UBR2 of the N-End Rule Pathway Is Required for Chromosome Stability via Histone Ubiquitylation in Spermatocytes and Somatic Cells

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells

n.v.t.

The STONE model for N and P emission to groundwater and surface waters has been developed to evaluate the environmental benefits of eutrophication abatement plans. Due to possible severe socio-economic consequences of these abatement plans, it is of importance that the model is well documented, calibrated and tested. This report describes the first phase of the STONE test. STONE results were compared with previously published results and with monitoring data. About 13,000 recent point source observations of nitrate in the upper groundwater were available, along with several hundred of observations showing N and P in local surface water systems. During this phase of the STONE test, the observations were lumped to statistical summaries, such as frequency distributions, means, etc. It was concluded that the STONE results compared quite well with these observed values. These results, however, present only limited information about underlying processes, spatial patterns and temporal dynamics. These issues will be addressed during the second phase of the STONE test. Results from the second phase of the STONE test will be reported in 2002.STONE is ontwikkeld om landsdekkend voor Nederland de effecten van bemesting en mestbeleid op de emissies van stikstof en fosfaat uit de landbouw naar grond- en oppervlaktewater te verkennen. De nadruk in de hier gerapporteerde plausibiliteitsstudie ligt op vaststelling van de geloofwaardigheid, het realiteitsgehalte, van getalswaarden en ruimtelijke verdeling van data in STONE versie 2.0. Hiervoor zijn resultaten van STONE 2.0 globaal vergeleken met meetgegevens en met eerdere modelresultaten. Conclusie is dat STONE 2.0 meer plausibel is dan STONE 1.3, de versie gebruikt voor Milieuverkenning 5. De resultaten van deze studie vormen een belangrijk input voor het rapport "De status van het rekeninstrumentarium STONE versie 2.0". In het rapport wordt het toepassingsbereik van STONE 2.0 beschreven voor potentiele gebruikers en afnemers

n.v.t.

STONE is ontwikkeld om landsdekkend voor Nederland de effecten van bemesting en mestbeleid op de emissies van stikstof en fosfaat uit de landbouw naar grond- en oppervlaktewater te verkennen. De nadruk in de hier gerapporteerde plausibiliteitsstudie ligt op vaststelling van de geloofwaardigheid, het realiteitsgehalte, van getalswaarden en ruimtelijke verdeling van data in STONE versie 2.0. Hiervoor zijn resultaten van STONE 2.0 globaal vergeleken met meetgegevens en met eerdere modelresultaten. Conclusie is dat STONE 2.0 meer plausibel is dan STONE 1.3, de versie gebruikt voor Milieuverkenning 5. De resultaten van deze studie vormen een belangrijk input voor het rapport "De status van het rekeninstrumentarium STONE versie 2.0". In het rapport wordt het toepassingsbereik van STONE 2.0 beschreven voor potentiele gebruikers en afnemers.The STONE model for N and P emission to groundwater and surface waters has been developed to evaluate the environmental benefits of eutrophication abatement plans. Due to possible severe socio-economic consequences of these abatement plans, it is of importance that the model is well documented, calibrated and tested. This report describes the first phase of the STONE test. STONE results were compared with previously published results and with monitoring data. About 13,000 recent point source observations of nitrate in the upper groundwater were available, along with several hundred of observations showing N and P in local surface water systems. During this phase of the STONE test, the observations were lumped to statistical summaries, such as frequency distributions, means, etc. It was concluded that the STONE results compared quite well with these observed values. These results, however, present only limited information about underlying processes, spatial patterns and temporal dynamics. These issues will be addressed during the second phase of the STONE test. Results from the second phase of the STONE test will be reported in 2002.DG

Quality of care in European home care programs using the second generation interRAI Home Care Quality Indicators (HCQIs)

Evaluating the quality of care provided to older individuals is a key step to ensure that needs are being met and to target interventions to improve care. To this aim, interRAI's second-generation home care quality indicators (HCQIs) were developed in 2013. This study assesses the quality of home care services in six European countries using these HCQIs as well as the two derived summary scales