PCAF regulates the stability of the transcriptional regulator and cyclin-dependent kinase inhibitor p27Kip1

P27(Kip1) (p27) is a member of the Cip/Kip family of cyclin-dependent kinase inhibitors. Recently, a new function of p27 as transcriptional regulator has been reported. It has been shown that p27 regulates the expression of target genes mostly involved in splicing, cell cycle, respiration and translation. We report here that p27 directly binds to the transcriptional coactivator PCAF by a region including amino acids 91-120. PCAF associates with p27 through its catalytic domain and acetylates p27 at lysine 100. Our data showed that overexpression of PCAF induces the degradation of p27 whereas in contrast, the knockdown of PCAF stabilizes the protein. A p27 mutant in which K100 was substituted by arginine (p27-K100R) cannot be acetylated by PCAF and has a half-life much higher than that of p27WT. Moreover, p27-K100R remains stable along cell-cycle progression. Ubiquitylation assays and the use of proteasome inhibitors indicate that PCAF induces p27 degradation via proteasome. We also observed that knockdown of skp2 did not affect the PCAF induced degradation of p27. In conclusion, our data suggest that the p27 acetylation by PCAF regulates its stability.

Stress reaction of kidney epithelial cells to inorganic solid-core nanoparticles.

A route of accumulation and elimination of therapeutic engineered nanoparticles (NPs) may be the kidney. Therefore, the interactions of different solid-core inorganic NPs (titanium-, silica-, and iron oxide-based NPs) were studied in vitro with the MDCK and LLC-PK epithelial cells as representative cells of the renal epithelia. Following cell exposure to the NPs, observations include cytotoxicity for oleic acid-coated iron oxide NPs, the production of reactive oxygen species for titanium dioxide NPs, and cell depletion of thiols for uncoated iron oxide NPs, whereas for silica NPs an apparent rapid and short-lived increase of thiol levels in both cell lines was observed. Following cell exposure to metallic NPs, the expression of the tranferrin receptor/CD71 was decreased in both cells by iron oxide NPs, but only in MDCK cells by titanium dioxide NPs. The tight association, then subsequent release of NPs by MDCK and LLC-PK kidney epithelial cells, showed that following exposure to the NPs, only MDCK cells could release iron oxide NPs, whereas both cells released titanium dioxide NPs. No transfer of any solid-core NPs across the cell layers was observed.

Spatial variability of aggregate stability in latosols under sugarcane

The spatial variability of soils under a same management system is differentiated, as expressed in the properties. The spatial variability of aggregate stability of a eutrophic Red Latosol (ERL) and a dystrophic Red Latosol (DRL) under sugarcane was characterized. Samples were collected in a regular 10 m grid, in the layers 0.0-0.2 and 0.2-0.4 m, with 100 points per area, and the following properties were determined: geometric mean diameter (GMD) of aggregates, mean weight diameter (MWD) of aggregates, percent of aggregates in the > 2.0 mm class and organic matter (OM) content. The eutrophic Red Latosol (ERL) had a higher aggregate stability thn the dystrophic Red Latosol (DRL), which may be attributed to the higher clay and OM content and the gibbsitic mineralogy of this soil class. The differentiated evolution of the studied Oxisols explains the wider range and lower variation coefficient and variability, for all properties studied in the eutrophic Red Latosol.

Aggregate stability as affected by short and long-term tillage systems and nutrient sources of a hapludox in southern Brazil

The ability of a soil to keep its structure under the erosive action of water is usually high in natural conditions and decreases under frequent and intensive cultivation. The effect of five tillage systems (NT = no-till; CP = chisel plowing and one secondary disking; CT = primary and two secondary distings; CTb = CT with crop residue burning; and CTr = CT with removal of crop residues from the field), combined with five nutrient sources (C = control, no nutrient application; MF = mineral fertilizers according to technical recommendations for each crop; PL = 5 Mg ha-1 y-1 fresh matter of poultry litter; CM = 60 m³ ha-1 y-1 slurry cattle manure; and SM = 40 m³ ha-1 y-1 slurry swine manure) on wet-aggregate stability was determined after nine years (four sampled soil layers) and on five sampling dates in the 10th year (two sampled soil layers) of the experiment. The size distribution of the air-dried aggregates was strongly affected by soil bulk density, and greater values of geometric mean diameter (GMD AD) found in some soil tillage or layer may be partly due to the higher compaction degree. After nine years, the GMD AD on the surface was greater in NT and CP compared to conventional tillage systems (CT, CTb and CTr), due to the higher organic matter content, as well as less soil mobilization. Aggregate stability in water, on the other hand, was affected by the low variation in previous gravimetric moisture of aggregates, which contributed to a high coefficient of variation of this attribute. The geometric mean diameter of water-stable aggregates (GMD WS) was highest in the 0.00-0.05 m layer in the NT system, in the layers 0.05-0.10 and 0.12-0.17 m in the CT, and values were intermediate in CP. The stability index (SI) in the surface layers was greater in treatments where crop residues were kept in the field (NT, CP and CT), which is associated with soil organic matter content. No differences were found in the layer 0.27-0.32 m. The effect of nutrient sources on GMD AD and GMD WS was small and did not affect SI.

Scientific value of systematic reviews: survey of editors of core clinical journals.

BACKGROUND: Synthesizing research evidence using systematic and rigorous methods has become a key feature of evidence-based medicine and knowledge translation. Systematic reviews (SRs) may or may not include a meta-analysis depending on the suitability of available data. They are often being criticised as 'secondary research' and denied the status of original research. Scientific journals play an important role in the publication process. How they appraise a given type of research influences the status of that research in the scientific community. We investigated the attitudes of editors of core clinical journals towards SRs and their value for publication.¦METHODS: We identified the 118 journals labelled as "core clinical journals" by the National Library of Medicine, USA in April 2009. The journals' editors were surveyed by email in 2009 and asked whether they considered SRs as original research projects; whether they published SRs; and for which section of the journal they would consider a SR manuscript.¦RESULTS: The editors of 65 journals (55%) responded. Most respondents considered SRs to be original research (71%) and almost all journals (93%) published SRs. Several editors regarded the use of Cochrane methodology or a meta-analysis as quality criteria; for some respondents these criteria were premises for the consideration of SRs as original research. Journals placed SRs in various sections such as "Review" or "Feature article". Characterization of non-responding journals showed that about two thirds do publish systematic reviews.¦DISCUSSION: Currently, the editors of most core clinical journals consider SRs original research. Our findings are limited by a non-responder rate of 45%. Individual comments suggest that this is a grey area and attitudes differ widely. A debate about the definition of 'original research' in the context of SRs is warranted.

Two-stage prograde and retrograde Variscan metamorphism of glaucophane-eclogites, blueschists and greenschists from Ile de Groix (Brittany, France)

On Ile de Groix, Variscan metamorphic former tholeiitic and alkaline basalts occur as glaucophane-eclogites, blueschists and greenschists in isolated lenses and layers within metapelites. Whole-rock delta O-18(SMOW) values of the metabasites show limited variations (10.4-12.0 parts per thousand) and no systematic differences among rock types and metamorphic grades. This provides no argument for large-scale blueschist-to-greenschist transformation driven by infiltration of externally derived fluids. Metamorphic mineralogical changes should have been triggered by internal fluids. Element variations in interlayered blue- and greenschists can be attributed to magmatic fractionation. Assemblages with garnet, clinopyroxene and glaucophane of a high-pressure/low-temperature (HP-LT) metamorphism M1, and NaCa-amphiboles (barroisite, magnesiohornblende, actinolite) of a medium-pressure/medium-temperature metamorphism M2 crystallized during deformation Dl. Detailed core-rim zonation profiles display increasing and then decreasing Al-IV in glaucophane of M1. NaCa-amphiboles of M2, mantling glaucophane and crystallized in porphyroblasts, show first increasing, then decreasing, Al-IV and Al-IV. Empirically calibrated thermobarometers allowed P-T path reconstructions. In glaucophane-eclogites of a metamorphic zone I, a prograde evolution to M1 peak conditions at 400-500 degreesC/10-12 kbar was followed by a retrograde P-T path within the glaucophane stability field. The subsequent M2 evolution was again prograde up to > 600 degreesC at 8 kbar and then retrograde. Similarly, in metamorphic zones II and III, prograde and retrograde paths of MI and M2 at lower maximal temperatures and pressures exist. The almost complete metamorphic cycle during M2 signalizes that the HP-LT rocks escaped from an early erosion by a moderate second burial event and explains the longlasting slow uplift with low average cooling rates.

On the monotonic core

The monotonic core of a cooperative game with transferable utility (T.U.-game) is the set formed by all its Population Monotonic Allocation Schemes. In this paper we show that this set always coincides with the core of a certain game associated to the initial game.

On the dimension of the core of the assignment game

The set of optimal matchings in the assignment matrix allows to define a reflexive and symmetric binary relation on each side of the market, the equal-partner binary relation. The number of equivalence classes of the transitive closure of the equal-partner binary relation determines the dimension of the core of the assignment game. This result provides an easy procedure to determine the dimension of the core directly from the entries of the assignment matrix and shows that the dimension of the core is not as much determined by the number of optimal matchings as by their relative position in the assignment matrix.

Multi-sided Böhm-Bawerk assignment markets: the nucleolus and the core-center

En aquest treball mostrem que, a diferència del cas bilateral, per als mercats multilaterals d'assignació coneguts amb el nom de Böhm-Bawerk assignment games, el nucleolus i el core-center, i. e. el centre de masses del core, no coincideixen en general. Per demostrar-ho provem que donant un m-sided Böhm-Bawerk assignment game les dues solucions anteriors poden obtenir-se respectivament del nucleolus i el core-center d'un joc convex definit en el conjunt format pels m sectors. Encara més, provem que per calcular el nucleolus d'aquest últim joc només les coalicions formades per un jugador o m-1 jugadors són importants. Aquests resultats simplifiquen el càlcul del nucleolus d'un multi-sided ¿¿ohm-Bawerk assignment market amb un número molt elevat d'agents.

The Lorenz-maximal core allocations and the kernel in some classes of assignment games

En aquest treball demostrem que en la classe de jocs d'assignació amb diagonal dominant (Solymosi i Raghavan, 2001), el repartiment de Thompson (que coincideix amb el valor tau) és l'únic punt del core que és maximal respecte de la relació de dominància de Lorenz, i a més coincideix amb la solucié de Dutta i Ray (1989), també coneguda com solució igualitària. En segon lloc, mitjançant una condició més forta que la de diagonal dominant, introduïm una nova classe de jocs d'assignació on cada agent obté amb la seva parella òptima almenys el doble que amb qualsevol altra parella. Per aquests jocs d'assignació amb diagonal 2-dominant, el repartiment de Thompson és l'únic punt del kernel, i per tant el nucleolo.

On the coincidence between the Shimomura's bargaining sets and the core

[cat] En l'article es dona una condició necessària per a que els conjunts de negociació definits per Shimomura (1997) i el nucli d'un joc cooperatiu amb utilitat transferible coincideixin. A tal efecte, s'introdueix el concepte de vectors de màxim pagament. La condició necessària consiteix a verificar que aquests vectors pertanyen al nucli del joc.

Regular population monotonic allocation schemes and the core

A subclass of games with population monotonic allocation schemes is studied, namelygames with regular population monotonic allocation schemes (rpmas). We focus on theproperties of these games and we prove the coincidence between the core and both theDavis-Maschler bargaining set and the Mas-Colell bargaining set