"Towards Predictive R-loop Computational Biology: Genome-Scale Prediction of R-loops Reveals Their association with Complex Promoter Structures, G-Quadruplexes and Transcriptionally Active Enhancers"

Published date : 26 Jun 2018

R-loops are three-stranded RNA:DNA hybrid structures essential for many normal and pathobiological processes. Previously, we generated a quantitative R-loop forming sequence (RLFS) model, quantitative model of R-loop-forming sequences (QmRLFS) and predicted ∼660 000 RLFSs; most of them located in genes and gene-flanking regions, G-rich regions and disease-associated genomic loci in the human genome. Here, we conducted a comprehensive comparative analysis of these RLFSs using experimental data and demonstrated the high performance of QmRLFS predictions on the nucleotide and genome scales.

type
Journal Paper
journal
Nuclei Acids Research, 2018 Jun 26. doi: 10.1093/nar/gky554
Impact Factor
11.561

Enhanced Delta-Notch Lateral Inhibition Model Incorporating Intracellular Notch Heterogeneity and Tension-Dependent Rate of Delta-Notch Binding that Reproduces Sprouting Angiogenesis Patterns

Published date : 22 Jun 2018

Endothelial cells adopt unique cell fates during sprouting angiogenesis, differentiating into tip or stalk cells. The fate selection process is directed by Delta-Notch lateral inhibition pathway. Classical Delta-Notch models produce a spatial pattern of tip cells separated by a single stalk cell, or the salt-and-pepper pattern. However, classical models cannot explain alternative tip-stalk patterning, such as tip cells that are separated by two or more stalk cells.

type
Journal Paper
journal
Scientific Reports 8, No. 9519, 2018, doi: 10.1038/s41598-018-27645-1
Impact Factor
4.122

SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements

Published date : 19 Jun 2018

The RNA-binding protein SRSF3 (also known as SRp20) has critical roles in the regulation of pre-mRNA splicing. Zygotic knockout of Srsf3 results in embryo arrest at the blastocyst stage. However, SRSF3 is also present in oocytes, suggesting that it might be critical as a maternally inherited factor. Here we identify SRSF3 as an essential regulator of alternative splicing and of transposable elements to maintain transcriptome integrity in mouse oocyte.

type
Journal Paper
journal
Cell Discovery 4, Article no: 33 (2018), doi: 10.1038/s41421-018-0032-3
Impact Factor
4.462

Potent tocolytic activity of ethyl acetate fraction of Ananas comosus on rat and human uteri

Published date : 18 Jun 2018

The aim of this study was to investigate the tocolytic properties of Ananas comosus extract in rat and human uterine tissue in vitro and in the rat in vivo. Organ bath technique was employed to perform functional studies in vitro. The PhysioTel transmitter was implanted in SD rats to measure the changes in intrauterine pressure (IUP) in vivo. Analyses of F2 was performed using LC-HRMS.

type
Journal Paper
journal
Biomedicine & Pharmacotheraphy, Vol. 105, Sept 2018, Pg 824-834, doi: 10.1016/j.biopha.2018.06.021
Impact Factor
2.759

Reversing allosteric communication: From detecting allosteric sites to inducing and tuning targeted allosteric response

Published date : 18 Jun 2018

The omnipresence of allosteric regulation together with the fundamental role of structural dynamics in this phenomenon have initiated a great interest to the detection of regulatory exosites and design of corresponding effectors.

type
Journal Paper
journal
PLoS Computational Biology, 18 Jun 2018, doi:10.1371/journal.pcbi.1006228
Impact Factor
3.955

Orthosteric and allosteric action of the C5a receptor antagonists

Published date : 11 Jun 2018

The C5a receptor (C5aR) is a G-protein-coupled receptor (GPCR) that can induce strong inflammatory response to the anaphylatoxin C5a. Targeting C5aR has emerged as a novel anti-inflammatory therapeutic method. However, developing potent C5aR antagonists as drugs has proven difficult. Here, we report two crystal structures of human C5aR in ternary complexes with the peptide antagonist PMX53 and a non-peptide antagonist, either avacopan or NDT9513727.

type
Journal Paper
journal
Natural Structural & Molecular Biology, Vol 25, June 2018, Pg 472-481, doi:10.1038/s41594-018-0067-z
Impact Factor
12.595

Allosteric Effects between the Antibody Constant and Variable Regions: A Study of IgA Fc Mutations on Antigen Binding

Published date : 08 Jun 2018

Therapeutic antibodies have shifted the paradigm of disease treatments from small molecules to biologics, especially in cancer therapy. Despite the increasing number of antibody candidates, much remains unknown about the antibody and how its various regions interact. Recent findings showed that the antibody constant region can govern localization effects that are useful in reducing side effects due to systemic circulation by the commonly used IgG isotypes. Given their localized mucosal effects, IgA antibodies are increasingly promising therapeutic biologics.

type
Journal Paper
journal
Antibodies 2018, 7(2), 20, doi: 10.3390/antib7020020

A Funneled Conformational Landscape Governs Flavivirus Fusion Peptide Interaction with Lipid Membranes

Published date : 06 Jun 2018

During host cell infection by flaviviruses such as dengue and Zika, acidic pH within the endosome triggers a conformational change in the envelope protein on the outer surface of the virion. This results in exposure of the ∼15 residue fusion peptide (FP) region, freeing it to induce fusion between the viral and endosomal membranes. A better understanding of the conformational dynamics of the FP in the presence of membranes, and the basis for its selectivity for anionic lipid species present within the endosome, would facilitate its therapeutic targeting with antiviral drugs and antibodies.

type
Journal Paper
journal
Journal of Chemical Theory and Computation, 2018 Jul 10;14(7):3920-3932. doi: 10.1021/acs.jctc.8b00438
Impact Factor
5.399

Influence of pH on the activity of thrombin-derived antimicrobial peptides

Published date : 06 Jun 2018

The wound environment is characterized by physiological pH changes. Proteolysis of thrombin by wound-derived proteases, such as neutrophil elastase, generates antimicrobial thrombin-derived C-terminal peptides (TCPs), such as HVF18 (HVFRLKKWIQKVIDQFGE). Presence of such TCPs in human wound fluids in vivo, as well as the occurrence of an evolutionarily conserved His residue in the primary amino acid sequence of TCPs, prompted us to investigate the pH-dependent antibacterial action of HVF18, as well as of the prototypic GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE).

type
Journal Paper
journal
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2018 Jun 6, doi: 10.1016/j.bbamem.2018.06.002
Impact Factor
3.438

Molecular basis for dengue virus broad cross-neutralization by humanized monoclonal antibody 513

Published date : 31 May 2018

Dengue is a widespread viral disease with 3.6 billion people at risk worldwide. Humanized monoclonal antibody (mAb) 513, currently undergoing clinical trials in Singapore, targets an epitope on the envelope protein domain III exposed at the surface of the viral particle. This antibody potently neutralizes all four dengue virus serotypes in a humanized mouse model that recapitulates human dengue infection, without signs of antibody-mediated enhancement of the disease.

type
Journal Paper
journal
Scientific Reports, 2018 May 31;8(1):8449 doi: 10.1038/s41598-018-26800-y
Impact Factor
4.122