פרסומים

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer with an extremely low survival rate. It is characterized by a chronic inflammatory process with intense mast cell infiltrate that is associated with reduced survival. The aim of this study was to test the hypothesis that mast cells have an enhancing effect on NSCLC proliferation. To assess the tumor-promoting potential of mast cells, we used the human alveolar basal adenocarcinoma (A549) and the mouse Lewis lung carcinoma (LLC) cell lines, umbilical cord blood-derived mast cells (CBMC) and the mast cell-deficient mouse Sash model. The proliferation rate of A549/LLC cells was markedly increased by mast cells and histamine. Histamine proliferating activity was mediated via H(1), H(2) and H(4) receptors and caused ERK phosphorylation. LLC induced in Sash mice or in wild-type mice treated with the mast cell stabilizer nedocromil sodium displayed an accelerated growth (number of metastic colonies in the lungs, total lung area and lung/total mice weight ratio). In summary, we have shown a significant effect of mast cells and histamine in enhancing NSCLC/LLCX growth in vitro, while in a mouse LLC model in vivo we have found that mast cells are important negative regulators of cancer development. Therefore our results would indicate a pro-tumorogenic effect of the mast cells in vitro on established lung tumor cell lines, and anti-tumorogenic effect in mice at lung cancer induction. In conclusion, mast cell/anti-histamine targeted therapies should carefully consider this dual effect.

Lumpy skin disease (LSD) is a severe viral disease of cattle. Circumstantial evidence suggests that the virus is transmitted mechanically by blood-feeding arthropods. We compared the importance of transmission via direct and indirect contact in field conditions by using mathematical tools. We analyzed a dataset collected during the LSD outbreak in 2006 in a large dairy herd, which included ten separated cattle groups. Outbreak dynamics and risk factors for LSD were assessed by a transmission model. Transmission by three contact modes was modelled; indirect contact between the groups within a herd, direct contact or contact via common drinking water within the groups and transmission by contact during milking procedure. Indirect transmission was the only parameter that could solely explain the entire outbreak dynamics and was estimated to have an overall effect that was over 5 times larger than all other possible routes of transmission, combined. The R0 value induced by indirect transmission per the presence of an infectious cow for 1 day in the herd was 15.7, while the R0 induced by direct transmission was 0.36. Sensitivity analysis showed that this result is robust to a wide range of assumptions regarding mean and standard deviation of incubation period and regarding the existence of sub-clinically infected cattle. These results indicate that LSD virus spread within the affected herd could hardly be attributed to direct contact between cattle or contact through the milking procedure. It is therefore concluded that transmission mostly occurs by indirect contact, probably by flying, blood-sucking insects. This has important implications for control of LSD.

This study determined the role of MMP9/gelatinase B during the migration onset of Neural Crest Cells (NCC) in avian embryos. NCC are neuroepithelial progenitors that convert into mesenchyme and migrate along defined paths throughout the embryo. To engage in migration, NCC loose cell contacts, detach from the neural tube and invade the surrounding environment. Multiple signals and transcription factors that regulate these events have been identified. Nevertheless, little is known regarding effectors that act downstream to execute the actual NCC migration. Matrix metalloproteinases (MMPs) compose a large family of enzymes whose principal substrates are basement membranes, adhesion proteins and the extracellular matrix (ECM) components. A major subgroup of MMPs, the gelatinases (MMP9 and 2) are central to many adult physiological and pathological processes, such as tumor metastasis and angiogenesis, in which cell-cell and cell-matrix contacts are degraded to allow migration. As NCC undergo similar processes during development, we hypothesized that MMP9 may also promote the migration of NCC.MMP9 was found to be expressed in delaminating and migrating NCC of both cranial and trunk axial levels. Blocking MMP9 resulted in a dramatic inhibition of NCC delamination and migration, without perturbing specification or survival. This inhibition occurred at regions containing both premigratory and migrating cells, indicative for the central role of MMP9 in executing the detachment of NCC from the neural tube as well as their migration. Conversely, excess MMP9 enhanced mesenchymalization and delamination of NCC and accelerated progenitors to undergo precocious migration. Examination of the mechanistic activity of MMP9 revealed its capability to degrade the adhesion molecule N-cadherin as well as the basement-membrane protein laminin within or around NCC, respectively. Altogether, our study reveals MMP9 as a novel effector which is required for NCC delamination and migration.

A methodology is developed for the analysis of multivariate data by maximal entropy and it is shown how the surprisal reduces to the more familiar bivariate and univariate forms. When multivariate data is available it is shown how the uni- or bi-variate surprisal parameters can be expressed as a sum of terms containing contributions of different pathways. But if averaging so as to reduce the number of variables is performed before the data analysis then all that one can determine is the sum but not the individual contributions: averaging completely hides essential details and correlations. The formalism is illustrated by an application to ultrafast translational equilibration that occurs when a cold rare gas cluster impacts a hard surface at a hypersonic speed.

Consider the problem of maximizing the revenue from selling a number of goods to a single buyer. We show that, unlike the case of one good, when the buyer's values for the goods increase the seller's maximal revenue may well decrease. We also provide a characterization of revenue-maximizing mechanisms (more generally, of "seller-favorable" mechanisms) that circumvents nondifferentiability issues. Finally, through simple and transparent examples, we clarify the need for and the use of randomization when maximizing revenue in the multiple-goods versus the one-good case.

Due to its prevalence, obesity is now considered a global epidemic. It is linked to increased risk of colorectal cancer, the third most common cancer and the second leading cause of death among adults in Western countries. Obese adipose tissue differs from lean adipose tissue in its immunogenic profile, body fat distribution and metabolic profile. Obese adipose tissue releases free fatty acids, adipokines and many pro-inflammatory chemokines. These factors are known to play a key role in regulating malignant transformation and cancer progression. Obese adipose tissue is infiltrated by macrophages that participate in inflammatory pathways activated within the tissue. Adipose tissue macrophages consist of two different phenotypes. M1 macrophages reside in obese adipose tissue and produce pro-inflammatory cytokines, and M2 macrophages reside in lean adipose tissue and produce anti-inflammatory cytokines, such as interleukin-10 (IL-10). The metabolic networks that confer tumour cells with their oncogenic properties, such as increased proliferation and the ability to avoid apoptosis are still not well understood. We review the interactions between adipocytes and immune cells that may alter the metabolism towards promotion of colorectal cancer.

The coherent photoisomerization of a chromophore in condensed phase is a rare process in which light energy is funneled into specific molecular vibrations during electronic relaxation from the excited to the ground state. In this work, we employed ultrafast spectroscopy and computational methods to investigate the molecular origin of the coherent motion accompanying the photoisomerization of indanylidene–pyrroline (IP) molecular switches. UV/Vis femtosecond transient absorption gave evidence for an excited- and ground-state vibrational wave packet, which appears as a general feature of the IP compounds investigated. In close resemblance to the coherent photoisomerization of rhodopsin, the sudden onset of a far-red-detuned and rapidly blue-shifting photoproduct signature indicated that the population arriving on the electronic ground state after nonadiabatic decay through the conical intersection (CI) is still very focused in the form of a vibrational wave packet. Semiclassical trajectories were employed to investigate the reaction mechanism. Their analysis showed that coupled double-bond twisting and ring inversions, already populated during the excited-state reactive motion, induced periodic changes in π-conjugation that modulate the ground-state absorption after the non-adiabatic decay. This prediction further supports that the observed ground-state oscillation results from the reactive motion, which is in line with a biomimetic, coherent photoisomerization scenario. The IP compounds thus appear as a model system to investigate the mechanism of mode-selective photomechanical energy transduction. The presented mechanism opens new perspectives for energy transduction at the molecular level, with applications to the design of efficient molecular devices.

Past research has shown that people judge a TV interviewee more favorably when the interviewer's nonverbal behavior toward the interviewee is friendly rather than hostile. This study examined whether students who participated in a media literacy course could be less susceptible to this media bias. Two groups of high school students (media literacy students and a control group) were shown a brief interview in which the interviewer's nonverbal behavior was friendly or hostile toward the interviewed politician. Results showed that the control group showed a nonverbal media bias effect and judged the interviewee more favorably when the interviewer was friendlier, whereas this effect disappeared among media literacy students. In contrast, a halo effect (whereby the interviewee's overall favorability was influenced by the degree to which participants personally liked the interviewee), which is not at all related to the content of media literacy education, was evident among both the students

Background Dual diagnosis (DD) refers to the coexistence of intellectual disability and psychiatric disorder. In order to provide individuals with DD with adequate care, it is essential for mental health workers to have adequate knowledge and positive attitudes. These may be achieved through proper training. Aims To summarise the available literature examining the knowledge, attitudes and training of psychiatrists and other professional caregivers in regard to serving people with DD. Methods A search strategy was developed to find manuscripts published in English since 1995. Results Twenty-seven studies on knowledge, attitudes and training in the field of DD were identified and reviewed in this paper. Conclusion The findings of this review stress the need to improve the knowledge, competence and attitudes of practitioners within the DD field via training and practice opportunities. In light of this review, recommendations for improving training opportunities and for conducting future research are made.

Combining poly(2-vinyl pyridine) (P2VP) with organometallic surfactants based on a Pd-SCS pincer complex in the solid state leads to the formation of mesomorphic structures even with the lack of coordinative bonding between the pyridine groups and the surfactant molecules. Through a combination of spectroscopic methods and quantum chemical calculations we reveal that the interaction responsible for the formation of the supramolecular, comb polymer architectures leading to these mesomorphic structures is a dipolar stacking interaction between the Pd-C bond of the surfactant and the pyridine ring of the polymer. This conclusion is further supported by comparison to a system where coordinative binding between the surfactant and the polymer was induced. Additional DSC analysis shows that, unlike the system featuring coordinative binding, the weak binding to the polymer through dipolar stacking facilitates the crystallization of the alkyl residues. Such organized assemblies of metal precursors can serve for the creation of hybrid materials and organized nanocomposites.