Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs

Cue-directed axon guidance depends partly on local translation in growth cones. Many mRNA transcripts are known to reside in developing axons, yet little is known about their subcellular distribution or, specifically, which transcripts are in growth cones. Here laser capture microdissection (LCM) was used to isolate the growth cones of retinal ganglion cell (RGC) axons of two vertebrate species, mouse and Xenopus, coupled with unbiased genomewide microarray profiling. An unexpectedly large pool of mRNAs defined predominant pathways in protein synthesis, oxidative phosphorylation, cancer, neurological disease, and signaling. Comparative profiling of "young" (pathfinding) versus "old" (target-arriving) Xenopus growth cones revealed that the number and complexity of transcripts increases dramatically with age. Many presynaptic protein mRNAs are present exclusively in old growth cones, suggesting that functionally related sets of mRNAs are targeted to growth cones in a developmentally regulated way. Remarkably, a subset of mRNAs was significantly enriched in the growth cone compared with the axon compartment, indicating that mechanisms exist to localize mRNAs selectively to the growth cone. Furthermore, some receptor transcripts (e.g., EphB4), present exclusively in old growth cones, were equally abundant in young and old cell bodies, indicating that RNA trafficking from the soma is developmentally regulated. Our findings show that them RNA repertoire in growth cones is regulated dynamically with age and suggest that mRNA localization is tailored to match the functional demands of the growing axon tip as it transforms into the presynaptic terminal. Copyright © 2010 the authors

Multiparametric prostate MRI quality assessment using a semi-automated PI-QUAL software program

The technical requirements for the acquisition of multiparametric magnetic resonance imaging (mpMRI) of the prostate have been clearly outlined in the Prostate Imaging Reporting and Data System (PI-RADS) guidelines, but there is still huge variability in image quality among centres across the world. It has been difficult to quantify what constitutes a good-quality image, and a first attempt to address this matter has been the publication of the Prostate Imaging Quality (PI-QUAL) score and its dedicated scoring sheet. This score includes the assessment of technical parameters that can be obtained from the DICOM files along with a visual evaluation of certain features on prostate MRI (e.g., anatomical structures). We retrospectively analysed the image quality of 10 scans from different vendors and magnets using a semiautomated dedicated PI-QUAL software program and compared the time needed for assessing image quality using two methods (semiautomated assessment versus manual filling of the scoring sheet). This semiautomated software is able to assess the technical parameters automatically, but the visual assessment is still performed by the radiologist. There was a significant reduction in the reporting time of prostate mpMRI quality according to PI-QUAL using the dedicated software program compared to manual filling (5'54″ versus 7'59″; p = 0.005). A semiautomated PI-QUAL software program allows the radiologist to assess the technical details related to the image quality of prostate mpMRI in a quick and reliable manner, allowing clinicians to have more confidence that the quality of mpMRI of the prostate is sufficient to determine patient care

Sequential prostate MRI reporting in men on active surveillance: initial experience of a dedicated PRECISE software program

BACKGROUND AND OBJECTIVES: There is interest in using sequential multiparametric magnetic resonance imaging (mpMRI) to assess men on active surveillance (AS) for prostate cancer. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations propose standardised reporting mpMRI data for these men. This includes accurate size measurements of lesions over time, but such approach is time consuming for the radiologist and there is a strong need of dedicated tools to report serial scans in a systematic manner. We present the results from an initial validation cohort using dedicated PRECISE reporting software to allow automated comparison between sequential scans on AS. MATERIALS AND METHODS: We retrospectively analysed baseline and follow-up scans of 20 men randomised to 6 months of daily dutasteride (n = 10) or placebo (n = 10) from the MAPPED trial. Men underwent 3T mpMRI at baseline and after 6 months, and a dedicated radiologist reported the scans using both a widespread commercially-available platform (Osirix®) and a semi-automated dedicated PRECISE reporting tool (MIM®). Tumour volume by planimetry in all sequences and conspicuity on diffusion-weighted imaging were assessed. Reporting time was recorded, and we used the Wilcoxon test for statistical analysis. RESULTS: Median tumour volumes and conspicuity were similar using both approaches. The reporting time of the follow-up scan was quicker using the PRECISE reporting workflow both in the whole population (12'33″ vs 10'52″; p = 0.005) and in the dutasteride arm (15'50″ vs 12'59″; p = 0.01). A structured report including clinical and imaging data was generated according to the PRECISE recommendations and a comparison table between lesion characteristics at baseline and follow-up scans was also included. CONCLUSION: We conclude that a dedicated PRECISE reporting tool for sequential scans in men on AS results in a significant reduction in the reporting time and allows the radiologist to easily compare scans over time. This tool will help with our understanding of the natural history of mpMRI changes during AS

Transition Metal Migration Can Facilitate Ionic Diffusion in Defect Garnet-Based Intercalation Electrodes

The importance of metal migration during multielectron redox activity has been characterized, revealing a competing demand to satisfy bonding requirements and local strains in structures upon alkali intercalation. The local structural evolution required to accommodate intercalation in Y2(MoO4)3 and Al2(MoO4)3 has been contrasted by operando characterization methods, including X-ray absorption spectroscopy and diffraction, along with nuclear magnetic resonance measurements. Computational modeling further rationalized behavioral differences. The local structure of Y2(MoO4)3 was maintained upon lithiation, while the structure of Al2(MoO4)3 underwent substantial local atomic rearrangements as the more ionic character of the bonds in Al2(MoO4)3 allowed Al to mix off its starting octahedral position to accommodate strain during cycling. However, this mixing was prevented in the more covalent Y2(MoO4)3, which accommodated strain through rotational motion of polyhedral subunits. Knowing that an increased ionic character can facilitate the diffusion of redox-inactive metals when cycling multielectron electrodes offers a powerful design principle when identifying next-generation intercalation hosts

Correlated Polyhedral Rotations in the Absence of Polarons during Electrochemical Insertion of Lithium in ReO₃

Understanding the structural transformations that materials undergo during (de)insertion of Li ions is crucial for designing high-performance intercalation hosts as these deformations can lead to significant capacity fade. Herein, we present a study of the metallic defect perovskite ReO₃ to determine whether these distortions are driven by polaronic charge transport (i.e., the electrons and ions moving through the lattice in a coupled way) due to the semiconducting nature of most oxide hosts. Employing numerous techniques, including electrochemical probes, operando X-ray diffraction, X-ray photoelectron spectroscopy, and density functional theory calculations, we find that the cubic structure of ReO₃ experiences multiple phase changes involving the correlated twisting of rigid octahedral subunits upon lithiation. This results in exceptionally poor long-term cyclability due to large strains upon lithiation, even though metallic character is maintained throughout. This suggests that phase transformations during alkali ion intercalation are the result of local strains in the lattice and not exclusively due to polaron migration

Charged Particle Production in Proton-, Deuteron-, Oxygen- and Sulphur-Nucleus Collisions at 200 GeV per Nucleon

The transverse momentum and rapidity distributions of net protons and negatively charged hadrons have been measured for minimum bias proton-nucleus and deuteron-gold interactions, as well as central oxygen-gold and sulphur-nucleus collisions at 200 GeV per nucleon. The rapidity density of net protons at midrapidity in central nucleus-nucleus collisions increases both with target mass for sulphur projectiles and with the projectile mass for a gold target. The shape of the rapidity distributions of net protons forward of midrapidity for d+Au and central S+Au collisions is similar. The average rapidity loss is larger than 2 units of rapidity for reactions with the gold target. The transverse momentum spectra of net protons for all reactions can be described by a thermal distribution with `temperatures' between 145 +- 11 MeV (p+S interactions) and 244 +- 43 MeV (central S+Au collisions). The multiplicity of negatively charged hadrons increases with the mass of the colliding system. The shape of the transverse momentum spectra of negatively charged hadrons changes from minimum bias p+p and p+S interactions to p+Au and central nucleus-nucleus collisions. The mean transverse momentum is almost constant in the vicinity of midrapidity and shows little variation with the target and projectile masses. The average number of produced negatively charged hadrons per participant baryon increases slightly from p+p, p+A to central S+S,Ag collisions.Comment: 47 pages, submitted to Z. Phys.

A semi-automated software program to assess the impact of second reads in prostate MRI for equivocal lesions: results from a UK tertiary referral centre

Purpose: To investigate the utility of a prostate magnetic resonance imaging (MRI) second read using a semi-automated software program in the one-stop clinic, where patients undergo multiparametric MRI, review and biopsy planning in one visit. We looked at concordance between readers for patients with equivocal scans and the possibility for biopsy deferral in this group. Methods: We present data from 664 consecutive patients. Scans were reported by seven different expert genitourinary radiologists using dedicated software (MIM®) and a Likert scale. All scans were rescored by another expert genitourinary radiologist using a customised workflow for second reads that includes annotated biopsy contours for accurate visual targeting. The number of scans in which a biopsy could have been deferred using biopsy results and prostate specific antigen density was assessed. Gleason score ≥ 3 + 4 was considered clinically significant disease. Concordance between first and second reads for equivocal scans (Likert 3) was evaluated. Results: A total of 209/664 (31%) patients scored Likert 3 on first read, 128 of which (61%) were concordant after second read. 103/209 (49%) of patients with Likert 3 scans were biopsied, with clinically significant disease in 31 (30%) cases. Considering Likert 3 scans that were both downgraded and biopsied using the workflow-generated biopsy contours, 25/103 (24%) biopsies could have been deferred. Conclusions: Implementing a semi-automated workflow for accurate lesion contouring and targeting biopsies is helpful during the one-stop clinic. We observed a reduction of indeterminate scans after second reading and almost a quarter of biopsies could have been deferred, reducing the potential biopsy-related side effects

Gonorrhoea and male bladder cancer in a prospective study

In a prospective cohort study, a close to two-fold elevated risk of bladder cancer was found among men reporting a history of gonorrhoea (relative risk=1.92, 95% CI=1.10–3.33). Our finding warrants further examination of the role of gonorrhoea in bladder carcinogenesis