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Order and Complexity in the RNA World
The basic idea of the RNA world as an early step towards life relies on a molecular evolution process based on self-replicating RNA strands. It is probably the oldest and most convincing model for efficient prebiotic evolution. Obviously, the functionality of RNA sequences depends on order (i.e., the definition of their sequence) as well as on complexity (i.e., the length of their sequence). Order and complexity seem to be crucial parameters in the course of RNA evolution. In the following, an attempt is made to define these parameters and to identify characteristic mechanisms of their development. Using a general RNA world scenario including the free monomer units, the sequential order is defined based on statistical thermodynamics. The complexity, on the other hand, is determined by the size of a minimal algorithm fully describing the system. Under these conditions, a diagonal line in an order/complexity-diagram represents the progress of molecular evolution. Elementary steps such as repeated random polymerization and selection follow characteristic pathways and finally add up to a state of high system functionality. Furthermore, the model yields a thermodynamic perspective on molecular evolution, as the development of a defined polymer sequence has a distinct influence on the entropy of the overall system.
Journal Article
Spontaneous Formation of Functional Structures in Messy Environments
Even though prebiotic chemistry initially deals with simple molecules, its composition rapidly gains complexity with oligomerization. Starting with, e.g., 20 monomers (such as the 20 proteinogenic amino acids), we expect 400 different dimers, 3,200,000 pentamers, or more than 1013 decamers. Hence, the starting conditions are very messy but also form a very powerful pool of potentially functional oligomers. A selecting structure (a “selector” such as membrane multilayers or vesicles) may pick and accumulate those molecules from the pool that fulfill a simple function (such as the suitability to integrate into a bilayer membrane). If this “selector” is, in turn, subject to a superimposed selection in a periodic process, the accumulated oligomers may be further trimmed to fulfill more complex functions, which improve the survival rate of the selectors. Successful oligomers will be passed from generation to generation and further improved in subsequent steps. After thousands of generations, the selector, together with its integrated oligomers, can form a functional unit of considerable order and complexity. The actual power of this process of random formation and selection has already been shown in laboratory experiments. In this concept paper, earlier results are summarized and brought into a new context.
Journal Article
Direct numerical simulation of complete transition to turbulence via oblique breakdown at Mach 3
A pair of oblique waves at low amplitudes is introduced in a supersonic flat-plate boundary layer at Mach 3. Its downstream development and the concomitant process of laminar to turbulent transition is then investigated numerically using linear-stability theory, parabolized stability equations and direct numerical simulations (DNS). In the present paper, the linear regime is studied first in great detail. The focus of the second part is the early and late nonlinear regimes. It is shown how the disturbance wave spectrum is filled up by nonlinear interactions and which flow structures arise and how these structures locally break down to small scales. Finally, the study answers the question whether a fully developed turbulent boundary layer can be reached by oblique breakdown. It is shown that the skin friction develops such as is typical of transitional and turbulent boundary layers. Initially, the skin friction coefficient increases in the streamwise direction in the transitional region and finally decays when the early turbulent state is reached. Downstream of the maximum in the skin friction, the flow loses its periodicity in time and possesses characteristic mean-flow and spectral properties of a turbulent boundary layer. The DNS data clearly demonstrate that oblique breakdown can lead to a fully developed turbulent boundary layer and therefore it is a relevant mechanism for transition in two-dimensional supersonic boundary layers.
Journal Article
Life in The Context of Order and Complexity
It is generally accepted that life requires structural complexity. However, a chaotic mixture of organic compounds like the one formed by extensive reaction sequences over time may be extremely complex, but could just represent a static asphalt-like dead end situation. Likewise, it is accepted that life requires a certain degree of structural order. However, even extremely ordered structures like mineral crystals show no tendency to be alive. So neither complexity nor order alone can characterize a living organism. In order to come close to life, and in order for life to develop to higher organisms, both conditions have to be fulfilled and advanced simultaneously. Only a combination of the two requirements, complexity and structural order, can mark the difference between living and dead matter. It is essential for the development of prebiotic chemistry into life and characterizes the course and the result of Darwinian evolution. For this reason, it is worthwhile to define complexity and order as an essential pair of characteristics of life and to use them as fundamental parameters to evaluate early steps in prebiotic development. A combination of high order and high complexity also represents a universal type of biosignature which could be used to identify unknown forms of life or remnants thereof.
Journal Article
Female reproductive maturation in the absence of kisspeptin/GPR54 signaling
Kisspeptin-releasing neurons, affecting gonadotropin releasing hormone secretion, are thought to coordinate puberty onset. The authors generated mice lacking kisspeptin-expressing cells and found that puberty onset in female mice was unaffected. These animals were also fertile, despite having smaller ovaries.
Puberty onset is initiated in the brain by activation of gonadotropin-releasing hormone (GnRH) neurosecretion. Different permissive signals must be integrated for the initiation of reproductive maturation; however, the neural circuits controlling timely awakening of the reproductive axis are not understood. The identification of the neuropeptide kisspeptin as a potent activator of GnRH neuronal activity suggests that kisspeptin-releasing neurons might coordinate puberty onset. To test this hypothesis, we generated mice that specifically lack kisspeptin cells. Puberty onset in females was unaffected by kisspeptin neuron ablation. Furthermore, the animals were fertile, albeit with smaller ovaries. Consistent with this, female mice lacking neurons that express the kisspeptin receptor GPR54 were also fertile. Acute ablation of kisspeptin neurons in adult mice inhibited fertility, suggesting that there is compensation for the loss of kisspeptin neurons early in development. Our data indicate that the initiation and completion of reproductive maturation can occur in the absence of kisspeptin/GPR54 signaling.
Journal Article
The microanatomic segregation of selection by apoptosis in the germinal center
Germinal centers (GCs) are areas within lymphoid organs where mature B cells expand and differentiate during normal immune responses. GCs are separated into two anatomic compartments: the dark zone, where B cells divide and undergo somatic hypermutation, and the light zone, where they are selected for affinity-enhancing mutations after interacting with T follicular helper cells. Mayer et al. studied apoptosis reporter mice and found that both GC zones experience very high rates of apoptosis (see the Perspective by Bryant and Hodgkin). However, the underlying mechanisms were distinct and microanatomically segregated. Light-zo ne B cells underwent apoptosis by default unless they were rescued by positive selection. In contrast, apoptotic dark-zone B cells were highly enriched among cells with genes damaged by random antibody-gene mutations. Science , this issue p. eaao2602 ; see also p. 171 The selection of germinal center B cells by apoptosis is regulated by microanatomically distinct mechanisms. B cells undergo rapid cell division and affinity maturation in anatomically distinct sites in lymphoid organs called germinal centers (GCs). Homeostasis is maintained in part by B cell apoptosis. However, the precise contribution of apoptosis to GC biology and selection is not well defined. We developed apoptosis-indicator mice and used them to visualize, purify, and characterize dying GC B cells. Apoptosis is prevalent in the GC, with up to half of all GC B cells dying every 6 hours. Moreover, programmed cell death is differentially regulated in the light zone and the dark zone: Light-zone B cells die by default if they are not positively selected, whereas dark-zone cells die when their antigen receptors are damaged by activation-induced cytidine deaminase.
Journal Article
Aesthetics of iris reconstruction with a custom-made artificial iris prosthesis
Patients with large iris defects not only suffer from functional disadvantages but also from aesthetic limitations. The aim of this study was to evaluate the aesthetic outcome of iris reconstruction using an artificial iris (AI). In this study, 82 eyes of 79 consecutive patients with mostly traumatic partial or total aniridia that underwent iris reconstruction surgery using a custom-made silicone AI (HumanOptics, Erlangen, Germany). Pre- and postoperative photographs of 66 patients were analysed subjectively and objectively. Subjective evaluation was based questionnaires. Objective evaluation included measurement of pupil centration and iris colour analysis. Averaged hues from iris areas were transferred to numerical values using the LAB-colour-system. Single parameters and overall difference value (ΔE) were compared between AI and remaining iris (RI), as well as AI and fellow eye iris (FI). Patients, eye doctors and laymen rated the overall aesthetic outcome with 8.9 ±1.4, 7.7 ±1.1 and 7.3 ±1.1 out of 10 points, respectively. Mean AI decentration was 0.35 ±0.24 mm. Better pupil centration correlated with a higher overall score for aesthetic outcome (p<0.05). The AI was on average 4.65 ±10 points brighter than RI and FI. Aniridia treatment using a custom-made artificial iris prosthesis offers a good aesthetic outcome. Pupil centration was a key factor that correlated with the amount of aesthetic satisfaction. The AI was on average slightly brighter than the RI and FI.
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