The importance of long non-coding RNAs in neuropsychiatric disorders.

Mol Aspects Med. 2019 12;70:127-140

Authors: Hosseini E, Bagheri-Hosseinabadi Z, De Toma I, Jafarisani M, Sadeghi I

Abstract
In the last decade, transcriptome analyses have discovered thousands of long non-coding RNAs (lncRNAs) which are assumed as a fundamental part of the gene regulatory networks in the cell. Intriguingly, lncRNAs are abundantly enriched in the brain, displaying elaborate spatiotemporal expression profiles and modulation. They diversely participate in the delicate regulation of the central nervous system (CNS) development including self-renewal maintenance, cell fate decision, synapse plasticity, synaptogenesis and memory formation. Moreover, lncRNAs have vastly demonstrated correlations with mental illnesses such as neuropsychiatric disorders (NPDs), implying the vital jobs of these yet poorly-understood transcripts. Here, we underlie the accumulating evidence for the significance of lncRNAs in neural networks and their impairment in several NPDs including autism spectrum disorder (ASD), schizophrenia (SZ), intellectual disability (ID), major depressive disorder (MDD), Rett syndrome (RTT) and others.

PMID: 31319085 [PubMed - indexed for MEDLINE]

How water flow, geometry, and material properties drive plant movements.

J Exp Bot. 2019 07 23;70(14):3549-3560

Authors: Morris RJ, Blyth M

Abstract
Plants are dynamic. They adjust their shape for feeding, defence, and reproduction. Such plant movements are critical for their survival. We present selected examples covering a range of movements from single cell to tissue level and over a range of time scales. We focus on reversible turgor-driven shape changes. Recent insights into the mechanisms of stomata, bladderwort, the waterwheel, and the Venus flytrap are presented. The underlying physical principles (turgor, osmosis, membrane permeability, wall stress, snap buckling, and elastic instability) are highlighted, and advances in our understanding of these processes are summarized.

PMID: 31112593 [PubMed - indexed for MEDLINE]

MERIT: Systematic Analysis and Characterization of Mutational Effect on RNA Interactome Topology.

Hepatology. 2019 08;70(2):532-546

Authors: Li Y, McGrail DJ, Xu J, Li J, Liu NN, Sun M, Lin R, Pancsa R, Zhang J, Lee JS, Wang H, Mills GB, Li X, Yi S, Sahni N

Abstract
The interaction between RNA-binding proteins (RBPs) and RNA plays an important role in regulating cellular function. However, decoding genome-wide protein-RNA regulatory networks as well as how cancer-related mutations impair RNA regulatory activities in hepatocellular carcinoma (HCC) remains mostly undetermined. We explored the genetic alteration patterns of RBPs and found that deleterious mutations are likely to occur on the surface of RBPs. We then constructed protein-RNA interactome networks by integration of target binding screens and expression profiles. Network analysis highlights regulatory principles among interacting RBPs. In addition, somatic mutations selectively target functionally important genes (cancer genes, core fitness genes, or conserved genes) and perturb the RBP-gene regulatory networks in cancer. These regulatory patterns were further validated using independent data. A computational method (Mutational Effect on RNA Interactome Topology) and a web-based, user-friendly resource were further proposed to analyze the RBP-gene regulatory networks across cancer types. Pan-cancer analysis also suggests that cancer cells selectively target "vulnerability" genes to perturb protein-RNA interactome that is involved in cancer hallmark-related functions. Specifically, we experimentally validated four pairs of RBP-gene interactions perturbed by mutations in HCC, which play critical roles in cell proliferation. Based on the expression of perturbed RBP and target genes, we identified three subtypes of HCC with different survival rates. Conclusion: Our results provide a valuable resource for characterizing somatic mutation-perturbed protein-RNA regulatory networks in HCC, yielding valuable insights into the genotype-phenotype relationships underlying human cancer, and potential biomarkers for precision medicine.

PMID: 30153342 [PubMed - indexed for MEDLINE]

36 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/18

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

90 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

cnnAlpha: Protein Disordered Regions Prediction by Reduced Amino Acid Alphabets and Convolutional Neural Networks.

Proteins. 2020 Jun 14;:

Authors: Oberti M, Vaisman II

Abstract
Intrinsically disordered regions (IDR) play an important role in key biological processes and are closely related to human diseases. IDRs have great potential to serve as targets for drug discovery, most notably in disordered binding regions. Accurate prediction of IDRs is challenging because their genome wide occurrence and a low ratio of disordered residues make them difficult targets for traditional classification techniques. Existing computational methods mostly rely on sequence profiles to improve accuracy which is time consuming and computationally expensive. This article describes an ab initio sequence-only prediction method - which tries to overcome the challenge of accurate prediction posed by IDRs - based on reduced amino acid alphabets and convolutional neural networks (CNNs). We experiment with six different 3-letter reduced alphabets. We argue that the dimensional reduction in the input alphabet facilitates the detection of complex patterns within the sequence by the convolutional step. Experimental results show that our proposed IDR predictor performs at the same level or outperforms other state-of-the-art methods in the same class, achieving accuracy levels of 0.76 and AUC of 0.85 on the publicly available Critical Assessment of protein Structure Prediction dataset (CASP10). Therefore, our method is suitable for proteome-wide disorder prediction yielding similar or better accuracy than existing approaches at a faster speed. This article is protected by copyright. All rights reserved.

PMID: 32535960 [PubMed - as supplied by publisher]

Rimeporide as a first- in-class NHE-1 inhibitor: Results of a phase Ib trial in young patients with Duchenne Muscular Dystrophy.

Pharmacol Res. 2020 Jun 11;:104999

Authors: Previtali SC, Gidaro T, Díaz-Manera J, Zambon A, Carnesecchi S, Roux-Lombard P, Spitali P, Signorelli M, Szigyarto CA, Johansson C, Gray J, Labolle D, Thomé FP, Pitchforth J, Domingos J, Muntoni F

Abstract
Rimeporide, a first-in-class sodium/proton exchanger Type 1 inhibitor (NHE-1 inhibitor) is repositioned by EspeRare for patients with Duchenne Muscular Dystrophy (DMD). Historically, NHE-1 inhibitors were developed for cardiac therapeutic interventions. There is considerable overlap in the pathophysiological mechanisms in Congestive Heart Failure (CHF) and in cardiomyopathy in DMD, therefore NHE-1 inhibition could be a promising pharmacological approach to the cardiac dysfunctions observed in DMD. Extensive preclinical data was collected in various animal models including dystrophin-deficient (mdx) mice to characterise Rimeporide's anti-fibrotic and anti-inflammatory properties and there is evidence that NHE-1 inhibitors could play a significant role in modifying DMD cardiac and also skeletal pathologies, as the NHE-1 isoform is ubiquitous. We report here the first study with Rimeporide in DMD patients. This 4-week treatment, open label phase Ib, multiple oral ascending dose study, enrolled 20 ambulant boys with DMD (6-11 years), with outcomes including safety, pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers. Rimeporide was safe and well-tolerated at all doses. PK evaluations showed that Rimeporide was well absorbed orally reaching pharmacological concentrations from the lowest dose, with exposure increasing linearly with dose and with no evidence of accumulation upon repeated dosing. Exploratory PD biomarkers showed positive effect upon a 4-week treatment, supporting its therapeutic potential in patients with DMD, primarily as a cardioprotective treatment, and provide rationale for further efficacy studies.

PMID: 32535224 [PubMed - as supplied by publisher]

Comparative analysis of the intracellular responses to disease-related aggregation-prone proteins.

J Proteomics. 2020 Jun 11;:103862

Authors: Melnik A, Cappelletti V, Vaggi F, Piazza I, Tognetti M, Schwarz C, Cereghetti G, Ahmed MA, Soste M, Matlack K, de Souza N, Csikasz-Nagy A, Picotti P

Abstract
Aggregation-prone proteins (APPs) have been implicated in numerous human diseases but the underlying mechanisms are incompletely understood. Here we comparatively analysed cellular responses to different APPs. Our study is based on a systematic proteomic and phosphoproteomic analysis of a set of yeast proteotoxicity models expressing different human disease-related APPs, which accumulate intracellular APP inclusions and exhibit impaired growth. Clustering and functional enrichment analyses of quantitative proteome-level data reveal that the cellular response to APP expression, including the chaperone response, is specific to the APP, and largely differs from the response to a more generalized proteotoxic insult such as heat shock. We further observe an intriguing association between the subcellular location of inclusions and the location of the cellular response, and provide a rich dataset for future mechanistic studies. Our data suggest that care should be taken when designing research models to study intracellular aggregation, since the cellular response depends markedly on the specific APP and the location of inclusions. Further, therapeutic approaches aimed at boosting protein quality control in protein aggregation diseases should be tailored to the subcellular location affected by inclusion formation. SIGNIFICANCE: We have examined the global cellular response, in terms of protein abundance and phosphorylation changes, to the expression of five human neurodegeneration-associated, aggregation-prone proteins (APPs) in a set of isogenic yeast models. Our results show that the cellular response to each APP is unique to that protein, is different from the response to thermal stress, and is associated with processes at the subcellular location of APP inclusion formation. These results further our understanding of how cells, in a model organism, respond to expression of APPs implicated in neurodegenerative diseases like Parkinson's, Alzheimer's, and ALS. They have implications for mechanisms of toxicity as well as of protective responses in the cell. The specificity of the response to each APP means that research models of these diseases should be tailored to the APP in question. The subcellular localization of the response suggest that therapeutic interventions should also be targeted within the cell.

PMID: 32535145 [PubMed - as supplied by publisher]

Detection of molecular signatures and pathways shared in inflammatory bowel disease and colorectal cancer: A bioinformatics and systems biology approach.

Genomics. 2020 Jun 11;:

Authors: Al Mustanjid M, Mahmud SMH, Royel MRI, Rahman MH, Islam T, Rahman MR, Moni MA

Abstract
Emerging evidence indicates IBD is a risk factor for the increasing incidence of colorectal cancer (CRC) development. We used a system biology approach to identify common molecular signatures and pathways that interact between IBD and CRC and the indispensable pathological mechanisms. First, we identified 177 common differentially expressed genes (DEGs) between IBD and CRC. Gene set enrichment, protein-protein, DEGs-transcription factors, DEGs-microRNAs, protein-drug interaction, gene-disease association, Gene Ontology, pathway enrichment analyses were conducted to these common genes. The inclusion of common DEGs with bimolecular networks disclosed hub proteins (LYN, PLCB1, NPSR1, WNT5A, CDC25B, CD44, RIPK2, ASAP1), transcription factors (SCD, SLC7A5, IKZF3, SLC16A1, SLC7A11) and miRNAs (mir-335-5p, mir-26b-5p, mir-124-3p, mir-16-5p, mir-192-5p, mir-548c-3p, mir-29b-3p, mir-155-5p, mir-21-5p, mir-15a-5p). Analysis of the interaction between protein and drug discovered ASAP1 interacts with cysteine sulfonic acid and double oxidized cysteine drug compounds. Gene-disease association analysis retrieved ASAP1 also associated with pulmonary and bladder neoplasm diseases.

PMID: 32535071 [PubMed - as supplied by publisher]

Non-alcoholic steatohepatitis and progression of carotid atherosclerosis in patients with type 2 diabetes: a Korean cohort study.

Cardiovasc Diabetol. 2020 Jun 13;19(1):81

Authors: Lee HH, Cho Y, Choi YJ, Huh BW, Lee BW, Kang ES, Park SW, Cha BS, Lee EJ, Lee YH, Huh KB

Abstract
BACKGROUND: There is increasing concern regarding cardiovascular risk in individuals with non-alcoholic fatty liver disease. This study was conducted to evaluate whether hepatic steatosis with or without fibrosis is associated with the progression of carotid atherosclerosis in patients with type 2 diabetes.
METHODS: From a longitudinal cohort, we enrolled 1120 patients with type 2 diabetes who underwent repeated carotid artery ultrasonography every 1-2 years. Ultrasonographic findings at baseline and after 6-8 years were compared. Presence of hepatic steatosis was mainly assessed by abdominal ultrasonography; patients with hepatic steatosis were further evaluated for hepatic fibrosis according to fibrosis-4 index. We investigated the association between liver status and atherosclerosis progression.
RESULTS: Of 1120 patients, 636 (56.8%) were classified as having hepatic steatosis at baseline. After 6-8 years, 431 (38.5%) showed atherosclerosis progression. Hepatic steatosis was significantly associated with atherosclerosis progression (adjusted odds ratio[AOR]: 1.370, 95% CI 1.025-1.832; p < 0.05). Among patients with hepatic steatosis, only individuals with fibrosis showed significant association with atherosclerosis progression (AOR: 1.615, 95% CI 1.005-2.598; p < 0.05). The association between hepatic fibrosis and atherosclerosis progression was significant in all metabolic subgroups regardless of age, body mass index, presence of metabolic syndrome, or insulin sensitivity (all p < 0.05). Furthermore, subjects with hepatic steatosis & fibrosis and ≥ 4 components of metabolic syndrome criteria showed markedly increased risk of atherosclerosis progression (AOR: 2.430, 95% CI 1.087-5.458; p < 0.05).
CONCLUSIONS: Hepatic steatosis with fibrosis is independently associated with the progression of carotid atherosclerosis in patients with type 2 diabetes.

PMID: 32534588 [PubMed - as supplied by publisher]

Forty Years of Research and Treatment in Immunology and Allergy: In Honor of Professor Reza Farid Hosseini.

Iran J Allergy Asthma Immunol. 2020 May 17;19(S1):18-26

Authors: Jafari R, Moin M, Kashanchi F, Rajbar A

Abstract
In light of various supports of prodigious figures in the field of immunology and allergy, the subject area has been faced a great leap during the last century. The current state of the discipline owes an abundant appreciation for the scholars motivated in escalating the true nature of the science, who left no stone unturned in improving the general common sense and understanding of the human knowledge in general, and immunology and allergy in particular. Professor Reza Farid Hosseini is among the dignitaries who invested his life and energy on weaving the tapestry of the immunology and allergy. He delivered a great deal of influence on the field by his ethical devotion to science and was a significant contributor in the realms of the human immune system. His presence drastically rehabilitated the place of the Immunology in Iran, and the current paper seeks to review the personal and academic life of Professor Reza Farid Hosseini in honor and appreciation for his in-depth involvement in the field. The paper summarizes Professor Farid's childhood, school, and higher education, compilations, and translation of books, his contribution to the research both inside and outside of Iran, and scientific activities of Dr. Farid Hosseini.

PMID: 32534507 [PubMed - as supplied by publisher]

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

32 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/13

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34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/12

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33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

30 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/10

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/10

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

61 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/09

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

55 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2020/06/09

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.