A Conserved 20S Proteasome Assembly Factor Requires a Cterminal HbYX Motif for Proteasomal Precursor Binding

Dedicated chaperones facilitate the assembly of the eukaryotic proteasome, but how they function remains largely unknown. Here we show that a yeast 20S proteasome assembly factor, Pba1–Pba2, requires a previously overlooked C-terminal hydrophobic-tyrosine-X (HbYX) motif for function. HbYX motifs in proteasome activators open the 20S proteasome entry pore, but Pba1–Pba2 instead binds inactive proteasomal precursors. We discovered an archaeal ortholog of this factor, here named PbaA, that also binds preferentially to proteasomal precursors in a HbYX motif–dependent fashion using the same proteasomal α-ring surface pockets as are bound by activators. PbaA and the related PbaB protein can be induced to bind mature 20S proteasomes if the active sites in the central chamber are occupied by inhibitors. Our data are consistent with an allosteric mechanism in which the maturation of the proteasome active sites determines the binding of assembly chaperones, potentially shielding assembly intermediates or misassembled complexes from nonproductive associations until assembly is complete

Fluorescent and photo-oxidizing TimeSTAMP tags track protein fates in light and electron microscopy.

Protein synthesis is highly regulated throughout nervous system development, plasticity and regeneration. However, tracking the distributions of specific new protein species has not been possible in living neurons or at the ultrastructural level. Previously we created TimeSTAMP epitope tags, drug-controlled tags for immunohistochemical detection of specific new proteins synthesized at defined times. Here we extend TimeSTAMP to label new protein copies by fluorescence or photo-oxidation. Live microscopy of a fluorescent TimeSTAMP tag reveals that copies of the synaptic protein PSD95 are synthesized in response to local activation of growth factor and neurotransmitter receptors, and preferentially localize to stimulated synapses in rat neurons. Electron microscopy of a photo-oxidizing TimeSTAMP tag reveals new PSD95 at developing dendritic structures of immature neurons and at synapses in differentiated neurons. These results demonstrate the versatility of the TimeSTAMP approach for visualizing newly synthesized proteins in neurons

Feasibility of applying ultrasound strain imaging to detect renal transplant chronic allograft nephropathy

Feasibility of applying ultrasound strain imaging to detect renal transplant chronic allograft nephropathy.Chronic renal transplant fibrosis, often termed Chronic Allograft Nephropathy, may progress undetected. Since renal fibrosis may be accompanied by a change in measurable elastic tissue properties, ultrasound strain measurements may be useful in its detection. Ultrasound strain imaging was performed for two subjects with renal transplants; one with normal renal function and one with mild renal insufficiency and biopsy demonstrated fibrosis. Subjects underwent ultrasound examination with application of a controlled deformation using phase-sensitive, two-dimensional speckle tracking to evaluate internal tissue motion to measure tissue displacement and strain. Measurements over multiple beams for an equivalent deformational stress showed there was a threefold differences in renal cortical strain between the two subjects. These data suggest that ultrasound elasticity imaging may prove useful in measuring mechanical changes related to fibrosis within the transplant kidney

Perturbative Expansion around the Gaussian Effective Potential of the Fermion Field Theory

We have extended the perturbative expansion method around the Gaussian effective action to the fermionic field theory, by taking the 2-dimensional Gross-Neveu model as an example. We have computed both the zero temperature and the finite temperature effective potentials of the Gross-Neveu model up to the first perturbative correction terms, and have found that the critical temperature, at which dynamically broken symmetry is restored, is significantly improved for small value of the flavour number.Comment: 14pages, no figures, other comments Typographical errors are corrected and new references are adde

High-energy magnon dispersion in the half-filled Hubbard model: A comparison with La2_2CuO4_4

We use quantum Monte Carlo methods and single-mode approximation to study the magnon dispersion in the 2D half-filled Hubbard and phonon-coupled Heisenberg models. We find that in the Hubbard model with $U/t< 8$, high-energy magnon dispersion is similar to those observed in inelastic neutron scattering experiments in ${La}_2{CuO}_4$. On the other hand, our studies of a 2D Heisenberg model coupled to dynamic optical bond phonons, fails to reproduce the experimental dispersion. These results can be interpreted as evidence for intermediate $U/t$ and charge fluctuations in the cuprate materials

Two--magnon scattering and the spin--phonon interaction beyond the adiabatic approximation

We consider a model of Raman scattering for a two--dimensional $S=1/2$ Heisenberg Anti-Ferromagnet which includes a {\it dynamical} spin--phonon interaction. We observe a broadening of the line shape due to increased coupling with excited high--energy spin states. Our results are close to a model of random static exchange interactions, first introduced in this context by Haas {\it et al.} [J. Appl. Phys. {\bf 75}, 6340, (1994)], which, when extended to large numbers of spins, explains experiments in the parent insulating compounds of high-$T_c$ superconductors.Comment: 14 pages (revtex format), 8 postscript figure

Artificial Intelligence Tool for Assessment of Indeterminate Pulmonary Nodules Detected with CT

Background: Limited data are available regarding whether computer-aided diagnosis (CAD) improves assessment of malignancy risk in indeterminate pulmonary nodules (IPNs). Purpose: To evaluate the effect of an artificial intelligence-based CAD tool on clinician IPN diagnostic performance and agreement for both malignancy risk categories and management recommendations. Materials and Methods: This was a retrospective multireader multicase study performed in June and July 2020 on chest CT studies of IPNs. Readers used only CT imaging data and provided an estimate of malignancy risk and a management recommendation for each case without and with CAD. The effect of CAD on average reader diagnostic performance was assessed using the Obuchowski-Rockette and Dorfman-Berbaum-Metz method to calculate estimates of area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Multirater Fleiss κ statistics were used to measure interobserver agreement for malignancy risk and management recommendations. Results: A total of 300 chest CT scans of IPNs with maximal diameters of 5-30 mm (50.0% malignant) were reviewed by 12 readers (six radiologists, six pulmonologists) (patient median age, 65 years; IQR, 59-71 years; 164 [55%] men). Readers\u27 average AUC improved from 0.82 to 0.89 with CAD (P \u3c .001). At malignancy risk thresholds of 5% and 65%, use of CAD improved average sensitivity from 94.1% to 97.9% (P = .01) and from 52.6% to 63.1% (P \u3c .001), respectively. Average reader specificity improved from 37.4% to 42.3% (P = .03) and from 87.3% to 89.9% (P = .05), respectively. Reader interobserver agreement improved with CAD for both the less than 5% (Fleiss κ, 0.50 vs 0.71; P \u3c .001) and more than 65% (Fleiss κ, 0.54 vs 0.71; P \u3c .001) malignancy risk categories. Overall reader interobserver agreement for management recommendation categories (no action, CT surveillance, diagnostic procedure) also improved with CAD (Fleiss κ, 0.44 vs 0.52; P = .001). Conclusion: Use of computer-aided diagnosis improved estimation of indeterminate pulmonary nodule malignancy risk on chest CT scans and improved interobserver agreement for both risk stratification and management recommendations

GALEX Ultraviolet Photometry of Globular Clusters in M31

We present ultraviolet photometry for globular clusters (GCs) in M31 from 15 square deg of imaging using the Galaxy Evolution Explorer (GALEX). We detect 200 and 94 GCs with certainty in the near-ultraviolet (NUV; 1750 - 2750 Angstroms) and far-ultraviolet (FUV; 1350 - 1750 Angstroms) bandpasses, respectively. Our rate of detection is about 50% in the NUV and 23% in the FUV, to an approximate limiting V magnitude of 19. Out of six clusters with [Fe/H]>-1 seen in the NUV, none is detected in the FUV bandpass. Furthermore, we find no candidate metal-rich clusters with significant FUV flux, because of the contribution of blue horizontal-branch (HB) stars, such as NGC 6388 and NGC 6441, which are metal-rich Galactic GCs with hot HB stars. We show that our GALEX photometry follows the general color trends established in previous UV studies of GCs in M31 and the Galaxy. Comparing our data with Galactic GCs in the UV and with population synthesis models, we suggest that the age range of M31 and Galactic halo GCs are similar.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Links to the full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS/ after November 22, 200

Present and Future CP Measurements

We review theoretical and experimental results on CP violation summarizing the discussions in the working group on CP violation at the UK phenomenology workshop 2000 in Durham.Comment: 104 pages, Latex, to appear in Journal of Physics