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Παρασκευή 27 Οκτωβρίου 2017

Biophysical Variation within the M1 Type of Ganglion Cell Photoreceptor

Publication date: 24 October 2017
Source:Cell Reports, Volume 21, Issue 4
Author(s): Alan J. Emanuel, Kush Kapur, Michael Tri H. Do
Intrinsically photosensitive retinal ganglion cells of the M1 type encode environmental irradiance for functions that include circadian and pupillary regulation. Their distinct role, morphology, and molecular markers indicate that they are stereotyped circuit elements, but their physiological uniformity has not been investigated in a systematic fashion. We have profiled the biophysical parameters of mouse M1s and found that extreme variation is their hallmark. Most parameters span 1–3 log units, and the full range is evident in M1s that innervate brain regions serving divergent functions. Biophysical profiles differ among cells possessing similar morphology and between neighboring M1s recorded simultaneously. Variation in each parameter is largely independent of that in others, allowing for flexible individualization. Accordingly, a common stimulus drives heterogeneous spike outputs across cells. By contrast, a population of directionally selective retinal ganglion cells appeared physiologically uniform under similar conditions. Thus, M1s lack biophysical constancy and send diverse signals downstream.

Graphical abstract

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Teaser

Emanuel et al. demonstrate that a type of sensory cell with a defined role and morphology nevertheless exhibits log units of variation in its biophysical parameters. Variation drives functional individualization, even in spike outputs, and is fully available to downstream brain regions serving divergent functions.


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Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase Revealed Using High-Throughput Magnetic Tweezers

Publication date: 24 October 2017
Source:Cell Reports, Volume 21, Issue 4
Author(s): David Dulin, Jamie J. Arnold, Theo van Laar, Hyung-Suk Oh, Cheri Lee, Angela L. Perkins, Daniel A. Harki, Martin Depken, Craig E. Cameron, Nynke H. Dekker
RNA viruses pose a threat to public health that is exacerbated by the dearth of antiviral therapeutics. The RNA-dependent RNA polymerase (RdRp) holds promise as a broad-spectrum, therapeutic target because of the conserved nature of the nucleotide-substrate-binding and catalytic sites. Conventional, quantitative, kinetic analysis of antiviral ribonucleotides monitors one or a few incorporation events. Here, we use a high-throughput magnetic tweezers platform to monitor the elongation dynamics of a prototypical RdRp over thousands of nucleotide-addition cycles in the absence and presence of a suite of nucleotide analog inhibitors. We observe multiple RdRp-RNA elongation complexes; only a subset of which are competent for analog utilization. Incorporation of a pyrazine-carboxamide nucleotide analog, T-1106, leads to RdRp backtracking. This analysis reveals a mechanism of action for this antiviral ribonucleotide that is corroborated by cellular studies. We propose that induced backtracking represents a distinct mechanistic class of antiviral ribonucleotides.

Graphical abstract

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Teaser

Dulin et al. find that a prototypical RNA-dependent RNA polymerase (RdRp) visits several states during nucleotide synthesis, of which only one incorporates nucleotide analogs with therapeutic potential. Different analogs exhibit distinct kinetic signatures, with an analog thought to induce chain termination actually promoting RdRp backtracking.


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Understanding Tissue-Specific Gene Regulation

Publication date: 24 October 2017
Source:Cell Reports, Volume 21, Issue 4
Author(s): Abhijeet Rajendra Sonawane, John Platig, Maud Fagny, Cho-Yi Chen, Joseph Nathaniel Paulson, Camila Miranda Lopes-Ramos, Dawn Lisa DeMeo, John Quackenbush, Kimberly Glass, Marieke Lydia Kuijjer
Although all human tissues carry out common processes, tissues are distinguished by gene expression patterns, implying that distinct regulatory programs control tissue specificity. In this study, we investigate gene expression and regulation across 38 tissues profiled in the Genotype-Tissue Expression project. We find that network edges (transcription factor to target gene connections) have higher tissue specificity than network nodes (genes) and that regulating nodes (transcription factors) are less likely to be expressed in a tissue-specific manner as compared to their targets (genes). Gene set enrichment analysis of network targeting also indicates that the regulation of tissue-specific function is largely independent of transcription factor expression. In addition, tissue-specific genes are not highly targeted in their corresponding tissue network. However, they do assume bottleneck positions due to variability in transcription factor targeting and the influence of non-canonical regulatory interactions. These results suggest that tissue specificity is driven by context-dependent regulatory paths, providing transcriptional control of tissue-specific processes.

Graphical abstract

image

Teaser

Understanding gene regulation is important for many fields in biology and medicine. Sonawane et al. reconstruct and investigate regulatory networks for 38 human tissues. They find that regulation of tissue-specific function is largely independent of transcription factor expression and that tissue specificity appears to be mediated by tissue-specific regulatory network paths.


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Scholar : These new articles for Computer-Aided Design and Applications are available online

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Original Articles

Surface detection and modeling of an arbitrary point cloud from 3D sketching
Ariel Schwartz , Ronit Schneor , Gila Molcho & Miri Weiss Cohen
Pages: 1-11 | DOI: 10.1080/16864360.2017.1375673


Channel geometry optimization for vertical axis wind turbines in skyscrapers
Seifeddine Kefi, Ajay Joneja , Tim K.T. Tse & Sunwei Li
Pages: 1-8 | DOI: 10.1080/16864360.2017.1375671


Free access to articles in this Editor's Choice collection from the Journal of Control and Decision. Don't miss it!

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Scholar : These new articles for Voice and Speech Review are available online

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Forum

A case study in coaching challenges: vocal fitness and idiolect in Switzerland
Melissa Agnew & Andrea Moor
Pages: 1-7 | DOI: 10.1080/23268263.2017.1390043


Remembering Rocco Dal Vera
D'Arcy Smith & Julia Guichard
Pages: 1-5 | DOI: 10.1080/23268263.2017.1395595


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Publication date: January 2018
Source:Biomaterials, Volume 150





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Designing immunostimulatory double stranded messenger RNA with maintained translational activity through hybridization with poly A sequences for effective vaccination

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Publication date: January 2018
Source:Biomaterials, Volume 150
Author(s): Satoshi Uchida, Naoto Yoshinaga, Kayoko Yanagihara, Eiji Yuba, Kazunori Kataoka, Keiji Itaka
Messenger (m)RNA vaccines require a safe and potent immunostimulatory adjuvant. In this study, we introduced immunostimulatory properties directly into mRNA molecules by hybridizing them with complementary RNA to create highly immunogenic double stranded (ds)RNAs. These dsRNA formulations, comprised entirely of RNA, are expected to be safe and highly efficient due to antigen expression and immunostimulation occurring simultaneously in the same antigen presenting cells. In this strategy, design of dsRNA is important. Indeed, hybridization using full-length antisense (as)RNA drastically reduced translational efficiency. In contrast, by limiting the hybridized portion to the mRNA poly A region, efficient translation and intense immunostimulation was simultaneously obtained. The immune response to the poly U-hybridized mRNAs (mRNA:pU) was mediated through Toll-like receptor (TLR)-3 and retinoic acid-inducible gene (RIG)-I. We also demonstrated that mRNA:pU activation of mouse and human dendritic cells was significantly more effective than activation using single stranded mRNA. In vivo mouse immunization experiments using ovalbumin showed that mRNA:pU significantly enhanced the intensity of specific cellular and humoral immune responses, compared to single stranded mRNA. Our novel mRNA:pU formulation can be delivered using a variety of mRNA carriers depending on the purpose and delivery route, providing a versatile platform for improving mRNA vaccine efficiency.



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Two cases of occupationally acquired Mycobacterium marinum infection in Chinese restaurant workers in Melbourne, Australia



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Scholar : These new articles for Eating Disorders are available online

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New for Eating Disorders and online now on Taylor & Francis Online:

Prevention Series

Randomized controlled trial of REbeL: A peer education program to promote positive body image, healthy eating behavior, and empowerment in teens
Laura Eickman, Jessica Betts, Lauren Pollack, Frances Bozsik, Marshall Beauchamp & Jennifer Lundgren
Pages: 1-16 | DOI: 10.1080/10640266.2017.1349005


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Scholar : Philosophical Magazine, Volume 97, Issue 34, December 2017 is now available online on Taylor & Francis Online

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Philosophical Magazine, Volume 97, Issue 34, December 2017 is now available online on Taylor & Francis Online.



This new issue contains the following articles:

Part A: Materials Science

Influence of the mode of deformation on recrystallisation kinetics in Nickel through experiments, theory and phase field model
C. N. Athreya, A. Mukilventhan, Satyam Suwas , Srikanth Vedantam & V. Subramanya Sarma
Pages: 3211-3228 | DOI: 10.1080/14786435.2017.1370146


Effects of torsional deformation on the microstructures and mechanical properties of a CoCrFeNiMo0.15 high-entropy alloy
Wenqian Wu, Lin Guo, Bin Liu, Song Ni, Yong Liu & Min Song
Pages: 3229-3245 | DOI: 10.1080/14786435.2017.1369191


Non-singular dislocation continuum theories: strain gradient elasticity vs. Peierls–Nabarro model
Markus Lazar
Pages: 3246-3275 | DOI: 10.1080/14786435.2017.1375608


First principles study of structural, magnetic and electronic properties of CrAs
Carmine Autieri & Canio Noce
Pages: 3276-3295 | DOI: 10.1080/14786435.2017.1375607


A general model for hydrogen trapping at the inclusion-matrix interface and its relation to crack initiation
W. Qin & J. A. Szpunar
Pages: 3296-3316 | DOI: 10.1080/14786435.2017.1378451


Browse articles in this special issue on: 'Advancements in Civil and Structural Engineering'

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Scholar : Behaviour & Information Technology, Volume 36, Issue 11, November 2017 is now available online on Taylor & Francis Online

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Behaviour & Information Technology, Volume 36, Issue 11, November 2017 is now available online on Taylor & Francis Online.



This new issue contains the following articles:

Original Articles

The effect of temporal psychological distance on reliance on word-of-mouth for information about destination image attributes
Wee-Kheng Tan
Pages: 1101-1110 | DOI: 10.1080/0144929X.2017.1349179


Old risks, new challenges: exploring differences in security between home computer and mobile device use
Tanya McGill & Nik Thompson
Pages: 1111-1124 | DOI: 10.1080/0144929X.2017.1352028


Exploring perceptions of data analytics in the internal audit function
Fengchun Tang, Carolyn Strand Norman & Valaria P. Vendrzyk
Pages: 1125-1136 | DOI: 10.1080/0144929X.2017.1355014


Understanding user experience of news applications by Taxonomy of Experience (ToE)
Wen-Chia Wang
Pages: 1137-1147 | DOI: 10.1080/0144929X.2017.1359337


Parental perspectives on children's use of portable digital devices
Katerina Sergi, Ronald Gatewood Jr., Anastasia Elder & Jianzhong Xu
Pages: 1148-1161 | DOI: 10.1080/0144929X.2017.1360941


Assessing the determinants of flow experience in the adoption of learning management systems: the moderating role of perceived institutional support
Ikram Ullah Khan , Zahid Hameed, Yugang Yu & Safeer Ullah Khan
Pages: 1162-1176 | DOI: 10.1080/0144929X.2017.1362475


Altered video task: a non-verbal measure of what-who-where recall in young children
Katarzyna Bobrowicz & Maciej Haman
Pages: 1177-1192 | DOI: 10.1080/0144929X.2017.1364422


An ethnographic study of packaging-free purchasing: designing an interactive system to support sustainable social practices
Amon Rapp, Alessandra Marino, Rossana Simeoni & Federica Cena
Pages: 1193-1217 | DOI: 10.1080/0144929X.2017.1365170


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Scholar : These new articles for Alcheringa: An Australasian Journal of Palaeontology are available online

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Original Articles

A new dysagrionid damselfly (Odonata: Zygoptera: Palaeodysagrion) from mid-Cretaceous Burmese amber
Daran Zheng, Su-Chin Chang & Bo Wang
Pages: 1-5 | DOI: 10.1080/03115518.2017.1381991


Browse papers on image & data fusion, GIS, LiDAR & more in the International Journal of Image and Data Fusion's exclusive Editor's Choice collection.

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Scholar : These new articles for Annals of GIS are available online

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New for Annals of GIS and online now on Taylor & Francis Online:

Original Articles

A fishnet-constrained land use mix index derived from remotely sensed data
Yanqing Xu, Lei Wang, Cong Fu & Tim Kosmyna
Pages: 1-11 | DOI: 10.1080/19475683.2017.1382570


Browse articles in this special issue on: 'Advancements in Civil and Structural Engineering'

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Scholar : These new articles for Atlantic Studies are available online

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New for Atlantic Studies and online now on Taylor & Francis Online:

Original Articles

Crossing oceans: an afterword
Keith L. Camacho
Pages: 1-3 | DOI: 10.1080/14788810.2017.1392071


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Scholar : These new articles for American Review of Canadian Studies are available online

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BOOK REVIEW

Roughneck
Jason Blake
Pages: 1-2 | DOI: 10.1080/02722011.2017.1392059


Mixed blessings: indigenous encounters with Christianity in Canada
Stephanie Pettigrew
Pages: 1-2 | DOI: 10.1080/02722011.2017.1392010


Between Education and Catastrophe: The Battle over Public Schooling in Postwar Manitoba
James Farney
Pages: 1-2 | DOI: 10.1080/02722011.2017.1392012


Time and a Place: An Environmental History of Prince Edward Island
Brian Payne
Pages: 1-2 | DOI: 10.1080/02722011.2017.1392060


The World Won't Wait: Why Canada Needs to Rethink Its International Policies
Rod Clare
Pages: 1-2 | DOI: 10.1080/02722011.2017.1392062


Commemorating Canada: History, Heritage, and Memory, 1850s–1990s
Michelle Desveaux
Pages: 1-2 | DOI: 10.1080/02722011.2017.1392061


Policing and social media: social control in an era of new media
Alexandre Turgeon
Pages: 1-2 | DOI: 10.1080/02722011.2017.1392063


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Scholar : These new articles for The Law Teacher are available online

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New for The Law Teacher and online now on Taylor & Francis Online:

Learning Resources Review

Researching property law, edited by Susan Bright and Sarah Blandy, Palgrave, London, 2016, 205 pp., £31.99 (paperback), ISBN 978-1-137-48789-6
Lisa Woolley
Pages: 1-3 | DOI: 10.1080/03069400.2017.1376945


Policy and Education Developments

Teaching terrorism: the impact of the Counter-Terrorism and Security Act 2015 on academic freedom
Joanna Gilmore
Pages: 1-10 | DOI: 10.1080/03069400.2017.1377025


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Scholar : These new articles for Journal of Clinical and Experimental Neuropsychology are available online

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Original Articles

Auditory attention in autism spectrum disorder: An exploration of volumetric magnetic resonance imaging findings
Sanam J. Lalani , Tyler C. Duffield, Haley G. Trontel, Erin D. Bigler, Tracy J. Abildskov, Alyson Froehlich, Molly B. D. Prigge, Brittany G. Travers, Jeffrey S. Anderson , Brandon A. Zielinski, Andrew Alexander, Nicholas Lange & Janet E. Lainhart
Pages: 1-16 | DOI: 10.1080/13803395.2017.1373746


Routledge Psychology 2017 sponsor of BPS #PsychCrunch podcasts. Access 25 journal articles: http://bit.ly/psychcrunch2017

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The Arthur Prophet Memorial Lecture

British Dental Journal 223, 558 (2017). doi:10.1038/sj.bdj.2017.908



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Reflection

British Dental Journal 223, 549 (2017). doi:10.1038/sj.bdj.2017.894

Author: Stephen Hancocks



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Paediatric dentistry: A multidisciplinary approach

British Dental Journal 223, 551 (2017). doi:10.1038/sj.bdj.2017.895

Author: V. Argent



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Stress and burnout research project

British Dental Journal 223, 559 (2017). doi:10.1038/sj.bdj.2017.912



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Dental notation: Mental gymnastics

British Dental Journal 223, 551 (2017). doi:10.1038/sj.bdj.2017.896

Author: M. J. Trenouth



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Fracture resistance of zirconia-based all-ceramic crowns after bur adjustment

British Dental Journal 223, 587 (2017). doi:10.1038/sj.bdj.2017.918



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Identifying teeth correctly

British Dental Journal 223, 551 (2017). doi:10.1038/sj.bdj.2017.897

Author: V. Kostova



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Community dental team screen factory workers for mouth cancer

British Dental Journal 223, 558 (2017). doi:10.1038/sj.bdj.2017.910

Author: Tami Lampert



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Dental education: A gentle touch

British Dental Journal 223, 552 (2017). doi:10.1038/sj.bdj.2017.898

Author: R. Bettles



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Interview: Say no more... An insight into the Behavioural Insights Team

British Dental Journal 223, 560 (2017). doi:10.1038/sj.bdj.2017.914



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Patient benefits: Incorrect advice

British Dental Journal 223, 552 (2017). doi:10.1038/sj.bdj.2017.899

Author: J. Ballard



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Oral surgery II: Part 3. Cysts of the mouth and jaws and their management

British Dental Journal 223, 573 (2017). doi:10.1038/sj.bdj.2017.916

Authors: C. M. Hill & T. Renton



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From the archive: Sydney turns 100

British Dental Journal 223, 552 (2017). doi:10.1038/sj.bdj.2017.900

Author: P. Grennan



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An estimated carbon footprint of NHS primary dental care within England. How can dentistry be more environmentally sustainable?

British Dental Journal 223, 589 (2017). doi:10.1038/sj.bdj.2017.839

Authors: B. Duane, M. Berners Lee, S. White, R. Stancliffe & I. Steinbach



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Primary dental care: You're not serious

British Dental Journal 223, 552 (2017). doi:10.1038/sj.bdj.2017.901

Author: K. F. Marshall



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Eavesdroppers and nosey neighbours required

British Dental Journal 223, 558 (2017). doi:10.1038/sj.bdj.2017.909



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Alternative sugars: Syrup

British Dental Journal 223, 555 (2017). doi:10.1038/sj.bdj.2017.902

Elaine Gardner, British Dietetic Association (BDA) Spokesperson, discusses the sugar content in syrup and provides related oral health advice.



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Is it time to digitally enable dentistry with the rest of healthcare?

British Dental Journal 223, 559 (2017). doi:10.1038/sj.bdj.2017.911

Author: Tashfeen Kholasi



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Spreading the word about a devastating disease

British Dental Journal 223, 555 (2017). doi:10.1038/sj.bdj.2017.903



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BDA AGM

British Dental Journal 223, 559 (2017). doi:10.1038/sj.bdj.2017.913



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PI3K/Akt/mTOR pathway involvement in regulating growth hormone secretion in a rat pituitary adenoma cell line

Abstract

Purpose

Insulin-like growth factor 1 (IGF1) controls growth hormone (GH) secretion via a negative feed-back loop that may disclose novel mechanisms possibly useful to control GH hyper-secretion. Our aim was to understand whether PI3K/Akt/mTOR pathway is involved in IGF1 negative feedback on GH secretion.

Methods

Cell viability, GH secretion, Akt, and Erk 1/2 phosphorylation levels in the rat GH3 cell line were assessed under treatment with IGF1 and/or everolimus, an mTOR inhitior.

Results

We found that IGF1 improves rat GH3 somatotroph cell viability via the PI3K/Akt/mTOR pathway and confirmed that IGF1 exerts a negative feedback on GH secretion by a transcriptional mechanism. We demonstrated that the negative IGF1 loop on GH secretion requires Akt activation that seems to play a pivotal role in the control of GH secretion. Furthermore, Akt activation is independent of PI3K and probably mediated by mTORC2. In addition, we found that Erk 1/2 is not involved in GH3 cell viability regulation, but may have a role in controlling GH secretion, independently of IGF1.

Conclusion

Our data confirm that mTOR inhibitors may be useful to reduce pituitary adenoma cell viability, while Erk 1/2 pathway may be considered as a useful therapeutic target to control GH secretion. Our results open the field for further studies searching for effective drugs to control GH hyper-secretion.



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Can a Clinician-Scientist Training Program Develop Academic Orthopaedic Surgeons? One Program’s Thirty-Year Experience

Publication date: Available online 26 October 2017
Source:Journal of Surgical Education
Author(s): Aaron M. Brandt, Samantha A. Rettig, Neel K. Kale, Joseph D. Zuckerman, Kenneth A. Egol
BackgroundClinician-scientist numbers have been stagnant over the past few decades despite awareness of this trend. Interventions attempting to change this problem have been seemingly ineffective, but research residency positions have shown potential benefit.ObjectiveWe sought to evaluate the effectiveness of a clinician-scientist training program (CSTP) in an academic orthopedic residency in improving academic productivity and increasing interest in academic careers.MethodsResident training records were identified and reviewed for all residents who completed training between 1976 and 2014 (n = 329). There were no designated research residents prior to 1984 (pre-CSTP). Between 1984 and 2005, residents self-selected for the program (CSTP-SS). In 2005, residents were selected by program before residency (CSTP-PS). Residents were also grouped by program participation, research vs. clinical residents (RR vs. CR). Data were collected on academic positions and productivity through Internet-based and PubMed search, as well as direct e-mail or phone contact. Variables were then compared based on the time duration and designation.ResultsComparing all RR with CR, RR residents were more likely to enter academic practice after training (RR, 34%; CR, 20%; p = 0.0001) and were 4 times more productive based on median publications (RR, 14; CR, 4; p < 0.0001). Furthermore, 42% of RR are still active in research compared to 29% of CR (p = 0.04), but no statistical difference in postgraduate academic productivity identified.ConclusionsThe CSTP increased academic productivity during residency for the residents and the program. However, this program did not lead to a clear increase in academic productivity after residency and did not result in more trainees choosing a career as clinician-scientists.



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PI3K/Akt/mTOR pathway involvement in regulating growth hormone secretion in a rat pituitary adenoma cell line

Abstract

Purpose

Insulin-like growth factor 1 (IGF1) controls growth hormone (GH) secretion via a negative feed-back loop that may disclose novel mechanisms possibly useful to control GH hyper-secretion. Our aim was to understand whether PI3K/Akt/mTOR pathway is involved in IGF1 negative feedback on GH secretion.

Methods

Cell viability, GH secretion, Akt, and Erk 1/2 phosphorylation levels in the rat GH3 cell line were assessed under treatment with IGF1 and/or everolimus, an mTOR inhitior.

Results

We found that IGF1 improves rat GH3 somatotroph cell viability via the PI3K/Akt/mTOR pathway and confirmed that IGF1 exerts a negative feedback on GH secretion by a transcriptional mechanism. We demonstrated that the negative IGF1 loop on GH secretion requires Akt activation that seems to play a pivotal role in the control of GH secretion. Furthermore, Akt activation is independent of PI3K and probably mediated by mTORC2. In addition, we found that Erk 1/2 is not involved in GH3 cell viability regulation, but may have a role in controlling GH secretion, independently of IGF1.

Conclusion

Our data confirm that mTOR inhibitors may be useful to reduce pituitary adenoma cell viability, while Erk 1/2 pathway may be considered as a useful therapeutic target to control GH secretion. Our results open the field for further studies searching for effective drugs to control GH hyper-secretion.



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Rapid Fabrication of Microneedles using Magnetorheological Drawing Lithography

Publication date: Available online 26 October 2017
Source:Acta Biomaterialia
Author(s): Zhipeng Chen, Lei Ren, Jiyu Li, Lebin Yao, Yan Chen, Bin Liu, Lelun Jiang
Microneedles are micron-sized needles that are widely applied in biomedical fields owing to their painless, minimally invasive, and convenient operation. However, most microneedle fabrication approaches are costly, time consuming, involve multiple steps, and require expensive equipment. In this study, we present a novel magnetorheological drawing lithography (MRDL) method to efficiently fabricate microneedle, bio-inspired microneedle, and molding-free microneedle array. With the assistance of an external magnetic field, the 3D structure of a microneedle can be directly drawn from a droplet of curable magnetorheological fluid. The formation process of a microneedle consists of two key stages, elasto-capillary self-thinning and magneto-capillary self-shrinking, which greatly affect the microneedle height and tip radius. Penetration and fracture tests demonstrated that the microneedle had sufficient strength and toughness for skin penetration. Microneedle arrays and a bio-inspired microneedle were also fabricated, which further demonstrated the versatility and flexibility of the MRDL method.Statement of SignificanceMicroneedles have been widely applied in biomedical fields owing to their painless, minimally invasive, and convenient operation. However, most microneedle fabrication approaches are costly, time consuming, involve multiple steps, and require expensive equipment. Furthermore, most researchers have focused on the biomedical applications of microneedles but have given little attention to the optimization of the fabrication process. This research presents a novel magnetorheological drawing lithography (MRDL) method to fabricate microneedle, bio-inspired microneedle, and molding-free microneedle array. In this proposed technique, a droplet of curable magnetorheological fluid (CMRF) is drawn directly from almost any substrate to produce a 3D microneedle under an external magnetic field. This method not only inherits the advantages of thermal drawing approach without the need for a mask and light irradiation but also eliminates the requirement for drawing temperature adjustment. The MRDL method is extremely simple and can even produce the complex and multiscale structure of bio-inspired microneedle.

Graphical abstract

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Selecting the Correct Cellular Model for Assessing of the Biological Response of Collagen-based Biomaterials

Publication date: Available online 26 October 2017
Source:Acta Biomaterialia
Author(s): Natalia Davidenko, Samir Hamaia, Daniel V. Bax, Jean-Daniel Malcor, Carlos F. Schuster, Donald Gullberg, Richard W. Farndale, Serena M. Best, Ruth E. Cameron
Accurate evaluation of the biological performance of biomaterials requires the correct assessment of their native-like cell ligation properties. However, cell attachment studies often overlook the details of the substrate-cell binding mechanisms, be they integrin-mediated or non-specific, and ignore the class- and species-specificities of the cell adhesion receptor involved. In this work we have used different collagen (Col) substrates (fibrillar collagens I, II and III and network-forming Col IV), containing different affinity cell-recognition motifs, to establish the influence of the receptor identity and species-specificity on collagen-cell interactive properties. Receptor expression was varied by using cells of different origin, or transfecting collagen-binding integrins into integrin-null cells. These include mouse C2C12 myoblasts transfected with human α1, α2, α10 or α11; human fibrosarcoma HT1080 cells which constitutively express only human α2β1, and rat glioma Rugli cells, with only rat α1β1. Using these lines, the nature of integrin binding sites was studied in order to delineate the bioactivity of different collagen substrates. Integrin ligation was studied on collagen coatings alongside synthetic (GFOGER/ GLOGEN) and Toolkit (Col II-28/Col III-7) triple-helical peptides to evaluate (1) their affinity towards different integrins and (2) to confirm the activity of the inserted integrin in the transfected cells. Thin films of dermal and tendon Col I were used to evaluate the influence of the carbodiimide (EDC)-based treatment on the cellular response on Col of different origin. The results showed that the binding properties of transfected C2C12 cells to collagens depend on the identity of inserted integrin. Similar ligation characteristics were observed using α1+ and α10+ cells, but these were distinct from the similar binding features of α2+ and α11+ cells. Recombinant human and rat-α1 I domain binding to collagens and peptides correlated with the cell adhesion results, showing receptor class- and species-specificities. The understanding of the physiologically relevant cell anchorage characteristics of bio-constructs may assist in the selection of (1) the optimum collagen source for cellular supports and (2) the correct cellular model for their biological assessment. This, in turn, may allow reliable prediction of the biological performance of bio-scaffolds in vivo for specific TE applications.Statement of SignificanceIntegrins play a vital role in cellular responses to environmental cues during early-stage cell-substrate interaction. We describe physiologically relevant cell anchorage to collagen substrates that present different affinity cell-recognition motifs, to provide experimental tools to assist in understanding integrin binding. Using different cell types and recombinant integrin α1-I-domains, we found that cellular response was highly dependent on collagen type, origin and EDC-crosslinking status, as well as on the integrin class and species of origin. This comprehensive study establishes selectivity amongst the four collagen-binding integrins and species-specific properties that together may influence choice of cell type and receptor in different experimental settings. This work offers key guidance in selecting of the correct cellular model for the biological testing of collagen-based biomaterials.

Graphical abstract

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Editorial Board & Aims and Scope

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Publication date: October 2017
Source:Nano Today, Volume 16





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