Clinicopathological correlation and prognostic significance of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common type of cancer and the fourth most frequent cause of cancer death. Literature indicates that vascular endothelial growth factor is a predominant angiogenic factor and that angiogenesis plays an important role in the progression of CRC. PATIENTS AND METHODS: The present series consisted of tissue samples obtained from 672 patients who had undergone large bowel resection between 2005 and 2010 at the Braga Hospital, Portugal. Archival paraffin-embedded CRC tissue and normal adjacent samples were used to build up tissue microarray blocks and VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression was immunohistochemically assessed. RESULTS: We observed an overexpression of VEGF-C in CRC when tumour cells and normal-adjacent tissue were compared (p=0.004). In tumour samples, VEGF-C-positive cases were associated with VEGFR-3 expression (p=0.047). When assessing the correlation between VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expressions and the clinicopathological data, it was revealed that VEGF-A positive cases were associated with male gender (p=0.016) and well-differentiated tumours (p=0.001); VEGF-C with colon cancers (p=0.037), exophytic (p=0.048), moderately-differentiated (p=0.007) and T3/T4 (p=0.010) tumours; VEGFR-2 with invasive adenocarcinoma (p=0.007) and VEGFR-3 with the presence of hepatic metastasis (p=0.032). Overall survival curves for CRC were statistically significant for rectal cancer, VEGF-C expression and stage III (p=0.019) and VEGFR-3 expression and stage IV (p=0.047). CONCLUSION: Quantification of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression seems to provide valuable prognostic information in CRC and the correlation with clinicopathological data revealed an association with characteristics that contribute to progression, invasion and metastasis leading to poorer survival rates and prognosis

Ki-67 Expression in CRC Lymph Node Metastasis Does Not Predict Survival

Colorectal cancer is one of the most common malignancies and a leading cause of cancer death worldwide. Molecular markers may improve clinicopathologic staging and provide a basis to guide novel therapeutic strategies which target specific tumour-associated molecules according to individual tumour biology; however, so far, no ideal molecular marker has been found to predict disease progression. We tested Ki-67 proliferation marker in primary and lymph node metastasis of CRC. We observed a statistical significant difference between the positive rates of neoplastic cells positively stained by Ki-67 in both sites, with remarkable increased number of Ki-67 positive cells in primary tumor cells compared to cancer cells that invaded lymph nodes. We can speculate that the metastatic CRC in lymph node can be more resistant to the drugs that target cellular division

Persistence of magnetic field driven by relativistic electrons in a plasma

The onset and evolution of magnetic fields in laboratory and astrophysical plasmas is determined by several mechanisms, including instabilities, dynamo effects and ultra-high energy particle flows through gas, plasma and interstellar-media. These processes are relevant over a wide range of conditions, from cosmic ray acceleration and gamma ray bursts to nuclear fusion in stars. The disparate temporal and spatial scales where each operates can be reconciled by scaling parameters that enable to recreate astrophysical conditions in the laboratory. Here we unveil a new mechanism by which the flow of ultra-energetic particles can strongly magnetize the boundary between the plasma and the non-ionized gas to magnetic fields up to 10-100 Tesla (micro Tesla in astrophysical conditions). The physics is observed from the first time-resolved large scale magnetic field measurements obtained in a laser wakefield accelerator. Particle-in-cell simulations capturing the global plasma and field dynamics over the full plasma length confirm the experimental measurements. These results open new paths for the exploration and modelling of ultra high energy particle driven magnetic field generation in the laboratory

Techniques for Arbuscular Mycorrhiza Inoculum Reduction

It is well established that arbuscular mycorrhizal (AM) fungi can play a significant role in sustainable crop production and environmental conservation. With the increasing awareness of the ecological significance of mycorrhizas and their diversity, research needs to be directed away from simple records of their occurrence or casual speculation of their function (Smith and Read 1997). Rather, the need is for empirical studies and investigations of the quantitative aspects of the distribution of different types and their contribution to the function of ecosystems. There is no such thing as a fungal effect or a plant effect, but there is an interaction between both symbionts. This results from the AM fungi and plant community size and structure, soil and climatic conditions, and the interplay between all these factors (Kahiluoto et al. 2000). Consequently, it is readily understood that it is the problems associated with methodology that limit our understanding of the functioning and effects of AM fungi within field communities. Given the ubiquous presence of AM fungi, a major constraint to the evaluation of the activity of AM colonisation has been the need to account for the indigenous soil native inoculum. This has to be controlled (i.e. reduced or eliminated) if we are to obtain a true control treatment for analysis of arbuscular mycorrhizas in natural substrates. There are various procedures possible for achieving such an objective, and the purpose of this chapter is to provide details of a number of techniques and present some evaluation of their advantages and disadvantages. Although there have been a large number of experiments to investigated the effectiveness of different sterilization procedures for reducing pathogenic soil fungi, little information is available on their impact on beneficial organisms such as AM fungi. Furthermore, some of the techniques have been shown to affect physical and chemical soil characteristics as well as eliminate soil microorganisms that can interfere with the development of mycorrhizas, and this creates difficulties in the interpretation of results simply in terms of possible mycorrhizal activity. An important subject is the differentiation of methods that involve sterilization from those focussed on indigenous inoculum reduction. Soil sterilization aims to destroy or eliminate microbial cells while maintaining the existing chemical and physical characteristics of the soil (Wolf and Skipper 1994). Consequently, it is often used for experiments focussed on specific AM fungi, or to establish a negative control in some other types of study. In contrast, the purpose of inoculum reduction techniques is to create a perturbation that will interfere with mycorrhizal formation, although not necessarily eliminating any component group within the inoculum. Such an approach allows the establishment of different degrees of mycorrhizal formation between treatments and the study of relative effects. Frequently the basic techniques used to achieve complete sterilization or just an inoculum reduction may be similar but the desired outcome is accomplished by adjustments of the dosage or intensity of the treatment. The ultimate choice of methodology for establishing an adequate non-mycorrhizal control depends on the design of the particular experiments, the facilities available and the amount of soil requiring treatment

Lepton Acceleration in Pulsar Wind Nebulae

Pulsar Wind Nebulae (PWNe) act as calorimeters for the relativistic pair winds emanating from within the pulsar light cylinder. Their radiative dissipation in various wavebands is significantly different from that of their pulsar central engines: the broadband spectra of PWNe possess characteristics distinct from those of pulsars, thereby demanding a site of lepton acceleration remote from the pulsar magnetosphere. A principal candidate for this locale is the pulsar wind termination shock, a putatively highly-oblique, ultra-relativistic MHD discontinuity. This paper summarizes key characteristics of relativistic shock acceleration germane to PWNe, using predominantly Monte Carlo simulation techniques that compare well with semi-analytic solutions of the diffusion-convection equation. The array of potential spectral indices for the pair distribution function is explored, defining how these depend critically on the parameters of the turbulent plasma in the shock environs. Injection efficiencies into the acceleration process are also addressed. Informative constraints on the frequency of particle scattering and the level of field turbulence are identified using the multiwavelength observations of selected PWNe. These suggest that the termination shock can be comfortably invoked as a principal injector of energetic leptons into PWNe without resorting to unrealistic properties for the shock layer turbulence or MHD structure.Comment: 19 pages, 5 figures, invited review to appear in Proc. of the inaugural ICREA Workshop on "The High-Energy Emission from Pulsars and their Systems" (2010), eds. N. Rea and D. Torres, (Springer Astrophysics and Space Science series

Postictal Psychosis in Epilepsy: A Clinicogenetic Study

OBJECTIVE: Psychoses affecting people with epilepsy increase disease burden and diminish quality of life. We characterised post-ictal psychosis, which comprises about one-quarter of epilepsy-related psychoses, and has unknown causation. METHODS: We conducted a case-control cohort study including patients diagnosed with post-ictal psychosis, confirmed by psychiatric assessment, with available data regarding epilepsy, treatment, psychiatric history, psychosis profile and outcomes. After screening 3,288 epilepsy patients, we identified 83 with psychosis: 49 had post-ictal psychosis. Controls were 98 adults, matched by age and epilepsy type, with no history of psychosis. Logistic regression was used to investigate clinical factors associated with post-ictal psychosis; univariate associations with a P-value<0.20 were used to build a multivariate model. Polygenic risk scores for schizophrenia were calculated. RESULTS: Cases were more likely to have seizure clustering (OR 7.59, P<0.001), seizures with a recollected aura (OR 2.49, P=0.013) and a family history of psychiatric disease (OR 5.17, P=0.022). Cases showed predominance of right temporal epileptiform discharges (OR 4.87, P=0.007). There was no difference in epilepsy duration, neuroimaging findings or anti-seizure treatment between cases and controls. Polygenic risk scores for schizophrenia in an extended cohort of post-ictal psychosis cases (58) were significantly higher than in 1,366 epilepsy controls (R2 =3%, P=6x10-3 ), but not significantly different from 945 independent patients with schizophrenia (R2 =0.1%, P=0.775). INTERPRETATION: Post-ictal psychosis occurs under particular circumstances in people with epilepsy with a heightened genetic predisposition to schizophrenia, illustrating how disease biology (seizures) and trait susceptibility (schizophrenia) may interact to produce particular outcomes (post-ictal psychosis) in a common disease

Experimental and theoretical investigation of ligand effects on the synthesis of ZnO nanoparticles

ZnO nanoparticles with highly controllable particle sizes(less than 10 nm) were synthesized using organic capping ligands in Zn(Ac)2 ethanolic solution. The molecular structure of the ligands was found to have significant influence on the particle size. The multi-functional molecule tris(hydroxymethyl)-aminomethane (THMA) favoured smaller particle distributions compared with ligands possessing long hydrocarbon chains that are more frequently employed. The adsorption of capping ligands on ZnnOn crystal nuclei (where n = 4 or 18 molecular clusters of(0001) ZnO surfaces) was modelled by ab initio methods at the density functional theory (DFT) level. For the molecules examined, chemisorption proceeded via the formation of Zn...O, Zn...N, or Zn...S chemical bonds between the ligands and active Zn2+ sites on ZnO surfaces. The DFT results indicated that THMA binds more strongly to the ZnO surface than other ligands, suggesting that this molecule is very effective at stabilizing ZnO nanoparticle surfaces. This study, therefore, provides new insight into the correlation between the molecular structure of capping ligands and the morphology of metal oxide nanostructures formed in their presence

Glycine-rich RNA binding protein of Oryza sativa inhibits growth of M15 E. coli cells

<p>Abstract</p> <p>Background</p> <p>Plant glycine-rich RNA binding proteins have been implicated to have roles in diverse abiotic stresses.</p> <p>Findings</p> <p><it>E. coli </it>M15 cells transformed with full-length rice glycine-rich RNA binding protein4 (OsGR-RBP4), truncated rice glycine-rich RNA binding protein4 (OsGR-RBP4ΔC) and rice FK506 binding protein (OsFKBP20) were analyzed for growth profiles using both broth and solid media. Expression of OsGR-RBP4 and OsGR-RBP4ΔC proteins caused specific, inhibitory effect on growth of recombinant M15 <it>E. coli </it>cells. The bacterial inhibition was shown to be time and incubation temperature dependent. Removal of the inducer, IPTG, resulted in re-growth of the cells, indicating that effect of the foreign proteins was of reversible nature. Although noted at different levels of dilution factors, addition of purified Os-GR-RBP4 and OsGR-RBP4ΔC showed a similar inhibitory effect as seen with expression inside the bacterial cells.</p> <p>Conclusions</p> <p>Expression of eukaryotic, stress-associated OsGR-RBP4 protein in prokaryotic <it>E. coli </it>M15 cells proves injurious to the growth of the bacterial cells. <it>E. coli </it>genome does not appear to encode for any protein that has significant homology to OsGR-RBP4 protein. Therefore, the mechanism of inhibition appears to be due to some illegitimate interactions of the OsGR-RBP4 with possibly the RNA species of the trans-host bacterial cells. The detailed mechanism underlying this inhibition remains to be worked out.</p