Artificial graphene as a tunable Dirac material

Artificial honeycomb lattices offer a tunable platform to study massless Dirac quasiparticles and their topological and correlated phases. Here we review recent progress in the design and fabrication of such synthetic structures focusing on nanopatterning of two-dimensional electron gases in semiconductors, molecule-by-molecule assembly by scanning probe methods, and optical trapping of ultracold atoms in crystals of light. We also discuss photonic crystals with Dirac cone dispersion and topologically protected edge states. We emphasize how the interplay between single-particle band structure engineering and cooperative effects leads to spectacular manifestations in tunneling and optical spectroscopies.Comment: Review article, 14 pages, 5 figures, 112 Reference

Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation.

Adult somatic tissues have proven difficult to expand in vitro, largely because of the complexity of recreating appropriate environmental signals in culture. We have overcome this problem recently and developed culture conditions for adult stem cells that allow the long-term expansion of adult primary tissues from small intestine, stomach, liver and pancreas into self-assembling 3D structures that we have termed 'organoids'. We provide a detailed protocol that describes how to grow adult mouse and human liver and pancreas organoids, from cell isolation and long-term expansion to genetic manipulation in vitro. Liver and pancreas cells grow in a gel-based extracellular matrix (ECM) and a defined medium. The cells can self-organize into organoids that self-renew in vitro while retaining their tissue-of-origin commitment, genetic stability and potential to differentiate into functional cells in vitro (hepatocytes) and in vivo (hepatocytes and endocrine cells). Genetic modification of these organoids opens up avenues for the manipulation of adult stem cells in vitro, which could facilitate the study of human biology and allow gene correction for regenerative medicine purposes. The complete protocol takes 1-4 weeks to generate self-renewing 3D organoids and to perform genetic manipulation experiments. Personnel with basic scientific training can conduct this protocol.LB is supported by an EMBO Postdoctoral fellowship (EMBO ALTF 794-2014). CH is supported by a Cambridge Stem Cell Institute Seed Fund award and the Herchel Smith Fund. BK is supported by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society. MH is a Wellcome Trust Sir Henry Dale Fellow and is jointly funded by the Wellcome Trust and the Royal Society (104151/Z/14/Z).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nprot.2016.097

Sterol Intermediates of Cholesterol Biosynthesis Inhibit Hair Growth and Trigger an Innate Immune Response in Cicatricial Alopecia

Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders

Role of protein kinase C and epidermal growth factor receptor signalling in growth stimulation by neurotensin in colon carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Neurotensin has been found to promote colon carcinogenesis in rats and mice, and proliferation of human colon carcinoma cell lines, but the mechanisms involved are not clear. We have examined signalling pathways activated by neurotensin in colorectal and pancreatic carcinoma cells.</p> <p>Methods</p> <p>Colon carcinoma cell lines HCT116 and HT29 and pancreatic adenocarcinoma cell line Panc-1 were cultured and stimulated with neurotensin or epidermal growth factor (EGF). DNA synthesis was determined by incorporation of radiolabelled thymidine into DNA. Levels and phosphorylation of proteins in signalling pathways were assessed by Western blotting.</p> <p>Results</p> <p>Neurotensin stimulated the phosphorylation of both extracellular signal-regulated kinase (ERK) and Akt in all three cell lines, but apparently did so through different pathways. In Panc-1 cells, neurotensin-induced phosphorylation of ERK, but not Akt, was dependent on protein kinase C (PKC), whereas an inhibitor of the β-isoform of phosphoinositide 3-kinase (PI3K), TGX221, abolished neurotensin-induced Akt phosphorylation in these cells, and there was no evidence of EGF receptor (EGFR) transactivation. In HT29 cells, in contrast, the EGFR tyrosine kinase inhibitor gefitinib blocked neurotensin-stimulated phosphorylation of both ERK and Akt, indicating transactivation of EGFR, independently of PKC. In HCT116 cells, neurotensin induced both a PKC-dependent phosphorylation of ERK and a metalloproteinase-mediated transactivation of EGFR that was associated with a gefitinib-sensitive phosphorylation of the downstream adaptor protein Shc. The activation of Akt was also inhibited by gefitinib, but only partly, suggesting a mechanism in addition to EGFR transactivation. Inhibition of PKC blocked neurotensin-induced DNA synthesis in HCT116 cells.</p> <p>Conclusions</p> <p>While acting predominantly through PKC in Panc-1 cells and via EGFR transactivation in HT29 cells, neurotensin used both these pathways in HCT116 cells. In these cells, neurotensin-induced activation of ERK and stimulation of DNA synthesis was PKC-dependent, whereas activation of the PI3K/Akt pathway was mediated by stimulation of metalloproteinases and subsequent transactivation of the EGFR. Thus, the data show that the signalling mechanisms mediating the effects of neurotensin involve multiple pathways and are cell-dependent.</p

Measurement properties of patient‐reported outcome measures for eczema control: a systematic review

Atopic eczema (herein referred to as ‘eczema’) is a skin disease characterized by remitting and relapsing symptoms. The Harmonising Outcome Measures for Eczema (HOME) initiative was developed to establish a core outcome set (COS) for eczema to be measured for all future eczema trials. The core outcome set for atopic eczema clinical trials includes the domain for patient-reported eczema control, but a review of the validation of available eczema control instruments was lacking. We aimed to review the literature and systematically assess the measurement properties of validated patient-reported outcome instruments that capture eczema control. PubMed and Ovid EMBASE were searched up to 24 January 2020 for any study that reported on PROM instrument development or validation. The COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) criteria were used to assess the quality of eligible studies. We screened 12 036 titles and abstracts and 58 full texts. A total of 12 papers were included, reporting on seven PROMS. These were assessed with respect to development, reliability, construct validity and responsiveness. Two instruments, Recap of Atopic Eczema (RECAP) and the Atopic Dermatitis Control Tool (ADCT), have been developed and validated to a sufficient standard to support their recommendation as patient-reported outcome instruments for measuring control of atopic eczema as part of the HOME Core Outcome Set

A method to determine spatial access to specialized palliative care services using GIS

Background: Providing palliative care is a growing priority for health service administratorsworldwide as the populations of many nations continue to age rapidly. In many countries, palliativecare services are presently inadequate and this problem will be exacerbated in the coming years.The provision of palliative care, moreover, has been piecemeal in many jurisdictions and there islittle distinction made at present between levels of service provision. There is a pressing need todetermine which populations do not enjoy access to specialized palliative care services in particular.Methods: Catchments around existing specialized palliative care services in the Canadian provinceof British Columbia were calculated based on real road travel time. Census block face populationcounts were linked to postal codes associated with road segments in order to determine thepercentage of the total population more than one hour road travel time from specialized palliativecare.Results: Whilst 81% of the province\u27s population resides within one hour from at least onespecialized palliative care service, spatial access varies greatly by regional health authority. Based onthe definition of specialized palliative care adopted for the study, the Northern Health Authorityhas, for instance, just two such service locations, and well over half of its population do not havereasonable spatial access to such care.Conclusion: Strategic location analysis methods must be developed and used to accurately locatefuture palliative services in order to provide spatial access to the greatest number of people, andto ensure that limited health resources are allocated wisely. Improved spatial access has thepotential to reduce travel-times for patients, for palliative care workers making home visits, and fortravelling practitioners. These methods are particularly useful for health service planners – andprovide a means to rationalize their decision-making. Moreover, they are extendable to a numberof health service allocation problems