Bacterial Hsp70 resolves misfolded states and accelerates productive folding of a multi-domain protein

The ATP-dependent Hsp70 chaperones (DnaK in E. coli) mediate protein folding in cooperation with J proteins and nucleotide exchange factors (E. coli DnaJ and GrpE, respectively). The Hsp70 system prevents protein aggregation and increases folding yields. Whether it also enhances the rate of folding remains unclear. Here we show that DnaK/DnaJ/GrpE accelerate the folding of the multi-domain protein firefly luciferase (FLuc) 20-fold over the rate of spontaneous folding measured in the absence of aggregation. Analysis by single-pair FRET and hydrogen/deuterium exchange identified inter-domain misfolding as the cause of slow folding. DnaK binding expands the misfolded region and thereby resolves the kinetically-trapped intermediates, with folding occurring upon GrpE-mediated release. In each round of release DnaK commits a fraction of FLuc to fast folding, circumventing misfolding. We suggest that by resolving misfolding and accelerating productive folding, the bacterial Hsp70 system can maintain proteins in their native states under otherwise denaturing stress conditions. The Hsp70 system prevents protein aggregation and increases folding yields, but it is unknown whether it also enhances the rate of folding. Here the authors combine refolding assays, FRET and hydrogen/deuterium exchange-mass spectrometry measurements to study the folding of firefly luciferase and find that the bacterial Hsp70 actively promotes the folding of this multi-domain protein

Production and processing of organically grown fiber nettle (Urtica dioica L.) and its potential use in the natural textiles industry: A review

In Europe, the perennial stinging nettle was cultivated during the 19th century until the Second World War and has a long history as a fiber plant. Clone varieties dating back to the early 20th century are still maintained at European research institutions. The fiber content of clones ranges from 1.2 to 16% dry matter, and fiber yields range from 0.14 to 1.28 Mg/ha. Varietal purity of fiber nettle can only be achieved by planting cuttings. The harvesting of fiber starts in the second year of growth and the crop may produce well for several years. Several agronomic practices influence fiber quality, but causal relations are not yet well understood. Various parts of the fiber nettle plant can be used as food, fodder and as raw material for different purposes in cosmetics, medicine, industry and biodynamic agriculture. Organically produced fibers are in demand by the green textile industry and show potential that is economically promising

Temporal and dimensional effects in evolutionary graph theory

The spread in time of a mutation through a population is studied analytically and computationally in fully-connected networks and on spatial lattices. The time, t_*, for a favourable mutation to dominate scales with population size N as N^{(D+1)/D} in D-dimensional hypercubic lattices and as N ln N in fully-connected graphs. It is shown that the surface of the interface between mutants and non-mutants is crucial in predicting the dynamics of the system. Network topology has a significant effect on the equilibrium fitness of a simple population model incorporating multiple mutations and sexual reproduction. Includes supplementary information.Comment: 6 pages, 4 figures Replaced after final round of peer revie

Tiefenverteilung von Wurzeln bei Winterweizen

The production and distribution of roots was examined for two winter wheat cultivars (Capo and Saturnus). Plants were grown in PVC tubes of 150 cm length that were placed in a field. The length of roots in 20 cm soil sections was measured at three times. Mean root length densities decreased from 7-15 cm cm-3 soil in the top 20 cm soil to 2 cm cm-3 at soil depths below 80 cm. Only slight differences were obtained for the two cultivars and between harvests. Saturnus produced relatively greater root lengths in upper soil horizons, while Capo spread its roots further down the soil profile. Maximum rooting depth was between 150 to 160 cm

ER Stress-Induced eIF2-alpha Phosphorylation Underlies Sensitivity of Striatal Neurons to Pathogenic Huntingtin

A hallmark of Huntington's disease is the pronounced sensitivity of striatal neurons to polyglutamine-expanded huntingtin expression. Here we show that cultured striatal cells and murine brain striatum have remarkably low levels of phosphorylation of translation initiation factor eIF2 alpha, a stress-induced process that interferes with general protein synthesis and also induces differential translation of pro-apoptotic factors. EIF2 alpha phosphorylation was elevated in a striatal cell line stably expressing pathogenic huntingtin, as well as in brain sections of Huntington's disease model mice. Pathogenic huntingtin caused endoplasmic reticulum (ER) stress and increased eIF2 alpha phosphorylation by increasing the activity of PKR-like ER-localized eIF2 alpha kinase (PERK). Importantly, striatal neurons exhibited special sensitivity to ER stress-inducing agents, which was potentiated by pathogenic huntingtin. We could strongly reduce huntingtin toxicity by inhibiting PERK. Therefore, alteration of protein homeostasis and eIF2 alpha phosphorylation status by pathogenic huntingtin appears to be an important cause of striatal cell death. A dephosphorylated state of eIF2 alpha has been linked to cognition, which suggests that the effect of pathogenic huntingtin might also be a source of the early cognitive impairment seen in patients

General-Relativistic Curvature of Pulsar Vortex Structure

The motion of a neutron superfluid condensate in a pulsar is studied. Several theorems of general-relativistic hydrodynamics are proved for a superfluid. The average density distribution of vortex lines in pulsars and their general-relativistic curvature are derived.Comment: 18 pages, 1 figure

Metaheuristics for the Vehicle Routing Problem with Loading Constraints

We consider a combination of the capacitated vehicle routing problem and a class of additional loading constraints involving a parallel machine scheduling problem. The work is motivated by a real-world transportation problem occurring to a wood-products retailer, which delivers its products to a number of customers in a specific region. We solve the problem by means of two different metaheuristics algorithms: a Tabu Search and an Ant Colony Optimization. Extensive computational results are given for both algorithms, on instances derived from the vehicle routing literature and on real-world instances

Elucidating the structure of chiral molecules by using amplified vibrational circular dichroism: from theory to experimental realization

Recent experimental observations of enhanced vibrational circular dichroism (VCD) in molecular systems with low-lying electronically excited states suggest interesting new applications of VCD spectroscopy. The theory describing VCD enhancement through vibronic coupling schemes was derived by Nafie in 1983, but only recently experimental evidence of VCD amplification has demonstrated the extent to which this effect can be exploited as a structure elucidation tool to probe local structure. In this Concept paper, we give an overview of the physics behind vibrational circular dichroism, in particular the equations governing the VCD amplification effect, and review the latest experimental developments with a prospective view on the application of amplified VCD to locally probe biomolecular structure

Pure Anderson Motives and Abelian \tau-Sheaves

Pure t-motives were introduced by G. Anderson as higher dimensional generalizations of Drinfeld modules, and as the appropriate analogs of abelian varieties in the arithmetic of function fields. In order to construct moduli spaces for pure t-motives the second author has previously introduced the concept of abelian \tau-sheaf. In this article we clarify the relation between pure t-motives and abelian \tau-sheaves. We obtain an equivalence of the respective quasi-isogeny categories. Furthermore, we develop the elementary theory of both structures regarding morphisms, isogenies, Tate modules, and local shtukas. The later are the analogs of p-divisible groups.Comment: final version as it appears in Mathematische Zeitschrif