Integrated Omics Profiling Reveals Novel Patterns of Epigenetic Programming in Cancer-Associated Myofibroblasts

There is increasing evidence that stromal myofibroblasts play a key role in tumour development, however the mechanisms by which they become reprogrammed to assist in cancer progression remain unclear. As cultured Cancer Associated Myofibroblasts (CAMs) retain an ability to enhance the proliferation and migration of cancer cells in vitro, it is possible that epigenetic reprogramming of CAMs within the tumour microenvironment may confer long-term pro-tumorigenic changes in gene expression. This study reports the first comparative multi-omics analysis of cancer-related changes in gene expression and DNA-methylation in primary myofibroblasts derived from gastric and oesophageal tumours. In addition, we identify novel CAM-specific DNA methylation signatures, which are not observed in patient-matched Adjacent Tissue-derived Myofibroblasts (ATMs), or corresponding Normal Tissue-derived Myofibroblasts (NTMs). Analysis of correlated changes in DNA methylation and gene expression show that different patterns of gene-specific DNA methylation have the potential to confer pro-tumourigenic changes in metabolism, cell signalling and differential responses to hypoxia. These molecular signatures provide new insights into potential mechanisms of stromal reprogramming in gastric and oesophageal cancer, while also providing a new resource to facilitate biomarker identification and future hypothesis driven studies into mechanisms of stromal reprogramming and tumour progression in solid tumours

Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts

Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p=0.0139), and nucleocapsid-specific (p=0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n=26), when compared with those who convert to PCR-positive (n=26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines

Tomographic Probability Representation for States of Charge moving in Varying Field

The coherent and Fock states of a charge moving in varying homogeneous magnetic field are studied in the tomographic probability representation of quantum mechanics. The states are expressed in terms of quantum tomograms. The coherent states tomograms are shown to be described by normal distributions with varying dispersions and means. The Fock state tomograms are given in the form of probability distributions described by multivariable Hermite polynomials with time-dependent arguments.Comment: 12 pages, submitted to "Optics and Spectroscopy

Delimitation of Funga as a valid term for the diversity of fungal communities: the Fauna, Flora & Funga proposal (FF&F)

As public policies and conservation requirements for biodiversity evolve there is a need for a term for the kingdom Fungi equivalent to Fauna and Flora. Thisneed is considered to be urgent in order to simplify projects oriented toward implemention of educational and conservation goals. In an informal meeting held duringthe IX Congreso Latinoamericano de Micología by the authors, the idea of clarifying this matter initiated an extensive search of pertinent terminologies. As a result ofthese discussions and reviews, we propose that the word Funga be employed as an accurate and encompassing term for these purposes. This supports the proposal of thethree Fs, Fauna, Flora and Funga, to highlight parallel terminology referring to treatments of these macrorganism of particular geographical areas. Alternative terms andproposals are acknowledged and discussedFil: Kuhar, José Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Furci, Giuliana. Fundación Fungi; ChileFil: Drechsler-Santos, Elisandro Ricardo. Universidade Federal de Santa Catarina; BrasilFil: Pfister, Donald H.. Harvard University; Estados Unido

Submicron infrared imaging of an oesophageal cancer cell with chemical specificity using an IR-FEL

This work reports the use of an infrared spectroscopic version of scanning near-field optical microscopy (IR-SNOM) and shows that it is possible to reveal subcellular entities via their chemical constituents in a label-free human oesophageal adenocarcinoma cell (OE33). This work presents the first high spatial resolution (~0.15 μm) study of features imaged at various wavelengths within a cancer cell. The clear illumination of sub-micron sized moieties within a cell is a major step forward and is a key requirement for understanding cancer and for the study of other diseases and healthy tissue. The stable and tuneable light source was provided by the infrared free electron laser on the ALICE accelerator at Daresbury. The images reveal a structure with a size and wavelength absorption that are consistent with a chromosome and open the possibility of observing other localized structures, such as microvesicles, that play an important role in the development and spread of cancers

Mixed marriages and transnational families in the intercultural context : a case study of African-Spanish couples in Catalonia, Spain

Premi a l'excel·lència investigadora. Àmbit de les Ciències Socials. 2008One of the consequences of international migration and the permanent settlement of immigrants in southern EU countries is the growing number of inter-country marriages and the formation of transnational families. Using both quantitative and qualitative data, this article examines patterns of endogamy and exogamy (i.e. marriage within/outside a particular group or category) among African immigrants in Catalonia, focusing on bi-national Senegalese- and Gambian-Spanish couples. Socio-demographic profiles, transnationality, the dynamics of cultural change or retention, and the formation of transcultural identities are explored. The evidence presented suggests that social-class factors are more important than cultural origins in patterns of endogamy and exogamy, in the dynamics of living together and in the bringing-up of children of mixed unions. Such a conclusion negates culturalists' explanations of endogamy and exogamy while, at the same time, emphasising the role of social actors as active subjects in these processes. I further argue that mixed couples and their offspring deal-to a greater or lesser extent-with multiple localisations and cultural backgrounds (i.e. here and there), rather than experiencing a 'clash between two cultures'. Therefore, it would be a mistake to pretend that multicultural links do not exist and that they cannot be revitalised and functional. The paper starts and ends by addressing the complexities of processes of interculturalism, resisting an interpretation of hybridity and segregation as contradictory or exclusive realities

The association of hydration status with physical signs, symptoms and survival in advanced cancer-The use of Bioelectrical Impedance Vector Analysis (BIVA) technology to evaluate fluid volume in palliative care: An observational study

Background Hydration in advanced cancer is a controversial area; however, current hydration assessments methods are poorly developed. Bioelectrical impedance vector analysis (BIVA) is an accurate hydration tool; however its application in advanced cancer has not been explored. This study used BIVA to evaluate hydration status in advanced cancer to examine the association of fluid status with symptoms, physical signs, renal biochemical measures and survival. Materials and methods An observational study of 90 adults with advanced cancer receiving care in a UK specialist palliative care inpatient unit was conducted. Hydration status was assessed using BIVA in addition to assessments of symptoms, physical signs, performance status, renal biochemical measures, oral fluid intake and medications. The association of clinical variables with hydration was evaluated using regression analysis. A survival analysis was conducted to examine the influence of hydration status and renal failure. Results The hydration status of participants was normal in 43 (47.8%), 'more hydrated' in 37 (41.1%) and 'less hydrated' in 10 (11.1%). Lower hydration was associated with increased symptom intensity (Beta = -0.29, p = 0.04) and higher scores for physical signs associated with dehydration (Beta = 10.94, p = 0.02). Higher hydration was associated with oedema (Beta = 2.55, p<0.001). Median survival was statistically significantly shorter in 'less hydrated' patients (44 vs. 68 days; p = 0.049) and in pre-renal failure (44 vs. 100 days; p = 0.003). Conclusions In advanced cancer, hydration status was associated with clinical signs and symptoms. Hydration status and pre-renal failure were independent predictors of survival. Further studies can establish the utility of BIVA as a standardised hydration assessment tool and explore its potential research application, in order to inform the clinical management of fluid balance in patients with advanced cancer

Electromagnetic Field Effect or Simply Stress? Effects of UMTS Exposure on Hippocampal Longterm Plasticity in the Context of Procedure Related Hormone Release

Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR) as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass) did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg). The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg) cannot be excluded

Stromal Fibroblasts in Digestive Cancer

The normal gastrointestinal stroma consists of extra-cellular matrix and a community of stromal cells including fibroblasts, myofibroblasts, smooth muscle cells, pericytes, endothelium and inflammatory cells. α-smooth muscle actin (α-SMA) positive stromal fibroblasts, often referred to as myofibroblasts or activated fibroblasts, are critical in the development of digestive cancer and help to create an environment that is permissive of tumor growth, angiogenesis and invasion. This review focusses on the contribution of activated fibroblasts in carcinogenesis and where possible directly applies this to, and draws on examples from, gastrointestinal cancer. In particular, the review expands on the definition, types and origins of activated fibroblasts. It examines the molecular biology of stromal fibroblasts and their contribution to the peritumoral microenvironment and concludes by exploring some of the potential clinical applications of this exciting branch of cancer research. Understanding the origin and biology of activated fibroblasts will help in the development of an integrated epithelial-stromal sequence to cancer that will ultimately inform cancer pathogenesis, natural history and future therapeutics

Finding gene regulatory network candidates using the gene expression knowledge base

BACKGROUND: Network-based approaches for the analysis of large-scale genomics data have become well established. Biological networks provide a knowledge scaffold against which the patterns and dynamics of ‘omics’ data can be interpreted. The background information required for the construction of such networks is often dispersed across a multitude of knowledge bases in a variety of formats. The seamless integration of this information is one of the main challenges in bioinformatics. The Semantic Web offers powerful technologies for the assembly of integrated knowledge bases that are computationally comprehensible, thereby providing a potentially powerful resource for constructing biological networks and network-based analysis. RESULTS: We have developed the Gene eXpression Knowledge Base (GeXKB), a semantic web technology based resource that contains integrated knowledge about gene expression regulation. To affirm the utility of GeXKB we demonstrate how this resource can be exploited for the identification of candidate regulatory network proteins. We present four use cases that were designed from a biological perspective in order to find candidate members relevant for the gastrin hormone signaling network model. We show how a combination of specific query definitions and additional selection criteria derived from gene expression data and prior knowledge concerning candidate proteins can be used to retrieve a set of proteins that constitute valid candidates for regulatory network extensions. CONCLUSIONS: Semantic web technologies provide the means for processing and integrating various heterogeneous information sources. The GeXKB offers biologists such an integrated knowledge resource, allowing them to address complex biological questions pertaining to gene expression. This work illustrates how GeXKB can be used in combination with gene expression results and literature information to identify new potential candidates that may be considered for extending a gene regulatory network. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-014-0386-y) contains supplementary material, which is available to authorized users