Epigenetics Decouples Mutational from Environmental Robustness. Did It Also Facilitate Multicellularity?

The evolution of ever increasing complex life forms has required innovations at the molecular level in order to overcome existing barriers. For example, evolving processes for cell differentiation, such as epigenetic mechanisms, facilitated the transition to multicellularity. At the same time, studies using gene regulatory network models, and corroborated in single-celled model organisms, have shown that mutational robustness and environmental robustness are correlated. Such correlation may constitute a barrier to the evolution of multicellularity since cell differentiation requires sensitivity to cues in the internal environment during development. To investigate how this barrier might be overcome, we used a gene regulatory network model which includes epigenetic control based on the mechanism of histone modification via Polycomb Group Proteins, which evolved in tandem with the transition to multicellularity. Incorporating the Polycomb mechanism allowed decoupling of mutational and environmental robustness, thus allowing the system to be simultaneously robust to mutations while increasing sensitivity to the environment. In turn, this decoupling facilitated cell differentiation which we tested by evaluating the capacity of the system for producing novel output states in response to altered initial conditions. In the absence of the Polycomb mechanism, the system was frequently incapable of adding new states, whereas with the Polycomb mechanism successful addition of new states was nearly certain. The Polycomb mechanism, which dynamically reshapes the network structure during development as a function of expression dynamics, decouples mutational and environmental robustness, thus providing a necessary step in the evolution of multicellularity.     

Did Osler suffer from "paranoia antitherapeuticum baltimorensis"?: A comparative content analysis of The Principles and Practice of Medicine and Harrison's Principles of Internal Medicine, 11th edition

One of the most important legacies of Sir William Osler was his textbook The Principles and Practice of Medicine. A common criticism of the book when it was first published was its deficiency in the area of therapeutics. In this article, the 1st edition of The Principles and Practice of Medicine is compared with the 11th edition of Harrison''s Principles of Internal Medicine. The analysis focuses on the treatment recommendations for 4 conditions that were covered in both books (diabetes mellitus, ischemic heart disease, pneumonia and typhoid fever). Osler''s textbook dealt with typhoid fever and pneumonia at greater length, whereas Harrison''s placed more emphasis on diabetes mellitus and ischemic heart disease. Notwithstanding Osler''s reputation as a therapeutic nihilist, the 2 books devoted equivalent space to treatment (in terms of proportion of total sentences for the conditions). For all conditions except ischemic heart disease, Osler concentrated on general measures and symptomatic care. Throughout Osler''s textbook numerous negative comments are made about the medicinal treatment of various conditions. A more accurate statement about Osler''s therapeutic approach was that he was a "medicinal nihilist." His demand for proof of efficacy before use of a medication remains relevant.     

Native or not? Isotope analysis of a female skeleton on the 9th century A.D. from Elsau, Canton Zurich, Switzerland

At Elsau near Winterthur (CH), a 9th century AD grave with a female skeleton was found in 2003. This grave was reopened one to six years after burial. After manipulating the partially decayed skeleton, the grave was filled with a layer of rocks and a claw of a sea eagle as well as the paw of a fox was placed on top. At least from this time onwards, the grave was situated in the annex of a church. Because of this special burial site for the 42 year old woman, who suffered from different severe illnesses, it is thought that she belonged to the upper class. The postmortal changes at the grave are exceptional and even after thorough research, no equivalent burial procedures are known from this area. To investigate the possibility if the woman migrated to the region of Elsau, the oxygen and strontium isotope composition of several teeth and one long bone of her skeleton was analysed. The results indicate a certain but restricted mobility within the northern Alpine foreland and as a result changes of the isotope composition of the food and drinking water during her childhood. Immigration from regions in which similar burial customs to those used for the woman persisted into the 9th century AD can be largely excluded based on the isotope composition of her skeletal remains. The mobility in the pre-Alpine region supports the interpretation that the woman belonged to the upper class, whose properties where widely distributed.     

Assessing past agrobiodiversity of Prunus avium L. (Rosaceae): a morphometric approach focussed on the stones from the archaeological site H?tel-Dieu (16th century, Tours, France)

Abundant and diverse Prunus fruitstone remains from cherries, plums, sloes, peaches, etc. are frequently recovered from archaeological waterlogged contexts such as wells, latrines, lake dwellings etc. in Europe. The distinction between most of the Prunus species, based on traditional morphological characters of the fruit stones, is usually not problematic. However the discrimination between P. avium L., P. cerasus L. and related cherry species, based on classical criteria alone, often turns out to be ambiguous because of the increasing number of varieties which have been bred since Roman times. By combining geometric and traditional morphometrical approaches, the overall variation in shape and size of stones from French and Swiss excavations dating from the 1st century to the 16th century a.d. were assessed. Among these important archaeobotanical data, the detailed examination of 100 waterlogged stones from the 16th century H?tel-Dieu cesspit at Tours, France, revealed that the morphological diversity is structured into two distinct morphotypes which diverge mainly according to geometrical features. Finally, the comparison between morphological features of these well-preserved archaeological stones and modern reference material including P. avium, P. cerasus and P. × gondouinii, suggests that these two morphotypes, which have been initially attributed to P. avium (long stones) and P. avium/cerasus (rounded stones) according to traditional morphological parameters, would correspond to two different cultivated varieties, both belonging to Prunus avium. Results presented in this work constitute new and preliminary data obtained during the development of this project that throw light on morphological variability and biosystematic aspects.     

Musings on the wanderer: what's new in our understanding of vago-vagal reflexes?: II. Integration of afferent signaling from the viscera by the nodose ganglia

To understand vago-vagal reflexes, one must have an appreciation of the events surrounding the encoding, integration, and central transfer of peripheral sensations by vagal afferent neurons. A large body of work has shown that vagal afferent neurons have nonuniform properties and that distinct subpopulations of neurons exist within the nodose ganglia. These sensory neurons display a considerable degree of plasticity; electrophysiological, pharmacological, and neurochemical properties have all been shown to alter after peripheral tissue injury. The validity of claims of selective recordings from populations of neurons activated by peripheral stimuli may be diminished, however, by the recent demonstration that stimulation of a subpopulation of nodose neurons can enhance the activity of unstimulated neuronal neighbors. To better understand the neurophysiological processes occurring after vagal afferent stimulation, it is essential that the electrophysiological, pharmacological, and neurochemical properties of nodose neurons are correlated with their sensory function or, at the very least, with their specific innervation target.