Archive for the ‘Cover articles’ Category

Fibrils, oligomers or just precursors? New probe characterises beta-amyloid aggregates

Beta-amyloid (Aβ) aggregates are infamous for forming the toxic plaques in the brain of Alzheimer’s disease patients. The detrimental effects are fairly well studied, but the mechanism of formation remains largely a mystery.

Now, thanks to Ifor D. W. Samuel, J. Carlos Penedo and colleagues at University of St. Andrews and Glasgow University, researchers have a new fluorescent probe to study the process of Aβ aggregation. This paper was featured on the cover of the January 2014 issue of Molecular Biosystems.


The most common probe of Aβ currently in use is Thioflavin T (ThT), which has been very successful at detecting the presence of aggregates. However, this probe has a limited pH range where it can be used. Aggregate structures can form at low concentrations of Aβ, and in the slightly acidic (pH = 6) endosome, but both of these are beyond the detection limits of ThT. For maximum utility, a probe would be able to track Aβ formation under any biological conditions.

Fig 1: Representative aggregation time course and relative fluorescence quenching during the HFIP-induced aggregation of Ab1–42

To address this disadvantage, Samuel & Penedo et al. have used a HiLyte Fluorescent probe attached to the N-terminal position of Aβ monomers. When monomers associate with each other, the probe undergoes fluorescence self-quenching (FSQ), a well-documented process where the presence of two probes proximal to each other will cause a decrease in the observed fluorescent signal. This decrease in signal can be monitored and correlated with the aggregation rate and type of Aβ structure formed.

First the researchers determined that the probe did not affect the final Aβstructures obtained by a TEM image comparison to ThT Aβ under various conditions (see Figure 1 below). They also showed that the rate of Aβ formation stayed the same. Because the HiLyte probe does not affect the normal Aβ function, they could then use the probe under biological conditions not accessible to ThT.

They found that they were able to detect fibrils under biological conditions (Figure 2a below), oligomers under endosomal conditions (Figure 2bbelow) and ADDLs (early precursor structures that occur at low Aβ concentrations). Each of these Aβ structures produced a different fluorescent signature, allowing them to be distinguished from each other. This ability to detect the different Aβ assembly rates will allow researchers to better characterize biological samples, hopefully leading to new treatment options for Alzheimer’s disease.

Fig 2: (a,b) Transmission electron micrographs of negatively stained Ab555


Read Samuel & Penedo et al’s HOT paper by following the link below!

DOI: 10.1039/C3MB70272C

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Proteomics 2013 themed issue online now!

The Proteomics 2013 issue is introduced by the President of the Italian Proteomics Association Andrea Urbani et al. following on from the ItPA meeting in June 2012.

This is followed by an Opinion piece from Matthias Gstaiger and Ruedi Aebersold at ETH Zurich, Switzerland, on the increasing understanding of genotype-phenotype relationships due to deciphering proteome organisation.

Digital and analogical reality in proteomics investigation
Andrea Urbani, Massimo Castagnola, Mauro Fasano, Luca Bini, Alessandra Modesti, Anna Maria Timperio and Paola Roncada 
DOI: 10.1039/C3MB90013D

Genotype–phenotype relationships in light of a modular protein interaction landscape
Matthias Gstaiger and Ruedi Aebersold 
DOI: 10.1039/C3MB25583B


 

Amongst the three review articles in this Proteomics themed issue, a HOT review article by Jorg Stulke et al. at Georg-August-Universitat Gottingen, Germany, is featured on the front cover. This review taking a fresh look at the genes and proteins of Bacillus subtilis was featured on the blog recently. It highlights the difficulties with defining the essential genes of a particular organism.

Essential genes in Bacillus subtilis: a re-evaluation after ten years
Fabian M. Commichau, Nico Pietack and Jörg Stülke 
DOI: 10.1039/C3MB25595F


 

The inside front cover features work from Damiana Pieragostino et al. in Italy in which shotgun proteomics is used to provide a profile of the proteins in the tears of patients with primary open angle glaucoma. They find a mix of inflammatory proteins as possible biomarkers for early diagnosis of the disease, which is a major global cause of blindness.

Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma naïve to therapy
Damiana Pieragostino, Luca Agnifili, Vincenzo Fasanella, Simona D’Aguanno, Rodolfo Mastropasqua, Carmine Di Ilio, Paolo Sacchetta, Andrea Urbani and Piero Del Boccio
DOI: 10.1039/C3MB25463A


 

The Proteomics issue is packed with more reviews, communications, a Method article and several HOT articles, see the full contents list here.

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MBS Issue 5 online! Focus on Chemical Biology in Asia

Coinciding with the 70th anniversary of the discovery of streptomycin, Issue 5 puts the focus on chemical biology research in Asia, beginning with an editorial from guest editors Minoru Yoshida, Seung Bum Park and Charles Boone. This issue contains 24 top articles from chemical biologists working in Asia.

Focus on chemical biology in Asia
Minoru Yoshida, Seung Bum Park and Charles Boone
DOI: 10.1039/C3MB90008H

The outside front cover highlights work from Pohang University of Science and Technology on overcoming the difficulties in delivering oligonucleotides to specific tissues using estrone-conjugated siRNAs.

Tissue specific delivery of estrone-conjugated siRNAs
Eun-Kyoung Bang, Eun Mi Jeon, Wanil Kim, Kyung-Ha Lee, Kyong-Tai Kim and Byeang Hyean Kim
DOI: 10.1039/C2MB25258A

A communication from Junko Ohkanda et al. at Osaka University is featured on the inside front cover. The researchers improve the efficiency of protein-protein interaction inhibitors by 200% using 14-3-3 peptides. This article was the subject of a blog post in January, read it here for further explanation.

Chemical ligation of epoxide-containing fusicoccins and peptide fragments guided by 14-3-3 protein
Toshio Maki, Akie Kawamura, Nobuo Kato and Junko Ohkanda
DOI: 10.1039/C2MB25388G

There are several intriguing review articles in Issue 5, including three HOT reviews:

Chemical biology-based approaches on fluorescent labeling of proteins in live cells
Deokho Jung, Kyoungmi Min, Juyeon Jung, Wonhee Jang and Youngeun Kwon
DOI: 10.1039/C2MB25422K

Small-molecular modulators of cancer-associated epigenetic mechanisms
Yukihiro Itoh, Takayoshi Suzuki and Naoki Miyata
DOI:10.1039/C3MB25410K

Synthetic cysteine surrogates used in native chemical ligation
Clarence T. T. Wong, Chun Ling Tung and Xuechen Li
DOI: 10.1039/C2MB25437A

Plus plenty more HOT primary research articles:

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

Innate immunomodulation by lipophilic termini of lipopolysaccharide; synthesis of lipid As from Porphyromonas gingivalis and other bacteria and their immunomodulative responses
Yukari Fujimoto, Atsushi Shimoyama, Akinori Saeki, Naohiro Kitayama, Chika Kasamatsu, Hiroko Tsutsui and Koichi Fukase
DOI: 10.1039/C3MB25477A

Read the issue in full

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Themed Issue 4 online now! Reviews from the Editorial and Advisory Board members

The fun outside front cover features the contribution of Seung Bum Park, MBS Associate Editor based at Seoul National University, Korea, to this month’s special issue featuring work from many of our Editorial and Advisory Board members. Seung Bum Park and colleagues review methods for identifying the targets of bioactive small molecules, the difficulties faces and the new shift towards covalent bonds via use of chemoreactive groups changing the nature of target protein identification.

From noncovalent to covalent bonds: a paradigm shift in target protein identification
Jongmin Park, Minseob Koh and Seung Bum Park
DOI: 10.1039/C2MB25502B

Editorial Board member Ulrike Eggert and colleague Xin Zhang review the more unusual, overlooked functions of G protein-coupled receptors in cells, such as in membrane trafficking and cell division in addition to their more widely known roles in cell signalling.

Non-traditional roles of G protein-coupled receptors in basic cell biology
Xin Zhang and Ulrike S. Eggert
DOI: 10.1039/C2MB25429H

Wilfred Weber, also a member of the Editorial Board, and Jonrad Muller at University of Freiburg, Germany, provide a fascinating look at how we can control biological processes in mammalian cells by the manipulation of light using optogenetic tools in their review article:

Optogenetic tools for mammalian systems
Konrad Müller and Wilfried Weber
DOI: 10.1039/C3MB25590E

 

These are just a couple of examples of the high quality review articles produced by board members past and present for this themed issue. Have a look at the whole issue here to see the ones that are of interest to you.

This issue also still contains plenty of high quality primary research articles in chemical biology, -omics and systems biology, including several HOT communications and articles such as:

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

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

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HOT article: A new antibacterial drug target? Investigation of chalcone 4-HD’s mechanism of action

The need for the discovery of more effective antibacterial agents is well-known and there are many different mechanisms by which antibacterial agents can act. One such way is by inhibiting protein biosynthesis in the bacteria. This can be achieved by interrupting the pathway by which amino-acyl-tRNA synthetase enzymes (AARS) catalyse the reaction between an amino acid and its tRNA.

Just one compound that inhibits these enzymes has made it to clinical settings and resistance against it is increasing.

Chalcones are natural product compounds that have been shown to have activity against tumors and bacteria. 4-HD is one such chalcone with antibacterial activity that has been well-studied recently. However no definite conclusions have been drawn regarding its mechanism of action and its biological targets are yet to be identified.

Researchers led by Stephan Sieber at Technische Universität München, Germany, attempt to discover the binding mode and bacterial targets of 4-HD in this HOT article:

Target profiling of 4-hydroxyderricin in S. aureus reveals seryl-tRNA synthetase binding and inhibition by covalent modification
Oliver A. Battenberg, Yinliang Yang, Steven H. L. Verhelst and Stephan A. Sieber
DOI: 10.1039/C2MB25446H

The team derive a molecular probe from 4-HD, introducing an alkyne group to identify the target downstream, using activity based protein profiling (ABPP) and MS identification. They characterise 4-HD and their probe using a chemical biology approach in bacteria S. aureus. The alkyne tag did not change the potent antibacterial effect or binding preferences of the chalcone.

chalcone, antibacterialA novel aspect of their procedure is the chemical linker they utilise in order to avoid decomposition of the probe during its release from biotin beads with heat treatment. The linker (Rh-biotin-diazo-N3) meant the biotin-bound proteins could be cleaved specifically and gently with sodium hydosulfite.

They conclude that the enzyme seryl-tRNA synthestase (STS) is inhibited by the probe, pointing to a possible mechanism of action for 4-HD. STS is part of the peptide biosynthesis pathway. None of this enzyme’s five cysteine residues has previously been shown to be necessary for catalysis and in this HOT article the team conclude that more than one is needed for binding. The team demonstrate that a mutation of any one of the five cysteine residues is enough to interrupt the pathway and result in antibacterial activity.

This HOT article was featured on the outside front cover of Issue 3

– read the article, which was made free to access for 6 weeks*, in full here

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

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Issue 3 online! Microdomain disruption, motifs in metabolism, H1N1, cell–cell communication and more…

The outside front cover features work from Stephan Sieber et al. at the Center for Integrated Protein Science, Germany, where they characterise an antibacterial chalcone and a probe derived from it using a chemical biology approach to look at the binding mode and bacterial targets.

Target profiling of 4-hydroxyderricin in S. aureus reveals seryl-tRNA synthetase binding and inhibition by covalent modification
Oliver A. Battenberg, Yinliang Yang, Steven H. L. Verhelst and Stephan A. Sieber
DOI: 10.1039/C2MB25446H


Work from Santiago Schnell et al. is highlighted on the colourful inside front cover. The researchers from University of Michigan present a thorough demonstration that the distribution and abundance of motifs in metabolic networks can indicate differences in biological functions between species.

Network motifs provide signatures that characterize metabolism
Erin R. Shellman, Charles F. Burant and Santiago Schnell
DOI: 10.1039/C2MB25346A


This issue contains a review article from Michelle Hill et al. at The University of Queensland in which they discuss the potential of using a systems approach to effectively study microdomains in membranes and how disruption of these microdomains has an effect on the whole cell. The look at the insights this could provide over looking at the microdomain in the membrane only.

Ripples in the pond – using a systems approach to decipher the cellular functions of membrane microdomains
Kerry L. Inder, Melissa Davis and Michelle M. Hill
DOI: 10.1039/C2MB25300C


There are of course a number of HOT articles in Issue 3:

Discovery and optimization of triazine derivatives as ROCK1 inhibitors: molecular docking, molecular dynamics simulations and free energy calculations
Mingyun Shen, Shunye Zhou, Youyong Li, Peichen Pan, Liling Zhang and Tingjun Hou
DOI: 10.1039/C2MB25408E

Pathway Pattern-based prediction of active drug components and gene targets from H1N1 influenza’s treatment with maxingshigan-yinqiaosan formula
Wen Dai, Jianxin Chen, Peng Lu, Yibo Gao, Lin Chen, Xi Liu, Jianglong Song, Haiyu Xu, Di Chen, Yiping Yang, Hongjun Yang and Luqi Huang
DOI: 10.1039/C2MB25372K

Inhibition mechanism exploration of quinoline derivatives as PDE10A inhibitors by in silico analysis
Qian Wu, Qingping Gao, Huanmei Guo, Dan Li, Jinghui Wang, Weimin Gao, Chunxiao Han, Yan Li and Ling Yang
DOI: 10.1039/C2MB25501D

A system mathematical model of a cell–cell communication network in amyotrophic lateral sclerosis
Hongwei Shao, Ying He, King C. P. Li and Xiaobo Zhou
DOI: 10.1039/C2MB25370D

 

Read the rest of the issue here!

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Mystery of the plague-causing bacteria

Despite being one of the most deadly human pathogens, the reason why plague-causing bacteria Yersinia pestis (YP) are so aggressive remains a mystery. It is even more perplexing that YP’s extremely close relative with which it shares 97% of its genetic material, Yersinia pseudotuberculosis (YPT), is no more dangerous than an annoying stomach ache.

Different Yersinia strains share quite a lot of common features responsible for their virulence. At the same time, each Yersinia strain has a package of specific genes which contribute to their pathogenesis. However scientists believe that these overt genetic differences do not fully explain the differences between Yersinia strain behaviours.

This recent paper published by Joshua Adkins and colleagues in the USA featured on the front cover of Molecular BioSystems Issue 1 attempts to shed some light on the matter of inter-Yersinia differences. They used a systems approach to look at differences in gene expression, protein levels and metabolites between the two strains in conditions that simulated infection.

The deadly YP expressed 70 more genes than YPT. Most of these genes are located on the virulence-regulating plasmid shared by all Yersinia strains. Higher expression of these genes in YP was only the first clue that the researchers might be on the right track.

The authors next looked at the levels of proteins encoded by these differentially expressed genes. At the proteomic level the differences in Yersinia strains behaviour during infection were even more striking – where previously genes were only slightly less expressed in YPT, there now was a complete lack of protein product.

Finally, the researchers tested the levels of glutamate and found that there was much more of it in YP than YPT, while at the same time there was no difference in the levels of enzymes involved in glutamate metabolism. This, the authors say, suggests that the difference here is caused not by genes or their expression, nor by protein levels, but by the changes that happen to proteins post-translation.

Adkins and colleagues’ results show that pathogenesis of the different Yersinia strains is governed by a multi-level virulence-regulation mechanism, much more complex than we would have expected. The mystery of  Yersinias’ virulence is only just starting to unravel.

As all of our HOT articles are free to access for 4 weeks and cover articles are free for 6 weeks*, you can read all about it now:

A multi-omic systems approach to elucidating Yersinia virulence mechanisms
J. N. Adkins et al.
DOI: 10.1039/C2MB25287B

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

Published on behalf of Rafal Marszalek, Molecular BioSystems web science writer. Rafal is an Assistant Editor of Genome Biology at BioMed Central

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Issue 1 – Charles Boone editorial and profiling pathogens

The front cover of Issue 1 2013 features research from a team of scientists in the USA led by Joshua Adkins at Pacific Northwest National Laboratory.

The bacteria Yersinia pestis, which causes plague, and Yersinia pseudotuberculosis, a non-fatal gastrointestinal pathogen, are genetically extremely similar but have starkly different modes of transmission and pathogenecities. The researchers carried out a systems biology approach using transcriptomic and proteomic profiling to find out the differences in mechanism between a highly lethal pathogen transmitted by a flea bite and its milder relation transmitted via the fecal oral route. They found evidence that the differences are due to differential expression of genes common to both, not just the presence of species-specific genes.

A multi-omic systems approach to elucidating Yersinia virulence mechanisms
J. N. Adkins et al.
DOI: 10.1039/C2MB25287B


Inside Issue 1, Editorial Board Chair Charles Boone has written an Editorial considering the promising future of Molecular BioSystems for our readers and authors.

He highlights particular developments that will bear fruit in 2013, including new e-developments, Open Access options, themed issues and conference attendance. Importantly, his editorial includes a thank you to all of our reviewers who continue to make a vital contribution to increasing the quality of the journal.

Simplifying the author and reader experience
Charles Boone
DOI: 10.1039/C2MB90047E

 


 Other HOT articles in the first issue of 2013

Influence of glucose on the human serum albumin–flavone interaction and their antioxidant activity
Shaolong Du, Yixi Xie and Xiaoqing Chen
DOI: 10.1039/C2MB25351H

Prediction of active sites of enzymes by maximum relevance minimum redundancy (mRMR) feature selection
Yu-Fei Gao, Bi-Qing Li, Yu-Dong Cai, Kai-Yan Feng, Zhan-Dong Li and Yang Jiang
DOI: 10.1039/C2MB25327E

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Issue 12 – proteome alterations in retinal pigmented epithelium cells and its relevance to diabetic retinopathy and a metabolomics study to sub-classify COPD patients

Issue 12’s front cover features work from Hong-Lin Chan and co-workers at the National Tsing Hua University in Taiwan.

In their study, the group identified in a retinal pigmented epithelium cell line 56 proteins that showed significant changes in protein expression, and 33 proteins showing significant changes in thiol reactivity, in response to high glucose concentration. Further investigations identified specific proteins that showed type 2 diabetic retinopathy-dependent alterations. The authors hope that some of the proteins could be targets for the prognosis and diagnosis of diabetic retinopathy.

High glucose-induced proteome alterations in retinal pigmented epithelium cells and its possible relevance to diabetic retinopathy
You-Hsuan Chen, Jing-Yi Chen, Yi-Wen Chen, Szu-Ting Lin and Hong-Lin Chan
DOI: 10.1039/C2MB25331C

The inside front cover comes from Baljit Ubhi and colleagues from the UK, Malaysia, China and the USA.

Working as part of the ECLIPSE (Evaluation of Chronic obstructive pulmonary disease to Longitudinally Identify Predictive Surrogate Endpoints) study, the authors used quantitative LC-MS/MS to measure 34 amino acids and dipeptides, and used these to stratify COPD patient groups. The technique was able to distinguish GOLD IV patients from controls, patients with and without emphysema and patients with and without cachexia. The authors predict that the technique could be used to stratify patients for the treatment of COPD, and ‘may provide a means of assessing response to therapy‘.

Targeted metabolomics identifies perturbations in amino acid metabolism that sub-classify patients with COPD
Baljit K. Ubhi, Kian Kai Cheng, Jiyang Dong, Tobias Janowitz, Duncan Jodrell, Ruth Tal-Singer, William MacNee, David A. Lomas, John H. Riley, Julian L. Griffin and Susan C. Connor
DOI: 10.1039/C2MB25194A

Other HOT articles in the issue include:

Estrogen Receptor α/β–cofactor motif interactions; interplay of tyrosine 537/488 phosphorylation and LXXLL motifs
Hoang D. Nguyen, Trang T. P. Phan, Maelle Carraz and Luc Brunsveld
DOI: 10.1039/C2MB25257K

Ter-dependent stress response systems: novel pathways related to metal sensing, production of a nucleoside-like metabolite, and DNA-processing
Vivek Anantharaman, Lakshminarayan M. Iyer and L. Aravind
DOI: 10.1039/C2MB25239B

Read the full issue here.

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Issue 9 – featuring a RNA-based system for performing Boolean logic computation and the spatial mapping of alkaloids in marine sponge

This month’s outside front cover features work from Jörg Hartig and co-workers at the University of Konstanz, Germany. In their paper, they introduce ‘a highly modular RNA-based system for performing Boolean logic computation at a post-transcriptional level in Escherichia coli‘.

The team use AND, NOR and ANDNOT logic gates in increasingly complex ways for conditional gene expression.

Post-transcriptional Boolean computation by combining aptazymes controlling mRNA translation initiation and tRNA activation
Benedikt Klauser, Athanasios Saragliadis, Simon Ausländer, Markus Wieland, Michael R. Berthold and Jörg S. Hartig
DOI: 10.1039/C2MB25091H


Work from Anthony Carroll and colleagues from Griffith University and Mater Hospital Services, Australia, features on the inside front cover. In their paper, they used MALDI mass spectrometry imaging to spatially map the distribution of brominated pyrrole-2-aminoimidazole (B-P-2-AI) alkaloids in the marine sponge Stylissa flabellata.

The team found that different B-P-2-AIs had different microchemical environments, and feel that the findings could mean that the method is used for targeting micro-regions of sponge specifically to investigate ‘symbiotic microbial candidates or genes that may be involved in the production of the correlated compounds’.

High resolution spatial mapping of brominated pyrrole-2-aminoimidazole alkaloids distributions in the marine sponge Stylissa flabellata via MALDI-mass spectrometry imaging
Jennifer E. Yarnold, Brett R. Hamilton, David T. Welsh, Gertruida F. Pool, Deon J. Venter and Anthony R. Carroll
DOI: 10.1039/C2MB25152C


Also featured in this issue are a review focusing on gene relevance networks, and HOT papers investigating the interactions between MIF and phenolic hydrazones and the metabolite analyses of Dupuytren’s disease.

Read the rest of the issue here

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