Aristotle's biological works as scientific literature

This contribution deals with the question of where and why in his biological writings Aristotle uses dialogical elements, examining which dialogical structures can be found and what the meaning of the dialogical structures is in respect of the argumentative strategies used in literature. This discursive style has to be seen in relation to the importance of the dialectical method which was practiced in the Platonic Academy and on which Aristotle reflected in his Topics. For Aristotle the dialectical method also becomes the method of the investigator researching for himself. But more than that one can see the reason for the dialogical structures in Aristotle's writings in his attempt to combine the way of acquiring knowledge with the way of presenting knowledge. It can thus be said that at the moment in which the dialectical procedure is translated into the medium of writing, a fact-oriented presentation is also an addressee-oriented representation. Nowadays we are more accustomed to a technical literature which, after completing the first step of the deduction of knowledge, presents the results in a systematic and hierarchical way in its literary representation; in such technical literature, normally an individual's thought process is not set out in writing. Admittedly, with the application of the dialectical method and with the attempt to set down one's own thought process in the medium of writing, other elements also come in.     

De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome

Brain malformations are individually rare but collectively common causes of developmental disabilities. Many forms of malformation occur sporadically and are associated with reduced reproductive fitness, pointing to a causative role for de novo mutations. Here, we report a study of Baraitser-Winter syndrome, a well-defined disorder characterized by distinct craniofacial features, ocular colobomata and neuronal migration defect. Using whole-exome sequencing of three proband-parent trios, we identified de novo missense changes in the cytoplasmic actin-encoding genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in 15 additional affected individuals identified disease-causing mutations in all probands, including two recurrent de novo alterations (ACTB, encoding p.Arg196His, and ACTG1, encoding p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actin proteins in development and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes.     

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair

Chronic kidney disease (CKD) represents a major health burden. Its central feature of renal fibrosis is not well understood. By exome sequencing, we identified mutations in FAN1 as a cause of karyomegalic interstitial nephritis (KIN), a disorder that serves as a model for renal fibrosis. Renal histology in KIN is indistinguishable from that of nephronophthisis, except for the presence of karyomegaly. The FAN1 protein has nuclease activity and acts in DNA interstrand cross-link (ICL) repair within the Fanconi anemia DNA damage response (DDR) pathway. We show that cells from individuals with FAN1 mutations have sensitivity to the ICL-inducing agent mitomycin C but do not exhibit chromosome breakage or cell cycle arrest after diepoxybutane treatment, unlike cells from individuals with Fanconi anemia. We complemented ICL sensitivity with wild-type FAN1 but not with cDNA having mutations found in individuals with KIN. Depletion of fan1 in zebrafish caused increased DDR, apoptosis and kidney cysts. Our findings implicate susceptibility to environmental genotoxins and inadequate DNA repair as novel mechanisms contributing to renal fibrosis and CKD.     

Why the impact of mechanical stimuli on stem cells remains a challenge

Mechanical stimulation affects growth and differentiation of stem cells. This may be used to guide lineage-specific cell fate decisions and therefore opens fascinating opportunities for stem cell biology and regenerative medicine. Several studies demonstrated functional and molecular effects of mechanical stimulation but on first sight these results often appear to be inconsistent. Comparison of such studies is hampered by a multitude of relevant parameters that act in concert. There are notorious differences between species, cell types, and culture conditions. Furthermore, the utilized culture substrates have complex features, such as surface chemistry, elasticity, and topography. Cell culture substrates can vary from simple, flat materials to complex 3D scaffolds. Last but not least, mechanical forces can be applied with different frequency, amplitude, and strength. It is therefore a prerequisite to take all these parameters into consideration when ascribing their specific functional relevance—and to only modulate one parameter at the time if the relevance of this parameter is addressed. Such research questions can only be investigated by interdisciplinary cooperation. In this review, we focus particularly on mesenchymal stem cells and pluripotent stem cells to discuss relevant parameters that contribute to the kaleidoscope of mechanical stimulation of stem cells.     

Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis

The central nervous system (CNS) is capable of gathering information on the body’s nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus.     

Convective-region geometry as the cause of Uranus' and Neptune's unusual magnetic fields

The discovery of Uranus' and Neptune's non-dipolar, non-axisymmetric magnetic fields destroyed the picture--established by Earth, Jupiter and Saturn--that planetary magnetic fields are dominated by axial dipoles. Although various explanations for these unusual fields have been proposed, the cause of such field morphologies remains unexplained. Planetary magnetic fields are generated by complex fluid motions in electrically conducting regions of the planets (a process known as dynamo action), and so are intimately linked to the structure and evolution of planetary interiors. Determining why Uranus and Neptune have different field morphologies is not only critical for studying the interiors of these planets, but also essential for understanding the dynamics of magnetic-field generation in all planets. Here we present three-dimensional numerical dynamo simulations that model the dynamo source region as a convecting thin shell surrounding a stably stratified fluid interior. We show that this convective-region geometry produces magnetic fields similar in morphology to those of Uranus and Neptune. The fields are non-dipolar and non-axisymmetric, and result from a combination of the stable fluid's response to electromagnetic stress and the small length scales imposed by the thin shell.     

Evolutionary change from induced to constitutive expression of an indirect plant resistance

Induced plant resistance traits are expressed in response to attack and occur throughout the plant kingdom. Despite their general occurrence, the evolution of such resistances has rarely been investigated. Here we report that extrafloral nectar, a usually inducible trait, is constitutively secreted by Central American Acacia species that are obligately inhabited by ants. Extrafloral nectar is secreted as an indirect resistance, attracting ants that defend plants against herbivores. Leaf damage induces extrafloral nectar secretion in several plant species; among these are various Acacia species and other Fabaceae investigated here. In contrast, Acacia species obligately inhabited by symbiotic ants nourish these ants by secreting extrafloral nectar constitutively at high rates that are not affected by leaf damage. The phylogeny of the genus Acacia and closely related genera indicate that the inducibility of extrafloral nectar is the plesiomorphic or 'original' state, whereas the constitutive extrafloral nectar flow is derived within Acacia. A constitutive resistance trait has evolved from an inducible one, obviously in response to particular functional demands.