Cortical dendritic spine development and plasticity: insights from in vivo imaging

Publication date: December 2018
Source:Current Opinion in Neurobiology, Volume 53
Author(s): Caitlin E Moyer, Yi Zuo
Dendritic spines are the postsynaptic sites of most excitatory synapses in the cerebral cortex. Their morphology and density change throughout life, reflecting the maturation and reorganization of excitatory circuits. The development of in vivo two-photon microscopy has enabled the monitoring of the same dendritic spines over time during different developmental periods. In this review we focus on recent in vivo imaging studies in rodents that have revealed cell type-specific and region-specific structural dynamics of dendritic spines. We also discuss how the contributions of local inhibitory neurons and long-distance excitatory and neuromodulatory inputs to the cortex influence dendritic spine development and dynamics. Such studies will facilitate our understanding of how environmental factors and experiences affect cortical synapse development.



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Current Treatment of Bilateral Retinoblastoma: The Impact of Intraarterial and Intravitreous Chemotherapy

Publication date: August 2018
Source:Neoplasia, Volume 20, Issue 8
Author(s): Jasmine H. Francis, Nelli Roosipu, Ariana M. Levin, Scott E. Brodie, Ira J. Dunkel, Y. Pierre Gobin, David H. Abramson
PURPOSE: To evaluate the management and outcomes of naïve bilateral retinoblastoma treated at a single-center over a 5-year period during the era of ophthalmic artery chemosurgery (OAC) and intravitreous chemotherapy. METHODS: Retrospective cohort study of 46 patients (92 eyes) with naïve bilateral retinoblastoma treated at Memorial Sloan Kettering Cancer Center between January 2012 and February 2017. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response. Patient, ocular, ocular progression-free, ocular recurrent event–free, and second ocular survivals were assessed by Kaplan-Meier estimates. Retinal toxicity was evaluated by electroretinography. Snellen visual acuity and complete blood count metrics were recorded. RESULTS: Sixty-four eyes (70%) in 41 patients (89%) received ophthalmic artery chemosurgery as part of their treatment. Twenty-six patients (56%) received tandem OAC (bilateral simultaneous infusions). Seven eyes were primarily enucleated. No eye receiving initial OAC was enucleated. There was a single secondary enucleation in an eye initially treated with focal therapy with anterior chamber recurrence. The 3-year Kaplan-Meier estimates for overall ocular, secondary ocular (survival after treatment for recurrence), progression-free, and recurrent event–free survival were 91.3% [95% confidence interval (CI) 83.4-95.5], 98.7% (95% CI 91.3-99.8), 91.5% (95% CI 83.0-95.8), and 78.9% (95% CI 68.2-86.3), respectively. Overall and secondary ocular survivals were 100% for International Classification of Retinoblastoma (ICRB) groups A-C. Overall ocular survival was 91.5% (95% CI 70-97.8) for ICRB group D and 71.4% (95% CI 47.1-79.4) for group E. Secondary ocular survival was 95.4% (95% CI 71.8-99.3) for ICRB group D and 100% for group E. There were no treatment-related deaths, three patients developed trilateral retinoblastoma (one died), and one patient (who did not receive OAC) developed metastatic disease and is in remission at 32-month follow-up. CONCLUSION: The majority (89%) of bilateral retinoblastoma patients in the current era and at this center were treated with OAC. This has resulted in saving a historic number of eyes. A quarter of eyes developed recurrent disease (defined as recurrent disease requiring any treatment including focal), the majority of which occurred in the first year after treatment, and all but one was saved. There has been no compromise in patient survival.



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Comparison of chairs based on HDsEMG of back muscles, biomechanical and comfort indices, for violin and viola players: a short-term study

Publication date: Available online 21 June 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Paolo Cattarello, Silvia Vinelli, Samuel D'Emanuele, Marco Gazzoni, Roberto Merletti
This work investigates the effect of different seats on violin and viola players sitting postures using High-Density-surface-Electromyography techniques (HDsEMG), biomechanical and comfort indices. Five types of chairs were assessed on 18 violin and three viola players by comparing: a) pelvic tilt and kyphosis and lordosis angles, b) subjective comfort indices, and c) EMG amplitude of erector spinae and trapezius.Sitting "as you like" on a standard orchestra chair is the condition with the highest subjective comfort (but not significantly different from other chairs). A saddle chair with low back support is associated to the lowest EMG of the erector spinae (p<0.05) and a saddle stool is associated to the spinal angles closest to those of the standing posture. In 12 out of 21 (57%) musicians, the erector spinae was activated in an intermittent manner, regardless of the chair used. These findings justify further research on the selected chairs, on muscle fatigue and on the intermittent postural control strategy.



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Building words and phrases in the left temporal lobe

Publication date: Available online 21 June 2018
Source:Cortex
Author(s): Graham Flick, Yohei Oseki, Amanda R. Kaczmarek, Meera Al Kaabi, Alec Marantz, Liina Pylkkänen
A central part of knowing a language is the ability to combine basic linguistic units to form complex representations. While our neurobiological understanding of how words combine into larger structures has significantly advanced in recent years, the combinatory operations that build words themselves remain unknown. Are complex words such as tombstone and starlet built with the same mechanisms that construct phrases from words, such as grey stone or bright star? Here we addressed this with two magnetoencephalography (MEG) experiments, which simultaneously varied demands associated with phrasal composition, and the processing of morphological complexity in compound and suffixed nouns. Replicating previous findings, we show that portions of the left anterior temporal lobe (LATL) are engaged in the combination of modifiers and monomorphemic nouns in phrases (e.g. brown rabbit). As regards compounding, we show that semantically transparent compounds (e.g. tombstone) also engage left anterior temporal cortex, though the spatiotemporal details of this effect differed from phrasal composition. Further, when a phrase was constructed from a modifier and a transparent compound (e.g. granite tombstone), the typical LATL phrasal composition response appeared at a delayed latency, which follows if an initial within-word operation (tomb + stone) must take place before the combination of the compound with the preceding modifier (granite + tombstone). In contrast to compounding, suffixation (i.e. star + let) did not engage the LATL in any consistent way, suggesting a distinct processing route. Finally, our results suggest an intriguing generalization that morpho-orthographic complexity that does not recruit the LATL may block the engagement of the LATL in subsequent phrase building. In sum, our findings offer a detailed spatiotemporal characterization of the lowest level combinatory operations that ultimately feed the composition of full sentences.



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Resting-state connectivity after visuo-motor skill learning is inversely associated with offline consolidation in Parkinson’s disease and healthy controls

Publication date: Available online 21 June 2018
Source:Cortex
Author(s): Aurélie L. Manuel, Nicolas Nicastro, Armin Schnider, Adrian G. Guggisberg
Procedural memory refers to skills acquired through practice and depends on cortico-striatal and cortico-cerebellar circuits. These circuits are typically affected in Parkinson's disease (PD), leading to impaired skill learning, including defective offline consolidation, early in the course of the disease. Evidence points to a role of slow oscillations (<4 Hz) during sleep for offline consolidation. However recent studies showed consolidation over the course of the day, suggesting that consolidation may arise during wakefulness too. Here we investigate whether functional connectivity (FC) at rest after visuo-motor skill learning is associated with the extent of offline improvements in healthy controls and PD patients. Nineteen participants (9 PD, 10 healthy controls) performed a mirror-drawing task. High-density 156-channel resting state EEG was recorded before and immediately after training. Performance on the task was measured again 24h later to test for offline consolidation. Delta-band (1-3.5 Hz) FC centered on the left parietal after training predicted offline consolidation. Weak FC was observed in most healthy controls and associated with marked overnight improvement, while strong FC was observed in most PD patients and associated with weak offline consolidation or loss of the skill. These findings indicate that offline consolidation starts immediately after visuo-motor skill learning in brain regions and frequencies typically involved in sleep-related consolidation.



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Immediate versus delayed reconstruction of head and neck cutaneous melanoma

The Laryngoscope, EarlyView.


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11-Oxygenated androgen precursors are the preferred substrates for aldo-keto reductase 1C3 (AKR1C3): implications for castration resistant prostate cancer

Publication date: Available online 21 June 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Monique Barnard, Jonathan L. Quanson, Elahe Mostaghel, Elzette Pretorius, Jacky L. Snoep, Karl-Heinz Storbeck
The progression of castration resistant prostate cancer (CRPC) is driven by the intratumoral conversion of adrenal androgen precursors to potent androgens. The expression of aldo-keto reductase 1C3 (AKR1C3), which catalyses the reduction of weak androgens to more potent androgens, is significantly increased in CRPC tumours. The oxidation of androgens to their inactive form is catalysed by 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2), but little attention is given to the expression levels of this enzyme. In this study, we show that the 11-oxygenated androgen precursors of adrenal origin are the preferred substrate for AKR1C3. In particular we show that the enzymatic efficiency of AKR1C3 is 8- and 24-fold greater for 11-ketoandrostenedione than for the classic substrates androstenedione and 5α-androstanedione, respectively. Using three independent experimental systems and a computational model we subsequently show that increased ratios of AKR1C3:17βHSD2 significantly favours the flux through the 11-oxygenated androgen pathway as compared to the classical or 5α-androstanedione pathways. Our findings reveal that the flux through the classical and 5α-androstanedione pathways are limited by the low catalytic efficiently of AKR1C3 towards classical androgens combined with the high catalytic efficiency of 17βHSD2, and that the expression of the oxidative enzyme therefore plays a vital role in determining the steady state concentration of active androgens. Using microarray data from prostate tissue we confirm that the AKR1C3:17βHSD2 ratio is significantly increased in patients undergoing androgen deprivation therapy as compared to benign tissue, and further increased in patients with CRPC. Taken together this study therefore demonstrates that the ratio of AKR1C3:17βHSD2 is more important than AKR1C3 expression alone in determining intratumoral androgen levels and that 11-oxygenated androgens may play a bigger role in CRPC than previously anticipated.

Graphical abstract

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