Imaging to study solid tumour origin and progression: lessons from research and clinical oncology

Biomedical imaging in recent decades has clarified our understanding of normal and pathological cellular processes in vivo. In particular, this approach recently provided insights into processes occurring at a molecular or genetic level rather than at the anatomical level. The evolution of this discipline by engineering have led to its integration into biomedical research to (1) increase sensitivity and resolution imaging and to (2) improve tissue and cell specificity. Currently, imaging approaches are used in three different biomedical areas: (a) identification of cellular processes in physiological and disease state; (b) in vivo single-cell imaging; and (c) identification of new prognostic and therapeutical strategies. In this review, we will focus on the state of art of biomedical imaging in cancer. Specifically, we will highlight the most important advances in imaging tools available for basic and translational cancer research, with a particular emphasis on solid tissue malignancies.Immunology and Cell Biology advance online publication, 4 April 2017; doi:10.1038/icb.2017.17

Technical Note: Intercomparison of ILAS-II version 2 and 1.4 trace species with MIPAS-B measurements

The Improved Limb Atmospheric Spectrometer (ILAS)-II sensor aboard the Japanese ADEOS-II satellite was launched into its sun-synchronous orbit on 14 December 2002 and performed solar occultation measurements of trace species, aerosols, temperature, and pressure in the polar stratosphere until 25 October 2003. Vertical trace gas profiles obtained with the balloon version of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS-B) provide one of the sparse data sets for validating ILAS-II version 2 and 1.4 data. The MIPAS-B limb emission spectra were collected on 20 March 2003 over Kiruna (Sweden, 68° N) at virtually the same location that has been sounded by ILAS-II about 5.5 h prior to the sampling of MIPAS-B. The intercomparison of the new ILAS-II version 2 (Northern Hemispheric sunrise) data to MIPAS-B vertical trace gas profiles shows a good to excellent agreement within the combined error limits for the species O<sub>3</sub>, N<sub>2</sub>O, CH<sub>4</sub>, H<sub>2</sub>O (above 21 km), HNO<sub>3</sub>, ClONO<sub>2</sub>, and CFC-11 (CCl<sub>3</sub>F) in the compared altitude range between 16 and 31 km such that these data appear to be very useful for scientific analysis. With regard to the previous version 1.4 ILAS-II data, significant improvements in the consistency with MIPAS-B are obvious especially for the species CH<sub>4</sub> and H<sub>2</sub>O, but also for O<sub>3</sub>, HNO<sub>3</sub>, ClONO<sub>2</sub>, NO<sub>2</sub>, and N<sub>2</sub>O<sub>5</sub>. However, comparing gases like NO<sub>2</sub>, N<sub>2</sub>O<sub>5</sub>, and CFC-12 (CCl<sub>2</sub>F<sub>2</sub>) exhibits only poor agreement with MIPAS-B such that these species cannot be assumed to be validated at the present time

Fostering social learning through role-play simulations to operationalize comprehensive climate risk management: Insights from applying the RESPECT role-play in Austria

This paper describes an analytical-deliberative process, centered around the RESPECT role-play simulation, conducted to foster the operationalization of comprehensive climate risk management (CRM) in Lienz, southern Austria, a city that is representative of many alpine regions. We hypothesize that fostering social learning via participatory stakeholder engagement processes aids closing prevailing science–policy–implementation gaps in CRM, which are often a result from insufficiently clear roles and responsibilities, diverging stakeholder interests, priorities and risk perceptions, and inexistent or incipient cooperation mechanisms. To test this hypothesis, we co-developed and conducted a role-play simulation centered on riverine-flood risk—the most pressing climate-related risk in the Lienz case-study region. Based on our analysis of qualitative data gathered ex ante and ex post the intervention, we found role-play simulations to have a high potential for fostering social learning in CRM. After taking part, the diverse societal stakeholders were found to better understand: i) the interacting dimensions and drivers of riverine-flood risks; ii) the diverging risk perceptions; and iii) each other’s interests and needs in addressing such risks at the individual and institutional level. Role-play simulations are a promising transdisciplinary method for engaging societal stakeholders beyond traditional policy- and decision-making communities in informed and inclusive public debate around challenges and solutions to CRM. The methodological and practical insights gained in this Austrian case study may be transferred to the management of other climate-related risks

The Transcription Factor REST Is Lost in Aggressive Breast Cancer

The function of the tumor suppressor RE1 silencing transcription factor (REST) is lost in colon and small cell lung cancers and is known to induce anchorage-independent growth in human mammary epithelial cells. However, nothing is currently known about the role of this tumor suppressor in breast cancer. Here, we test the hypothesis that loss of REST function plays a role in breast cancer. To assay breast tumors for REST function, we developed a 24-gene signature composed of direct targets of the transcriptional repressor. Using the 24- gene signature, we identified a previously undefined RESTless breast tumor subtype. Using gene set enrichment analysis, we confirmed the aberrant expression of REST target genes in the REST–less tumors, including neuronal gene targets of REST that are normally not expressed outside the nervous system. Examination of REST mRNA identified a truncated splice variant of REST present in the REST–less tumor population, but not other tumors. Histological analysis of 182 outcome-associated breast tumor tissues also identified a subpopulation of tumors that lack full-length, functional REST and over-express the neuroendocrine marker and REST target gene Chromogranin A. Importantly, patients whose tumors were found to be REST–less using either the 24-gene signature or histology had significantly poorer prognosis and were more than twice as likely to undergo disease recurrence within the first 3 years after diagnosis. We show here that REST function is lost in breast cancer, at least in part via an alternative splicing mechanism. Patients with REST–less breast cancer undergo significantly more early disease recurrence than those with fully functional REST, regardless of estrogen receptor or HER2 status. Importantly, REST status may serve as a predictor of poor prognosis, helping to untangle the heterogeneity inherent in disease course and response to treatment. Additionally, the alternative splicing observed in REST–less breast cancer is an attractive therapeutic target

Neutron Scattering and the B_{1g} Phonon in the Cuprates

The momentum dependent lineshape of the out-of-phase oxygen vibration as measured in recent neutron scattering measurements is investigated. Starting from a microscopic coupling of the phonon vibration to a local crystal field, the phonon lineshift and broadening is calculated as a function of transfered momentum in the superconducting state of YBa$_{2}$Cu$_{3}$O$_{7}$. It is shown that the anisotropy of the density of states, superconducting energy gap, and the electron-phonon coupling are all crucial in order to explain these experiments.Comment: new figures and discussio

Electronic Raman scattering in YBCO and other superconducting cuprates

Superconductivity induced structures in the electronic Raman spectra of high-Tc superconductors are computed using the results of ab initio LDA-LMTO three-dimensional band structure calculations via numerical integrations of the mass fluctuations, either in the whole 3D Brillouin zone or limiting the integrations to the Fermi surface. The results of both calculations are rather similar, the Brillouin zone integration yielding additional weak structures related to the extended van Hove singularities. Similar calculations have been performed for the normal state of these high-Tc cuprates. Polarization configurations have been investigated and the results have been compared to experimental spectra. The assumption of a simple d_(x^2-y^2)-like gap function allows us to explain a number of experimental features but is hard to reconcile with the relative positions of the A1g and B1g peaks.Comment: 14 pages, LaTeX (RevTeX), 5 PostScript figures, uses multicol.sty, submitted to PR