Work partitioning of transversally loaded muscle: experimentation and simulation

Skeletal muscles are surrounded by other muscles, connective tissue and bones, which may transfer transversal forces to the muscle belly. Simple Hill-type muscle models do not consider transversal forces. Thus, the aim of this study was to examine and model the influence of transversal muscle loading on contraction dynamics, e.g. on the rate of force development and on the maximum isometric muscle force (F_im). Isometric experiments with and without transversal muscle loading were conducted on rat muscles. The muscles were loaded (1.3 N cm^? 2) by a custom-made plunger which was able to move in transversal direction. Then the muscle was fully stimulated, the isometric force was measured at the distal tendon and the movement of the plunger was captured with a high-speed camera. The interaction between the muscle and the transversal load was modelled based on energy balance between the (1) work done by the contractile component (CC) and (2) the work done to lift the load, to stretch the series elastic structures and to deform the muscle. Compared with the unloaded contraction, the force rate was reduced by about 25% and F_im was reduced by 5% both in the experiment and in the simulation. The reduction in F_im resulted from using part of the work done by the CC to lift the load and deform the muscle. The response of the muscle to transversal loading opens a window into the interdependence of contractile and deformation work, which can be used to specify and validate 3D muscle models.     

When is a maternal effect adaptive?

Maternal effects have become an important field of study in evolutionary ecology and there is an ongoing debate regarding their adaptive significance. Some maternal effects can act to increase offspring fitness and are called 'adaptive maternal effects'. However, other maternal effects decrease offspring fitness and there is confusion regarding whether certain maternal effects are indeed adaptive or merely physiological inevitabilities. Here we suggest that the focus on the consequences of maternal effects for offspring fitness only and the use of 'snapshot' estimates of fitness have misdirected our effort to understand the evolution of maternal effects. We suggest that selection typically acts on maternal effects to maximise maternal rather than (or in addition to) offspring fitness. We highlight the importance of considering how maternal effects influence maternal fitness across a mother's lifetime and describe four broad types of maternal effects using an outcome-based approach. Overall, we suggest that many maternal effects will have an adaptive basis for mothers, regardless of whether these effects increase or decrease survival or reproductive success of individual offspring.     

Subretinal electronic chips allow blind patients to read letters and combine them to words

A light-sensitive, externally powered microchip was surgically implanted subretinally near the macular region of volunteers blind from hereditary retinal dystrophy. The implant contains an array of 1500 active microphotodiodes ('chip'), each with its own amplifier and local stimulation electrode. At the implant's tip, another array of 16 wire-connected electrodes allows light-independent direct stimulation and testing of the neuron-electrode interface. Visual scenes are projected naturally through the eye's lens onto the chip under the transparent retina. The chip generates a corresponding pattern of 38 × 40 pixels, each releasing light-intensity-dependent electric stimulation pulses. Subsequently, three previously blind persons could locate bright objects on a dark table, two of whom could discern grating patterns. One of these patients was able to correctly describe and name objects like a fork or knife on a table, geometric patterns, different kinds of fruit and discern shades of grey with only 15 per cent contrast. Without a training period, the regained visual functions enabled him to localize and approach persons in a room freely and to read large letters as complete words after several years of blindness. These results demonstrate for the first time that subretinal micro-electrode arrays with 1500 photodiodes can create detailed meaningful visual perception in previously blind individuals.     

The Validity of the Ussing Flux Ratio Equation in a Three-Dimensionally Inhomogeneous Membrane

Derivations of the Ussing flux ratio equation have, until now, required the membrane to be both bounded by parallel planes and homogeneous, except in the transmembrane direction. These constraints have been necessary for the theoretical demonstration that the equation is independent of membrane parameters in the absence of carriers, coupling, solvent drag, or “single-file” diffusion. In a new derivation, the flux ratio equation is shown to be valid in this kind of diffusion regime without regard to the three-dimensional structure of the membrane. Thus the constraints on both membrane homogeneity and membrane geometry are shown to be unnecessary. The general use of this equation to differentiate between simple, uncoupled diffusion and other membrane transport phenomena is thus placed on a firmer base. However, as in earlier derivations, it is necessary that isopotential, isobaric, constant concentration surfaces exist sufficiently close to the membrane on both of its sides.     

Investigation of metal sorption behavior of Slp1 from Lysinibacillus sphaericus JG-B53: a combined study using QCM-D,ICP-MS and AFM

Surface layer proteins (S-layer) of Lysinibacillus sphaericus JG-B53 are biological compounds with several bio-based technical applications such as biosorptive materials for metal removal or rare metals recovery from the environment. Despite their well-described applications, a deeper understanding of their metal sorption behavior still remains challenging. The metal sorption ability of Au³⁺, Pd²⁺, Pt²⁺ and Eu³⁺ was investigated by ICP-MS, AFM and QCM-D which enables the sorption detection in real-time during in situ experiments. Results indicate a high binding of Pd, followed by Au, Eu and Pt to the proteins. The comparison between different methods allowed a deeper understanding of the metal sorption of isolated S-layer either frees in liquid, adsorbed forming a protein layer or as the bacteria surface.     

Convergence in the biosynthesis of acetogenic natural products from plants,fungi, and bacteria

This review deals with polyketides to which nature has developed different biosynthetic pathways in the course of evolution. The anthraquinone chrysophanol is the first example of an acetogenic natural product that is, in an organism-specific manner, formed via more than one polyketide folding mode: In eukaryotes, like e.g., in fungi, in higher plants, and in insects, it is synthesized via folding mode F, while in prokaryotes it originates through mode S. It has, more recently, even been found to be synthesized by a third pathway, named mode S′. Thus, chrysophanol is the first polyketide synthase product that originates through a divergent–convergent biosynthesis (depending on the respective producing organisms). A second example of a striking biosynthetic convergence is the isoquinoline alkaloids. While all as yet investigated representatives of this large family of plant-derived metabolites (more than 2500 known representatives!) are formed from aromatic amino acids, the biosynthetic origin of naphthylisoquinoline alkaloids like dioncophylline A is unprecedented in following a route to isoquinolines in plants: we have shown that such naphthylisoquinolines represent the as yet only known polyketidic di- and tetrahydroisoquinolines, originating from acetate and malonate units, exclusively. Both molecular halves, the isoquinoline part and the naphthalene portion, are even synthesized from a joint polyketide precursor, the first proven case of the F-type folding mode in higher plants. The biosynthetic origins of the natural products presented in this paper were elucidated by feeding ¹³C₂-labeled acetate (or advanced precursors) to the respective producing organisms, with subsequent NMR analysis of their ¹³C₂ incorporation patterns using the potent cryoprobe methodology, thus making the full polyketide folding pattern visible.     

Delay of acute intracellular pH recovery after acidosis decreases endothelial cell activation

Reperfusion after ischemic conditions induces massive endothelial cell (EC) activation, an initial step of reperfusion injury. Reperfusion is characterized by reoxygenation, realkalinization and a localized increase of inflammatory stimuli. In this study, we focused on the influence of extracellular realkalinization on human umbilical vein endothelial cell (HUVEC) activation. We examined intracellular pH (pH(in)) and intracellular free calcium concentration ([Ca(2+)](in)), a second messenger known to mediate von Willebrand factor (VWF) exocytosis in endothelium, upon realkalinization. Furthermore, we measured the agonist-stimulated exocytosis of VWF, Interleukin-8 and soluble P-selectin (sP-Selectin) as markers of EC activation. To verify a morphological correlate of EC activation, we finally observed platelet-endothelial adherence during realkalinization using shear flow. Realkalinization of HUVEC was simulated by switching from bicarbonate buffered Ringer solution of an acidotic pH(ex) of 6.4 to a physiologic pH(ex) of 7.4. Extracellular realkalinization was accompanied by pH(in) recovery from 6.5 to 7.2 within 10 min. Application of cariporide, an inhibitor of the Na(+)/H(+) exchanger subtype 1 (NHE), during extracellular realkalinization significantly delayed the early kinetics of intracellular realkalinization. Histamine stimulated [Ca(2+)](in) was significantly increased upon realkalinization compared to control cells. Also agonist-stimulated release of VWF, Interleukin-8 and sP-Selectin was massively enhanced during pH(in) recovery in comparison to control. Furthermore, we observed an increased platelet binding to endothelium. Interestingly, each of these realkalinization-induced effects were significantly reduced by early application of cariporide. Therefore, delay of acute NHE-dependent pH(in) recovery may represent a promising mechanism for inhibition of EC activation upon reperfusion.     

The impact of the nucleosome code on protein-coding sequence evolution in yeast

Coding sequence evolution was once thought to be the result of selection on optimal protein function alone. Selection can, however, also act at the RNA level, for example, to facilitate rapid translation or ensure correct splicing. Here, we ask whether the way DNA works also imposes constraints on coding sequence evolution. We identify nucleosome positioning as a likely candidate to set up such a DNA-level selective regime and use high-resolution microarray data in yeast to compare the evolution of coding sequence bound to or free from nucleosomes. Controlling for gene expression and intra-gene location, we find a nucleosome-free "linker" sequence to evolve on average 5-6% slower at synonymous sites. A reduced rate of evolution in linker is especially evident at the 5' end of genes, where the effect extends to non-synonymous substitution rates. This is consistent with regular nucleosome architecture in this region being important in the context of gene expression control. As predicted, codons likely to generate a sequence unfavourable to nucleosome formation are enriched in linker sequence. Amino acid content is likewise skewed as a function of nucleosome occupancy. We conclude that selection operating on DNA to maintain correct positioning of nucleosomes impacts codon choice, amino acid choice, and synonymous and non-synonymous rates of evolution in coding sequence. The results support the exclusion model for nucleosome positioning and provide an alternative interpretation for runs of rare codons. As the intimate association of histones and DNA is a universal characteristic of genic sequence in eukaryotes, selection on coding sequence composition imposed by nucleosome positioning should be phylogenetically widespread.