Cerebrospinal fluid neurogranin in an inducible mouse model of neurodegeneration: A translatable marker of synaptic degeneration

Synapse impairment is thought to be an early event in Alzheimer's disease (AD); dysfunction and loss of synapses are linked to cognitive symptoms that precede neuronal loss and neurodegeneration. Neurogranin (Ng) is a somatodendritic protein that has been shown to be reduced in brain tissue but increased in the cerebrospinal fluid (CSF) of AD patients compared to age-matched controls. High levels of CSF Ng have been shown to reflect a more rapid AD progression. To gauge the translational value of Ng as a biomarker, we developed a new, highly sensitive, digital enzyme-linked immunosorbent assay (ELISA) on the Simoa platform to measure Ng in both mouse and human CSF. We investigated and confirmed that Ng levels are increased in the CSF of patients with AD compared to controls. In addition, we explored how Ng is altered in the brain and CSF of transgenic mice that display progressive neuronal loss and synaptic degeneration following the induction of p25 overexpression. In this model, we found that Ng levels increased in CSF when neurodegeneration was induced, peaking after 2 weeks, while they decreased in brain. Our data suggest that CSF Ng is a biomarker of synaptic degeneration with translational value

The merging/AGN connection II. Ionization of the circumnuclear regions

We report the first results of a study of a sample of 20 galaxy mergers/interacting systems, using the VIMOS and PMAS integral field spectrographs. For each object, we extracted the integrated spectrum of the central regions and analyzed the ionization state using classical diagnostic diagrams (Veilleux & Osterbrock 1987). There is evidence of AGN ionization in 4 of the objects, i.e. 20% of the sample, a considerably higher fraction than found in previous studies ~4%Comment: 4 pages, 2 figures, accepted for publishing in A&A Letter

Correlation effects during liquid infiltration into hydrophobic nanoporous mediums

Correlation effects arising during liquid infiltration into hydrophobic porous medium are considered. On the basis of these effects a mechanism of energy absorption at filling porous medium by nonwetting liquid is suggested. In accordance with this mechanism, the absorption of mechanical energy is a result expenditure of energy for the formation of menisci in the pores on the shell of the infinite cluster and expenditure of energy for the formation of liquid-porous medium interface in the pores belonging to the infinite cluster of filled pores. It was found that in dependences on the porosity and, consequently, in dependences on the number of filled pores neighbors, the thermal effect of filling can be either positive or negative and the cycle of infiltration-defiltration can be closed with full outflow of liquid. It can occur under certain relation between percolation properties of porous medium and the energy characteristics of the liquid-porous medium interface and the liquid-gas interface. It is shown that a consecutive account of these correlation effects and percolation properties of the pores space during infiltration allow to describe all experimental data under discussion

Is diversity good?

Prominent ethical and policy issues such as affirmative action and female enrollment in science and engineering revolve around the idea that diversity is good. However, even though diversity is an ambiguous concept, a precise definition is seldom provided. We show that diversity may be construed as a factual description, a craving for symmetry, an intrinsic good, an instrumental good, a symptom, or a side effect. These acceptions differ vastly in their nature and properties. The first one cannot lead to any action and the second one is mistaken. Diversity as intrinsic good is a mere opinion, which cannot be concretely applied; moreover, the most commonly invoked forms of diversity (sexual and racial) are not intrinsically good. On the other hand, diversity as instrumental good can be evaluated empirically and can give rise to policies, but these may be very weak. Finally, symptoms and side effects are not actually about diversity. We consider the example of female enrollment in science and engineering, interpreting the various arguments found in the literature in light of this polysemy. Keywords: ethics, policy, higher education, female students, minority students, affirmative actionComment: 7 page

Combined transcriptome studies identify AFF3 as a mediator of the oncogenic effects of beta-catenin in adrenocortical carcinoma

Adrenocortical cancer (ACC) is a very aggressive tumor, and genomics studies demonstrate that the most frequent alterations of driver genes in these cancers activate the Wnt/beta-catenin signaling pathway. However, the adrenal-specific targets of oncogenic beta-catenin-mediating tumorigenesis have not being established. A combined transcriptomic analysis from two series of human tumors and the human ACC cell line H295R harboring a spontaneous beta-catenin activating mutation was done to identify the Wnt/beta-catenin targets. Seven genes were consistently identified in the three studies. Among these genes, we found that AFF3 mediates the oncogenic effects of beta-catenin in ACC. The Wnt response element site located at nucleotide position - 1408 of the AFF3 transcriptional start sites (TSS) mediates the regulation by the Wnt/beta-catenin signaling pathway. AFF3 silencing decreases cell proliferation and increases apoptosis in the ACC cell line H295R. AFF3 is located in nuclear speckles, which play an important role in RNA splicing. AFF3 overexpression in adrenocortical cells interferes with the organization and/or biogenesis of these nuclear speckles and alters the distribution of CDK9 and cyclin T1 such that they accumulate at the sites of AFF3/speckles. We demonstrate that AFF3 is a new target of Wnt/beta-catenin pathway involved in ACC, acting on transcription and RNA splicing

Combined transcriptome studies identify AFF3 as a mediator of the oncogenic effects of beta-catenin in adrenocortical carcinoma

Adrenocortical cancer (ACC) is a very aggressive tumor, and genomics studies demonstrate that the most frequent alterations of driver genes in these cancers activate the Wnt/beta-catenin signaling pathway. However, the adrenal-specific targets of oncogenic beta-catenin-mediating tumorigenesis have not being established. A combined transcriptomic analysis from two series of human tumors and the human ACC cell line H295R harboring a spontaneous beta-catenin activating mutation was done to identify the Wnt/beta-catenin targets. Seven genes were consistently identified in the three studies. Among these genes, we found that AFF3 mediates the oncogenic effects of beta-catenin in ACC. The Wnt response element site located at nucleotide position - 1408 of the AFF3 transcriptional start sites (TSS) mediates the regulation by the Wnt/beta-catenin signaling pathway. AFF3 silencing decreases cell proliferation and increases apoptosis in the ACC cell line H295R. AFF3 is located in nuclear speckles, which play an important role in RNA splicing. AFF3 overexpression in adrenocortical cells interferes with the organization and/or biogenesis of these nuclear speckles and alters the distribution of CDK9 and cyclin T1 such that they accumulate at the sites of AFF3/speckles. We demonstrate that AFF3 is a new target of Wnt/beta-catenin pathway involved in ACC, acting on transcription and RNA splicing

Cavity QED with Diamond Nanocrystals and Silica Microspheres

Normal mode splitting is observed in a cavity QED system, in which nitrogen vacancy centers in diamond nanocrystals are coupled to whispering gallery modes in a silica microsphere. The composite nanocrystal-microsphere system takes advantage of the exceptional spin properties of nitrogen vacancy centers as well as the ultra high quality factor of silica microspheres. The observation of the normal mode splitting indicates that the dipole optical interaction between the relevant nitrogen vacancy center and whispering gallery mode has reached the strong coupling regime of cavity QED

The Average Mass-to-Light Profile of Galaxy Clusters

The systematic errors in the virial mass-to-light ratio, M_v/L, of galaxy clusters as an estimator of the field M/L value are assessed. We overlay 14 clusters in redshift space to create an ensemble cluster which averages over substructure and asymmetries. The combined sample, including background, contains about 1150 galaxies, extending to a projected radius of about twice r_200. The radius r_200, defined as where the mean interior density is 200 times the critical density, is expected to contain the bulk of the virialized cluster mass. The dynamically derived M(r_200)/L(r_200) of the ensemble is 0.82+/-0.14 . The M_v/L overestimate is attributed to not taking into account the surface pressure term in the virial equation. Under the assumption that the velocity anisotropy parameter is in the range 0<=\beta<=2/3, the galaxy distribution accurately traces the mass profile beyond about the central 0.3r_200. There are no color or luminosity gradients in the galaxy population beyond 2r_200, but there is 0.11+/-0.05 mag fading in the r band luminosities between the field and cluster galaxies. We correct the cluster virial mass-to-light ratio, M_v/L=289+/-50 h\msun/\lsun (calculated assuming q_0=0.1), for the biases in M_v and mean luminosity to estimate the field M/L=213+/-59 h\msun/\lsun. With our self-consistently derived field luminosity density, j/\rho_c=1136+/-138 h\msun/\lsun (at z~1/3), the corrected M/L indicates \Omega_0=0.19+/-0.06+/-0.04 (formal 1\sigma random error and estimated potential systematic errors).Comment: revised version accepted for publication in the ApJ, April 1, 1997 Also available at http://manaslu.astro.utoronto.ca/~carlberg/cnoc/profil