Prion protein interacts with bace1 and differentially regulates its activity towards wild type and swedish mutant amyloid precursor protein

In Alzheimer disease amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the β-secretase BACE1 is the rate-limiting step in the production of Aβ. We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of endogenous murine Aβ were significantly increased in PrP(C)-null mouse brain. Here we investigated the molecular and cellular mechanisms underlying this observation. PrP(C) interacted directly with the prodomain of the immature Golgi-localized form of BACE1. This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves APP(WT) but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP(Swe)). In transgenic mice expressing human APP with the Swedish and Indiana familial mutations (APP(Swe,Ind)), PrP(C) deletion had no influence on APP proteolytic processing, Aβ plaque deposition, or levels of soluble Aβ or Aβ oligomers. In cells, although PrP(C) inhibited the action of BACE1 on APP(WT), it did not inhibit BACE1 activity toward APP(Swe). The differential subcellular location of the BACE1 cleavage of APP(Swe) relative to APP(WT) provides an explanation for the failure of PrP(C) deletion to affect Aβ accumulation in APP(Swe,Ind) mice. Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease

Hair Follicle Dermal Cells Support Expansion of Murine and Human Embryonic and Induced Pluripotent Stem Cells and Promote Haematopoiesis in Mouse Cultures

In the hair follicle, the dermal papilla (DP) and dermal sheath (DS) support and maintain proliferation and differentiation of the epithelial stem cells that produce the hair fibre. In view of their regulatory properties, in this study, we investigated the interaction between hair follicle dermal cells (DP and DS) and embryonic stem cells (ESCs); induced pluripotent stem cells (iPSCs); and haematopoietic stem cells. We found that coculture of follicular dermal cells with ESCs or iPSCs supported their prolonged maintenance in an apparently undifferentiated state as established by differentiation assays, immunocytochemistry, and RT-PCR for markers of undifferentiated ESCs. We further showed that cytokines that are involved in ESC support are also expressed by cultured follicle dermal cells, providing a possible explanation for maintenance of ES cell stemness in cocultures. The same cytokines were expressed within follicles in situ in a pattern more consistent with a role in follicle growth activities than stem cell maintenance. Finally, we show that cultured mouse follicle dermal cells provide good stromal support for haematopoiesis in an established coculture model. Human follicular dermal cells represent an accessible and readily propagated source of feeder cells for pluripotent and haematopoietic cells and have potential for use in clinical applications

Further evidence that the Genebank standards for drying orthodox seeds may not be optimal for subsequent seed longevity

Open Access ArticleMaximizing seed longevity is important for genebanks to efficiently manage their accessions, reducing the frequency of costly regeneration cycles and the loss of genetic integrity. Research on rice seeds has shown that subsequent longevity in air-dry storage can be improved by drying seeds, which are metabolically active at harvest (moisture contents above a critical value close to 16.5%), for an initial period at a higher temperature (40°C–60°C) than that currently recommended by the current genebank standards (5°C–20°C). The aim of this study was to test whether similar benefits could be achieved in two legume species—cowpea and soya bean—by drying freshly harvested seeds, from two separate harvests, at 40°C and 35% relative humidity, for up to 8 days before equilibrium drying in a drying room (17°C and 15% relative humidity). Improvements in longevity were observed in three of the four accessions of soya bean, with the greatest improvement generally occurring after the maximum duration (8 days) at the higher temperature. However, of the five accessions of cowpea, only seeds of TVu-9698 and TVu-13209 from the first harvest, and of TVu-13193 from the second harvest, showed an improvement in longevity compared with drying following the standard protocol. A negative effect of high-temperature drying was also observed in one accession of cowpea, TVu-11980, but only in seeds harvested later in the season, 13 weeks after planting. This research not only provides evidence of the potential benefits of drying orthodox seeds at an alternative, higher, temperature instead of at the conventional lower temperature, before long-term storage, but also raises awareness of how genebanks can improve the management of their accessions

Global Search for New Physics with 2.0/fb at CDF

Data collected in Run II of the Fermilab Tevatron are searched for indications of new electroweak-scale physics. Rather than focusing on particular new physics scenarios, CDF data are analyzed for discrepancies with the standard model prediction. A model-independent approach (Vista) considers gross features of the data, and is sensitive to new large cross-section physics. Further sensitivity to new physics is provided by two additional algorithms: a Bump Hunter searches invariant mass distributions for "bumps" that could indicate resonant production of new particles; and the Sleuth procedure scans for data excesses at large summed transverse momentum. This combined global search for new physics in 2.0/fb of ppbar collisions at sqrt(s)=1.96 TeV reveals no indication of physics beyond the standard model.Comment: 8 pages, 7 figures. Final version which appeared in Physical Review D Rapid Communication

Observation of Orbitally Excited B_s Mesons

We report the first observation of two narrow resonances consistent with states of orbitally excited (L=1) B_s mesons using 1 fb^{-1} of ppbar collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the Fermilab Tevatron. We use two-body decays into K^- and B^+ mesons reconstructed as B^+ \to J/\psi K^+, J/\psi \to \mu^+ \mu^- or B^+ \to \bar{D}^0 \pi^+, \bar{D}^0 \to K^+ \pi^-. We deduce the masses of the two states to be m(B_{s1}) = 5829.4 +- 0.7 MeV/c^2 and m(B_{s2}^*) = 5839.7 +- 0.7 MeV/c^2.Comment: Version accepted and published by Phys. Rev. Let

Study of CP violation in Dalitz-plot analyses of B0 --> K+K-KS, B+ --> K+K-K+, and B+ --> KSKSK+

We perform amplitude analyses of the decays $B^0 \to K^+K^-K^0_S$, $B^+ \rightarrow K^+K^-K^+$, and $B^+ \to K^0_S K^0_S K^+$, and measure CP-violating parameters and partial branching fractions. The results are based on a data sample of approximately $470\times 10^6$ $B\bar{B}$ decays, collected with the BABAR detector at the PEP-II asymmetric-energy $B$ factory at the SLAC National Accelerator Laboratory. For $B^+ \to K^+K^-K^+$, we find a direct CP asymmetry in $B^+ \to \phi(1020)K^+$ of $A_{CP}= (12.8\pm 4.4 \pm 1.3)$, which differs from zero by $2.8 \sigma$. For $B^0 \to K^+K^-K^0_S$, we measure the CP-violating phase $\beta_{\rm eff} (\phi(1020)K^0_S) = (21\pm 6 \pm 2)^\circ$. For $B^+ \to K^0_S K^0_S K^+$, we measure an overall direct CP asymmetry of $A_{CP} = (4 ^{+4}_{-5} \pm 2)$. We also perform an angular-moment analysis of the three channels, and determine that the $f_X(1500)$ state can be described well by the sum of the resonances $f_0(1500)$, $f_2^{\prime}(1525)$, and $f_0(1710)$.Comment: 35 pages, 68 postscript figures. v3 - minor modifications to agree with published versio

Nucleosomes in gene regulation: theoretical approaches

This work reviews current theoretical approaches of biophysics and bioinformatics for the description of nucleosome arrangements in chromatin and transcription factor binding to nucleosomal organized DNA. The role of nucleosomes in gene regulation is discussed from molecular-mechanistic and biological point of view. In addition to classical problems of this field, actual questions of epigenetic regulation are discussed. The authors selected for discussion what seem to be the most interesting concepts and hypotheses. Mathematical approaches are described in a simplified language to attract attention to the most important directions of this field

Measurement of the Bs Lifetime in Fully and Partially Reconstructed Bs -> Ds- (phi pi-)X Decays in pbar-p Collisions at sqrt(s) = 1.96 TeV

We present a measurement of the Bs lifetime in fully and partially reconstructed Bs -> Ds(phi pi)X decays in 1.3 fb-1 of pbar-p collisions at sqrt(s) = 1.96 TeV collected by the CDF II detector at the Fermilab Tevatron. We measure tau(Bs) = 1.518 +/- 0.041 (stat.) +/- 0.027 (syst.) ps. The ratio of this result and the world average B0 lifetime yields tau(Bs)/tau(B0) = 0.99 +/-0.03, which is in agreement with recent theoretical predictions.Comment: submitted to Phys. Rev. Let

Observation of the Y(4140)Y(4140) structure in the J/ψ ϕJ/\psi\,\phi Mass Spectrum in B±→J/ψ ϕKB^\pm\to J/\psi\,\phi K cays

The observation of the $Y(4140)$ structure in $B^\pm\rightarrow J/\psi\,\phi K^\pm$ decays produced in $\bar{p} p$ collisions at \sqrt{s}=1.96~\TeV is reported with a statistical significance greater than 5 standard deviations. A fit to the $J/\psi\,\phi$ mass spectrum is performed assuming the presence of a Breit-Wigner resonance. The fit yields a signal of $19^{+6}_{-5}$ resonance events, and resonance mass and width of 4143.4^{+2.9}_{-3.0}(\mathrm{stat})\pm0.6(\mathrm{syst})~\MeVcc and 15.3^{+10.4}_{-6.1}(\mathrm{stat})\pm2.5(\mathrm{syst})~\MeVcc respectively. The parameters of this resonance-like structure are consistent with values reported from an earlier CDF analysis.Comment: 7 pages, 2 figures, submited to Phys. Rev. Let