Eläke- ja vammaisetuuksien, maahanmuuttajan erityistuen ja eläkkeensaajan asumistuen muutokset 1.1.2011

Kansaneläkeindeksi 1 508, elinkustannusindeksi 1 749 (pistelukujen keskiarvo heinäsyyskuulta 2010) Vuoden 2011 alusta kansaneläkkeisiin, perhe-eläkkeisiin, lapsikorotuksiin, rintamalisiin, vammaisetuuksiin (pl. ruokavaliokorvaukset) ja maahanmuuttajan erityistukiin tehtiin 0,4 prosentin indeksitarkistus. Eläke-etuusmenot kasvoivat 9,7 milj. euroa (0,4 %), vammaisetuusmenot 1,9 milj. euroa (0,4 %) ja maahanmuuttajan erityistukimenot 0,1 milj. euroa (0,3 %). Laskelmat perustuvat joulukuun 2010 etuuskantaan.

‘Optimaliserend Onderwijs’ voor elke leerling. Multiniveau theoretisch ontwerp en praktijkontwikkeling

Een review van onderwijsanalyses en (beleids)onderzoeken verricht in de periode 1916-2015 wijst uit dat de reguliere jaarklassensystematiek in het Nederlandse primair en voortgezet onderwijs aanleiding geeft tot prestatie- en motivatieproblemen bij risico-leerlingen. Dit zijn met name de leerlingen die qua ontwikkelingspotenties of leervorderingen (aanvankelijk) duidelijk naar beneden of naar boven afwijken van leeftijdsgenoten in een groep of klas. Ondervanging van deze problemen lijkt mogelijk via een preventieve systematiek van ‘Optimaliserend Onderwijs’ voor elk kind in de vóór- of vroegschoolse educatie en elke leerling in het primair of voortgezet onderwijs. Een eerste vraag betreft de inhoudelijke en vormgevingskenmerken van dit onderwijsontwerp: welke richtlijnen en specificaties daarvan kunnen het onderwijs, spelen en leren voor elke leerling, zo optimaal mogelijk inhoud en vorm geven en hoe ziet een model van dit Optimaliserend Onderwijs eruit? Een tweede vraag is gericht op de realisatie van dit onderwijsontwerp: hoe is deze onderwijssystematiek te ontwikkelen in de Nederlandse schoolpraktijk? Gebruik van de sneeuwbalmethode in met name Nederlandse onderzoeks- en designliteratuur leidt tot beantwoording van de eerste vraag in de vorm van een multiniveau theoretisch ontwerp van ‘Optimaliserend Onderwijs’. Kernpunten hierin zijn: landelijke (deel)curricula gekenmerkt door instructievarianten; integratie van dubbele diagnostiek (individueel-longitudinaal en vergelijkend-genormeerd); flexibele certificerings- en diplomeringsstructuur; een ondersteunende schoolorganisatie; gecontroleerde opbrengst-optimalisering per kind of leerling en op instellings- en schoolniveau; per vóór- of vroegschoolse instelling of school(bestuur) kunnen ook vrije ofwel eigen onderwijsinvullingen worden ingericht. Beantwoording van de tweede vraag gebeurt met behulp van (onderzoeks)literatuur over multiniveau onderwijsinnovatie in de schoolpraktijk. Aanbevolen wordt om, op basis van een gezamenlijk besluit van het ministerie van Onderwijs, Cultuur en Wetenschap, de Tweede Kamer, relevante onderwijsinstanties, schoolbesturen en ouderorganisaties, te komen tot inrichting van samenhangende ontwikkelingsprojecten en -onderzoeken. Via een projectenserie in instellingen voor vóór- of vroegschoolse educatie en scholen voor primair en voortgezet onderwijs kan gecontroleerd worden samengewerkt tussen leid(st)ers, leerkrachten en docenten, scholen, ontwikkelings- en andere onderwijsinstellingen, instellingen voor onderzoek en informatietechnologie, en onderwijspolitiek. Tussenresultaten van Optimaliserend Onderwijs worden steeds in andere instellingen en scholen beproefd en verder verspreid.

Elke Kleinau / Barbara Rendtorff (Hrsg.): Differenz, Diversität und Heterogenität in erziehungswissenschaftlichen Diskursen. Schriftenreihe der Sektion Frauen- und Geschlechterforschung in der Deutschen Gesellschaft für Erziehungswissenschaft(DGfE), Band 3, Opladen u.a.: Barbara Budrich Verlag 2013 (156 S.) [Rezension]

Rezension von: Elke Kleinau / Barbara Rendtorff (Hrsg.): Differenz, Diversität und Heterogenität in erziehungswissenschaftlichen Diskursen. Schriftenreihe der Sektion Frauen- und Geschlechterforschung in der Deutschen Gesellschaft für Erziehungswissenschaft(DGfE), Band 3, Opladen u.a.: Barbara Budrich Verlag 2013 (156 S.; ISBN 978-3-8474-0073-8)

Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4R24C/R24C/Tyr-NrasQ61K mice following neonatal UVR

To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4R24C/R24C/NrasQ61K mice topically with the T4 endonuclease V DNA repair enzyme (known as Dimericine) immediately prior to neonatal ultraviolet radiation (UVR) exposure, which has a powerful effect in exacerbating melanoma development in the mouse model. Dimericine has been shown to reduce the incidence of basal-cell and squamous cell carcinoma. Unexpectedly, we saw no difference in penetrance or age of onset of melanoma after neonatal UVR between Dimericine-treated and control animals, although the drug reduced DNA damage and cellular proliferation in the skin. Interestingly, epidermal melanocytes removed cyclobutane pyrimidine dimers (CPDs) more efficiently than surrounding keratinocytes. Our study indicates that neonatal UVR-initiated melanomas may be driven by mechanisms other than solely that of a large CPD load and/or their inefficient repair. This is further suggestive of different mechanisms by which UVR may enhance the transformation of keratinocytes and melanocytes.

Differential roles of the pRb and Arf/p53 pathways in murine naevus and melanoma genesis

We report on a systematic analysis of genotype-specific melanocyte (MC) UVR responses in transgenic mouse melanoma models along with tumour penetrance and comparative histopathology. pRb or p53 pathway mutations cooperated with NrasQ61K to transform MCs. We previously reported that MCs migrate from the follicular outer root sheath into the epidermis after neonatal UVR. Here, we found that Arf or p53 loss markedly diminished this response. Despite this, mice carrying these mutations developed melanoma with very early age of onset after neonatal UVR. Cdk4R24C did not affect the MC migration. Instead, independent of UVR exposure, interfollicular dermal MCs were more prevalent in Cdk4R24C mice. Subsequently, in adulthood, these mutants developed dermal MC proliferations reminiscent of superficial congenital naevi. Two types of melanoma were observed in this model. The location and growth pattern of the first was consistent with derivation from the naevi, while the second appeared to be of deep dermal origin. In animals carrying the Arf or p53 defects, no naevi were detected, with all tumours ostensibly skipping the benign precursor stage in progression.

The association between MC1R genotype and BRAF mutation status in cutaneous melanoma : findings from an Australian population

There is increasing epidemiological and molecular evidence that cutaneous melanomas arise through multiple causal pathways. The purpose of this study was to explore the relationship between germline and somatic mutations in a population-based series of melanoma patients to reshape and refine the divergent pathway model for melanoma. Melanomas collected from 123 Australian patients were analyzed for melanocortin-1 receptor (MC1R) variants and mutations in the BRAF and NRAS genes. Detailed phenotypic and sun exposure data were systematically collected from all patients. We found that BRAF-mutant melanomas were significantly more likely from younger patients and those with high nevus counts, and were more likely in melanomas with adjacent neval remnants. Conversely, BRAF-mutant melanomas were significantly less likely in people with high levels of lifetime sun exposure. We observed no association between germline MC1R status and somatic BRAF mutations in melanomas from this population. BRAF-mutant melanomas have different origins from other cutaneous melanomas. These data support the divergent pathways hypothesis for melanoma, which may require a reappraisal of targeted cancer prevention activities.

Melanocyte homeostasis in vivo tolerates Rb1 loss in a developmentally independent fashion

There has been uncertainty regarding the precise role that the pocket protein Rb1 plays in murine melanocyte homeostasis. It has been reported that the TAT-Cre mediated loss of exon 19 from a floxed Rb1 allele causes melanocyte apoptosis in vivo and in vitro. This is at variance with other findings showing, either directly or indirectly, that Rb1 loss in melanocytes has no noticeable effect in vivo, but in vitro leads to a semi-transformed phenotype. In this study, we show that Rb1-null melanocytes lacking exon 19 do not undergo apoptosis and survive both in vitro and in vivo, irrespective of the developmental stage at which Cre-mediated ablation of the exon occurs. Further, Rb1 loss has no serious long-term ramifications on melanocyte homeostasis in vivo, with Rb1-null melanocytes being detected in the skin after numerous hair cycles, inferring that the melanocyte stem cell population carrying the Cre-mediated deletion is maintained. Consequently, whilst Rb1 loss in the melanocyte is able to alter cellular behaviour in vitro, it appears inconsequential with respect to melanocyte homeostasis in the mouse skin.

Inverse expression states of the BRN2 and MITF transcription factors in melanoma spheres and tumour xenografts regulate the NOTCH pathway

The use of adherent monolayer cultures have produced many insights into melanoma cell growth and differentiation, but often novel therapeutics demonstrated to act on these cells are not active in vivo. It is imperative that new methods of growing melanoma cells that reflect growth in vivo are investigated. To this end, a range of human melanoma cell lines passaged as adherent cultures or induced to form melanoma spheres (melanospheres) in stem cell media have been studied to compare cellular characteristics and protein expression. Melanoma spheres and tumours grown from cell lines as mouse xenografts had increased heterogeneity when compared with adherent cells and 3D-spheroids in agar (aggregates). Furthermore, cells within the melanoma spheres and mouse xenografts each displayed a high level of reciprocal BRN2 or MITF expression, which matched more closely the pattern seen in human melanoma tumours in situ, rather than the propensity for co-expression of these important melanocytic transcription factors seen in adherent cells and 3D-spheroids. Notably, when the levels of the BRN2 and MITF proteins were each independently repressed using siRNA treatment of adherent melanoma cells, members of the NOTCH pathway responded by decreasing or increasing expression, respectively. This links BRN2 as an activator, and conversely, MITF as a repressor of the NOTCH pathway in melanoma cells. Loss of the BRN2-MITF axis in antisense-ablated cell lines decreased the melanoma sphere-forming capability, cell adhesion during 3D-spheroid formation and invasion through a collagen matrix. Combined, this evidence suggests that the melanoma sphere-culture system induces subpopulations of cells that may more accurately portray the in vivo disease, than the growth as adherent melanoma cells.

Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor

To identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR-211. We focused on this pigment-cell-enriched miRNA as it is derived from the microphthalmia-associated transcription factor (MITF)-regulated gene, TRPM1 (melastatin). We find that miR-211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR-211, including POU3F2 (BRN2). Inhibition of miR-211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR-211 represses BRN2 in differentiated cells. Over-expression of miR-211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting BRN2 translation. We propose a model for the apparent non-overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR-211 expression.