Archive for the ‘Cover articles’ Category

Non-linear EGFR pathway has linear response to ligand (say that five times fast)

The authors of the cover article for the August 2014 issue of Integrative Biology explore how extracellular signals are transmitted into the cells for the epidermal growth factor (EGF) pathway. In addition to shedding light on the complex nature of the EGFR pathway, this work provides insights that could be used to further understand mutations that cause cancerous cells to form. Signalling pathways, especially those involving growth factors, are often causes of the excessive growth and division rates of cancer cells

Cover Image, Integrative Biology August 2014

Extracellular signalling pathways are important for cell growth, division and death (apoptosis), but are difficult to study due to their transient nature and the presence of feedback loops. The epidermal growth factor (EGF) pathway also feeds into the MAPK signal cascade, so the quantitative responses of the cell to the initial signal is difficult to determine experimentally. Once the extracellular signal molecule (here EGF) binds to its receptor (EGFR), the cell acts on the signal, and then the original ligand is degraded. Further, the receptors themselves can be made and recycled during this process, adding another layer of complexity.

Figure 1A: The EGFR pathway

The researchers investigated the activation of the EGF receptor itself both experimentally and using a mathematical model (outlined in the paper). Using their mathematical model they predicted that the activation of EGFR (by phosphorylation) should be linearly related to the concentration of ligand EGF which binds to the cell. They then took serum starved cells, added varying concentrations of EGF and determined the amount of phosphorylated EGFR by high-throughput imaging of the immunofluorescence level. They determined that the activation level of the ligand was directly proportional to the ligand concentration, in agreement with the mathematical model.

Figure 4, bottom left panel: The linear relationship between receptor activation level and the amount of EGF added.

The study also showed that the activation of EGFR does not depend on the receptor turnover rate, the ligand binding affinity or the number of receptors available. The methods reported here could be used to describe other extracellular signalling pathways in future, leading to a greater understanding of these complicated and crucial systems.

Download the full article for free* until 21st October 2014!

The EGFR demonstrates linear signal transmission

Diego A. Oyarzun, Jo L. Bramhall, Fernando Lopez-Caamal, Frances M. Richards, Duncan I Jodrell, and Ben-Fillippo Krippendorff

DOI: 10.1039/c4ib00062e

*Access is free through a registered RSC account – click here to register

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Issue 5 now online! 3D cell culture, systems medicine, single-molecule imaging and more high impact Integrative Biology research

The research highlighted by this week’s front cover artwork comes from Hexin Chen and Qian Wang et al. at the University of South Carolina, USA.  This cover article was featured on the blog last week and will now be free to access for the next 6 weeks*. The team are focused on how 3D culture conditions affects cancer cell behaviour. In this cover article, they study the effect of fibrous scaffolds, discovering that the epithelial-to-mesenchymal transition of the MCF-7 cells is enhanced.

Expansion of breast cancer stem cells with fibrous scaffolds
Sheng Feng, Xinrui Duan, Pang-Kuo Lo, Shou Liu, Xinfeng Liu, Hexin Chen and Qian Wang
DOI: 10.1039/C3IB20255K


 

Issue 5 includes a review article from Editorial Board member Philip Day at University of Manchester, UK, and Ehsan Ghayoor Karimiani, Mashhad University of Medical Sciences, Iran. They review the impact of quantitative single cell measurements on future therapies for haematological malignancies. This article was also the subject of an interesting April blog post, which you could read now for a brief idea of what this interesting review covers.

Personalised treatment of haematological malignancies through systems medicine based on single molecules in single cells
Ehsan Ghayoor Karimiani and Philip Day
DOI: 10.1039/C3IB20258E    


 

You will also find a tutorial review on single molecule imaging (featured on the blog here) and of course highly significant primary research and two Technical Innovations in this month’s issue of Integrative Biology:

Single-molecule imaging in vivo: the dancing building blocks of the cell
Miguel Coelho, Nicola Maghelli and Iva M. Tolić-Nørrelykke 
DOI: 10.1039/C3IB40018B

A model of membrane contraction predicting initiation and completion of bacterial cell division
Claire E. Dow, Alison Rodger, David I. Roper and Hugo A. van den Berg
DOI: 10.1039/C3IB20273A

Three-dimensional photolithographic micropatterning: a novel tool to probe the complexities of cell migration
Joseph C. Hoffmann and Jennifer L. West
DOI: 10.1039/C3IB20280A

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

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Issue 4 online! EGF receptor cluster study, dynamic study of NK cells and large scale adjuvant screening

Issue 4 is online is here with these three fascinating articles featured on the cover. All of our cover articles are free to access for 6 weeks*!

A technical innovation from Björn Önfelt and colleagues at Royal Institute of Technology, Karolinska Institute and Science for Life Laboratory, Sweden, is highlighted on the outside front cover. They enable real-time, dynamic study of immune synapse formation and the cytotoxicity of natural killer cells, as individual NK cells in a population have different cytotoxic responses. The method is an assay using ultrasound-assisted cell–cell aggregation in a multi-well chip. The ultrasound allows the timing and positioning of the aggregation to be controlled and interaction between NK cells can be induced mimicking biological forces.

Live cell imaging in a micro-array of acoustic traps facilitates quantification of natural killer cell heterogeneity
Athanasia E. Christakou, Mathias Ohlin, Bruno Vanherberghen, Mohammad Ali Khorshidi, Nadir Kadri, Thomas Frisk, Martin Wiklund and Björn Önfelt
DOI: 10.1039/C3IB20253D


 

Following on from this, an article focused on a nanoimmunoassay on a microfluidic chip for vaccine adjuvant screening is featured as the inside front cover. The work led by Jeffrey Hubbell and Sebastian Maerkl at EPFL, Switzerland, is aimed at large scale, high-throughput biomarker quantification using a microarray robot. The reagents cost 1000 times less than those for traditional ELISA and low sample volumes of only a few nanolitres are required.

A high-throughput nanoimmunoassay chip applied to large-scale vaccine adjuvant screening
Jose L. Garcia-Cordero, Chiara Nembrini, Armando Stano, Jeffrey A. Hubbell and Sebastian J. Maerkl
DOI: 10.1039/C3IB20263A


 

The back cover illustrates the work of Khalid Salaita, Emory University, USA. The paper by Salita et al. looks at the assembly of the epidermal growth factor receptor (EGFR) into clusters after EGF has bound. Despite the wide study of EGF, the role of the clusters was previously unknown. To do this, they quantify the difference in phosphorylation of EGFR when the binding occurs on mobile (nanopatterned supported lipid bilayer) versus immobile (glass slide) surfaces. This is to control the clustering and assess the activation levels of the receptors able to cluster compared to those constrained from clustering normally. They find that cluster size affects receptor phosphorylation. This biological insight, interesting in itself, will be useful for surface-tethering in biomaterials.

Manipulating the lateral diffusion of surface-anchored EGF demonstrates that receptor clustering modulates phosphorylation levels
D. Stabley, S. Retterer, S. Marshall and K. Salaita
DOI: 10.1039/C3IB20239A

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

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Mechanobiology, stem cells, predicting chemoresistance, retinopathy analysis and chemoattractant effects all in Integrative Biology Issue 3, online now!

The outside front cover of this month’s issue showcases a Frontier article from Yubing Sun and Jianping Fu at the University of Michigan on mechanobiology and stem cells, which was also featured in a recent blog post. They highlight just how vital understanding of the mechano-sensitive properties of stem cells is to being able to explore the abilities of stem cells. As a cover article, this is now free to access for 6 weeks*:

Mechanobiology: a new frontier for human pluripotent stem cells
Yubing Sun and Jianping Fu
DOI: 10.1039/C2IB20256E


This issue contains an important contribution from the team of Douglas Lauffenburger, Chair of the Editorial Board, at MIT, USA, in which they demonstrate the ability to characterise quantitative data on phenotypic behaviour of individual endothelial cells in response to angiogenesis signalling and relate it to overall population behaviour.  They show that the behaviour of microvascular endothelial cells in a single population is heterogeneous and cannot be assumed to be the same for all cells in a given condition.

Endothelial cell phenotypic behaviors cluster into dynamic state transition programs modulated by angiogenic and angiostatic cytokines
Tharathorn Rimchala, Roger D. Kamm and Douglas A. Lauffenburger
DOI: 10.1039/C2IB20090B


There are a number of other HOT articles, including:

An integrative network inference approach to predict mechanisms of cancer chemoresistance
Paola Lecca
DOI: 10.1039/C2IB20205K

Read the recent blog post on this article here!

Non-dimensional analysis of retinal microaneurysms: critical threshold for treatment
Elishai Ezra, Eliezer Keinan, Yossi Mandel, Michael E. Boulton and Yaakov Nahmias
DOI: 10.1039/C3IB20259C

Read the recent blog post on this article here!

Convolution of chemoattractant secretion rate, source density, and receptor desensitization direct diverse migration patterns in leukocytes
Yana Wang and Darrell J. Irvine
DOI: 10.1039/C3IB20249F

 For the full online contents list, click here!

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

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Issue 2 Online Now! MSCs, microbial evolution, investigating vascular disease, model protocells and much more innovative biological research

ABC transporter

The front cover of this month’s issue highlights work by Valerică Raicu et al. on determining the dynamic structure of an important transmembrane transporter protein complex using FRET. This interesting HOT article is also the subject of the previous IBiology blog post.

Determination of the quaternary structure of a bacterial ATP-binding cassette (ABC) transporter in living cells
Deo R. Singh, Mohammad M. Mohammad, Suparna Patowary, Michael R. Stoneman, Julie A. Oliver, Liviu Movileanu and Valerică Raicu
DOI: 10.1039/C2IB20218B

 

 


microbial evolution

The first critical review in Issue 2 comes from Vadim Mozhayskiy and Ilias Tagkopoulos at the UC Davis Genome Center, USA. They take a critical look at in vivo and in vitro methods of studying microbial evolution and this absorbing review was also highlighted on the IBiology blog very recently.

Microbial evolution in vivo and in silico: methods and applications
Vadim Mozhayskiy and Ilias Tagkopoulos
DOI: 10.1039/C2IB20095C

 

 


intravital microscopy

Viviany Taqueti and Farouc Jaffer at Harvard Medical School, USA, review the developments in using high-resolution molecular imaging and intravital microscopy to investigate vascular disease in their fascinating critical review, which was also highlighted on the blog this January.

High-resolution molecular imaging via intravital microscopy: illuminating vascular biology in vivo
Viviany R. Taqueti and Farouc A. Jaffer
DOI: 10.1039/C2IB20194A

 

 


mechanotransduction

Marco Cecchini et al. critically review how mechanotransduction affects cell biology, using the mechanical inputs that can regulate mesenchymal stromal cells as a case in point. MSCs have great potential in biomedical applications, including transplantation; therefore this review is of importance as it covers the controversy in the literature surrounding their characterisation and use in different tissues.

 Endothelial differentiation of mesenchymal stromal cells: when traditional biology meets mechanotransduction
Orazio Vittorio, Emanuela Jacchetti, Simone Pacini and Marco Cecchini
DOI: 10.1039/C2IB20152F

 

 


microspectroscopy

Pedro Roda-Navarro at Universidad Complutense de Madrid, Spain summarises how microspectroscopy can now unveil the complexities of the molecular dynamics at the immunological synapse. This review also extends to how we can obtain quantitative information about the biochemical reactions in living cells, including quantitative imaging and theory.

 Microspectroscopy reveals mechanisms of lymphocyte activation
Pedro Roda-Navarro
DOI: 10.1039/C2IB20190A

 

 


model protocells

There are of course plenty of innovative primary research articles in this month’s issue, including HOT articles such as:

Theoretical conditions for the stationary reproduction of model protocells
Fabio Mavelli and Kepa Ruiz-Mirazo
DOI: 10.1039/C2IB20222K

 


 Intrigued? Browse the full issue here

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Issue 1 – Focus for 2013 and Cancer Nanotechnology Themed Issue

Welcome to a packed issue of Integrative Biology to begin the New Year!

Issue 1 begins with an editorial from Doug Lauffenburger, Chair of the Editorial Board in which he emphasises the focus of Integrative Biology in providing a ‘New Look at Biology’ and the interdisciplinary way in which our articles approach biological questions, opening up new lines of research and providing a platform for work that pushes known boundaries and conventions.

Our new look at biology
Douglas A. Lauffenburger
DOI: 10.1039/C2IB90056D


Guest Editor Piotr Grodzinski introduces the themed issue on Cancer Nanotechnology in his editorial, the aim of which is to present a select few articles that illustrate the ability of interdisciplinary work to answer biological problems, ultimately producing practical answers for clinical settings.

Themed issue on Cancer Nanotechnology
Piotr Grodzinski
DOI: 10.1039/C2IB90050E


The front cover of this themed issue features a Frontier Review from Steven Millward et al. providing a selective and critical look at the integration of in situ click chemistry with solid phase peptide libraries for ligand design.

In situ click chemistry: from small molecule discovery to synthetic antibodies
Steven W. Millward, Heather D. Agnew, Bert Lai, Su Seong Lee, Jaehong Lim, Arundhati Nag, Suresh Pitram, Rosemary Rohde and James R. Heath
DOI: 10.1039/C2IB20110K


On the inside front cover, a fascinating perspective by Alexander Stegh is highlighted on the progress towards personalized cancer nanomedicine and the large number of future challenges still faced to turn it into reality.

Toward personalized cancer nanomedicine – past, present, and future
Alexander H. Stegh
DOI: 10.1039/C2IB20104F


The work of the Nanotechnology Characterization Laboratory at the Frederick National Laboratory for Cancer Research, USA, is illustrated and described on this issue’s back cover. Read the perspective by Scott McNeil et al. here:

Common pitfalls in nanotechnology: lessons learned from NCI’s Nanotechnology Characterization Laboratory
Rachael M. Crist, Jennifer Hall Grossman, Anil K. Patri, Stephan T. Stern, Marina A. Dobrovolskaia, Pavan P. Adiseshaiah, Jeffrey D. Clogston and Scott E. McNeil
DOI: 10.1039/C2IB20117H


 

Issue 1 of 2013 is full of interesting editorials, reviews and primary research in the field of Cancer Nanotechnology, so why not take a look now here? Cover articles are free to access for 6 weeks!*

*Free access is provided to recognised institutions or to individuals through an RSC Publishing Personal Account. Registration is quick and easy at http://pubs.rsc.org/en/account/register.

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Issue 10 – tissue morphogenesis, natural killer cells and the NDRG4 gene

This month’s issue features work from Wesley Legant, Christopher Chen and Viola Vogel on the front cover.

The article uses microfabricated tissue gauges and Foerster Radius Energy Transfer (FRET) labeled biosensors to investigate the fibronectin assembly and matrix remodeling in a 3D microtissue model of tissue morphogenesis.

Force-induced fibronectin assembly and matrix remodeling in a 3D microtissue model of tissue morphogenesis
Wesley R. Legant, Christopher S. Chen and Viola Vogel
DOI: 10.1039/C2IB20059G


On the inside front cover, work from the USA is featured. In their article, Christopher Love and colleagues from the Massachusetts Institute of Technology and Harvard discuss their use of nanowells to monitor individual NK cell–target cell interactions.

Amongst other things, they found that lysis is most likely during an NK cell’s first encounter with a target.

Single-cell analysis of the dynamics and functional outcomes of interactions between human natural killer cells and target cells
Yvonne J. Yamanaka, Christoph T. Berger, Magdalena Sips, Patrick C. Cheney, Galit Alter and J. Christopher Love
DOI: 10.1039/C2IB20167D


The back cover this month features work from Dennis Hallahan, Jerry Jaboin and co-workers. In their article, they show that the down regulation of NDRG4 mRNA and protein expression in two aggressive cancer cell lines resulted in reduced cell survival, DNA fragmentation and G2-M cell cycle arrest.

The authors state the gene ‘may play a valuable role as a molecular target in [the] treatment’ of meningioma.

NDRG4, the N-Myc downstream regulated gene, is important for cell survival, tumor invasion and angiogenesis in meningiomas
Rama P. Kotipatruni, Daniel J. Ferraro, Xuan Ren, Robert P. Vanderwaal, Dinesh K. Thotala, Dennis E. Hallahan and Jerry J. Jaboin
DOI: 10.1039/C2IB20168B


The issue also includes a review from Jun Hu, Chunhai Fan and co-workers on nanomaterials-assisted PCR (nanoPCR) strategies, and their potential applications in genetic analysis (particularly gene typing and haplotyping) and diagnostics:

Genetic analysis with nanoPCR
Dun Pan, Lijuan Mi, Qing Huang, Jun Hu and Chunhai Fan
DOI: 10.1039/C2IB20076G

Read the rest of the issue here. Cover articles are free* to access for 6 weeks!

*Free access is provided to recognised institutions or to individuals through an RSC Publishing Personal Account. Registration is quick and easy at http://pubs.rsc.org/en/account/register.

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Mimicking heart tissue and understanding the spatial development of neurons on the cover of Issue 9

In this month’s issue we have a bumper crop of review articles on topics as varied as nanomedicine for brain repair, giant vesicles as cell models, the effects of curcumin and analogues on breast cancer and altering stem cell behaviour through engineering their microenvironments.

Integrative Biology coverWe also have several HOT articles in the issue, including the outside front cover article by Andre Levchenko and colleagues.  They have used autologous cardiosphere-derived cells and a nanopatterned hydrogel to overcome some of the difficulties associated with stem cell-based methods for heart tissue repair.  Their matrix was found to closely mimic the ECM and  ‘dramatically enhanced’ cardiomyogenesis.

Nanopatterned cardiac cell patches promote stem cell niche formation and myocardial regeneration
Deok-Ho Kim, Kshitiz, Rachel R. Smith, Pilnam Kim, Eun Hyun Ahn, Hong-Nam Kim, Eduardo Marbán, Kahp-Yang Suh and Andre Levchenko
DOI: 10.1039/C2IB20067H

Integrative Biology cover artworkThe inside front cover features work from Joshua Maurer et al who have used self-assembled monolayers to explore whether environment or predetermined factors control axonal development.  They show that a critical factor is environmental – rather than a preprogrammed molecular event – which is the length that a developing neurite is allowed to grow to.

Spatial confinement instigates environmental determination of neuronal polarity
Dawn M. Johnson,  Jad P. Abi-Mansour and Joshua A. Maurer
DOI: 10.1039/C2IB20126G

Don’t forget, our cover articles are free to access for 6 weeks – just sign in with your RSC Publishing Personal account.

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Issue 8 online now!

This month’s outside front cover features work from Jonathan Rocheleau and co-workers at the University of Toronto.

In their article, they introduce a novel method for flavoprotein autofluorescence imaging, to measure the dynamics of fatty acid oxidation linked to pancreatic islet metabolism. They were able to record real-time measurements from islets held stationary in flow using microfluidic devices.

Quantitative imaging of electron transfer flavoprotein autofluorescence reveals the dynamics of lipid partitioning in living pancreatic islets
Alan K. Lam, Pamuditha N. Silva, Svetlana M. Altamentova and Jonathan V. Rocheleau
DOI: 10.1039/C2IB20075A


Work from Konstantinos Konstantopoulos, Kathleen Stebe and colleagues from The Johns Hopkins University and the University of Pennsylvania, was the inspiration for the inside front cover this month.

The article focuses on receptor-mediated cell adhesion in shear flow, and uses an integrated experimental and mathematical approach to gain understanding of the process. Using a microfluidic device combined with a glass slide with P- or L-selectin immobilised onto specific sections, the critical patch length needed by HL-60 leukemic cells to start tethering under flow was investigated. The authors found that the length is prescribed by the minimum number of receptor–ligand bonds needed to start cell tethering and the tensile strength of the bonds.

Selectin-mediated adhesion in shear flow using micropatterned substrates: multiple-bond interactions govern the critical length for cell binding
ZiQiu Tong, Luthur Siu-Lun Cheung, Kathleen J. Stebe and Konstantinos Konstantopoulos
DOI: 10.1039/C2IB20036H


Lance Munn and collaborators at Massachusetts General Hospital and Harvard Medical School’s article features on the back cover of issue 8.

Their paper focuses on vascular anastomosis, and uses a microfluidic device to reproduce the process in vitro. Using a collagenous matrix, the vessels are able to sprout and grow together, forming perfused bridging connections. The authors feel that the device will ‘enable a new generation of studies of the mechanisms of angiogenesis and provide a novel and practical platform for drug screening’.

Anastomosis of endothelial sprouts forms new vessels in a tissue analogue of angiogenesis
Jonathan W. Song, Despina Bazou and Lance L. Munn
DOI: 10.1039/C2IB20061A

Also included in the issue is a review on the role of regucalcin in brain calcium signalling and papers focussing on a method to calculate the change of network metabolites for different time points of transcriptomic datasets and the differential effects of a soluble or immobilized VEGFR-binding peptide.

Read the rest of the issue online here.

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)

Focussing on single islets in type 2 diabetes

Quantitative imaging of electron transfer flavoprotein autofluorescence reveals the dynamics of lipid partitioning in living pancreatic islets A new microscopy technique developed by Alan Lam and colleagues from Toronto could help to reveal more about how pancreatic cells change at the onset of Type 2 diabetes.

It is estimated that around 6 % of the world’s population have Type 2 diabetes, which can be caused by obesity and lack of exercise. β-cells in a diabetic pancreas produce decreased amounts of insulin and are dysfunctional. It is thought that metabolism of glucose and fatty acid could play a role in this dysfunction, but their exact contribution to the pathology is yet to be elucidated.

To start to discover the mechanisms behind this, the authors use microfluidics to isolate single pancreatic islets then use confocal microscopy to look at autofluorescence of the protein flavin as an indication of electron transport chain activity. They then use this setup to characterise redox responses in the islets to fatty acid and glucose metabolism. This work could lead to a deeper understanding of the pathology of diabetes, giving us a better grounding on which to develop more effective treatments and cures.

To find out more about this interesting combination of modern technologies, download the paper here and look out for it in Issue 8!

Quantitative imaging of electron transfer flavoprotein autofluorescence reveals the dynamics of lipid partitioning in living pancreatic islets
Alan K. Lam,  Pamuditha N. Silva,  Svetlana M. Altamentova and Jonathan V. Rocheleau
DOI: 10.1039/C2IB20075A

Digg This
Reddit This
Stumble Now!
Share on Facebook
Bookmark this on Delicious
Share on LinkedIn
Bookmark this on Technorati
Post on Twitter
Google Buzz (aka. Google Reader)