Drosophila as a model system to study nonautonomous mechanisms affecting tumour growth and cell death

The study of cancer has represented a central focus in medical research for over a century. The great complexity and constant evolution of the pathology require the use of multiple research model systems and interdisciplinary approaches. This is necessary in order to achieve a comprehensive understanding into the mechanisms driving disease initiation and progression, to aid the development of appropriate therapies. In recent decades, the fruit fly Drosophila melanogaster and its associated powerful genetic tools have become a very attractive model system to study tumour-intrinsic and non-tumour-derived processes that mediate tumour development in vivo. In this review, we will summarize recent work on Drosophila as a model system to study cancer biology. We will focus on the interactions between tumours and their microenvironment, including extrinsic mechanisms affecting tumour growth and how tumours impact systemic host physiology

Multi-Platform Whole-Genome Microarray Analyses Refine the Epigenetic Signature of Breast Cancer Metastasis with Gene Expression and Copy Number

BACKGROUND: We have previously identified genome-wide DNA methylation changes in a cell line model of breast cancer metastasis. These complex epigenetic changes that we observed, along with concurrent karyotype analyses, have led us to hypothesize that complex genomic alterations in cancer cells (deletions, translocations and ploidy) are superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes observed in breast cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We undertook simultaneous high-resolution, whole-genome analyses of MDA-MB-468GFP and MDA-MB-468GFP-LN human breast cancer cell lines (an isogenic, paired lymphatic metastasis cell line model) using Affymetrix gene expression (U133), promoter (1.0R), and SNP/CNV (SNP 6.0) microarray platforms to correlate data from gene expression, epigenetic (DNA methylation), and combination copy number variant/single nucleotide polymorphism microarrays. Using Partek Software and Ingenuity Pathway Analysis we integrated datasets from these three platforms and detected multiple hypomethylation and hypermethylation events. Many of these epigenetic alterations correlated with gene expression changes. In addition, gene dosage events correlated with the karyotypic differences observed between the cell lines and were reflected in specific promoter methylation patterns. Gene subsets were identified that correlated hyper (and hypo) methylation with the loss (or gain) of gene expression and in parallel, with gene dosage losses and gains, respectively. Individual gene targets from these subsets were also validated for their methylation, expression and copy number status, and susceptible gene pathways were identified that may indicate how selective advantage drives the processes of tumourigenesis and metastasis. CONCLUSIONS/SIGNIFICANCE: Our approach allows more precisely profiling of functionally relevant epigenetic signatures that are associated with cancer progression and metastasis

Drosophila larval models of invasive tumorigenesis for in vivo studies on tumour/peripheral host tissue interactions during cancer cachexia

Cancer cachexia is a common deleterious paraneoplastic syndrome that represents an area of unmet clinical need, partly due to its poorly understood aetiology and complex multifactorial nature. We have interrogated multiple genetically defined larval Drosophila models of tumourigenesis against key features of human cancer cachexia. Our results indicate that cachectic tissue wasting is dependent on the genetic characteristics of the tumour and demonstrate that host malnutrition or tumour burden are not sufficient to drive wasting. We show that JAK/STAT and TNF-α/Egr signalling are elevated in cachectic muscle and promote tissue wasting. Furthermore, we introduce a dual driver system that allows independent genetic manipulation of tumour and host skeletal muscle. Overall, we present a novel Drosophila larval paradigm to study tumour/host tissue crosstalk in vivo, which may contribute to future research in cancer cachexia and impact the design of therapeutic approaches for this pathology

Exploring the experiences of having Guillain‐Barré Syndrome: A qualitative interview study

Background: Guillain-Barré syndrome (GBS) is a rare inflammatory disorder affecting the peripheral nerves. Although typically there is full neurological recovery, some people continue to experience residual physical, psychological or social problems longer term. Evidence describing the experiences of people with GBS is limited. Objective: We aimed to explore the experiences of people with GBS in the UK. Design: We used qualitative (face-to-face and telephone) interviews to explore experiences of people with GBS. Audio-recorded data were transcribed verbatim and analysed using the Framework Method supported by NVivo 11. Setting and Participants: We purposively recruited a sample of 16 volunteers with a prior diagnosis of GBS of varying age, sex, ethnicity, location, marital status, time since diagnosis and length of hospital stay to maximize differences in experience. Interviewees were required to have been discharged from hospital, able to give informed consent, able to speak and understand English and currently resident in the United Kingdom. Results: The key themes arising from the analysis were as follows: the importance of early diagnosis; the experiences of inpatient care; the importance of active support for recovery; the need for communication throughout the course of the illness; the need for greater awareness, knowledge and provision of information by health-care staff; and path to achieving function. Conclusion: This is the first qualitative study exploring experiences of people with GBS in the UK through their whole illness journey from onset to recovery. The findings contribute to our understanding of the experiences and support needs of people recovering from GBS

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

Late Glacial and Holocene Palaeolake History of the Última Esperanza Region of Southern Patagonia

We undertook multi-proxy analyses on two sediment cores from Lago Pato, a small lake basin at 51°S topographically separated from Lago del Toro in Torres del Paine (TdP), to provide insights into glacier dynamics and lake-level change in the TdP and Última Esperanza region over the last ∼30,000 cal a BP (30 ka). Lago Pato is situated in a region overridden by the Southern Patagonian Ice Field during the Last Glacial and in a transitional climatic zone of Southern Patagonia sensitive to seasonal- to millennial-scale changes in the Southern Hemisphere Westerly Winds (SWW). Results show that a deep ice-dammed and enlarged palaeolake encompassed Lago del Toro and Lago Pato c. 30–20 ka after the ice had retreated from local-Last Glacial Maximum (l-LGM) limits at c. 48–34 ka and during the build-up to the global-Last Glacial Maximum (g-LGM), c. 26–19 ka. Gaps in both sediment records between c. 20–13.4 ka and c. 20–10 ka suggest hiatuses in sediment accumulation during the g-LGM and Antarctic Cold Reversal (ACR) readvances and/or removal by lake lowering or flushing during the Late Glacial–early Holocene. The palaeolake level dropped from >100 m a.s.l. to ∼40–50 m a.s.l. towards the end of the ACR c. 13.4–13.0 ka, creating a shallower glaciolacustrine environment dammed by an ice tongue in the Estancia Puerto Consuelo–Última Esperanza fjord. Further lowering of the enlarged palaeolake level occurred when the ice thinned to <40 m a.s.l., eventually isolating Lago Pato from Lago del Toro and glaciogenic sediment input at c. 11.7 ka. After isolation, the ecology and water levels in Lago Pato became sensitive to regional climate shifts. The shallow, stable, and highly anoxic environment that developed after c. 11.7 ka is associated with weaker (or poleward shifted) SWW at 51°S and was replaced at c. 10 ka by an increasingly productive shallow-littoral lake with a variable lake-level and periodic shifts in anoxic-oxic bottom water conditions and ratios of benthic-planktonic diatoms. A more open Nothofagus forest, established at c. 8.6–7.5 ka, and more arid conditions c. 7.5–5.7 cal ka BP are linked to another phase of weaker (or poleward shifted) SWW at 51°S. More persistently wet conditions from c. 5.7 ka, with extensive closed Nothofagus forests and planktonic diatoms dominant, are associated with stronger (or equatorward shifted) SWW over 51°S. The abrupt return of benthic-to-tychoplanktonic diatoms after c. 3 ka reflects enhanced SWW at 51°S. Increasingly stable lacustrine and littoral wetland conditions established in the last ∼500 years reflect weaker SWW and lasted until recent decades

Physical pretreatment of biogenic-rich trommel fines for fast pyrolysis

Energy from Waste (EfW) technologies such as fluidized bed fast pyrolysis, are beneficial for both energy generation and waste management. Such technologies, however face significant challenges due to the heterogeneous nature, particularly the high ash contents of some municipal solid waste types e.g. trommel fines. A study of the physical/mechanical and thermal characteristics of these complex wastes is important for two main reasons; (a) to inform the design and operation of pyrolysis systems to handle the characteristics of such waste; (b) to control/modify the characteristics of the waste to fit with existing EFW technologies via appropriate feedstock preparation methods. In this study, the preparation and detailed characterisation of a sample of biogenic-rich trommel fines has been carried out with a view to making the feedstock suitable for fast pyrolysis based on an existing fluidized bed reactor. Results indicate that control of feed particle size was very important to prevent problems of dust entrainment in the fluidizing gas as well as to prevent feeder hardware problems caused by large stones and aggregates. After physical separation and size reduction, nearly 70. wt% of the trommel fines was obtained within the size range suitable for energy recovery using the existing fast pyrolysis system. This pyrolyzable fraction could account for about 83% of the energy content of the 'as received' trommel fines sample. Therefore there was no significant differences in the thermochemical properties of the raw and pre-treated feedstocks, indicating that suitably prepared trommel fines samples can be used for energy recovery, with significant reduction in mass and volume of the original waste. Consequently, this can lead to more than 90% reduction in the present costs of disposal of trommel fines in landfills. In addition, the recovered plastics and textile materials could be used as refuse derived fuel

The Eastern Origins of the Rise of the West and the “Return” of Asia

With the current interest in China (and India) proliferating within the Western Academy, this article claims that what we are witnessing today is not the rise but the “return” of China (and India). Many academics assume that the West has been the dominant civilization in the world economy in the last 500 years and that the current “rise” of China threatens to knock the West off its perch. However, this article provides an alternative take to this cherished axiom of Eurocentric world history by inverting the standard belief that the West pioneered modernity and then expanded outwards to remake the world. Thus, I argue not only that globalization preceded the rise of the West but that it was Eastern-led on the one hand and that it enabled the Western breakthrough into modernity on the other. This, in turn, rests on my claim that Chinese development stems back not to 1978 but to 960 ce as the Sung Dynasty emerged and subsequently undertook a quasi-industrial miracle. Moreover, between 1450/1492 and ca. 1830 China lay at the centre of the nascent global economy, fanning the integration process alongside other key non-Western regions such as India and West Asia/North Africa. And, while the West was the dominant player after ca. 1830 down to the turn of the third millennium, nevertheless, what we witness today is the return of China to the centre of the global economy whence it came