Human cancers over express genes that are specific to a variety of normal human tissues

We have analyzed gene expression data from 3 different kinds of samples: normal human tissues, human cancer cell lines and leukemic cells from lymphoid and myeloid leukemia pediatric patients. We have searched for genes that are over expressed in human cancer and also show specific patterns of tissue-dependent expression in normal tissues. Using the expression data of the normal tissues we identified 4346 genes with a high variability of expression, and clustered these genes according to their relative expression level. Of 91 stable clusters obtained, 24 clusters included genes preferentially expressed either only in hematopoietic tissues or in hematopoietic and 1-2 other tissues; 28 clusters included genes preferentially expressed in various non-hematopoietic tissues such as neuronal, testis, liver, kidney, muscle, lung, pancreas and placenta. Analysis of the expression levels of these 2 groups of genes in the human cancer cell lines and leukemias, identified genes that were highly expressed in cancer cells but not in their normal counterparts, and were thus over expressed in the cancers. The different cancer cell lines and leukemias varied in the number and identity of these over expressed genes. The results indicate that many genes that are over expressed in human cancer cells are specific to a variety of normal tissues, including normal tissues other than those from which the cancer originated. It is suggested that this general property of cancer cells plays a major role in determining the behavior of the cancers, including their metastatic potential.Comment: To appear in PNA

Modelling sea breeze climatologies and interactions on coasts in the southern North Sea: Implications for offshore wind energy

Current understanding of the behaviour of sea breezes in the offshore environment is limited but rapidly requires improvement due, not least, to the expansion of the offshore wind energy industry. Here we report on contrasting characteristics of three sea-breeze types on five coastlines around the southern North Sea from an 11 year model-simulated climatology. We present and test an identification method which distinguishes sea-breeze types which can, in principle, be adapted for other coastlines around the world. The coherence of the composite results for each type demonstrates that the method is very effective in resolving and distinguishing characteristics and features. Some features, such as jets and calm zones, are shown to influence offshore wind farm development areas, including the sites of the proposed wind farms up to 200 km offshore. A large variability in sea-breeze frequency between neighbouring coastlines of up to a factor of 3 is revealed. Additionally, there is a strong association between sea-breeze type on one coastline and that which may form coincidentally on another nearby. This association can be as high as 86% between, for example, the North Norfolk and East Norfolk coasts. We show, through associations between sea-breeze events on coastlines with contrasting orientations, that each coastline can be important for influencing the wind climate of another. Furthermore, we highlight that each sea-breeze type needs separate consideration in wind power resource assessment and that future larger turbines will be more sensitive to sea-breeze impacts

Neuronal ICAM-5 Inhibits Microglia Adhesion and Phagocytosis and Promotes an Anti-inflammatory Response in LPS Stimulated Microglia

The intercellular adhesion molecule-5 (ICAM-5) regulates neurite outgrowth and synaptic maturation. ICAM-5 overexpression in the hippocampal neurons induces filopodia formation in vitro. Since microglia are known to prune supernumerous synapses during development, we characterized the regulatory effect of ICAM-5 on microglia. ICAM-5 was released as a soluble protein from N-methyl-D-aspartic acid (NMDA)-treated neurons and bound by microglia. ICAM-5 promoted down-regulation of adhesion and phagocytosis in vitro. Microglia formed large cell clusters on ICAM-5-coated surfaces whereas they adhered and spread on the related molecule ICAM-1. ICAM-5 further reduced the secretion of the proinflammatory cytokines tumor necrosis factor a (TNF-alpha) and interleukin 1 beta (IL-1 beta), but on the contrary induced the secretion of the antiinflammatory IL-10 from lipopolysaccharide (LPS) stimulated microglia. Thus, ICAM-5 might be involved in the regulation of microglia in both health and disease, playing an important neuroprotective role when the brain is under immune challenges and as a "don't-eat-me" signal when it is solubilized from active synapses.Peer reviewe

How integrin phosphorylations regulate cell adhesion and signaling

Cell adhesion is essential for the formation of organs, cellular migration, and interaction with target cells and the extracellular matrix. Integrins are large protein alpha/13-chain heterodimers and form a major family of cell adhesion molecules. Recent research has dramatically increased our knowledge of how integrin phos-phorylations regulate integrin activity. Phosphorylations determine the signaling complexes formed on the cytoplasmic tails, regulating downstream signaling. alpha-Chain phosphorylation is necessary for inducing 13-chain phosphorylation in LFA-1, and the crosstalk from one integrin to another activating or inactivating its function is in part mediated by phosphorylation of 13-chains. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus receptor angiotensin-converting enzyme 2 (ACE2) and possible integrin coreceptors may crosstalk and induce a phosphorylation switch and autophagy.Peer reviewe

Light entrepreneurs in Finland : A longitudinal study of careers, income and pension accrual

This study examines how the careers, income and pension accrual of light entrepreneurs have developed over time. The main focus is on individuals who started as light entrepreneurs in 2017. They are followed from 2012 to 2022. The study also includes comparisons between light entrepreneurs and their peers who were not light entrepreneurs. The analyses are based on register data from Statistics Finland and the Finnish Centre for Pensions

In-situ and label-free optical monitoring of the adhesion and spreading of primary monocytes isolated from human blood: dependence on serum concentration levels

Adhesion and spreading of primary monocytes isolated from human blood were monitored utilizing optical waveguide lightmode spectroscopy (OWLS); a highly sensitive label-free biosensor technique using evanescent optical waves generated at a biocompatible surface. Appropriate development on a custom built setup enabled the OWLS cuvette to be operated as a 1.5 ml mini-incubator, controlling both temperature and CO2 levels. The incubator-equipped OWLS is readily applicable for delicate and long-term studies on sensitive primary cells, demonstrated here through monitoring the serum dependence of the adhesion and spreading of human monocytes. Moreover, the custom-built setup enables the simultaneous monitoring of the position and overall width of the OWLS resonant peaks. This unique feature makes it possible to distinguish the refractive index variations induced by the adsorption of secreted material from refractive index changes provoked by cellular spreading. A definite attachment and spreading activity was observed on the substratum (glassy silica-titania), when the serum level of the culturing medium was 0.0-0.01%. Increasing serum concentration resulted in a steep fall in monocyte surface adhesion and spreading. 1.0% serum level practically abolished all spreading activity measured by OWLS, and the number of attached cells was significantly decreased, too. Serum addition to fully spread cells provoked a reduction in the cell-substratum contact area, clearly detectable by the biosensor. Cell spreading was inhibited by pre-coating the sensor surface with considerable amounts of serum proteins. These findings suggest that monocyte spreading is inhibited by the adsorption of serum biomolecules to the substratum, rather than by soluble factors present in the serum. All of these results were obtained completely non-invasively with real time monitoring; demonstrating the capabilities of OWLS to sensitively monitor the adhesion properties of immune cells isolated from human blood. The current study is, therefore, a significant step towards the application of label-free optical biosensors in medical diagnostics

Regulation of Dynamic Cell Adhesion by Integrin-Integrin Crosstalk

Most cells express several integrins. The integrins are able to respond to various cellular functions and needs by modifying their own activation state, but in addition by their ability to regulate each other by activation or inhibition. This crosstalk or transdominant regulation is strictly controlled. The mechanisms resulting in integrin crosstalk are incompletely understood, but they often involve intracellular signalling routes also used by other cell surface receptors. Several studies show that the integrin cytoplasmic tails bind to a number of cytoskeletal and adaptor molecules in a regulated manner. Recent work has shown that phosphorylations of integrins and key intracellular molecules are of pivotal importance in integrin-cytoplasmic interactions, and these in turn affect integrin activity and crosstalk. The integrin β-chains play a central role in regulating crosstalk. In addition to Integrin-integrin crosstalk, crosstalk may also occur between integrins and related receptors, including other adhesion receptors, growth factor and SARS-CoV-2 receptors

Organizational ldeology and Leadership: A Semiotic View

The article suggests a reconsideration of the traditional ideology concept. The role of leadership increating and maintaining meanings within the organization is discussed within the emerging managementof meaning paradigm. A new approach is suggestedbased upon the ontological assumption of man as astorytelling animal and on the semiotic method ofviewing ideology as an interplay between the narrative and the cognitive

Regulation of Dynamic Cell Adhesion by Integrin-Integrin Crosstalk

Most cells express several integrins. The integrins are able to respond to various cellular functions and needs by modifying their own activation state, but in addition by their ability to regulate each other by activation or inhibition. This crosstalk or transdominant regulation is strictly controlled. The mechanisms resulting in integrin crosstalk are incompletely understood, but they often involve intracellular signalling routes also used by other cell surface receptors. Several studies show that the integrin cytoplasmic tails bind to a number of cytoskeletal and adaptor molecules in a regulated manner. Recent work has shown that phosphorylations of integrins and key intracellular molecules are of pivotal importance in integrin-cytoplasmic interactions, and these in turn affect integrin activity and crosstalk. The integrin β-chains play a central role in regulating crosstalk. In addition to Integrin-integrin crosstalk, crosstalk may also occur between integrins and related receptors, including other adhesion receptors, growth factor and SARS-CoV-2 receptors

Specific integrin alpha and beta chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms

Peer reviewe