Decreased copper in alzheimer's disease brain is predominantly in the soluble extractable fraction

Alzheimer's disease (AD) is the leading cause of dementia and represents a significant burden on the global economy and society. The role of transition metals, in particular copper (Cu), in AD has become of significant interest due to the dyshomeostasis of these essential elements, which can impart profound effects on cell viability and neuronal function. We tested the hypothesis that there is a systemic perturbation in Cu compartmentalization in AD, within the brain as well as in the periphery, specifically within erythrocytes. Our results showed that the previously reported decrease in Cu within the human frontal cortex was confined to the soluble (P<0.05) and total homogenate (P<0.05) fractions. No differences were observed in Cu concentration in erythrocytes. Our data indicate that there is a brain specific alteration in Cu levels in AD localized to the soluble extracted material, which is not reflected in erythrocytes. Further studies using metalloproteomics approaches will be able to elucidate the metabolic mechanism(s) that results in the decreased brain Cu levels during the progression of AD. © 2013 Alan Rembach et al

What drives security issuance decisions: Market timing, pecking order, or both?

We study market timing and pecking order in a sample of debt and equity issues and share repurchases of Canadian firms from 1998 to 2007. We find that only when firms are not financially constrained is there evidence that firms issue (repurchase) equity when their shares are overvalued (undervalued) and evidence that overvalued issuers earn lower postannouncement long-run returns. Similarly, we find that only when firms are not overvalued do they prefer debt to equity financing. These findings highlight an interaction between market timing and pecking order effects

Atopic dermatitis, cutaneous steroids and cataracts in children: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Atopic dermatitis is a chronic, pruritic, eczematous skin disease mediated through an immediate (type I) hypersensitivity reaction. Posterior sub-capsular cataracts are a recognised complication of atopic dermatitis in adults; however they are rare in children. The management of atopic dermatitis is based on the exclusion of allergens, the use of emollients, and on topical corticosteroids for disease exacerbations. Cataracts may be due to atopic dermatitis but may also occur secondary to the use of corticosteroids.</p> <p>Case presentation</p> <p>We describe two children with atopic dermatitis, treated with cutaneous corticosteroids, both of whom were diagnosed with bilateral posterior sub-capsular cataracts.</p> <p>Conclusion</p> <p>These cases demonstrate that atopic dermatitis and topical corticosteroids may be associated with cataracts in children as well as adults. The cause of cataracts in atopic dermatitis is not known, however, it has been suggested that habitual tapping and rubbing of the face may play a role. Care needs to be taken when prescribing corticosteroids. Inadequate treatment of atopic dermatitis may lead to other ocular complications such as keratitis and permanent visual loss.</p

Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs

The reference annotations made for a genome sequence provide the framework for all subsequent analyses of the genome. Correct annotation is particularly important when interpreting the results of RNA-seq experiments where short sequence reads are mapped against the genome and assigned to genes according to the annotation. Inconsistencies in annotations between the reference and the experimental system can lead to incorrect interpretation of the effect on RNA expression of an experimental treatment or mutation in the system under study. Until recently, the genome-wide annotation of 3-prime untranslated regions received less attention than coding regions and the delineation of intron/exon boundaries. In this paper, data produced for samples in Human, Chicken and A. thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing technology from Helicos Biosciences which locates 3-prime polyadenylation sites to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine examples are illustrated where this combination of data allowed: (1) gene and 3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb); (2) disentangling of gene expression in complex regions; (3) clearer interpretation of small RNA expression and (4) identification of novel genes. While the specific examples displayed here may become obsolete as genome sequences and their annotations are refined, the principles laid out in this paper will be of general use both to those annotating genomes and those seeking to interpret existing publically available annotations in the context of their own experimental dataComment: 44 pages, 9 figure

Zinc Overload Enhances APP Cleavage and Aβ Deposition in the Alzheimer Mouse Brain

BACKGROUND: Abnormal zinc homeostasis is involved in β-amyloid (Aβ) plaque formation and, therefore, the zinc load is a contributing factor in Alzheimer's disease (AD). However, the involvement of zinc in amyloid precursor protein (APP) processing and Aβ deposition has not been well established in AD animal models in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, APP and presenilin 1 (PS1) double transgenic mice were treated with a high dose of zinc (20 mg/ml ZnSO4 in drinking water). This zinc treatment increased APP expression, enhanced amyloidogenic APP cleavage and Aβ deposition, and impaired spatial learning and memory in the transgenic mice. We further examined the effects of zinc overload on APP processing in SHSY-5Y cells overexpressing human APPsw. The zinc enhancement of APP expression and cleavage was further confirmed in vitro. CONCLUSIONS/SIGNIFICANCE: The present data indicate that excess zinc exposure could be a risk factor for AD pathological processes, and alteration of zinc homeostasis is a potential strategy for the prevention and treatment of AD

Hadronic Mass Moments in Inclusive Semileptonic B Meson Decays

We have measured the first and second moments of the hadronic mass-squared distribution in B -> X_c l nu, for P(lepton) > 1.5 GeV/c. We find <M_X^2 - M_D[Bar]^2> = 0.251 +- 0.066 GeV^2, )^2 > = 0.576 +- 0.170 GeV^4, where M_D[Bar] is the spin-averaged D meson mass. From that first moment and the first moment of the photon energy spectrum in b -> s gamma, we find the HQET parameter lambda_1 (MS[Bar], to order 1/M^3 and beta_0 alpha_s^2) to be -0.24 +- 0.11 GeV^2. Using these first moments and the B semileptonic width, and assuming parton-hadron duality, we obtain |V_cb| = 0.0404 +- 0.0013.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Observation of the Ωc0\Omega_{c}^{0} Charmed Baryon at CLEO

The CLEO experiment at the CESR collider has used 13.7 fb$^{-1}$ of data to search for the production of the $\Omega_c^0$ (css-ground state) in $e^{+}e^{-}$ collisions at $\sqrt{s} \simeq 10.6$ {\rm GeV}. The modes used to study the $\Omega_c^0$ are $\Omega^- \pi^+$, $\Omega^- \pi^+ \pi^0$, $\Xi^- K^- pi^+ \pi^+$, $\Xi^0 K^- pi^+$, and $\Omega^- \pi^+ \pi^- \pi^+$. We observe a signal of 40.4$\pm$9.0(stat) events at a mass of 2694.6$\pm$2.6(stat)$\pm$1.9(syst) {\rm MeV/$c^2$}, for all modes combined.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Observation of B→ϕKB\to \phi K and B→ϕK∗B\to \phi K^{*}

We have studied two-body charmless hadronic decays of $B$ mesons into the final states phi K and phi K^*. Using 9.7 million $B\bar{B}$ pairs collected with the CLEO II detector, we observe the decays B- -> phi K- and B0 -> phi K*0 with the following branching fractions: BR(B- -> phi K-)=(5.5 +2.1-1.8 +- 0.6) x 10^{-6} and BR(B0 -> phi K*0)=(11.5 +4.5-3.7 +1.8-1.7) x 10^{-6}. We also see evidence for the decays B0 -> phi K0 and B- -> phi K*-. However, since the statistical significance is not overwhelming for these modes we determine upper limits of <12.3 x 10^{-6} and <22.5 x 10^{-6} (90% C.L.) respectively.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN

Evidence of New States Decaying into Ξc′π\Xi^{\prime}_{c}\pi

Using 13.7 $fb^{-1}$ of data recorded by the CLEO detector at CESR, we report evidence for two new charmed baryons: one decaying into $\Xi_c^{0 \prime}\pi^+$ with the subsequent decay $\Xi_c^{0 \prime} \to \Xi_c^0 \gamma$, and its isospin partner decaying into $\Xi_c^{+ \prime} \pi^-$ followed by $\Xi_c^{+\prime} \to \Xi_c^+\gamma$. We measure the following mass differences for the two states: $M(\Xi_c^0 \gamma \pi^+)-M(\Xi_c^0)$=318.2+-1.3+-2.9 MeV, and $M(\Xi_c^+ \gamma \pi^-)-M(\Xi_c^+)$=324.0+-1.3+-3.0 MeV. We interpret these new states as the $J^P = 1/2^- \Xi_{c1}$ particles, the charmed-strange analogs of the $\Lambda_{c1}^+(2593)$.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN