Biomolecular Function Discovery

Genome-wide Analysis of Protein-Coding Variants in Leprosy

Although genome-wide association studies (GWAS) have greatly advanced our understanding on the contribution of common non-coding variants to leprosy susceptibility, protein-coding variants have not been systematically investigated. We carried out a three-stage genome-wide association study of protein-coding variants in 7,048 leprosy patients and 14,398 healthy controls of Han Chinese.

type: 
Journal Paper
journal: 
Journal of Investigative Dermatology, 2017, Aug 22, doi: 10.1016/j.jid.2017.08.004
pubmed: 
28842327
Url: 
http://www.jidonline.org/article/S0022-202X(17)32793-8/pdf
Impact Factor: 
6.287

Charged residues next to transmembrane regions revisited: "Positive-inside rule" is complemented by the "negative inside depletion/outside enrichment rule"

BACKGROUND:
Transmembrane helices (TMHs) frequently occur amongst protein architectures as means for proteins to attach to or embed into biological membranes. Physical constraints such as the membrane's hydrophobicity and electrostatic potential apply uniform requirements to TMHs and their flanking regions; consequently, they are mirrored in their sequence patterns (in addition to TMHs being a span of generally hydrophobic residues) on top of variations enforced by the specific protein's biological functions.

RESULTS:

type: 
Journal Paper
journal: 
BMC Biology 2017 Jul 24;15(1):66. doi: 10.1186/s12915-017-0404-4
pubmed: 
28738801
Url: 
https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0404-4
Impact Factor: 
6.779
Date of acceptance: 
2017-08-07

Benchmarking selected computational gene network growing tools in context of virus-host interactions

Several available online tools provide network growing functions where an algorithm utilizing different data sources suggests additional genes/proteins that should connect an input gene set into functionally meaningful networks. Using the well-studied system of influenza host interactions, we compare the network growing function of two free tools GeneMANIA and STRING and the commercial IPA for their performance of recovering known influenza A virus host factors previously identified from siRNA screens.

type: 
Journal Paper
journal: 
Scientific Reports, 2017 Jul 19;7(1):5805. doi: 10.1038/s41598-017-06020-6
pubmed: 
28724991
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28724991
Impact Factor: 
4.259
Date of acceptance: 
2017-06-07

Systematic analysis of protein identity between Zika virus and other arthropod-borne viruses

Objective To analyse the proportions of protein identity between Zika virus and dengue, Japanese encephalitis, yellow fever, West Nile and chikungunya viruses as well as polymorphism between different Zika virus strains.

type: 
Journal Paper
journal: 
Bulletin of the World Health Organization, 2017, Jul 1: 95(7): Pg 517-525i
Url: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487971/
Impact Factor: 
4.939
Date of acceptance: 
2017-01-19

Molecular features of influenza A (H1N1) pdm09 prevalent in Mexico during winter seasons 2012-2014

Since the emergence of the pandemic H1N1pdm09 virus in Mexico and California, biannual increases in the number of cases have been detected in Mexico. As observed in previous seasons, pandemic A/H1N1 09 virus was detected in severe cases during the 2011-2012 winter season and finally, during the 2013-2014 winter season it became the most prevalent influenza virus. Molecular and phylogenetic analyses of the whole viral genome are necessary to determine the antigenic and pathogenic characteristics of influenza viruses that cause severe outcomes of the disease.

type: 
Journal Paper
journal: 
PLOs One, July 10, 2017, doi: 10.1371/journal.pone.0180419
pubmed: 
28692701
Url: 
https://www.ncbi.nlm.nih.gov/pubmed/28692701
Impact Factor: 
2.8
Date of acceptance: 
2017-07-20

Systems-based approach to examine the cytokine responses in primary mouse lung macrophages infected with low pathogenic avian Influenza virus circulating in South East Asia

BACKGROUND:
Influenza A virus (IAV) is a major public health concern, being responsible for the death of approximately half a million people each year. Zoonotic transmissions of the virus from swine and avian origin have occurred in the past, and can potentially lead to the emgergence of new IAV stains in future pandemics. Pulmonary macrophages have been implicated in disease severity in the lower airway, and understanding the host response of macrophages infected with avian influenza viruses should provide new therapeutic strategies.

RESULTS:

type: 
Journal Paper
journal: 
BMC Genomics. 2017 May 30;18(1):420. doi: 10.1186/s12864-017-3803-6
pubmed: 
28558796
Url: 
https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-3803-6
Impact Factor: 
3.867
Date of acceptance: 
2017-05-05

Cross-reactive dengue human monoclonal antibody prevents severe pathologies and death from Zika virus infections

Zika virus (ZIKV) infections have been linked with neurological complications and congenital Zika syndrome. Given the high level of homology between ZIKV and the related flavivirus dengue virus (DENV), we investigated the level of cross-reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs showed binding to ZIKV virions, with several exhibiting neutralizing capacities against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved fusion-loop peptide, a

type: 
Journal Paper
journal: 
JCI Insight. 2017 Apr 20;2(8). pii: 92428. doi: 10.1172/jci.insight.92428
Url: 
https://insight.jci.org/articles/view/92428
Date of acceptance: 
2017-04-21

Essential role of the flexible linker on the conformational equilibrium of bacterial peroxiredoxin reductase for effective regeneration of peroxiredoxin

Reactive oxygen species (ROS) can damage DNA, proteins, and lipids, so cells have antioxidant systems that regulate ROS. In many bacteria, a dedicated peroxiredoxin reductase, alkyl hydroperoxide reductase subunit F (AhpF), catalyzes the rapid reduction of the redox-active disulfide center of the antioxidant protein peroxiredoxin (AhpC) to detoxify ROS such as hydrogen peroxide, organic hydroperoxide, and peroxynitrite. AhpF is a flexible multi-domain protein that enables a series of electron transfers among the redox centers by accepting reducing equivalents from NADH.

type: 
Journal Paper
journal: 
The Journal of Biological Chemistry, 7 Mar 2017, doi : 10.1074/jbc.M117.775858
Url: 
http://www.jbc.org/content/early/2017/03/07/jbc.M117.775858
Impact Factor: 
4.258
Date of acceptance: 
2017-03-07

Discovery of a novel splice variant of Fcar (CD89) unravels sequence segments necessary for efficient secretion: a story of bad signal peptides and good ones that nevertheless do not make it

The IgA receptor, Fcar (CD89) consists of five sequence segments: two segments (S1, S2) forming the potential signal peptide, two extracellular EC domains that include the IgA binding site, and the transmembrane and cytoplasmic tail (TM/C) region. Numerous Fcar splice variants have been reported with various combinations of the sequence segments mentioned above. Here, we report a novel splice variant termed variant APD isolated from a healthy volunteer that lacks only the IgA-binding EC1 domain.

type: 
Journal Paper
journal: 
Cell Cycle 2016, doi: 10.1080/15384101.2017.1281480
Url: 
http://www.tandfonline.com/doi/full/10.1080/15384101.2017.1281480?scroll=top&needAccess=true
Impact Factor: 
3.952
Date of acceptance: 
2017-01-05

Towards allosterically increased catalytic activity of insulin degrading enzyme (IDE) against amyloid peptides

Physiological role of insulin degrading enzyme (IDE) in the intracytosolic clearance of amyloid beta (Aβ) and other amyloid-like peptides supports a hypothesis that human IDE hyperactivation could be therapeutically beneficial in the treatment of the late onset Alzhimer’s disease (AD). The major challenge towards this goal is to increase specific catalytic activity of IDE against the Aβ-substrate.

type: 
Journal Paper
journal: 
Biochemistry 2016, doi: 10.1021/acs.biochem.6b00783
Url: 
http://pubs.acs.org/doi/abs/10.1021/acs.biochem.6b00783
Impact Factor: 
2.87
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