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 These articles are HOT as recommended by the referees. And we’ve made them free to access for 4 weeks*.

Identifying subcellular localizations of mammalian protein complexes based on graph theory with a random forest algorithm
Zhan-Chao Li, Yan-Hua Lai, Li-Li Chen, Chao Chen, Yun Xie, Zong Dai and Xiao-Yong Zou 
DOI: 10.1039/C3MB25451H

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Quantifying the similarity of monotonic trajectories in rough and smooth fitness landscapes
Alexander E. Lobkovsky, Yuri I. Wolf and Eugene V. Koonin 
DOI: 10.1039/C3MB25553K

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A study of Caenorhabditis elegans DAF-2 mutants by metabolomics and differential correlation networks
Cecilia Castro, Jan Krumsiek, Nicolas J. Lehrbach, Steven A. Murfitt, Eric A. Miska and Julian L. Griffin
DOI: 10.1039/C3MB25539E

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A comprehensive analysis of the influence of drug binding kinetics on drug action at molecular and systems levels
Ning Yin, Jianfeng Pei and Luhua Lai
DOI: 10.1039/C3MB25471B

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DNA thermodynamic stability and supercoil dynamics determine the gene expression program during the bacterial growth cycle
Patrick Sobetzko, Monika Glinkowska, Andrew Travers and Georgi Muskhelishvili 
DOI: 10.1039/C3MB25515H

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Proteomic and ionomic profiling reveals significant alterations of protein expression and calcium homeostasis in cystic fibrosis cells
Domenico Ciavardelli, Melania D’Orazio, Luisa Pieroni, Ada Consalvo, Claudia Rossi, Paolo Sacchetta, Carmine Di Ilio, Andrea Battistoni and Andrea Urbani 
DOI: 10.1039/C3MB25594H

 

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Mechanism of action-based classification of antibiotics using high-content bacterial image analysis
Kelly C. Peach, Walter M. Bray, Dustin Winslow, Peter F. Linington and Roger G. Linington 
DOI: 10.1039/C3MB70027E

 

 

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

A group from the National University of Singapore and DSO National Laboratories, Singapore led by Mahesh Uttamchandani use gold nanoparticles to detect DNA sequences without the use of PCR.

PCR is normally needed to amplify the quantity of natural DNA samples for visual detection before they can be detected. For point-of-care applications in particular, the need for a PCR machine is cumbersome. In this communication, the researchers demonstrate a method for specific visual detection of a DNA sample without the need for PCR.

Gold nanoparticles are often coated with ligands for target specific detection. The different inter-particle distances provide a visual output when the target is added. Well-dispersed gold nanoparticles appear read and as the distance decreases this colour changes down the spectrum to purple and then to blue. Aggregation of the nanoparticles causes them to precipitate as black or grey sediments. It has been shown before that synthetic DNA sequences can be detected in this way using thiolated ligands. This study uses double stranded DNA samples at room temperature – surprising as single stranded DNA is optimal for adsorbing to the gold nanoparticle surface.

The researchers test their simple assay on genomic DNA extracts from Salmonella enterica. The sensitivity of the system leaves much to be desired compared to when PCR is used, however this easy protocol at room temperature with readily available agents and no need for electricity has some great advantages. The lack of PCR in detection of genomic DNA is a positive step forward for point-of-care diagnostics.

This short and urgent Communication is now free to access for the next four weeks*:

Direct visual detection of Salmonella genomic DNA using gold nanoparticles
Kamaladasan Kalidasan, Jia Ling Neo and Mahesh Uttamchandani
DOI: 10.1039/C3MB25527A

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

It is estimated that Toxoplasma gondii has infected almost 30% of people in the world, causing tissue damage in immunocompromised individuals that can lead to organ failure. It is also a commonly used model to study other related medically important parasites. In this HOT article, collaborators from the University of South Florida and Indiana University School of Medicine explore the lysine acetylation of parasite proteins, with a long-term view to the possibilities of disrupting lysine acetylation pathways with drugs to disrupt the invasion of the parasite.

Acetylation of proteins happens after they have been synthesised by translation and can change a protein’s properties markedly. It is thought to occur in disordered regions of proteins. The level of acetylation can be studied over the whole proteome and this is termed the acetylome. This study describes a comprehensive bioinformatics analysis of the acetylome of Toxoplasma at a particular stage of the life cycle. They look specifically at the disorder status of acetylated versus non-acetylated lysines. They conclude that dramatic change takes place when the parasite transitions during its life cycle from an intracellular to extracellular environment.

Free to access for the next 4 weeks*, you can read the discussion of their results now:

Protein intrinsic disorder in the acetylome of intracellular and extracellular Toxoplasma gondii
Bin Xue, Victoria Jeffers, William J. Sullivan and Vladimir N. Uversky
DOI: 10.1039/C3MB25517D

At Osaka University and Hyogo College of Medicine, Japan, researchers are investigating the structure–function relationship of lipopolysaccharides involved in stimulating the immune response.

In this HOT article, using a divergent synthetic approach Fukase et al. synthesize the lipophilic terminals, known as lipid As, of lipopolysaccharides from Gram-negative bacteria H. pylori and P. gingivalis. They study the structures’ cytokine induction activities, which are indicative of their immune function.

From this synthetic study, they explain the link between P. gingivalis infection and atherosclerosis. Lipid A 1 and 2 selectively induce IL-18 and inhibit IL-6 and IL-8, and a link between IL-18 and atherosclerosis is known.

Read their interesting divergent synthesis procedure and conclusions in full, as this HOT article is free to access for the next 4 weeks*:

Dual-labeled glycoclusters: synthesis and their application in monitoring lectin-mediated endocytosis
Xizhe Tian, Kyung-Hwa Baek and Injae Shin 
DOI: 10.1039/C3MB25491G

 

Predicting exactly where one protein will be located inside a cell is a tricky challenge, complicated even more when the protein can exist in two places at once inside the cell or moves positions. Most current computational methods can only deal with the proteins with a single location.

In this HOT article, researchers at Donghua University, China, and the Gordon Life Science Institute, California, USA, propose a new multi-label learning approach.  They use a new predictor specialised for predicting the subcellular locations of animal proteins with both single and multiple sites to improve upon the various shortcomings of previous methods.

They define a new statistical predictor, iLoc-Animal, using a new classification involving protein sequences and a Gene Ontology approach. Five metrics were defined to rigorously measure the prediction quality. They cross-validate the system using a benchmarked dataset of 5000 different animal proteins and 20 defined subcellular locations where these proteins locate, including the cell membrane and mitochondria. This is an incredibly complex system, making the achievement of formulating a useful high-throughput predictor tool significant.

This HOT article is now free to access for the next 4 weeks* and the authors have also make the web-server iLoc-Animal freely accessible at http://www.jci-bioinfo.cn/iLoc-Animal. 

iLoc-Animal: a multi-label learning classifier for predicting subcellular localization of animal proteins
Wei-Zhong Lin, Jian-An Fang, Xuan Xiao and Kuo-Chen Chou
DOI: 10.1039/C3MB25466F

*Free access to individuals is provided through an RSC Publishing personal account. Registration is quick, free and simple

Researchers at the National Institutes of Health, USA, and MRC Laboratory of Molecular Biology, UK, take a close look at the influence of phosphorylation on protein binding in this HOT article.

Led by Anna Panchenko, their focus is on protein binding in relation to intrinsically disordered human protein complexes i.e. proteins with no single defined structure.  Some disordered proteins are thought to undergo folding when binding to another protein interface, causing a change from disorder to order.  

In this work, the team find that phosphorylation, binding and disorder–order transitions are all related processes. Disorder and binding states affect phosphorylation of serine more than threonine.  Tyrosine is more often in ordered protein interfaces, explaining why tyrosine phosphorylation is often associated with structured domains. On the other hand, serine is usually found in disordered regions especially in protein–protein interaction networks and the researchers conclude that this is due to the vital role of serine in disorder–order transitions.

The work also goes into mechanisms of how intrinsic disorder is involved in the way phosphorylation affects binding. The team ask how phosphorylation might prevent disorder–order transitions occurring during a binding event. Phosphorylation sites have a direct role in binding and binding regulated by disorder is known to have a number of advantages. The association of these influences is the logical conclusion of this work, now free to access for 4 weeks*:

Regulation of protein–protein binding by coupling between phosphorylation and intrinsic disorder: analysis of human protein complexes
Hafumi Nishi, Jessica H. Fong, Christiana Chang, Sarah A. Teichmann and Anna R. Panchenko
DOI: 10.1039/C3MB25514J