Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas

While allelic losses and mutations of tumor suppressor genes implicated in the etiology of astrocytoma have been widely assessed, the role of epigenetics is still a matter of study. We analyzed the frequency of promoter hypermethylation by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT, RASSF1A, p14ARF, and p16INK4A), in astrocytoma samples and cell lines. RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN showed a slight methylation signal in only one GBM and one pilocytic astrocytoma, and in two cell lines; while p14ARF and p16INK4A did not show any evidence of methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no alterations. Lack or reduced expression of RASSF1A in cell lines was correlated with the presence of methylation. RASSF1A promoter hypermethylation might be used as a diagnostic marker for secondary GBM and pediatric GBM. Promoter hypermethylation might not be an important inactivation mechanism in other genes like PTEN, p14ARF and p16INK4A, in which other alterations (mutations, homozygous deletions) are prevalent

Operational Research in Education

Operational Research (OR) techniques have been applied, from the early stages of the discipline, to a wide variety of issues in education. At the government level, these include questions of what resources should be allocated to education as a whole and how these should be divided amongst the individual sectors of education and the institutions within the sectors. Another pertinent issue concerns the efficient operation of institutions, how to measure it, and whether resource allocation can be used to incentivise efficiency savings. Local governments, as well as being concerned with issues of resource allocation, may also need to make decisions regarding, for example, the creation and location of new institutions or closure of existing ones, as well as the day-to-day logistics of getting pupils to schools. Issues of concern for managers within schools and colleges include allocating the budgets, scheduling lessons and the assignment of students to courses. This survey provides an overview of the diverse problems faced by government, managers and consumers of education, and the OR techniques which have typically been applied in an effort to improve operations and provide solutions

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing

Intracellular Zn2+ detection with quantum dot-based FLIM nanosensors

Fluorescence Lifetime Imaging Microscopy (FLIM) has been employed for the detection of intracellular Zn2+ levels, implicated in various signalling pathways, using a family of quantum dot (QD) nanosensors. The sensing mechanism was based on photoinduced electron transfer (PET) between an azacycle receptor group and the QD nanoparticles.This work was supported by Fundación Ramon Areces and grant CTQ2014-56370-R from Ministerio de Economia y Competitividad of Spain

The impact of measurement errors in the identification of regulatory networks

<p>Abstract</p> <p>Background</p> <p>There are several studies in the literature depicting measurement error in gene expression data and also, several others about regulatory network models. However, only a little fraction describes a combination of measurement error in mathematical regulatory networks and shows how to identify these networks under different rates of noise.</p> <p>Results</p> <p>This article investigates the effects of measurement error on the estimation of the parameters in regulatory networks. Simulation studies indicate that, in both time series (dependent) and non-time series (independent) data, the measurement error strongly affects the estimated parameters of the regulatory network models, biasing them as predicted by the theory. Moreover, when testing the parameters of the regulatory network models, p-values computed by ignoring the measurement error are not reliable, since the rate of false positives are not controlled under the null hypothesis. In order to overcome these problems, we present an improved version of the Ordinary Least Square estimator in independent (regression models) and dependent (autoregressive models) data when the variables are subject to noises. Moreover, measurement error estimation procedures for microarrays are also described. Simulation results also show that both corrected methods perform better than the standard ones (i.e., ignoring measurement error). The proposed methodologies are illustrated using microarray data from lung cancer patients and mouse liver time series data.</p> <p>Conclusions</p> <p>Measurement error dangerously affects the identification of regulatory network models, thus, they must be reduced or taken into account in order to avoid erroneous conclusions. This could be one of the reasons for high biological false positive rates identified in actual regulatory network models.</p

Knowledge on the action to be taken and recognition of symptoms of stroke in a community: findings from the May Measurement Month 2017 blood pressure screening Programme in Malaysia

Background: Information regarding the knowledge on the action to be taken during stroke and good recognition of stroke symptoms is mandatory in helping to plan out educational strategies to deliver health education to the community. Methods: This is a cross-sectional study of adults aged 18 and above attending a blood pressure screening program in community in conjunction with May Measurement Month 2017 in Malaysia. A structured self-administered questionnaire was given to the participants who gave verbal consent. Data analysis was done using SPSS v. 23 and multiple logistic regression was used to identify the determinants of knowledge on actions to be taken during stroke and recognition of stroke symptoms. Results: Out of 4096 respondents, 82.9–92.1% of them able to recognise the common stroke symptoms. and 74.2% of the study respondents will go to hospital within 4.5 h of stroke onset. According to binomial logistic regression analyses, adults aged 45 years old and above (OR 1.39 95%CI 1.01–1.92), being Malay (OR 1.74, 95% CI 1.27–2.40), being non-smokers (OR = 2.491, 95% CI: 1.64–3.78), hypertensives (OR: 1.57, 95% CI: 1.02–2.42)and diabetics (OR: 2.54, 95% CI:1.38–4.69) are determinants of right actions to be taken during stroke. Meanwhile, respondents aged 45 years old and older (OR = 1.68, 95% CI: 1.39–2.03), being Malay (OR = 1.49, 95% CI: 1.24–1.79), hypertensive (OR = 1.32, 95% CI: 1.04–1.66) and those who had a previous history of stroke (OR = 2.25, 95% CI: 1.01–5.00) are determinants of good recognition of stroke symptoms. Conclusions: The overall knowledge of stroke in our study population was good. Older age, being Malay, non-smokers, hypertensives and diabetics are determinants of right actions to be taken during stroke. Meanwhile, older age, being Malay, hypertensive and those who had a previous history of stroke are determinants of good recognition of stroke symptoms

The combined effect of plastics and food waste accelerates the thermal decomposition of refuse-derived fuels and fuel blends

Mechanical treatments such as shredding or extrusion are applied to municipal solid wastes (MSW) to produce refuse-derived fuels (RDF). In this way, a waste fraction (mainly composed by food waste) is removed and the quality of the fuel is improved. In this research, simultaneous thermal analysis (STA) was used to investigate how different mechanical treatments applied to MSW influence the composition and combustion behaviour of fuel blends produced by combining MSW or RDF with wood in different ratios. Shredding and screening resulted in a more efficient mechanical treatment than extrusion to reduce the chlorine content in a fuel, which would improve its quality. This study revealed that when plastics and food waste are combined in the fuel matrix, the thermal decomposition of the fuels are accelerated. The combination of MSW or RDF and woody materials in a fuel blend has a positive impact on its decomposition

Frontal and insular input to the dorsolateral temporal pole in primates: Implications for auditory memory

The temporal pole (TP) has been involved in multiple functions from emotional and social behavior, semantic processing,memory, language in humans and epilepsy surgery, to the fronto-temporal neurodegenerative disorder (semantic) dementia. However, the role of the TP subdivisions is still unclear, in part due to the lack of quantitative data about TP connectivity. This study focuses in the dorsolateral subdivision of the TP: area 38DL. Area 38DL main input originates in the auditory processing areas of the rostral superior temporal gyrus. Among other connections, area 38DL conveys this auditory highly processed information to the entorhinal, rostral perirhinal, and posterior parahippocampal cortices, presumably for storage in long-term memory (Muñoz-López et al., 2015). However, the connections of the TP with cortical areas beyond the temporal cortex suggest that this area is part of a wider network. With the aim to quantitatively determine the topographical, laminar pattern and weighting of the lateral TP afferents from the frontal and insular cortices, we placed a total of 11 tracer injections of the fluorescent retrograde neuronal tracers Fast Blue and Diamidino Yellow at different levels of the lateral TP in rhesus monkeys. The results showed that circa 50% of the total cortical input to area 38DL originates in medial frontal areas 14, 25, 32, and 24 (25%); orbitofrontal areas Pro and PAll (15%); and the agranular, parainsular and disgranular insula (10%). This study sets the anatomical bases to better understand the function of the dorsolateral division of the TP. More specifically, these results suggest that area 38DL forms part of the wider limbic circuit that might contribute, among other functions, with an auditory component to multimodal memory processing

Interpreting Cancer Genomes Using Systematic Host Perturbations by Tumour Virus Proteins

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations associated with cancer predisposition and large numbers of somatic genomic alterations. However, it remains challenging to distinguish between background, or “passenger” and causal, or “driver” cancer mutations in these datasets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations. To test the hypothesis that genomic variations and tumour viruses may cause cancer via related mechanisms, we systematically examined host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways that go awry in cancer, such as Notch signalling and apoptosis. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches result in increased specificity for cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate prioritization of cancer-causing driver genes so as to advance understanding of the genetic basis of human cancer