Evolution of a novel adrenal cell type that promotes parental care.

Cell types with specialized functions fundamentally regulate animal behaviour, and yet the genetic mechanisms that underlie the emergence of novel cell types and their consequences for behaviour are not well understood1. Here we show that the monogamous oldfield mouse (Peromyscus polionotus) has recently evolved a novel cell type in the adrenal gland that expresses the enzyme AKR1C18, which converts progesterone into 20α-hydroxyprogesterone. We then demonstrate that 20α-hydroxyprogesterone is more abundant in oldfield mice, where it induces monogamous-typical parental behaviours, than in the closely related promiscuous deer mice (Peromyscus maniculatus). Using quantitative trait locus mapping in a cross between these species, we ultimately find interspecific genetic variation that drives expression of the nuclear protein GADD45A and the glycoprotein tenascin N, which contribute to the emergence and function of this cell type in oldfield mice. Our results provide an example by which the recent evolution of a new cell type in a gland outside the brain contributes to the evolution of social behaviour.

Soft cluster-induced desorption/ionization mass spectrometry: How soft is soft?

Desorption/ionization induced by neutral clusters (DINeC) is used as an ultrasoft desorption/ionization method for the analysis of fragile biomolecules by means of mass spectrometry (MS). As a test molecule, the glycopeptide vancomycin was measured with DINeC-MS, and resulting mass spectra were compared to the results obtained with electrospray ionization (ESI), matrix assisted laser desorption ionization, and time-of-flight secondary ion MS. Of the desorption-based techniques, DINeC spectra show the lowest abundance of fragments comparable to ESI spectra. The soft desorption nature of DINeC was further demonstrated when applied to MS analysis of teicoplanin.

Chemoaffinity in topographic mapping revisited--is it more about fiber-fiber than fiber-target interactions?

Axonal projections between two populations of neurons, which preserve neighborhood relationships, are called topographic. They are ubiquitous in the brain. The development of the retinotectal projection, mapping the retinal output onto the roof of the midbrain, has been studied for decades as a model system. The rigid precision of normal retinotopic mapping has prompted the chemoaffinity hypothesis, positing axonal targeting to be based on fixed biochemical affinities between fibers and targets. In addition, however, abundant evidence has been gathered mainly in the 1970s and 80s that the mapping can adjust to variegated targets with stunning flexibility demonstrating the extraordinary robustness of the guidance process. The identification of ephrins and Eph-receptors as the underlying molecular cues has mostly been interpreted as supporting the fiber-target chemoaffinity hypothesis, while the evidence on mapping robustness has largely been neglected. By having a fresh look on the old data, we expound that they indicate, in addition to fiber-target chemoaffinity, the existence of a second autonomous guidance influence, which we call fiber-fiber chemoaffinity. Classical in vitro observations suggest both influences be composed of opposing monofunctional guidance activities. Based on the molecular evidence, we propose that those might be ephrin/Eph forward and reverse signaling, not only in fiber-target but also in fiber-fiber interactions. In fact, computational models based on this assumption can reconcile the seemingly conflicting findings on rigid and flexible topographic mapping. Supporting the suggested parsimonious and powerful mechanism, they contribute to an understanding of the evolutionary success of robust topographic mass wiring of axons.

Matrix-free formation of gas-phase biomolecular ions by soft cluster-induced desorption.

All in a ball: Neutral molecular clusters consisting of a few thousand molecules can be seen as tiny snow balls; if they are thrown fast enough onto a surface, they are able to pick up biomolecules such as insulin from that surface. Since they break down and evaporate during and after the collision, bare biomolecular ions are available for mass spectrometry after such an energetic throw.

Prognostic value of disseminated colorectal tumor cells in the liver: results of follow-up examinations.

BACKGROUND AND AIMS: Dissemination of tumor cells is an initial step in metastatic disease. Detection of disseminated tumor cells (DTC) in blood, bone marrow and lymph nodes has been associated with reduced disease-free survival, but to date there are no data for hepatic DTC. We investigated the prognostic relevance of hepatic DTC that are present in patients with colorectal cancer (CRC) at the time of surgery. PATIENTS AND METHODS: In 121 patients with CRC clinically diagnosed for liver metastasis by ultrasound, CT, and exploration during surgery DNA from liver biopsy specimens obtained during surgery was examined by a PCR-RFLP assay for K-ras mutations as a marker for DTC. At the time of surgery 54 of the 121 were mutated in K-ras codons 12 or 13. After a median follow-up of 405 days all survivors were reevaluated by ultrasound/CT. RESULTS: Patients with a K-ras mutation in their primary tumor had a significantly lower probability of survival and higher risk of harboring a synchronous second colorectal carcinoma than patients with a K-ras wild-type tumor. Based on specimens taken intraoperatively DTC were found in the liver of 14 of 54 patients (26%). At follow-up only 10 of 40 patients (25%) with DTC-free liver had died of their disease but 9 of the 14 patients with hepatic DTC. Among the 14 patients with hepatic DTC 10 (71%) had developed new liver metastasis, compared to 12 of 40 (30%) in those without hepatic DTC. CONCLUSION: Hepatic DTC in colorectal cancer patients is associated with reduced overall survival and increased risk of hepatic metastasis development. Further studies are necessary to corroborate our results since the number of patients studied is still limited.