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

Nurturing the young shoots of talent: Using action research for exploration and theory building

This is an Author's Accepted Manuscript of an article published in European Early Childhood Education Research Journal, 19(4), 433-450, 2011, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/1350293X.2011.623515.This paper reports the outcomes of a set of action research projects carried out by teacher researchers in 14 local education authorities in England, working collaboratively with university tutors, over a period of three years. The common aim of all the projects was to explore practical ways of nurturing the gifts and talents of children aged four–seven years. The project was funded by the Department of Education and Skills in England as part of the government's gifted and talented programme. The project teachers felt that their understanding of issues relating to nurturing the gifts and talents of younger children was enhanced through their engagement in the project. It was possible to map the findings of the projects to the English government's National Quality Standards for gifted and talented education which include: (1) identification; (2) effective provision in the classroom; (3) enabling curriculum entitlement and choice; (4) assessment for learning; (5) engaging with community, families and beyond. The findings are also analysed within the framework of good practice in educating children in the first years of schooling. Participating practitioners felt that action research offered them a suitable methodology to explore the complexity of the topic of giftedness through cycles of planning, action and reflection and personal theory building

Review

Molecular chaperones are highly conserved proteins that promote proper folding of other proteinsin vivo. Diverse chaperone systems assistde novoprotein folding and trafficking, the assembly of oligomeric complexes, and recovery from stress-induced unfolding. A fundamental function of molecular chaperones is to inhibit unproductive protein interactions by recognizing and protecting hydrophobic surfaces that are exposed during folding or following proteotoxic stress. Beyond this basic principle, it is now clear that chaperones can also actively and specifically accelerate folding reactions in an ATP-dependent manner. We focus on the bacterial Hsp70 and chaperonin systems as paradigms, and review recent work that has advanced our understanding of how these chaperones act as catalysts of protein folding

Influence of leaf trichome type, and density on the host plant selection by the greenhouse whitefly, Trialeurodes vaporariorum (Hemiptera: Aleyrodidae)

Host selection by adult greenhouse whitefly Trialeurodes vaporariorum (Westwood) was assessed on two pelargonium plant cultivars, Pelargonium x domesticum (regal) and P. x hortorum (zonal) using Petri dish bioassay chambers in choice and no-choice tests. Plant characteristics which could influence the oviposition preference of the whitely i.e., type and density of trichomes on the abaxial leaf surface was determined. A strong host preference was observed for the regal compared to the zonal pelargonium by the adult whiteflies. In no-choice tests, adults laid a significantly higher number of eggs on regal than on zonal leaves both at 24 and 48 hours post-exposure, respectively. After exposure to the adult whitefly, the number of 42 eggs in choice tests were similar between cultivars at 24 hours, but were higher for regal at 48 and 72 hours. The total number of trichomes (sng: straight non-glandular + sg: straight glandular) per 0.50 cm2 44 was significantly less on regal (Mean ± SE sng + sg; 43.1 ± 1.5) than on zonal leaves (60.5 ± 1.2); however, the sng trichomes were significantly higher on the zonal (49.4 ± 0.96) than the regal leaves (28.6 ± 1.00). Also, the number of sg trichomes was slightly higher for the regal cultivar leaves compared to the zonal, being 14.4 ± 1.2 and 11.2 ± 0.5, respectively. Results suggest that the trichome density, type and the ability to express glandular exudates can affect adult whitefly Pelargonium cultivar preference and plays an important role in their host plant selection for oviposition

Breaking the Double Impasse: Securing and Supporting Diverse Housing Tenures in the United States

What might be described as a double impasse characterizes debate on U.S. housing tenure with advocates fighting for rental or ownership housing on one side and Third Way or mixed-tenure solutions on the other. Breaking this impasse requires disengaging from conceptions of an idealized form of tenure and instead advocating making virtually all tenures as secure and supported as possible, so that diverse households are able to live in homes that best fit their changing needs over their life cycles. This essay (a) presents data on the variety of tenures in the United States; (b) conveys a new two-dimensional map of tenure according to their degrees of control and potential for wealth-building; and (c) shows how U.S. institutions shape their risks and subsidies. Most U.S. tenures are at least somewhat risky, including those that receive the greatest federal subsidies. A new housing system is needed to secure and support as many tenures as possible

Hypofractionated image-guided radiotherapy for the treatment of acoustic neuromas: A dosimetrically acceptable alternative to stereotactic radiosurgery in a resource-constrained environment

Purpose: Treatment options for acoustic neuromas (ANs) are limited in low- and middle-income countries. The aim of this study was to investigate whether hypofractionated image-guided radiotherapy (IGRT) is a clinically acceptable treatment option for departments where no other radiosurgery options are available. Methods and materials: Fifteen dynamic conformal arc plans that had been clinically utilised were evaluated against the Radiation Therapy Oncology Group (RTOG) radiosurgery criteria and published indices. Analysis involved evaluating critical structure doses and the volume of normal tissue receiving 12 and 10 Gy single fraction equivalent dose (V12Eq and V10Eq). Results: Overall, there was only one RTOG protocol deviation in the whole patient group, where quality of coverage was compromised in order to achieve brainstem tolerance. Conformity indices were within clinically acceptable limits (CIPaddick ≥ 0.6) despite being inferior to the published Universitair Ziekenhuis Brussel (UZB) Gamma Knife and CyberKnife results (p < 0.0001). Homogeneity was superior to the Gamma Knife (p < 0.0001) and Novalis dynamic conformal arc (p = 0.0002) results. Gradient index results were inferior to all published techniques, but doses to the normal structures were well controlled with the exception of the cochlea. The V10Eq data showed increased sensitivity when compared with V12Eq. Conclusion: Dynamic arc IGRT allows for good coverage of AN lesions, but the dose fall-off is not as steep as that obtained with mainstream radiosurgery systems. Contouring and planning should include detailed critical structures analysis. For normal brain parenchyma analysis, V10Eq is a superior risk indicator when compared to V12Eq for this technique. Dynamic arc IGRT offers a dosimetrically acceptable treatment alternative for patients without serviceable hearing, in departments where there are no mainstream radiosurgery treatment options available

MicroRNA responses to acute resistance exercise protocols: a pilot study

INTRODUCTION: MicroRNAs (miRNAs) are non-coding RNAs that have an important role in regulating gene expression. Although circulating miRNAs are considered good markers of response to acute resistance training (RT) (1), change in expression according to the applied stimulus (e.g. high-intensity low-volume vs. low-intensity high-volume) has yet to be investigated. The aim of this study was therefore to evaluate the impact of RT protocols on circulating miRNA levels. We selected miRNA 29a, 128a, 486 as they have been previously shown to be implicated in skeletal muscle regeneration and structural adaptation (i.e. hypertrophy

Periodic points in random substitution subshifts

We study various aspects of periodic points for random substitution subshifts. In order to do so, we introduce a new property for random substitutions called the disjoint images condition. We provide a procedure for determining the property for compatible random substitutions—random substitutions for which a well-defined abelianisation exists. We find some simple necessary criteria for primitive, compatible random substitutions to admit periodic points in their subshifts. In the case that the random substitution further has disjoint images and is of constant length, we provide a stronger criterion. A method is outlined for enumerating periodic points of any specified length in a random substitution subshift

Risks of stillbirth and neonatal death with advancing gestation at term: A systematic review and meta-analysis of cohort studies of 15 million pregnancies

Data Availability Statement: Data is held in a secure system in Barts Research Centre and available at https://www.barc-research.org.Peer reviewe

Chemical composition and antibacterial activity of essential oils from the medicinal plant Mentha cervina L. grown in Portugal

Mentha cervina is a medicinal plant traditionally used in Portugal in folk medicine, in different gastric disorders and inflammations of the respiratory tract. In order to validate those traditional uses, M. cervina essential oils (EOs) were characterized by GC and GC–MS and their antimicrobial activity was tested against 23 bacterial strains (including multiresistant strains). The EOs were dominated by the monoterpenes pulegone (52–75%), isomenthone (8–24%), limonene (4–6%), and menthone (1–2%). The antibacterial activity of these EOs was compared to that of the main components standards. The most effective antibacterial activity was expressed by the EOs against the Gram-negative bacteria, Escherichia coli and Acinetobacter baumanni, with MIC values of 1 mg/ml. The EOs complex mixtures were more active than the individual aromatic components supporting the hypothesis that the EOs antibacterial activity is a function of the synergistic effect of their different aromatic components. These results show the potential role of M. cervina EOs as antibacterial agents and validate the traditional use of this plant