals Improved Pre-miRNA Classification by Reducing the Effect of Class Imbalance

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Yingli Zhong ◽  
Ping Xuan ◽  
Ke Han ◽  
Weiping Zhang ◽  
Jianzhong Li
Keyword(s):  
Cross Validation ◽  
State Of The Art ◽  
Class Imbalance ◽  
Superior Performance ◽  
Biological Processes ◽  
Classification Models ◽  
New Classification ◽  
Negative Effect ◽  
Human Animal ◽  
Species Specific

MicroRNAs (miRNAs) play important roles in the diverse biological processes of animals and plants. Although the prediction methods based on machine learning can identify nonhomologous and species-specific miRNAs, they suffered from severe class imbalance on real and pseudo pre-miRNAs. We propose a pre-miRNA classification method based on cost-sensitive ensemble learning and refer to it as MiRNAClassify. Through a series of iterations, the information of all the positive and negative samples is completely exploited. In each iteration, a new classification instance is trained by the equal number of positive and negative samples. In this way, the negative effect of class imbalance is efficiently relieved. The new instance primarily focuses on those samples that are easy to be misclassified. In addition, the positive samples are assigned higher cost weight than the negative samples. MiRNAClassify is compared with several state-of-the-art methods and some well-known classification models by testing the datasets about human, animal, and plant. The result of cross validation indicates that MiRNAClassify significantly outperforms other methods and models. In addition, the newly added pre-miRNAs are used to further evaluate the ability of these methods to discover novel pre-miRNAs. MiRNAClassify still achieves consistently superior performance and can discover more pre-miRNAs.

scholarly journals High-Throughput Sequencing Reveals Diverse Sets of Conserved, Nonconserved, and Species-Specific miRNAs in Jute

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Md. Tariqul Islam ◽  
Ahlan Sabah Ferdous ◽  
Rifat Ara Najnin ◽  
Suprovath Kumar Sarker ◽  
Haseena Khan
Keyword(s):  
High Throughput Sequencing ◽  
Target Genes ◽  
Kegg Pathway ◽  
Translational Repression ◽  
Biological Processes ◽  
Rt Pcr ◽  
Stem Loop ◽  
Evolutionarily Conserved ◽  
Pathway Analyses ◽  
Species Specific

MicroRNAs play a pivotal role in regulating a broad range of biological processes, acting by cleaving mRNAs or by translational repression. A group of plant microRNAs are evolutionarily conserved; however, others are expressed in a species-specific manner. Jute is an agroeconomically important fibre crop; nonetheless, no practical information is available for microRNAs in jute to date. In this study, Illumina sequencing revealed a total of 227 known microRNAs and 17 potential novel microRNA candidates in jute, of which 164 belong to 23 conserved families and the remaining 63 belong to 58 nonconserved families. Among a total of 81 identified microRNA families, 116 potential target genes were predicted for 39 families and 11 targets were predicted for 4 among the 17 identified novel microRNAs. For understanding better the functions of microRNAs, target genes were analyzed by Gene Ontology and their pathways illustrated by KEGG pathway analyses. The presence of microRNAs identified in jute was validated by stem-loop RT-PCR followed by end point PCR and qPCR for randomly selected 20 known and novel microRNAs. This study exhaustively identifies microRNAs and their target genes in jute which will ultimately pave the way for understanding their role in this crop and other crops.

scholarly journals Comparative Genome Sequence Analysis Reveals the Extent of Diversity and Conservation for Glycan-Associated Proteins inBurkholderiaspp.

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Hui San Ong ◽  
Rahmah Mohamed ◽  
Mohd Firdaus-Raih
Keyword(s):  
Comparative Analysis ◽  
Genome Sequence ◽  
Defense Mechanisms ◽  
Surface Proteins ◽  
Ecological Niches ◽  
Specific Gene ◽  
Sequence Comparisons ◽  
Virulence Protein ◽  
Associated Proteins ◽  
Species Specific

Members of theBurkholderiafamily occupy diverse ecological niches. In pathogenic family members, glycan-associated proteins are often linked to functions that include virulence, protein conformation maintenance, surface recognition, cell adhesion, and immune system evasion. Comparative analysis of availableBurkholderiagenomes has revealed a core set of 178 glycan-associated proteins shared by allBurkholderiaof which 68 are homologous to known essential genes. The genome sequence comparisons revealed insights into species-specific gene acquisitions through gene transfers, identified an S-layer protein, and proposed that significantly reactive surface proteins are associated to sugar moieties as a potential means to circumvent host defense mechanisms. The comparative analysis using a curated database of search queries enabled us to gain insights into the extent of conservation and diversity, as well as the possible virulence-associated roles of glycan-associated proteins in members of theBurkholderiaspp. The curated list of glycan-associated proteins used can also be directed to screen other genomes for glycan-associated homologs.

scholarly journals Thermodynamically stable and genetically unstable G-quadruplexes are depleted in genomes across species

2019 ◽  
Vol 47 (12) ◽  
pp. 6098-6113 ◽  
Author(s):  
Emilia Puig Lombardi ◽  
Allyson Holmes ◽  
Daniela Verga ◽  
Marie-Paule Teulade-Fichou ◽  
Alain Nicolas ◽  
...  
Keyword(s):  
Negative Selection ◽  
Genome Stability ◽  
Genome Instability ◽  
Regulation Of Gene Expression ◽  
Biological Processes ◽  
Single Nucleotide ◽  
Folding Potential ◽  
Species Specific

Abstract G-quadruplexes play various roles in multiple biological processes, which can be positive when a G4 is involved in the regulation of gene expression or detrimental when the folding of a stable G4 impairs DNA replication promoting genome instability. This duality interrogates the significance of their presence within genomes. To address the potential biased evolution of G4 motifs, we analyzed their occurrence, features and polymorphisms in a large spectrum of species. We found extreme bias of the short-looped G4 motifs, which are the most thermodynamically stable in vitro and thus carry the highest folding potential in vivo. In the human genome, there is an over-representation of single-nucleotide-loop G4 motifs (G4-L1), which are highly conserved among humans and show a striking excess of the thermodynamically least stable G4-L1A (G3AG3AG3AG3) sequences. Functional assays in yeast showed that G4-L1A caused the lowest levels of both spontaneous and G4-ligand-induced instability. Analyses across 600 species revealed the depletion of the most stable G4-L1C/T quadruplexes in most genomes in favor of G4-L1A in vertebrates or G4-L1G in other eukaryotes. We discuss how these trends might be the result of species-specific mutagenic processes associated to a negative selection against the most stable motifs, thus neutralizing their detrimental effects on genome stability while preserving positive G4-associated biological roles.

scholarly journals BIOLOGISTICS AND THE STRUGGLE FOR EFFICIENCY: CONCEPTS AND PERSPECTIVES

2009 ◽  
Vol 12 (06) ◽  
pp. 533-548 ◽  
Author(s):  
DIRK HELBING ◽  
ANDREAS DEUTSCH ◽  
STEFAN DIEZ ◽  
KARSTEN PETERS ◽  
YANNIS KALAIDZIDIS ◽  
...  
Keyword(s):  
Self Assembly ◽  
Supply And Demand ◽  
Logistic Models ◽  
Efficient Solutions ◽  
Self Control ◽  
World Population ◽  
Biological Processes ◽  
Population Limitation ◽  
Design Systems ◽  
Technical Solutions

The growth of world population, limitation of resources, economic problems, and environmental issues force engineers to develop increasingly efficient solutions for logistic systems. Pure optimization for efficiency, however, has often led to technical solutions that are vulnerable to variations in supply and demand, and to perturbations. In contrast, nature already provides a large variety of efficient, flexible, and robust logistic solutions. Can we utilize biological principles to design systems, which can flexibly adapt to hardly predictable, fluctuating conditions? We propose a bio-inspired "BioLogistics" approach to deduce dynamic organization processes and principles of adaptive self-control from biological systems, and to transfer them to man-made logistics (including nanologistics), using principles of modularity, self-assembly, self-organization, and decentralized coordination. Conversely, logistic models can help revealing the logic of biological processes at the systems level.

scholarly journals Game of Tissues: How the Epidermis Thrones C. elegans Shape

2020 ◽  
Vol 8 (1) ◽  
pp. 7 ◽  
Author(s):  
Cátia A. Carvalho ◽  
Limor Broday
Keyword(s):  
Cell Structure ◽  
Epithelial Morphogenesis ◽  
Special Importance ◽  
Biological Processes ◽  
Feedback Mechanisms ◽  
C Elegans ◽  
Tissue Interactions ◽  
Continuous Sheet ◽  
Morphogenic Process ◽  
Organismal Development

The versatility of epithelial cell structure is universally exploited by organisms in multiple contexts. Epithelial cells can establish diverse polarized axes within their tridimensional structure which enables them to flexibly communicate with their neighbors in a 360° range. Hence, these cells are central to multicellularity, and participate in diverse biological processes such as organismal development, growth or immune response and their misfunction ultimately impacts disease. During the development of an organism, the first task epidermal cells must complete is the formation of a continuous sheet, which initiates its own morphogenic process. In this review, we will focus on the C. elegans embryonic epithelial morphogenesis. We will describe how its formation, maturation, and spatial arrangements set the final shape of the nematode C. elegans. Special importance will be given to the tissue-tissue interactions, regulatory tissue-tissue feedback mechanisms and the players orchestrating the process.

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