scholarly journals iSUMOK-PseAAC: prediction of lysine sumoylation sites using statistical moments and Chou’s PseAAC

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11581
Author(s):  
Yaser Daanial Khan ◽  
Nabeel Sabir Khan ◽  
Sheraz Naseer ◽  
Ahmad Hassan Butt
Keyword(s):  
State Of The Art ◽  
Statistical Moments ◽  
Post Translational Modification ◽  
Sumoylation Site ◽  
Developmental Defects ◽  
Response To Stress ◽  
Sensitivity Specificity ◽  
Validation Testing ◽  
Fold Cross Validation ◽  
Lateral Sclerosis

Sumoylation is the post-translational modification that is involved in the adaption of the cells and the functional properties of a large number of proteins. Sumoylation has key importance in subcellular concentration, transcriptional synchronization, chromatin remodeling, response to stress, and regulation of mitosis. Sumoylation is associated with developmental defects in many human diseases such as cancer, Huntington’s, Alzheimer’s, Parkinson’s, Spin cerebellar ataxia 1, and amyotrophic lateral sclerosis. The covalent bonding of Sumoylation is essential to inheriting part of the operative characteristics of some other proteins. For that reason, the prediction of the Sumoylation site has significance in the scientific community. A novel and efficient technique is proposed to predict the Sumoylation sites in proteins by incorporating Chou’s Pseudo Amino Acid Composition (PseAAC) with statistical moments-based features. The outcomes from the proposed system using 10 fold cross-validation testing are 94.51%, 94.24%, 94.79% and 0.8903% accuracy, sensitivity, specificity and MCC, respectively. The performance of the proposed system is so far the best in comparison to the other state-of-the-art methods. The codes for the current study are available on the GitHub repository using the link: https://github.com/csbioinfopk/iSumoK-PseAAC.

Neurofilament Proteins as Prognostic Biomarkers in Neurological Disorders

2020 ◽  
Vol 25 (43) ◽  
pp. 4560-4569 ◽  
Author(s):  
Yichen Lee ◽  
Bo H. Lee ◽  
William Yip ◽  
Pingchen Chou ◽  
Bak-Sau Yip
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Nervous System ◽  
Trinucleotide Repeat ◽  
Muscular Atrophy ◽  
Electric Signal ◽  
Motor Neuropathy ◽  
Post Translational Modification ◽  
Neurofilament Proteins ◽  
Type Iv ◽  
Lateral Sclerosis

Neurofilaments: light, medium, and heavy (abbreviated as NF-L, NF-M, and NF-H, respectively), which belong to Type IV intermediate filament family (IF), are neuron-specific cytoskeletal components. Neurofilaments are axonal structural components and integral components of synapses, which are important for neuronal electric signal transmissions along the axons and post-translational modification. Abnormal assembly of neurofilaments is found in several human neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), infantile spinal muscular atrophy (SMA), and hereditary sensory-motor neuropathy (HSMN). In addition, those pathological neurofilament accumulations are known in α-synuclein in Parkinson’s disease (PD), Aβ and tau in Alzheimer’s disease (AD), polyglutamine in CAG trinucleotide repeat disorders, superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP43), neuronal FUS proteins, optineurin (OPTN), ubiquilin 2 (UBQLN2), and dipeptide repeat protein (DRP) in amyotrophic lateral sclerosis (ALS). When axon damage occurs in central nervous disorders, neurofilament proteins are released and delivered into cerebrospinal fluid (CSF), which are then circulated into blood. New quantitative analyses and assay techniques are well-developed for the detection of neurofilament proteins, particularly NF-L and the phosphorylated NF-H (pNF-H) in CSF and serum. This review discusses the potential of using peripheral blood NF quantities and evaluating the severity of damage in the nervous system. Intermediate filaments could be promising biomarkers for evaluating disease progression in different nervous system disorders.

Understanding cellular glycan surfaces in the central nervous system

2018 ◽  
Vol 47 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Sameera Iqbal ◽  
Mina Ghanimi Fard ◽  
Arun Everest-Dass ◽  
Nicolle H. Packer ◽  
Lindsay M. Parker
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Development ◽  
Analytical Techniques ◽  
Detection Methods ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Enzymatic Process ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Abstract Glycosylation, the enzymatic process by which glycans are attached to proteins and lipids, is the most abundant and functionally important type of post-translational modification associated with brain development, neurodegenerative disorders, psychopathologies and brain cancers. Glycan structures are diverse and complex; however, they have been detected and targeted in the central nervous system (CNS) by various immunohistochemical detection methods using glycan-binding proteins such as anti-glycan antibodies or lectins and/or characterized with analytical techniques such as chromatography and mass spectrometry. The glycan structures on glycoproteins and glycolipids expressed in neural stem cells play key roles in neural development, biological processes and CNS maintenance, such as cell adhesion, signal transduction, molecular trafficking and differentiation. This brief review will highlight some of the important findings on differential glycan expression across stages of CNS cell differentiation and in pathological disorders and diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, schizophrenia and brain cancer.

scholarly journals Distinctive functional regime of endogenous lncRNAs in dark regions of human genome

2020 ◽  
Author(s):  
Anyou Wang ◽  
Rong Hai
Keyword(s):  
Human Genome ◽  
Rna Processing ◽  
Self Regulation ◽  
Post Translational Modification ◽  
Protein Coding ◽  
Noncoding Regions ◽  
Coding Regions ◽  
Rnaseq Data ◽  
Response To Stress ◽  
Eukaryotic Genomes

AbstractEukaryotic genomes gradually gain noncoding regions when advancing evolution and human genome actively transcribes >90% of its noncoding regions1, suggesting their criticality in evolutionary human genome. Yet <1% of them have been functionally characterized2, leaving most human genome in dark. Here we systematically decode endogenous lncRNAs located in unannotated regions of human genome and decipher a distinctive functional regime of lncRNAs hidden in massive RNAseq data. LncRNAs divergently distribute across chromosomes, independent of protein-coding regions. Their transcriptions barely initiate on promoters through polymerase II, but mostly on enhancers. Yet conventional enhancer activators(e.g. H3K4me1) only account for a small proportion of lncRNA activation, suggesting alternatively unknown mechanisms initiating the majority of lncRNAs. Meanwhile, lncRNA-self regulation also notably contributes to lncRNA activation. LncRNAs trans-regulate broad bioprocesses, including transcription and RNA processing, cell cycle, respiration, response to stress, chromatin organization, post-translational modification, and development. Overall lncRNAs govern their owned regime distinctive from protein’s.

scholarly journals Screening for Prostate Cancer: To Screen or Not To Screen? A Review of The State-of-The Art

2019 ◽  
pp. 19-24
Author(s):  
Lajos Döbrőssy
Keyword(s):  
Prostate Cancer ◽  
State Of The Art ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Conclusive Evidence ◽  
Screening Tests ◽  
Health Concern ◽  
Average Risk ◽  
Randomized Controlled ◽  
Sensitivity Specificity

Prostate cancer is a major public health concern, particularly in the welfare countries, for this reason, screening should be considered to reduce the number of deaths. Screening tests are available, i.e. digital rectal examination; trans-rectal ultrasonography and prostate specific antigen, nevertheless their sensitivity, specificity and positive predictive value are far from being perfect. Evidences from randomized screening trials are still indebted for conclusive evidence. The screening might cause more harm than good due to over diagnosis and over-treatment as a result of limited specificity of the screening tests. According to our point a view, opportunistic screening as part of diagnostics of patients having suspicion for uncertain symptoms of prostatic disorder is fully justified but mass screening of the population of average risk should not be introduced until supportive evidence from randomized controlled trials would be available.

Stem cells in amyotrophic lateral sclerosis: state of the art

2009 ◽  
Vol 9 (10) ◽  
pp. 1245-1258 ◽  
Author(s):  
Letizia Mazzini ◽  
Alessandro Vercelli ◽  
Ivana Ferrero ◽  
Katia Mareschi ◽  
Marina Boido ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amyotrophic Lateral Sclerosis ◽  
State Of The Art ◽  
Lateral Sclerosis

scholarly journals A novel computational model for predicting potential LncRNA-disease associations based on both direct and indirect features of LncRNA-disease pairs

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yubin Xiao ◽  
Zheng Xiao ◽  
Xiang Feng ◽  
Zhiping Chen ◽  
Linai Kuang ◽  
...  
Keyword(s):  
Computational Model ◽  
Cross Validation ◽  
State Of The Art ◽  
Prediction Methods ◽  
Good Prediction ◽  
Average Case ◽  
Comparison Results ◽  
Disease Associations ◽  
Fold Cross Validation

Abstract Background Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are closely associated with human diseases, and it is useful for the diagnosis and treatment of diseases to get the relationships between lncRNAs and diseases. Due to the high costs and time complexity of traditional bio-experiments, in recent years, more and more computational methods have been proposed by researchers to infer potential lncRNA-disease associations. However, there exist all kinds of limitations in these state-of-the-art prediction methods as well. Results In this manuscript, a novel computational model named FVTLDA is proposed to infer potential lncRNA-disease associations. In FVTLDA, its major novelty lies in the integration of direct and indirect features related to lncRNA-disease associations such as the feature vectors of lncRNA-disease pairs and their corresponding association probability fractions, which guarantees that FVTLDA can be utilized to predict diseases without known related-lncRNAs and lncRNAs without known related-diseases. Moreover, FVTLDA neither relies solely on known lncRNA-disease nor requires any negative samples, which guarantee that it can infer potential lncRNA-disease associations more equitably and effectively than traditional state-of-the-art prediction methods. Additionally, to avoid the limitations of single model prediction techniques, we combine FVTLDA with the Multiple Linear Regression (MLR) and the Artificial Neural Network (ANN) for data analysis respectively. Simulation experiment results show that FVTLDA with MLR can achieve reliable AUCs of 0.8909, 0.8936 and 0.8970 in 5-Fold Cross Validation (fivefold CV), 10-Fold Cross Validation (tenfold CV) and Leave-One-Out Cross Validation (LOOCV), separately, while FVTLDA with ANN can achieve reliable AUCs of 0.8766, 0.8830 and 0.8807 in fivefold CV, tenfold CV, and LOOCV respectively. Furthermore, in case studies of gastric cancer, leukemia and lung cancer, experiment results show that there are 8, 8 and 8 out of top 10 candidate lncRNAs predicted by FVTLDA with MLR, and 8, 7 and 8 out of top 10 candidate lncRNAs predicted by FVTLDA with ANN, having been verified by recent literature. Comparing with the representative prediction model of KATZLDA, comparison results illustrate that FVTLDA with MLR and FVTLDA with ANN can achieve the average case study contrast scores of 0.8429 and 0.8515 respectively, which are both notably higher than the average case study contrast score of 0.6375 achieved by KATZLDA. Conclusion The simulation results show that FVTLDA has good prediction performance, which is a good supplement to future bioinformatics research.

scholarly journals N- and O-Glycosylation Pathways in the Microalgae Polyphyletic Group

2020 ◽  
Vol 11 ◽  
Author(s):  
Elodie Mathieu-Rivet ◽  
Narimane Mati-Baouche ◽  
Marie-Laure Walet-Balieu ◽  
Patrice Lerouge ◽  
Muriel Bardor
Keyword(s):  
Recombinant Proteins ◽  
Metabolic Pathways ◽  
Phylogenetic Diversity ◽  
State Of The Art ◽  
Protein Glycosylation ◽  
Expression Systems ◽  
Post Translational Modification ◽  
Photosynthetic Organisms ◽  
Biological Features ◽  
Heterologous Expression Systems

The term microalga refers to various unicellular and photosynthetic organisms representing a polyphyletic group. It gathers numerous species, which can be found in cyanobacteria (i.e., Arthrospira) as well as in distinct eukaryotic groups, such as Chlorophytes (i.e., Chlamydomonas or Chlorella) and Heterokonts (i.e., diatoms). This phylogenetic diversity results in an extraordinary variety of metabolic pathways, offering large possibilities for the production of natural compounds like pigments or lipids that can explain the ever-growing interest of industrials for these organisms since the middle of the last century. More recently, several species have received particular attention as biofactories for the production of recombinant proteins. Indeed, microalgae are easy to grow, safe and cheap making them attractive alternatives as heterologous expression systems. In this last scope of applications, the glycosylation capacity of these organisms must be considered as this post-translational modification of proteins impacts their structural and biological features. Although these mechanisms are well known in various Eukaryotes like mammals, plants or insects, only a few studies have been undertaken for the investigation of the protein glycosylation in microalgae. Recently, significant progresses have been made especially regarding protein N-glycosylation, while O-glycosylation remain poorly known. This review aims at summarizing the recent data in order to assess the state-of-the art knowledge in glycosylation processing in microalgae.

scholarly journals Gut–Brain Axis and Neurodegeneration: State-of-the-Art of Meta-Omics Sciences for Microbiota Characterization

2020 ◽  
Vol 21 (11) ◽  
pp. 4045 ◽  
Author(s):  
Bruno Tilocca ◽  
Luisa Pieroni ◽  
Alessio Soggiu ◽  
Domenico Britti ◽  
Luigi Bonizzi ◽  
...  
Keyword(s):  
Nervous System ◽  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
State Of The Art ◽  
Integrated Approach ◽  
Microbial Genomes ◽  
Physiological Processes ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Recent advances in the field of meta-omics sciences and related bioinformatics tools have allowed a comprehensive investigation of human-associated microbiota and its contribution to achieving and maintaining the homeostatic balance. Bioactive compounds from the microbial community harboring the human gut are involved in a finely tuned network of interconnections with the host, orchestrating a wide variety of physiological processes. These includes the bi-directional crosstalk between the central nervous system, the enteric nervous system, and the gastrointestinal tract (i.e., gut–brain axis). The increasing accumulation of evidence suggest a pivotal role of the composition and activity of the gut microbiota in neurodegeneration. In the present review we aim to provide an overview of the state-of-the-art of meta-omics sciences including metagenomics for the study of microbial genomes and taxa strains, metatranscriptomics for gene expression, metaproteomics and metabolomics to identify and/or quantify microbial proteins and metabolites, respectively. The potential and limitations of each discipline were highlighted, as well as the advantages of an integrated approach (multi-omics) to predict microbial functions and molecular mechanisms related to human diseases. Particular emphasis is given to the latest results obtained with these approaches in an attempt to elucidate the link between the gut microbiota and the most common neurodegenerative diseases, such as multiple sclerosis (MS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS).

scholarly journals Age-dependent degeneration of an identified adult leg motor neuron in a Drosophila SOD1 model of ALS

Biology Open ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. bio049692
Author(s):  
Anthony Agudelo ◽  
Victoria St. Amand ◽  
Lindsey Grissom ◽  
Danielle Lafond ◽  
Toni Achilli ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Gene Replacement ◽  
Loss Of Function ◽  
Developmental Defects ◽  
Age Related ◽  
Disease Mutations ◽  
Discs Large ◽  
Age Dependent ◽  
Motor Neuron Loss ◽  
Lateral Sclerosis

ABSTRACTMutations in superoxide dismutase 1 (SOD1) cause familial amyotrophic lateral sclerosis (ALS) in humans. ALS is a neurodegenerative disease characterized by progressive motor neuron loss leading to paralysis and inevitable death in affected individuals. Using a gene replacement strategy to introduce disease mutations into the orthologous Drosophila sod1 (dsod1) gene, here, we characterize changes at the neuromuscular junction using longer-lived dsod1 mutant adults. Homozygous dsod1H71Y/H71Y or dsod1null/null flies display progressive walking defects with paralysis of the third metathoracic leg. In dissected legs, we assessed age-dependent changes in a single identified motor neuron (MN-I2) innervating the tibia levitator muscle. At adult eclosion, MN-I2 of dsod1H71Y/H71Y or sod1null/null flies is patterned similar to wild-type flies indicating no readily apparent developmental defects. Over the course of 10 days post-eclosion, MN-I2 shows an overall reduction in arborization with bouton swelling and loss of the post-synaptic marker discs-large (dlg) in mutant dsod1 adults. In addition, increases in polyubiquitinated proteins correlate with the timing and extent of MN-I2 changes. Because similar phenotypes are observed between flies homozygous for either dsod1H71Y or dsod1null alleles, we conclude these NMJ changes are mainly associated with sod loss-of-function. Together these studies characterize age-related morphological and molecular changes associated with axonal retraction in a Drosophila model of ALS that recapitulate an important aspect of the human disease.This article has an associated First Person interview with the first author of the paper.

scholarly journals The Physiological Implications of S-Nitrosoglutathione Reductase (GSNOR) Activity Mediating NO Signalling in Plant Root Structures

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1206
Author(s):  
Leslie Ventimiglia ◽  
Bulent Mutus
Keyword(s):  
Plant Root ◽  
Post Translational Modification ◽  
No Donor ◽  
Stunted Growth ◽  
Cellular Environment ◽  
Redox Active ◽  
Irreversible Reduction ◽  
Wide Range ◽  
Response To Stress ◽  
Cysteine Thiols

Nitrogen remains an important macronutrient in plant root growth due to its application in amino acid production, in addition to its more elusive role in cellular signalling through nitric oxide (NO). NO is widely accepted as an important signalling oxidative radical across all organisms, leading to its study in a wide range of biological pathways. Along with its more stable NO donor, S-nitrosoglutathione (GSNO), formed by NO non-enzymatically in the presence of glutathione (GSH), NO is a redox-active molecule capable of mediating target protein cysteine thiols through the post translational modification, S-nitrosation. S-nitrosoglutathione reductase (GSNOR) thereby acts as a mediator to pathways regulated by NO due to its activity in the irreversible reduction of GSNO to oxidized glutathione (GSSG) and ammonia. GSNOR is thought to be pleiotropic and often acts by mediating the cellular environment in response to stress conditions. Under optimal conditions its activity leads to growth by transcriptional upregulation of the nitrate transporter, NRT2.1, and through its interaction with phytohormones like auxin and strigolactones associated with root development. However, in response to highly nitrosative and oxidative conditions its activity is often downregulated, possibly through an S-nitrosation site on GSNOR at cys271, Though GSNOR knockout mutated plants often display a stunted growth phenotype in all structures, they also tend to exhibit a pre-induced protective effect against oxidative stressors, as well as an improved immune response associated with NO accumulation in roots.

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