Expression of iron-related genes in human brain and brain tumors

<p>Abstract</p> <p>Background</p> <p>Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (<it>HAMP</it>), HFE, neogenin (<it>NEO1</it>), transferrin receptor 1 (<it>TFRC</it>), transferrin receptor 2 (<it>TFR2</it>), and hemojuvelin (<it>HFE2</it>) in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines.</p> <p>Results</p> <p>Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens.</p> <p>Conclusion</p> <p>These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.</p

Biochem Soc Trans

Abnormal protein aggregation and intracellular or extracellular accumulation of misfolded and aggregated proteins are key events in the pathogenesis of different neurodegenerative diseases. Furthermore, endoplasmic reticulum stress and impairment of the ubiquitin-proteasome system probably contribute to neurodegeneration in these diseases. A characteristic feature of AD (Alzheimer's disease) is the abnormal accumulation of Abeta (amyloid beta-peptide) in the brain. Evidence shows that the AD-associated PS (presenilin) also forms aggregates under certain conditions and that another AD-associated protein, ubiquilin-1, controls protein aggregation and deposition of aggregated proteins. Here, we review the current knowledge of ubiquilin-1 and PS in protein aggregation and related events that potentially influence neurodegeneration

Ownership and governance of Finnish infrastructure networks

This research report investigates and analyzes the pros and cons of different ownership and governance models of infrastructure networks. The report covers most infrastructure networks: transportation networks (roads, streets, railways, airports, harbors) and utility networks (water and sewage, energy and electricity). There is no unifying solution that would fit all sectors in terms of the most efficient ownership model. However, in many sectors reforms are needed towards more elaborated client-supplier frameworks to ensure greater efficiency and cost transparency. Surprisingly, traditional organizational structures do not seem to impact on financial returns of those networks that provide user-financed services. In Finland technical infrastructure networks are typically owned, administered and managed by the public sector as they are considered public goods and critical assets for the wellbeing of citizens. In many ways the sectors have remained passive and with little interaction towards more innovative service provision solutions or organizational models. In terms of developing the networks’ services and their profitability, the greatest business opportunity would result from allowing open entry to market and competition in contracting. This would mean abandonment of negotiated contracts and proactive evolution of functional markets. The scope of business opportunities will increase in all aspect of service delivery; from management to engineering and economic studies, asset management systems, construction and maintenance works, and the labor to do all that

Psykiatrian palvelut tulevat kotiin

Liikkuvilla palveluilla pyritään tulevaisuudessa monipuolistamaan myös psykiatrian lähipalveluja. Satakunnan sairaanhoitopiirissä työmuoto on tuttu etenkin lastenpsykiatrian puolella. Toiminta edellyttää hyvää suunnittelua ja koordinointia

Dictionary Matching with One Gap

The dictionary matching with gaps problem is to preprocess a dictionary $D$ of $d$ gapped patterns $P_1,\ldots,P_d$ over alphabet $\Sigma$, where each gapped pattern $P_i$ is a sequence of subpatterns separated by bounded sequences of don't cares. Then, given a query text $T$ of length $n$ over alphabet $\Sigma$, the goal is to output all locations in $T$ in which a pattern $P_i\in D$, $1\leq i\leq d$, ends. There is a renewed current interest in the gapped matching problem stemming from cyber security. In this paper we solve the problem where all patterns in the dictionary have one gap with at least $\alpha$ and at most $\beta$ don't cares, where $\alpha$ and $\beta$ are given parameters. Specifically, we show that the dictionary matching with a single gap problem can be solved in either $O(d\log d + |D|)$ time and $O(d\log^{\varepsilon} d + |D|)$ space, and query time $O(n(\beta -\alpha )\log\log d \log ^2 \min \{ d, \log |D| \} + occ)$, where $occ$ is the number of patterns found, or preprocessing time and space: $O(d^2 + |D|)$, and query time $O(n(\beta -\alpha ) + occ)$, where $occ$ is the number of patterns found. As far as we know, this is the best solution for this setting of the problem, where many overlaps may exist in the dictionary.Comment: A preliminary version was published at CPM 201

Complete measurements of quantum observables

We define a complete measurement of a quantum observable (POVM) as a measurement of the maximally refined version of the POVM. Complete measurements give information from the multiplicities of the measurement outcomes and can be viewed as state preparation procedures. We show that any POVM can be measured completely by using sequential measurements or maximally refinable instruments. Moreover, the ancillary space of a complete measurement can be chosen to be minimal.Comment: Based on talk given in CEQIP 2012 conferenc

Genotypic and phenotypic diversity of Lactobacillus rhamnosus clinical isolates, their comparison with strain GG and their recognition by complement system

Lactobacillus rhamnosus strains are ubiquitous in fermented foods, and in the human body where they are commensals naturally present in the normal microbiota composition of gut, vagina and skin. However, in some cases, Lactobacillus spp. have been implicated in bacteremia. The aim of the study was to examine the genomic and immunological properties of 16 clinical blood isolates of L. rhamnosus and to compare them to the well- studied L. rhamnosus probiotic strain GG. Blood cultures from bacteremic patients were collected at the Helsinki University Hospital laboratory in 2005-2011 and L. rhamnosus strains were isolated and characterized by genomic sequencing. The capacity of the L. rhamnosus strains to activate serum complement was studied using immunological assays for complement factor C3a and the terminal pathway complement complex (TCC). Binding of complement regulators factor H and C4bp was also determined using radioligand assays. Furthermore, the isolated strains were evaluated for their ability to aggregate platelets and to form biofilms in vitro. Genomic comparison between the clinical L. rhamnosus strains showed them to be clearly different from L. rhamnosus GG and to cluster in two distinct lineages. All L. rhamnosus strains activated complement in serum and none of them bound complement regulators. Four out of 16 clinical blood isolates induced platelet aggregation and/or formed more biofilms than L. rhamnosus GG, which did not display platelet aggregation activity nor showed strong biofilm formation. These findings suggest that clinical L. rhamnosus isolates show considerable heterogeneity but are clearly different from L. rhamnosus GG at the genomic level. All L. rhamnosus strains are still normally recognized by the human complement system.Peer reviewe

Long-term prognosis of haemangioblastoma of the CNS: Impact of von Hippel-Lindau disease

Peer reviewe

Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration

Staphylococcus aureus Panton-Valentine leukocidin is a pore-forming toxin targeting the human C5a receptor (hC5aR), enabling this pathogen to battle the immune response by destroying phagocytes through targeted lysis. The mechanisms that contribute to rapid cell lysis are largely unexplored. Here, we show that cell lysis may be enabled by a process of toxins targeting receptor clusters and present indirect evidence for receptor recycling that allows multiple toxin pores to be formed close together. With the use of live cell single-molecule super-resolution imaging, Forster resonance energy transfer and nanoscale total internal reflection fluorescence colocalization microscopy, we visualized toxin pore formation in the presence of its natural docking ligand. We demonstrate disassociation of hC5aR from toxin complexes and simultaneous binding of new ligands. This effect may free mobile receptors to amplify hyperinflammatory reactions in early stages of microbial infections and have implications for several other similar bicomponent toxins and the design of new antibiotics.Haapasalo, K., Wollman, A. J. M., de Haas, C. J. C., van Kessel, K. P. M., van Strijp, J. A. G., Leake, M. C. Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration.Peer reviewe