Inferring putative transmission clusters with Phydelity

Published date : 09 Oct 2019

Current phylogenetic clustering approaches for identifying pathogen transmission clusters are limited by their dependency on arbitrarily defined genetic distance thresholds for within-cluster divergence. Incomplete knowledge of a pathogen's underlying dynamics often reduces the choice of distance threshold to an exploratory, ad hoc exercise that is difficult to standardise across studies. Phydelity is a new tool for the identification of transmission clusters in pathogen phylogenies.

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Journal Paper
journal
Virus Evolution, Vol. 5, Issue 2, Jul, 2019, doi: 10.1093/ve/vez039
Impact Factor
5.408

Linker length affects photostability of protein-targeted sensor of cellular microviscosity

Published date : 26 Sep 2019

Viscosity sensitive fluorophores termed 'molecular rotors' represent a convenient and quantitative tool for measuring intracellular viscosity via Fluorescence Lifetime Imaging Microscopy (FLIM). We compare the FLIM performance of two BODIPY-based molecular rotors bound to HaloTag protein expressed in different subcellular locations.

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Journal Paper
journal
Methods and Applications in Fluorescence, 2019 Sep 26. doi: 10.1088/2050-6120/ab481f
Impact Factor
2.165

c-Met activation leads to the establishment of a TGFβ-receptor regulatory network in bladder cancer progression

Published date : 25 Sep 2019

Treatment of muscle-invasive bladder cancer remains a major clinical challenge. Aberrant HGF/c-MET upregulation and activation is frequently observed in bladder cancer correlating with cancer progression and invasion. However, the mechanisms underlying HGF/c-MET-mediated invasion in bladder cancer remains unknown. As part of a negative feedback loop SMAD7 binds to SMURF2 targeting the TGFβ receptor for degradation. Under these conditions, SMAD7 acts as a SMURF2 agonist by disrupting the intramolecular interactions within SMURF2.

type
Journal Paper
journal
Nature Communicationsvolume 10, Article number: 4349 (2019), doi: 10.1038/s41467-019-12241-2
Impact Factor
11.878

Influenza A Hemagglutinin Passage Bias Sites and Host Specificity Mutations

Published date : 22 Sep 2019

Animal studies aimed at understanding influenza virus mutations that change host specificity to adapt to replication in mammalian hosts are necessarily limited in sample numbers due to high cost and safety requirements. As a safe, higher-throughput alternative, we explore the possibility of using readily available passage bias data obtained mostly from seasonal H1 and H3 influenza strains that were differentially grown in mammalian (MDCK) and avian cells (eggs).

type
Journal Paper
journal
Cells 2019, Aug 22, 8(9), 958; doi: 10.3390/cells8090958
Impact Factor
5.656

Molecular basis of dengue virus serotype 2 morphological switch from 29°C to 37°C

Published date : 19 Sep 2019

The ability of DENV2 to display different morphologies (hence different antigenic properties) complicates vaccine and therapeutics development. Previous studies showed most strains of laboratory adapted DENV2 particles changed from smooth to “bumpy” surfaced morphology when the temperature is switched from 29°C at 37°C. Here we identified five envelope (E) protein residues different between two alternative passage history DENV2 NGC strains exhibiting smooth or bumpy surface morphologies.

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Journal Paper
journal
PLOS Pathogens, Sep 2019, Vol. 15, Issue 9, doi 10.1371/journal.ppat.1007996
Impact Factor
6.463

Utility of In Vitro Bioactivity as a Lower Bound Estimate of In Vivo Adverse Effect Levels and in Risk-Based Prioritization

Published date : 18 Sep 2019

Use of high-throughput, in vitro bioactivity data in setting a point-of-departure (POD) has the potential to accelerate the pace of human health safety evaluation by informing screening level assessments. The primary objective of this work was to compare PODs based on high-throughput predictions of bioactivity, exposure predictions, and traditional hazard information for 448 chemicals.

type
Journal Paper
journal
Toxicological Sciences, 2019, Sep 18, 10.1093/toxsci/kfz201
Impact Factor
3.564

Rare Human Missense Variants can affect the Function of Disease-Relevant Proteins by Loss and Gain of Peroxisomal Targeting Motifs

Published date : 17 Sep 2019

Single nucleotide variants (SNVs) resulting in amino acid substitutions (i.e., missense variants) can affect protein localization by changing or creating new targeting signals. Here, we studied the potential of naturally occurring SNVs from the Genome Aggregation Database (gnomAD) to result in the loss of an existing peroxisomal targeting signal 1 (PTS1) or gain of a novel PTS1 leading to mistargeting of cytosolic proteins to peroxisomes.

type
Journal Paper
journal
International Journal of Molecular Sciences, Vol. 20, Issue 18, Sep 17, doi: 10.3390/ijms20184609
Impact Factor
4.183

BRAF inhibitors promote intermediate BRAF(V600E) conformations and binary interactions with activated RAS

Published date : 14 Sep 2019

Oncogenic BRAF mutations initiate tumor formation by unleashing the autoinhibited kinase conformation and promoting RAS-decoupled proliferative RAF-MEK-ERK signaling. We have engineered luciferase-based biosensors to systematically track full-length BRAF conformations and interactions affected by tumorigenic kinase mutations and GTP loading of RAS. Binding of structurally diverse αC-helix-OUT BRAF inhibitors (BRAFi) showed differences in specificity and efficacy by shifting patient mutation–containing BRAF reporters from the definitive opened to more closed conformations.

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Journal Paper
journal
Science Advances, 14 Aug 2019, Vol. 5, no. 8, doi: 10.1126/sciadv.aav8463
Impact Factor
11.5

PI3K Catalytic Subunits α and β Modulate Cell Death and IL-6 Secretion Induced by Talc Particles in Human Lung Carcinoma Cells

Published date : 12 Sep 2019

Hydrated magnesium silicate (or "talc" particles) is a sclerosis agent commonly used in the management of malignant pleural effusions (MPE), a common symptom of metastatic diseases including lung cancers. However, the direct effects of talc particles to lung carcinoma cells, which can be found in the MPE fluids from lung cancer patients, are not fully understood. Here, we report a study of the signaling pathways that can modulate the cell death and interleukin (IL)-6 secretion induced by talc particles in human lung carcinoma cells.

type
Journal Paper
journal
American Journal of Respiratory Cell and Molecular Biology, 2019 Sep 12. doi: 10.1165/rcmb.2019-0050OC
Impact Factor
4.34

Three-dimensional structure of Megabalanus rosa Cement Protein 20 revealed by multi-dimensional NMR and molecular dynamics simulations

Published date : 09 Sep 2019

Barnacles employ a protein-based cement to firmly attach to immersed substrates. The cement proteins (CPs) have previously been identified and sequenced. However, the molecular mechanisms of adhesion are not well understood, in particular, because the three-dimensional molecular structure of CPs remained unknown to date. Here, we conducted multi-dimensional nuclear magnetic resonance (NMR) studies and molecular dynamics (MD) simulations of recombinant Megabalanus rosa Cement Protein 20 (rMrCP20).

type
Journal Paper
journal
Philosophical Transactions B, 2019, doi: 10.1098/rstb.2019.0198
Impact Factor
5.666