Natural history of Arabidopsis thaliana and oomycete symbioses

Molecular ecology of plant–microbe interactions has immediate significance for filling a gap in knowledge between the laboratory discipline of molecular biology and the largely theoretical discipline of evolutionary ecology. Somewhere in between lies conservation biology, aimed at protection of habitats and the diversity of species housed within them. A seemingly insignificant wildflower called Arabidopsis thaliana has an important contribution to make in this endeavour. It has already transformed botanical research with deepening understanding of molecular processes within the species and across the Plant Kingdom; and has begun to revolutionize plant breeding by providing an invaluable catalogue of gene sequences that can be used to design the most precise molecular markers attainable for marker-assisted selection of valued traits. This review describes how A. thaliana and two of its natural biotrophic parasites could be seminal as a model for exploring the biogeography and molecular ecology of plant–microbe interactions, and specifically, for testing hypotheses proposed from the geographic mosaic theory of co-evolution

Standardized research protocols enable transdisciplinary research of climate variation impacts in corn production systems

The important questions about agriculture, climate, and sustainability have become increasingly complex and require a coordinated, multifaceted approach for developing new knowledge and understanding. A multistate, transdisciplinary project was begun in 2011 to study the potential for both mitigation and adaptation of corn-based cropping systems to climate variations. The team is measuring the baseline as well as change of the system\u27s carbon (C), nitrogen (N), and water footprints, crop productivity, and pest pressure in response to existing and novel production practices. Nine states and 11 institutions are participating in the project, necessitating a well thought out approach to coordinating field data collection procedures at 35 research sites. In addition, the collected data must be brought together in a way that can be stored and used by persons not originally involved in the data collection, necessitating robust procedures for linking metadata with the data and clearly delineated rules for use and publication of data from the overall project. In order to improve the ability to compare data across sites and begin to make inferences about soil and cropping system responses to climate across the region, detailed research protocols were developed to standardize the types of measurements taken and the specific details such as depth, time, method, numbers of samples, and minimum data set required from each site. This process required significant time, debate, and commitment of all the investigators involved with field data collection and was also informed by the data needed to run the simulation models and life cycle analyses. Although individual research teams are collecting additional measurements beyond those stated in the standardized protocols, the written protocols are used by the team for the base measurements to be compared across the region. A centralized database was constructed to meet the needs of current researchers on this project as well as for future use for data synthesis and modeling for agricultural, ecosystem, and climate sciences

How do MNC R&D laboratory roles affect employee international assignments?

Research and development (R&D) employees are important human resources for multinational corporations (MNCs) as they are the driving force behind the advancement of innovative ideas and products. International assignments of these employees can be a unique way to upgrade their expertise; allowing them to effectively recombine their unique human resources to progress existing knowledge and advance new ones. This study aims to investigate the effect of the roles of R&D laboratories in which these employees work on the international assignments they undertake. We categorise R&D laboratory roles into those of the support laboratory, the locally integrated laboratory and the internationally interdependent laboratory. Based on the theory of resource recombinations, we hypothesise that R&D employees in support laboratories are not likely to assume international assignments, whereas those in locally integrated and internationally interdependent laboratories are likely to assume international assignments. The empirical evidence, which draws from research conducted on 559 professionals in 66 MNC subsidiaries based in Greece, provides support to our hypotheses. The resource recombinations theory that extends the resource based view can effectively illuminate the international assignment field. Also, research may provide more emphasis on the close work context of R&D scientists rather than analyse their demographic characteristics, the latter being the focus of scholarly practice hitherto

CXCR4/CXCL12 Participate in Extravasation of Metastasizing Breast Cancer Cells within the Liver in a Rat Model

INTRODUCTION: Organ-specific composition of extracellular matrix proteins (ECM) is a determinant of metastatic host organ involvement. The chemokine CXCL12 and its receptor CXCR4 play important roles in the colonization of human breast cancer cells to their metastatic target organs. In this study, we investigated the effects of chemokine stimulation on adhesion and migration of different human breast cancer cell lines in vivo and in vitro with particular focus on the liver as a major metastatic site in breast cancer. METHODS: Time lapse microscopy, in vitro adhesion and migration assays were performed under CXCL12 stimulation. Activation of small GTPases showed chemokine receptor signalling dependence from ECM components. The initial events of hepatic colonisation of MDA-MB-231 and MDA-MB-468 cells were investigated by intravital microscopy of the liver in a rat model and under shRNA inhibition of CXCR4. RESULTS: In vitro, stimulation with CXCL12 induced increased chemotactic cell motility (p,0.05). This effect was dependent on adhesive substrates (type I collagen, fibronectin and laminin) and induced different responses in small GTPases, such as RhoA and Rac-1 activation, and changes in cell morphology. In addition, binding to various ECM components caused redistribution of chemokine receptors at tumour cell surfaces. In vivo, blocking CXCR4 decreased extravasation of highly metastatic MDA-MB-231 cells (p < 0.05), but initial cell adhesion within the liver sinusoids was not affected. In contrast, the less metastatic MDA-MB-468 cells showed reduced cell adhesion but similar migration within the hepatic microcirculation. CONCLUSION: Chemokine-induced extravasation of breast cancer cells along specific ECM components appears to be an important regulator but not a rate-limiting factor of their metastatic organ colonization.Claudia Wendel, André Hemping-Bovenkerk, Julia Krasnyanska, Sören Torge Mees, Marina Kochetkova, Sandra Stoeppeler and Jörg Haie

Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

OBJECTIVE: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin-K-antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. METHODS: Individual patient data analysis from 7 prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk. RESULTS: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y =0.65, 95%-CI [0.52, 0.81]) and <85 years (HR<85y =0.79, 95%-CI [0.66, 0.95]) in simple (pinteraction =0.129), adjusted (pinteraction =0.094) or weighted (pinteraction =0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and <85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). INTERPRETATION: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old

Knowledge Base, Exporting Activities, Innovation Openness and Innovation Performance: A SEM Approach Towards a Unifying Framework

In this paper we demonstrate the complexity that regulates the innovation-exports nexus. In particular we argue that innovation and exports should be treated as latent variables in order to account for as many facets possible thus, accounting for multifaceted heterogeneity. In this context, the role of innovation openness ought to be highlighted within a unified framework, as it is considered an additional activity of firms' knowledge creation strategy. In this line, innovation and exporting orientation are ruled by the firms' strategic mix comprised of internal knowledge creation processes and the diversity of innovation openness. Theoretical and empirical links between these major components are identified and measured employing a Structural Equation Modelling (SEM) approach on a sample of Greek R&D-active manufacturing firms. Empirical findings corroborate the complexity of relationships and indicate that the firms' knowledge base and open innovation strategy regulate via complementary and substitution relationships firms' innovation and export performance

Drivers for international innovation activities in developed and emerging countries

This paper aims to shed light on firm specific drivers that lead firms to internationalise their innovation activities. The paper draws a comprehensive picture of driving forces by including firm capabilities, characteristics of the firm’s competitive environment and the influence of innovation obstacles in the home country. In particular, the role of the potential driving forces is tested on the probability to carry out different innovative activities abroad (R&D, design/conception of new products, manufacturing of innovative products and implementation of new processes). In a second step these driving forces are used to observe their impact on the decision to locate innovation activities in various countries and regions (China, Eastern Europe, Western Europe and North America) as well as in groups of countries with similar levels of knowledge (country clubs). The analysis is based on the Mannheim Innovation Panel survey which represents the German CIS (Community Innovation Survey) contribution. Two survey waves are combined and result in a sample of about 1400 firms. The results show that the decision to perform innovation activities abroad is mainly driven by organisational capabilities such as absorptive capacities, international experience and existing technological competences of the respective firm. Innovation barriers at the German home base such as lack of labour and high innovation costs foster the set up of later-stage innovation activities abroad while the lack of demand demonstrates a barrier to the internationalisation decision for the development and manufacturing of new products. Location decisions receive the strongest influencing effects from the international experience of the firm. Firms which innovate in developing countries seem to require a more extensive level of international experience by international R&D cooperation

Bilayer-spanning DNA nanopores with voltage-switching between open and closed state.

Membrane-spanning nanopores from folded DNA are a recent example of biomimetic man-made nanostructures that can open up applications in biosensing, drug delivery, and nanofluidics. In this report, we generate a DNA nanopore based on the archetypal six-helix-bundle architecture and systematically characterize it via single-channel current recordings to address several fundamental scientific questions in this emerging field. We establish that the DNA pores exhibit two voltage-dependent conductance states. Low transmembrane voltages favor a stable high-conductance level, which corresponds to an unobstructed DNA pore. The expected inner width of the open channel is confirmed by measuring the conductance change as a function of poly(ethylene glycol) (PEG) size, whereby smaller PEGs are assumed to enter the pore. PEG sizing also clarifies that the main ion-conducting path runs through the membrane-spanning channel lumen as opposed to any proposed gap between the outer pore wall and the lipid bilayer. At higher voltages, the channel shows a main low-conductance state probably caused by electric-field-induced changes of the DNA pore in its conformation or orientation. This voltage-dependent switching between the open and closed states is observed with planar lipid bilayers as well as bilayers mounted on glass nanopipettes. These findings settle a discrepancy between two previously published conductances. By systematically exploring a large space of parameters and answering key questions, our report supports the development of DNA nanopores for nanobiotechnology.The SH lab is supported by the Leverhulme Trust (RPG-170), UCL Chemistry, EPSRC (Institutional Sponsorship Award), the National Physical Laboratory, and Oxford Nanopore Technologies. KG acknowledges funding from the Winton Program of Physics for Sustainability, Gates Cambridge and the Oppenheimer Trust. UFK was supported by an ERC starting grant #261101.This is the final version of the article. It was first published by ACS under the ACS AuthorChoice license at http://dx.doi.org/10.1021/nn5039433 This permits copying and redistribution of the article or any adaptations for non-commercial purposes