New and Exciting in PLoS Biology and PLoS Medicine

There is some interesting stuff published in PLoS Medicine and PLoS Biology today:

What Should Be Done To Tackle Ghostwriting in the Medical Literature?:

Background to the debate: Ghostwriting occurs when someone makes substantial contributions to a manuscript without attribution or disclosure. It is considered bad publication practice in the medical sciences, and some argue it is scientific misconduct. At its extreme, medical ghostwriting involves pharmaceutical companies hiring professional writers to produce papers promoting their products but hiding those contributions and instead naming academic physicians or scientists as the authors. To improve transparency, many editors' associations and journals allow professional medical writers to contribute to the writing of papers without being listed as authors provided their role is acknowledged. This debate examines how best to tackle ghostwriting in the medical literature from the perspectives of a researcher, an editor, and the professional medical writer.

Mutation Patterns in the Human Genome: More Variable Than Expected:

The development, survival, and reproduction of an organism depend on the genetic information that is carried in its genome, yet the transmission of genetic information is not perfectly accurate: new mutations occur at each generation. These mutations are the primary cause of the genetic diversity on which natural selection can operate, and hence are the sine qua non of evolution. A better knowledge of mutation processes is crucial for investigating the causes of genetic diseases or cancer and for understanding evolutionary processes. This knowledge is also important for different practical reasons. First, comparative sequence analysis is widely used to find functional elements within genomes. The basic principle of this approach is that functional elements are affected by natural selection, and hence can be recognized because they evolve either slower or faster than expected given the local mutation rate. Hence, to be able to annotate genomic sequences, it is necessary to have a good knowledge of the underlying pattern of mutation. Moreover, this knowledge is also essential for ensuring the accuracy of the methods that analyze sequence divergence to determine the phylogeny of species or the demographical history of populations. Finally, the study of mutational processes also provides valuable information about genome function in processes such as replication, repair, transcription, and recombination. During the last few years, several important factors affecting mutation rates have been uncovered. However, a paper in this issue of PLoS Biology [1] reveals an unexpected additional layer of complexity in the determinants of mutation rates.

Cryptic Variation in the Human Mutation Rate:

Understanding the process of mutation is important, not only mechanistically, but also because it has implications for the analysis of sequence evolution and population genetic inference. The mutation rate is known to differ between sites within the human genome. The most dramatic example of this is when a C is followed by G; both the C and G nucleotides have a rate of mutation that is between 10- and 20-fold higher than the rate at other sites. In addition, is it known that the mutation rate may be influenced by the nucleotides flanking the site. Here we show that there is also very substantial variation in the mutation rate that is not associated with the flanking nucleotides, or the CpG effect. Although this variation does not depend upon the adjacent nucleotides, there are nonrandom patterns of nucleotides surrounding sites that appear to be hypermutable, suggesting there are complex context effects that influence the mutation rate.

Gene Regulatory Network Interactions in Sea Urchin Endomesoderm Induction:

In recent years, "gene regulatory networks" (GRNs) have provided integrated views of gene interactions that control biological processes. One of the earliest networks to be activated in the developing zygotes is the one controlling endomesoderm development. In the sea urchin, this network includes several subnetworks that function in adjacent tiers of cells that form the endoderm and mesoderm of the developing embryo. Although classic embryological manipulations have shown that the precursors of the embryonic skeleton induce endomesoderm fate in adjacent cells, the GRNs regulating this interaction are not understood. To investigate these networks, we ectopically activated a GRN that operates in skeletogenic precursors and characterized the responding GRN in neighboring cells, which adopt an endomesoderm fate. By testing the responsiveness of every core factor in the responding GRN, which allowed us to identify a subset that executes the response to the induction, we demonstrated that the signaling molecule, ActivinB, is an essential component of this induction and that its function is physiologically relevant: it is required during normal embryonic development to activate the same GRN that responds to signals from skeletogenic precursors. Furthermore, the network response to ActivinB signaling reveals greater complexity in an additional uncharacterized inductive signal emitted by skeletogenic precursors. Our results thus highlight how interacting GRNs can be used to understand a fundamental signaling process.