502 citations and counting… but what do they mean? (if anything)

Evaluation of research and researchers is a perilous activity. Sometimes, the number of citations of a piece of work is used as an indicator. As my most cited article passed the 500 citations mark (according to Google Scholar), I have had a brief look at the 15 articles that, this year, cite our 2004 paper. Thanks to all colleagues who did read and, hopefully, enjoyed that paper.

The original article developed peptides as capping ligands for gold nanoparticles. The work included rational design of a peptide sequence (CALNN), observation of a small plasmon shift (2 nm) upon formation of the peptide self-assembled monolayer, analysis of systematic variations around that original sequence (some of which caused aggregation) and associated data analysis, including the use of an aggregation parameter.

Of the 15 articles that cited it in 2016:

  • One is a master thesis in Finnish.
  • Three were reviews (2, 10, 11).
  • Two seem to be pretty random citations (3, 7) and another one is relevant but not quite appropriate (5).
  • Two cited our work because they used a similar approach for their data analysis/interpretation (1, 14).
  • Four cited our work as an example of highly stable and biocompatible nanoparticle (4, 6, 8, 12).
  • and… ONE actually builds on our work by developing their own peptide sequence based on CALNN (13).

I am not quite completely sure what to conclude from this (limited) analysis. Comments welcome!

Articles are listed below with the context of the citation.

1. Priya A. Nair and K. Sreenivasan: “Non enzymatic colorimetric detection of glucose using cyanophenyl boronic acid included β-cyclodextrin stabilized gold nanoparticles”

The aggregation parameter was then determined from the equation (AA0)/A0, where A is the integrated absorbance between 550 and 650 nm for the system with glucose added and A0 is the integrated absorbance between 550 and 650 nm of the blank solution. A similar type of indicator has been used to analyze the aggregation of gold and silver particle induced aggregation in the presence of different analytes.23,24

2. J. Yang, Celina and B. Chithrani, Devika: “Nuclear Targeting of Gold Nanoparticles for Improved Therapeutics.”

(can’t access).

3. Adél Vágó et al: “One-step green synthesis of gold nanoparticles by mesophilic filamentous fungi” [incidentally, last two authors missing in the bibliography, sorry Mathias and Dave!]

Chemical and physical methods have certain drawbacks such as use of harsh chemicals, stringent synthesis conditions, energy and capital intensive production and formation of toxic residues [7], [8] and [9].

I suppose that could be construed as a criticism of our work (in which case it is welcome), or, alternatively, as a somewhat random citation to support what is an often made but pretty weak argument.

4. Yukiho HOSOMOMI et al: “Biocatalytic Formation of Gold Nanoparticles Decorated with Functional Proteins inside Recombinant Escherichia coli Cells”

Among these materals, protein-decorated Au NPs are of great importance because they can confer colloidal stability and bioactivity to Au NPs.[14, 15]

5. Hongyu Yang et al: “The reactivity study of peptide A3-capped gold and silver nanoparticles with heavy metal ions”

Among the series of metal binding peptides, peptide A3, with a sequence of AYYSGAPPMPPF, is one of the few sequences that can stabilize both gold and silver nanoparticles with a desirable control of the size, shape and composition [15]. It contains amino acids that are capable of interacting with both gold and silver surfaces by hydrogen bonding or hydrophobic interactions [16], [17] and [18].

[Our paper does not show this. Although our work is quite relevant to their study and could reasonably be cited, it is not appropriate in support of this statement…].

6. Jiaxue Gao et al: “Multiple detection of single nucleotide polymorphism by microarray-based resonance light scattering assay with enlarged gold nanoparticle probes”

During the last two decades, gold nanoparticles (GNPs) have been extensively employed for the development of ultrasensitive detection and imaging methods in analytical or biological sciences because GNPs have unique optical properties (i.e. surface plasma resonance (SPR) absorption and resonance light scattering (RLS)), a variety of surface coatings and great biocompatibility.33–40

7. Xiangqian Jia et al “Micromixer Based Preparation of Functionalized Liposomes and Targeting Drug Delivery”

As promising interface molecules, peptides may be a good choice of recognition element to modify liposomes in order to increase the targeting specificity.(22-26)

Pretty random citation?

8. Yong Li et al: “A biomimetic colorimetric logic gate system based on multi-functional peptide-mediated gold nanoparticle assembly”

Furthermore, through the rational design of peptide sequences, the peptide could recognize the target and mediate the dispersibility of AuNPs. Modulation of the dispersibility of AuNPs, accompanied by their plasmonic properties, changes the solution colour in an on–off/off–on manner.23–27

Very relevant and seems like a cool intriguing paper.

9. Abrin L. Schmucker et al. “Plasmonic paper: a porous and flexible substrate enabling nanoparticle-based combinatorial chemistry”

Consequently, developing surface modification strategies that also circumvent aggregation is necessary and researchers have gone to great lengths to address this challenge. Indeed, a current state-of-the-art “toolbox” of compatible reagents has been developed to impart stability and functionality which includes ligands such as DNA,24,25 polymers,26 peptides,27–29 etc.

10. Cláudia Couto et al. “Gold nanoparticles and bioconjugation: a pathway for proteomic applications”

The successful formation of SAMs can be monitored in the UV-Visible spectrum, as was the case of SAMs produced with a pentapeptide ligand that induced a shift of approximately 2 nm in the AuNPs plasmonic band.[40]

11. Annalisa Calò et al. “Nanoscale device architectures derived from biological assemblies: The case of tobacco mosaic virus and (apo)ferritin”

Inorganic building blocks of less than 10 nm size can be synthesized using two procedures, the capping method and the mold method. The capping method1–4) is mainly employed in nanoparticle (NP) synthesis and assembly and allows the production of structures, i.e., metal nanoparticles, surrounded by organic molecules,1–5) while the mold method allows the fabrication of building blocks of a tailored shape inside or outside a mold unit.6,7)

12. Akash Gupta et al. “Ultrastable and Biofunctionalizable Gold Nanoparticles”

One of the principal barriers to the industrial and general use of AuNPs is their poor capability to endure freeze-drying cycles.(23) This is one of the major reasons why most of the commercially available AuNPs are sold as solutions. In addition, many reports have shown that, when AuNPs are subjected to lyophilization,(42) larger AuNPs agglomerates are formed, and these aggregates cannot be dispersed again in solution.(43) Variations in the stabilizing agent help to control the shape and size of the final structures, though complete stability was achievable in only a few cases.(44, 45)

13. Yi Wang et al. “Smartphone spectrometer for colorimetric biosensing”

A specific peptide receptor (CALNN-Peg4-FYSHSFHENWPS)1,40 with high affinity to cTnl was synthesized and immobilized on the surface of 36 nm AuNPs through the cysteine residue (see the ESI† for the Experimental details). In the presence of cTnl, AuNPs aggregate due to bridging of peptides (on separate AuNPs) resulting in a red shift of the LSPR peak. The colour of the AuNP solution concomitantly changes from red to purple. After extensive aggregation the suspension becomes colourless because of precipitation of AuNP aggregates at the bottom of the cuvette. The average size of the aggregates formed, as revealed by dynamic light scattering (DLS), also increases with the time of incubation of cTnI (see Fig. S5 in the the ESI†).

Yes! That paper is actually one that not only cites our work but actually builds on our 2004 ms where we introduced the CALNN peptide sequence.

14. Pei Liu et al; “Gold nanoprobe functionalized with specific fusion protein selection from phage display and its application in rapid, selective and sensitive colorimetric biosensing of Staphylococcus aureus”

The spectra showed a slightly broadened plasmon band, which was red-shifted from 523 to 525 nm after protein modification (Fig. 2C). The red-shift is induced by the introduction of the protein layer (Levy et al., 2004).

 

 

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3 comments

  1. Standard issue. There are mistakes made, but given how many off target citations one can accrue, I suspect the main cause is that bibliographies are often not very good works of scholarship. Since retracted papers are still cited as ‘fact’, this is perhaps not so surprising. It certainly adds weight to the argument that metric data are not very useful in evaluating the importance of a publication.

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  2. At least you have a paper that has been cited >500 times (I don’t). My conclusion is that my research, if for any body, is only relevant for myself… The sad part is that there are MANY researchers even worst than me. I think I should do something else, but nobody outside of Science wants to hire a guy that his whole life has done only research. So, who should do research then? Only ultra-prominent scientists that publish every month in Science and Nature (many of which are quite fraudulent)?… I don’t know. One of the obvious problems to me is the lack of stringency in the Biology graduate programs. I am not aware of anybody that ever failed in a PhD program in Biological Sciences (and I know a lot of people in the field), so it should not be surprising that most of our publications are irrelevant (I am not referring to yours). I will stop here, because I may be peeing outside the box…

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    1. Some deep soul searching here jjovel… Some papers are not cited for many years and then suddenly become very important. It is not necessarily the case that because your work is currently not recognized that it will never be. However, you do need to believe in it if only so that you have the satisfaction of doing good work. I have the feeling that it is not completely the case? I do not know you, so I don’t know what a “whole life only doing research” means, but many people go from academia to industry successfully. In industry your papers, cited or not, won’t matter so much but other skills acquired in research will. On the “ultra-prominent scientists that publish every months in Science and Nature …”, do not get me started. Best wishes for your continuation.

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