Quantum Dots Do Not Affect the Behaviour of Mouse Embryonic Stem Cells and Kidney Stem Cells and Are Suitable for Short-Term Tracking

Quantum dots (QDs) are small nanocrystals widely used for labelling cells in order to enable cell tracking in complex environments in vitro, ex vivo and in vivo. They present many advantages over traditional fluorescent markers as they are resistant to photobleaching and have narrow emission spectra. Although QDs have been used effectively in cell tracking applications, their suitability has been questioned by reports showing they can affect stem cell behaviour and can be transferred to neighbouring cells. Using a variety of cellular and molecular biology techniques, we have investigated the effect of QDs on the proliferation and differentiation potential of two stem cell types: mouse embryonic stem cells and tissue-specific stem cells derived from mouse kidney. We have also tested if QDs released from living or dead cells can be taken up by neighbouring cells, and we have determined if QDs affect the degree of cell-cell fusion; this information is critical in order to assess the suitability of QDs for stem cell tracking. We show here that QDs have no effect on the viability, proliferation or differentiation potential of the two stem cell types. Furthermore, we show that the extent of transfer of QDs to neighbouring cells is <4%, and that QDs do not increase the degree of cell-cell fusion. However, although the QDs have a high labelling efficiency (>85%), they are rapidly depleted from both stem cell populations. Taken together, our results suggest that QDs are effective cell labelling probes that are suitable for short-term stem cell tracking

A resource-based view and dynamic capabilities approach in the context of a region’s international attractiveness: The recent case of Western Australia

This exploratory study proposes a framework based on the resource view theory and the dynamic capabilities approach to further the understanding of a region’s attractiveness, particularly from an international perspective. The case of Western Australia is examined through in-depth, face-to-face interviews with nine country consuls experienced in international trade. The findings revealed significant ways in which Western Australia could enhance its future commercial appeal. The findings revealed the value of synergies between this state and other countries, particularly exchanging expertise, transferring knowledge, or exporting know-how, education, both university and industry-focused, research and development and expertise. These forms of regional attractiveness emphasise the strategic role of industry resources and dynamic capabilities, thus, underscoring the usefulness and applicability of the proposed framework. While the state’s mineral exports will continue to drive its economy, harnessing its potential in other areas is crucial to adapt to changing business environments and to build sustained competitive advantage. © 2018, The Author(s) 2018

Prospects for the development of probiotics and prebiotics for oral applications

There has been a paradigm shift towards an ecological and microbial community-based approach to understanding oral diseases. This has significant implications for approaches to therapy and has raised the possibility of developing novel strategies through manipulation of the resident oral microbiota and modulation of host immune responses. The increased popularity of using probiotic bacteria and/or prebiotic supplements to improve gastrointestinal health has prompted interest in the utility of this approach for oral applications. Evidence now suggests that probiotics may function not only by direct inhibition of, or enhanced competition with, pathogenic micro-organisms, but also by more subtle mechanisms including modulation of the mucosal immune system. Similarly, prebiotics could promote the growth of beneficial micro-organisms that comprise part of the resident microbiota. The evidence for the use of pro or prebiotics for the prevention of caries or periodontal diseases is reviewed, and issues that could arise from their use, as well as questions that still need to be answered, are raised. A complete understanding of the broad ecological changes induced in the mouth by probiotics or prebiotics will be essential to assess their long-term consequences for oral health and disease

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Comparative proteomic analysis of two contrasting cultivars reveals the mechanism of sugar beet response to freezing stress

Sugar beet (Beta vulgaris L.) is an economic crop integrating grain and feed production, and is a major source of sucrose. Freezing stress can cause dehydration and necrosis of seedlings. Therefore, it is important to study the basic physiological and proteomic mechanisms of different sugar beet cultivars under freezing stress. In this study, compared with freezing-sensitive (SME) cultivar, the freezing-tolerant (TBP) cultivar showed higher photosynthetic rate, antioxidant enzyme activity, proline and abscisic acid levels, lower malondialdehyde and gibberellin levels and relative conductivity under freezing stress. Moreover, comparative proteomic analysis revealed that proteins mapped to photosynthesis, tryptophan synthesis, anthocyanin synthesis, tricarboxylic acid cycle, reactive oxygen species scavenging and sucrose metabolism pathways were more abundant in TBP, indicating that these metabolic pathways may be beneficial to improve freezing tolerance. In particular, compared with SME cultivar, proteins involved in tryptophan synthesis were found to be upregulated only in TBP cultivar under freezing stress, including phospho-2-dehydro-3-deoxyheptonate aldolase 1, probable inactive shikimate kinase like 1, and anthranilate synthase alpha subunit 2. In addition, quantitative real-time polymerase chain reaction analysis showed that mRNA expression of these three proteins was significantly upregulated in the freezing stress (-5 celcius) vs. control group in the TBP cultivar. Additionally, tryptophan content in TBP leaves increased significantly under freezing stress, while in SME it showed no significant change. Furthermore, the application of exogenous tryptophan solution significantly reduced the mortality rate of sugar beet seedlings (17day-old) under freezing stress. This study provides a foundation for further functional analysis to fully understand the molecular mechanisms of adaptation to freezing stress in sugar beet