Immunocytochemical localization of the neural-specific regulatory subunit of the type II cyclic AMP-dependent protein kinase to postsynaptic structures in the rat brain.

The cellular and subcellular distribution of a major cyclic AMP binding protein in the central nervous system, the neural-specific regulatory subunit of the type II cyclic AMP-dependent protein kinase (RII-B), was analyzed in rat brains with light and electron microscopic immunocytochemical methods. The distribution of the non-neural isoform of the regulatory subunit of the enzyme (RII-H) was also analyzed. It was found that RII-B immunoreactivity was predominantly localized to neurons whereas glial and endothelial cells were unlabeled. In the neurons the RII-B immunoreactivity occurred in the perikaryal cytoplasm and in the dendrites; there was no significant accumulation of immunoreaction product in nuclei, myelinated axons and axon terminals. Although immunoreactivity was never detected in axon terminals, it was characteristically associated with the postsynaptic densities and the surrounding non-synaptic sites in somata, dendrites and dendritic spines. The localization of RII-B antigenic sites did not show specificity to any type of neuron or synapse, but the amount of immunoreactivity varied. The distribution of RII-H immunoreactivity was similar to that of RII-B except that RII-H immunoreaction product was also observed in glial cells and occurred more frequently in myelinated axons. Our data confirm that RII-B is one of the major cyclic AMP binding proteins in neurons, and provide morphological support for the involvement of the type II cyclic AMP-dependent protein kinase in postsynaptic neural functions

Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo.

BackgroundProstate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study.MethodsProstaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice.ResultsProstate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3-5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5-4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8-AR-PSA-) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells.ConclusionHuman prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells

Symptom-led staging for semantic and non-fluent/agrammatic variants of primary progressive aphasia. Alzheimer's & Dementia

INTRODUCTION: Here we set out to create a symptom-led staging system for the canonical semantic and non-fluent/agrammatic variants of primary progressive aphasia (PPA), which present unique diagnostic and management challenges not well captured by functional scales developed for Alzheimer’s disease and other dementias. METHODS: An international PPA caregiver cohort was surveyed on symptom development under six provisional clinical stages and feedback was analyzed using a mixed-methods sequential explanatory design. RESULTS: Both PPA syndromes were characterized by initial communication dysfunction and non-verbal behavioral changes, with increasing syndromic convergence and functional dependency at later stages. Milestone symptoms were distilled to create a prototypical progression and severity scale of functional impairment: the PPA Progression Planning Aid (“PPA-Squared”). DISCUSSION: This work introduces a symptom-led staging scheme and functional scale for semantic and non-fluent/agrammatic variants of PPA. Our findings have implications for diagnostic and care pathway guidelines, trial design, and personalized prognosis and treatment for PPA

The most primitive CM chondrites, Asuka 12085, 12169, and 12236, of subtypes 3.0–2.8: Their characteristic features and classification

CM chondrites (CMs) are the most abundant group of carbonaceous chondrites. CMs experienced varying degrees of secondary aqueous alteration and heating that modified or destroyed their primitive features. We have studied three chondrites, Asuka (A) 12085, A 12169, and A 12236. Their modal compositions, chondrule size distributions, and bulk composition indicate that they are CMs. However, the common occurrence of melilite in CAIs and glass in chondrules, abundant Fe–Ni metal, the absence of tochilinite-cronstedtite intergrowths, and almost no phyllosilicates, all suggest that these chondrites, especially A 12169, experienced only minimal aqueous alteration. The textures and compositions of metal and sulfides, the lack of ferroan rims on AOA olivines, the compositional distribution of ferroan olivine, and the Raman spectra of their matrices, indicate that these chondrites experienced neither significant heating nor dehydration. These chondrites, especially A 12169, are the most primitive CMs so far reported. The degree of the alteration increases from A 12169, through A 12236, to A 12085. We propose the criteria for subtypes of 3.0–2.8 for CMs. A 12169, A 12236, and A 12085 are classified as subtype 3.0, 2.9, and 2.8, respectively. The oxygen isotopic composition of the Asuka CMs is consistent with these samples having experienced only a limited degree of aqueous alteration. The CM and CO groups are probably not derived from a single heterogeneous parent body. These chondrites are also of particular significance in view of the imminent return of sample material from the asteroids Ryugu and Bennu

Precision Measurement of B(D+ -> mu+ nu) and the Pseudoscalar Decay Constant fD+

We measure the branching ratio of the purely leptonic decay of the D+ meson with unprecedented precision as B(D+ -> mu+ nu) = (3.82 +/- 0.32 +/- 0.09)x10^(-4), using 818/pb of data taken on the psi(3770) resonance with the CLEO-c detector at the CESR collider. We use this determination to derive a value for the pseudoscalar decay constant fD+, combining with measurements of the D+ lifetime and assuming |Vcd| = |Vus|. We find fD+ = (205.8 +/- 8.5 +/- 2.5) MeV. The decay rate asymmetry [B(D+ -> mu+ nu)-B(D- -> mu- nu)]/[B(D+ -> mu+ nu)+B(D- -> mu- nu)] = 0.08 +/- 0.08, consistent with no CP violation. We also set 90% confidence level upper limits on B(D+ -> tau+ nu) < 1.2x10^(-3) and B(D+ -> e+ nu) < 8.8x10^(-6).Comment: 24 pages, 11 figures and 6 tables, v2 replaced some figure vertical axis scales, v3 corrections from PRD revie

Measurement of B[Y(5S)->Bs(*) anti-Bs(*)] Using phi Mesons

Knowledge of the Bs decay fraction of the Y(5S) resonance, fs, is important for Bs meson studies at the Y(5S) energy. Using a data sample collected by the CLEO III detector at CESR consisting of 0.423/fb on the Y(5S) resonance, 6.34/fb on the Y(4S) and 2.32/fb in the continuum below the Y(4S), we measure B(Y(5S) -> phi X)=(13.8 +/- 0.7 {+2.3}{-1.5})% and B(Y(4S) -> phi X) = (7.1 +/- 0.1 +/-0.6)%; the ratio of the two rates is (1.9 +/- 0.1 {+0.3}{-0.2}). This is the first measurement of the phi meson yield from the Y(5S). Using these rates, and a model dependent estimate of B(Bs -> phi X), we determine fs = (24.6 +/- 2.9 {+11.0}{-5.3})%. We also update our previous independent measurement of fs made using the inclusive Ds yields to now be (16.8 +/- 2.6 {+6.7}{-3.4)%, due to a better estimate of the number of hadronic events. We also report the total Y(5S) hadronic cross section above continuum to be sigma(e^+e^- -> Y(5S))=(0.301 +/- 0.002 +/- 0.039) nb. This allows us to extract the fraction of B mesons as (58.9+/-10.0+/-9.2)%, equal to 1-fs. averaging the three methods gives a model dependent result of fs=(21 {+6}{-3})%.Comment: 23 pages postscript,also available through http://www.lns.cornell.edu/public/CLNS/2006/, Submitted to PR

Dalitz Plot Analysis of Ds to K+K-pi+

We perform a Dalitz plot analysis of the decay Ds to K+K-pi+ with the CLEO-c data set of 586/pb of e+e- collisions accumulated at sqrt(s) = 4.17 GeV. This corresponds to about 0.57 million D_s+D_s(*)- pairs from which we select 14400 candidates with a background of roughly 15%. In contrast to previous measurements we find good agreement with our data only by including an additional f_0(1370)pi+ contribution. We measure the magnitude, phase, and fit fraction of K*(892) K+, phi(1020)pi+, K0*(1430)K+, f_0(980)pi+, f_0(1710)pi+, and f_0(1370)pi+ contributions and limit the possible contributions of other KK and Kpi resonances that could appear in this decay.Comment: 21 Pages,available through http://www.lns.cornell.edu/public/CLNS/, submitted to PR

Search for Lepton Flavor Violation in Upsilon Decays

In this Letter we describe a search for lepton flavor violation (LFV) in the bottomonium system. We search for leptonic decays of Upsilon(nS)(n=1,2, and 3) into muon and tau using the data collected with the CLEO III detector. We identify the tau lepton using its leptonic decay into electron and utilize multidimensional likelihood fitting with PDF shapes measured from independent data samples. We report our estimates of 95% CL upper limits on LFV branching fractions of Upsilon mesons. We interpret our results in terms of the exclusion plot for the energy scale of a hypothetical new interaction versus its effective LFV coupling in the framework of effective field theory.Comment: 10 pages, 3 figures, available through http://www.lns.cornell.edu/public/CLNS/, submitted to PR