FEBS Letters is this month carrying out an interesting experiment that could make literature searching easier for both human and computers.

The experiment centres on Structured Digital Abstracts (SDA). SDA are extensions of the normal journal article abstracts that describe the relationship between two biological entities, mentioning the method used to study the relationship. Each sentence is preceded by one or more identifiers pointing to the corresponding database entries that contain the full details of the interaction e.g. protein A interacts with protein B, by method X.

The aim of SDA is to assist data entry, text mining and literature searching by extracting the salient data from the article into simple sentences using a defined structure and controlled vocabularies.

Gianni Cesareni, Editor of FEBS Letters explains:

Many articles in biological journals describe relationships between entities (genes, proteins, etc.) yet this information cannot be efficiently used because of difficulties in retrieving from text. Databases capture this valuable information and organize it in a structured format ready for automatic analysis. The experiment of using SDAs will facilitate database entry and improve disclosure, to the benefit of authors and readers.

This month’s edition FEBS letters contains a number of articles annotated with SDA, along with some articles on SDA itself.

This is a simple but very good idea and I would certainly appreciate anything that makes literature searching easier.

But I can’t help noting the delicious irony in the title of the first article in the issue that trumpets the arrival of SDA: “Finally: The digital, democratic age of scientific abstracts”. Read more »

A minireview recently in Genomics caught my eye with the title Coexpression, coregulation, and cofunctionality of neighboring genes in eukaryotic genomes that sounded just like a passage that I recalled from Richard Dawkins’ The Selfish Gene:

…the ‘environment’ of a gene consists largely of other genes, each of which is itself being selected for its ability to cooperate with its environment of other genes. (page 39) … Genes are selected, not as ‘good’ in isolation, but as good at working against the background of other genes in the gene pool. A good gene must be compatible with, and complementary to, the other genes with whom it has to share a long succession of bodies. (page 84)

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Just Science week has been fun, reading four recent journal articles on focal adhesion kinase (FAK). It has helped me refresh myself on FAK as I got back to writing fellowship applications - although it had the added effect of taking time away from said writing activities. So today I thought a recap was in order, and add an insightful review that came out a year and a half ago which is still very helpful.

An excerpt from Integrin signaling in directed cell migration, by Konstandinos Moissoglu and Martin Alexander Schwartz: Read more »

After the past three days of blogging focal adhesion kinase (FAK), each focusing on an important regulator of cell adhesion dynamics and cell motility, I’m going to turn my attention to phosphatidyl inositol-3 kinase (PI3K). PI3K has a regulatory subunit (p85), and a catalytic subunit (p110) capable of catalyzing the phosphorylation of the D3 position of the inositol ring of a class of lipid components of the cell membrane. In the inactive state, p85 binds to p110, blocking its activity; but when the Src homology 2 (SH2) domain of p85 finds a phosphotyrosine-containing sequence in another protein that it likes, it dissociates from p110, which is then active.

Among the phosphotyrosine-containing activators of PI3K are FAK (through integrin receptors) and growth factor receptors (or receptor tyrosine kinases, RTK’s). In a recent study, Teet Velling and colleagues in Sweden sought to distinguish between FAK and RTK mechanisms of PI3K activation in EGFR and ?1 integrins utilize different signaling pathways to activate Akt. Read more »

In keeping with this week’s trend of just science blogging on FAK, let’s take a look at another critical protein-protein interaction - this time with the scaffolding protein Paxillin. Specifically, how do FAK and Paxillin interact and why?

Conveniently, there’s a recent paper by Danielle Scheswohl et al., from the Schaller lab: Multiple paxillin binding sites regulate FAK function. The motivation to the paper can be found in the abstract: “Recent structural analyses have revealed two paxillin-binding sites in the [focal adhesion targeting, or FAT] domain of FAK. To define the role of paxillin binding to each site on FAK, point mutations have been engineered to specifically disrupt paxillin binding to each docking site on the FAT domain of FAK individually or in combination.” The paxillin binding sites are at the interface of ?-helices 1/4 and the interface of ?-helices 2/3 within the FAT domain (4 helices total). Paxillin is a scaffolding protein containing multiple domains that mediate protein-protein interactions, including five N-terminal LD motifs, four C-terminal LIM domains, and SH2 and SH3 domain binding sites. The second (LD2) and fourth LD motifs (LD4) of paxillin have been identified as FAK-binding sites and each of these sites binds to FAK with similar affinity. Read more »

Yesterday, I ended a post about FAK, Pyk2 and regulation of RhoA activity by asking “So, what about Rac regulation by [FAK] and Pyk2?”

Today, let’s discuss a paper relating FAK/Pyk2 function studies on Rac1: Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase. Katherine Owen, et al., focus on how “Primary bone marrow macrophages isolated from mice in which FAK is conditionally deleted from cells of the myeloid lineage exhibited elevated protrusive activity, altered adhesion dynamics, impaired chemotaxis, elevated basal Rac1 activity, and a marked inability to form stable lamellipodia necessary for directional locomotion.” Read more »

Focal adhesion kinase is an important signaling molecule in integrin-mediated cell signaling and cell adhesion. In FAK genetic knockout (FAK-null) cells, its closely homologous relative proline-rich kinase (Pyk2) is upregulated in FAK-null fibroblasts to partially compensate, but the mechanisms of Pyk2 upregulation and compensation remain undefined¹. A recent study by Yangmi Lim, David Schlaepfer, and colleagues takes a step towards elucidating the latter, by demonstrating both FAK and Pyk2 signaling through a RhoA guanine nucleotide exchange factor (GEF)².
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You know about adenine, thymine, guanine, cytosine. Now get used to SICS and MMO2.

In this JACS article published this month, researchers at the Scripps Institute reported the identification of these two artificial bases. They are efficiently incorporated during in vivo DNA synthesis by the Klenow fragment of E.coli DNA polymerase and pair together with high fidelity.

At the moment the applications for these new bases are are limited mainly to providing new building blocks for the in vivo synthesis of DNA-based nanostructures. However, work is ongoing to incorporate them into living cells and make them code for specific amino acids. Although it is far from clear whether this can be done, if achieved it will lead to some new, very powerful tools for protein engineering.

One of the several popular views regarding the origin of life stems from thermodynamics. Harold Morowitz refers to it as “Metabolism recapitulates biogenesis”.

In PLoS Biology there’s an interesting essay that was submitted posthumously by the chemist Leslie Orgel on this subject - The Implausibility of Metabolic Cycles on the Prebiotic Earth. Orgel takes a hearty dose of skepticism to contemporary hypotheses presented by Wächtershäuser and Morowitz^3,4, including the reverse citric acid cycle in particular. For clarification: the reverse citric acid cycle has been proposed to have operated nonenzymatically, not only fixing carbon but (in a chaotic soup-like mixture of inorganic catalysts) also producing metabolic intermediates for many of the amino acids, nucleotides, etc., required for the later RNA world.
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Form follows physics in the fly eye, say Sascha Hilgenfeldt, Sinem Erisken, and Richard Carthew

Simple forces, complex shapes: While most biological features appear complex in their geometries and varieties of components, appearances can be deceiving. That finding is supported by a recent modeling study by Hilgenfeldt, et al., looking at the arrangement of cone cells in the Drosophilia eye. They found that cell elasticity and adhesion strength alone can explain the cell arrangement, into the image shown (source: Hilgenfeldt/NAS).
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