Differential MicroRNA Expression in Glioblastoma as a Therapeutic Target or Potential Biomarker

MicroRNA (miRNA) is an epigenetic factor that plays an important role in the post-transcriptional regulation of gene and protein expression. Recent research has shown that in many types of cancer, differentially expressed levels of certain types of miRNA are significantly correlated with the transformation of and ongoing issues caused by cancer cells. Specifically, in Glioblastoma, one of the most lethal and aggressive human cancers, differential levels of miRNAs contribute to the cell’s lack of pro-apoptotic gene presence and its high resistance to current treatments. Results from current studies could provide information about which microRNAs are differentially expressed in glioblastoma when compared to normal astrocytes. Differentially expressed microRNAs may be used as a biomarker for diagnosis or a potential therapeutic target for Glioblastoma treatment

Characterization of bacterial lipooligosaccharides by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry

Matrix-assisted laser desorption ionization (MALDI) with a time-of-flight analyzer has been used to analyze bacterial lipooligosaccharides (LOS). Crude LOS preparations from pathogenic strains of Haemophilus influenzae and Haemophilus ducreyi and a commercial preparation of lipopolysaccharide from Salmonella typhimurium were treated with hydrazine to remove O-linked fatty acids on the lipid A moiety. The resulting O-deacylated LOS forms were water soluble and more amenable to cocrystallization with standard MALDI matrices such as 2,5-dihydroxybenzoic acid and 1-hydroxyisoquinoline. Under continuous extraction conditions, O-deacylated LOS yielded broad peaks with abundant salt adducts as well as forming prompt fragments through β-elimination of phosphoric acid, that is, [M-H3PO4-H]. However, when a time delay was used between ionization and extraction (“delayed extraction”) a significant improvement was seen in both mass resolution and the stability of the molecular ions against β-elimination of phosphoric acid, especially in the negative-ion mode. Both an external two-point calibration and an internal single-point calibration were used to assign masses, the latter of which provided the highest degree of accuracy (better than 0.01% in most cases). At higher laser powers, the LOS molecules cleave readily between the oligosaccharide and lipid A moieties yielding a number of prompt fragments. Postsource decay (PSD) analysis of selected molecular ions provided a set of fragments similar to those seen in the linear spectra, although they were more limited in number because they were derived from a single LOS-glycoform. Both the prompt and PSD fragments provided important structural information, especially in assigning the phosphate and phosphoethanolamine substitution pattern of the lipid A and oligosaccharide portions of LOS. Last, with the addition of ethylenediaminetetraacetic acid followed by pulsed sonication, the relatively insoluble (and impure) LOS preparations yielded MALDI spectra similar to the O-deacylated LOS, although these intact LOS preparations required higher laser powers to ionize and were generally more affected by competing impurities

An Automated Method for the Analysis of Stable Isotope Labeling Data in Proteomics

An algorithm is presented for the generation of a reliable peptide component peak table from liquid chromatography-mass spectrometry (LC-MS) and subsequent quantitative analysis of stable isotope coded peptide samples. The method uses chemical noise filtering, charge state fitting, and deisotoping toward improved analysis of complex peptide samples. Overlapping peptide signals in mass spectra were deconvoluted by correlation with modeled peptide isotopic peak profiles. Isotopic peak profiles for peptides were generated in silico from a protein database producing reference model distributions. Doublets of heavy and light labeled peak clusters were identified and compared to provide differential quantification of pairs of stable isotope coded peptides. Algorithms were evaluated using peptides from digests of a single protein and a seven-protein mixture that had been differentially coded with stable isotope labeling agents and mixed in known ratios. The experimental results correlated well with known mixing ratios

Economic crisis and the construction of a neo-liberal regulatory regime in Korea

A consistent theme of the literature on the ontology of the 1997 South Korean crisis is the key role played by regulatory failures and the growing weakness of the state. This paper seeks to briefly highlight both the insights and the limitations of this approach to understanding the crisis. Having done so, we shall set out the argument that the crisis created an opportunity for reformist Korean élites to advance their longstanding, but previously frustrated, project to create a comprehensive unambiguously neo-liberal regulatory regime. This paper will also seek to highlight the implications of our reading of the development of the Korean political economy for broader debates on economic liberalisation, crisis and the future of the developmental state

Mineral nutrition in penaeid shrimp

This review summarises the current knowledge of mineral nutrition for penaeid shrimp. It investigates how the aquatic environment and the lifecycle of shrimp affect requirements and the role that minerals play in shrimp health. Methods of supplying minerals via either water or to feed, and novel ways of supplementing minerals within feed, are discussed. The requirements for individual minerals are summarised with recommendations for minimum levels of dietary inclusion for semi-intensive and intensive commercial shrimp culture presented where data permits. Estimates of dietary requirement remain broad for most minerals for the main shrimp production species (Penaeus vannamei, Penaeus monodon and Penaeus japonicus), with some essential minerals remaining unstudied (Table 2 in Section 5.10). Mineral nutrition will become more important as intensification and diversification of production systems provide new challenges to shrimp aquaculture.</p

Warfare, Fiscal Capacity, and Performance

We exploit differences in casualties sustained in pre-modern wars to estimate the impact of fiscal capacity on economic performance. In the past, states fought different amounts of external conflicts, of various lengths and magnitudes. To raise the revenues to wage wars, states made fiscal innovations, which persisted and helped to shape current fiscal institutions. Economic historians claim that greater fiscal capacity was the key long-run institutional change brought about by historical conflicts. Using casualties sustained in pre-modern wars to instrument for current fiscal institutions, we estimate substantial impacts of fiscal capacity on GDP per worker. The results are robust to a broad range of specifications, controls, and sub-samples

Changing Human Visual Field Organization from Early Visual to Extra-Occipital Cortex

BACKGROUND: The early visual areas have a clear topographic organization, such that adjacent parts of the cortical surface represent distinct yet adjacent parts of the contralateral visual field. We examined whether cortical regions outside occipital cortex show a similar organization. METHODOLOGY/PRINCIPAL FINDINGS: The BOLD responses to discrete visual field locations that varied in both polar angle and eccentricity were measured using two different tasks. As described previously, numerous occipital regions are both selective for the contralateral visual field and show topographic organization within that field. Extra-occipital regions are also selective for the contralateral visual field, but possess little (or no) topographic organization. A regional analysis demonstrates that this weak topography is not due to increased receptive field size in extra-occipital areas. CONCLUSIONS/SIGNIFICANCE: A number of extra-occipital areas are identified that are sensitive to visual field location. Neurons in these areas corresponding to different locations in the contralateral visual field do not demonstrate any regular or robust topographic organization, but appear instead to be intermixed on the cortical surface. This suggests a shift from processing that is predominately local in visual space, in occipital areas, to global, in extra-occipital areas. Global processing fits with a role for these extra-occipital areas in selecting a spatial locus for attention and/or eye-movements

The role of population PK-PD modelling in paediatric clinical research

Children differ from adults in their response to drugs. While this may be the result of changes in dose exposure (pharmacokinetics [PK]) and/or exposure response (pharmacodynamics [PD]) relationships, the magnitude of these changes may not be solely reflected by differences in body weight. As a consequence, dosing recommendations empirically derived from adults dosing regimens using linear extrapolations based on body weight, can result in therapeutic failure, occurrence of adverse effect or even fatalities. In order to define rational, patient-tailored dosing schemes, population PK-PD studies in children are needed. For the analysis of the data, population modelling using non-linear mixed effect modelling is the preferred tool since this approach allows for the analysis of sparse and unbalanced datasets. Additionally, it permits the exploration of the influence of different covariates such as body weight and age to explain the variability in drug response. Finally, using this approach, these PK-PD studies can be designed in the most efficient manner in order to obtain the maximum information on the PK-PD parameters with the highest precision. Once a population PK-PD model is developed, internal and external validations should be performed. If the model performs well in these validation procedures, model simulations can be used to define a dosing regimen, which in turn needs to be tested and challenged in a prospective clinical trial. This methodology will improve the efficacy/safety balance of dosing guidelines, which will be of benefit to the individual child

Quantifying cerebral asymmetries for language in dextrals and adextrals with random-effects meta analysis

Speech and language-related functions tend to depend on the left hemisphere more than the right in most right-handed (dextral) participants. This relationship is less clear in non-right handed (adextral) people, resulting in surprisingly polarized opinion on whether or not they are as lateralized as right handers. The present analysis investigates this issue by largely ignoring methodological differences between the different neuroscientific approaches to language lateralization, as well as discrepancies in how dextral and adextral participants were recruited or defined. Here we evaluate the tendency for dextrals to be more left hemisphere dominant than adextrals, using random effects meta analyses. In spite of several limitations, including sample size (in the adextrals in particular), missing details on proportions of groups who show directional effects in many experiments, and so on, the different paradigms all point to proportionally increased left hemispheric dominance in the dextrals. These results are analyzed in light of the theoretical importance of these subtle differences for understanding the cognitive neuroscience of language, as well as the unusual asymmetry in most adextrals

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio