Author Correction: Deubiquitinase Usp12 functions noncatalytically to induce autophagy and confer neuroprotection in models of Huntington's disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Monitoring External Training Loads and Neuromuscular Performance for Division I Basketball Players over the Preseason

Limited research has paralleled concomitant changes in external training load (eTL) and countermovement jump (CMJ) performance. Therefore, this investigation characterized eTL and CMJ performance changes across preseason training in Division 1 male collegiate basketball athletes, while examining the influence of position (Guard vs. Forward/Center) and scholarship status (Scholarship = S vs. Walk-on = WO). During 22 practices, eTL was monitored in 14 male athletes, with weekly CMJs performed to quantify neuromuscular performance (Jump Height [JH], Flight Time:Contraction Time [FT:CT], Reactive Strength Index Modified [RSIMod ]). PlayerLoad per minute was significantly higher during W1 and W2 (5.4 ± 1.3au and 5.3 ± 1.2au, respectively; p < 0.05) compared to subsequent weeks, but no additional differences in eTL parameters across time were observed. Scholarship athletes displayed greater PlayerLoad (S = 777.1 ± 35.6, WO = 530.1 ± 56.20; Inertial Movement Analysis (IMA) IMA_High (S = 70.9 ± 15.2, WO = 41.3 ± 15.2); IMA_Medium (S = 159.9 ± 30.7, WO = 92.7 ± 30.6); and IMA_Low (S = 700.6 ± 105.1, WO = 405 ± 105.0;) (p < 0.05), with no observed differences in eTL by position. Moderate decreases in FT:CT and RSIMod paralleled increased eTL. Significant increases in practice intensity (W1 and W2) did not impact CMJ performance, suggesting athletes could cope with the prescribed training loads. However, moderate perturbations in FT:CT and RSIMod paralleled the weeks with intensified training. Cumulatively, scholarship status appears to influence eTL while player position does not.The authors would like to thank Mr. Brady Brown and Mr. Keldon Peak for their assistance with this project. Additionally, the authors thank the Basketball Programs at the University of Oklahoma for their continued support of research directed at enhancing athlete performance, while also improving overall student-athlete welfare. Finally, the authors would also like to thank all of the student-athletes that graciously volunteered their time to enroll and participate in this study. The experiments comply with the current laws of the country in which they were performed. The authors have no conflict of interest to declare. Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

Massively Parallel Sequencing and Analysis of the Necator americanus Transcriptome

The blood-feeding hookworm Necator americanus infects hundreds of millions of people. To elucidate fundamental molecular biological aspects of this hookworm, the transcriptome of adult Necator americanus was studied using next-generation sequencing and in silico analyses. Contigs (n = 19,997) were assembled from the sequence data; 6,771 of them had known orthologues in the free-living nematode Caenorhabditis elegans, and most encoded proteins with WD40 repeats (10.6%), proteinase inhibitors (7.8%) or calcium-binding EF-hand proteins (6.7%). Bioinformatic analyses inferred that C. elegans homologues are involved mainly in biological pathways linked to ribosome biogenesis (70%), oxidative phosphorylation (63%) and/or proteases (60%). Comparative analyses of the transcriptomes of N. americanus and the canine hookworm, Ancylostoma caninum, revealed qualitative and quantitative differences. Essential molecules were predicted using a combination of orthology mapping and functional data available for C. elegans. Further analyses allowed the prioritization of 18 predicted drug targets which did not have human homologues. These candidate targets were inferred to be linked to mitochondrial metabolism or amino acid synthesis. This investigation provides detailed insights into the transcriptome of the adult stage of N. americanus

An Automated Microscope System to Monitor Dynamic Stress Responses in Neurons

Despite years of incremental progress in our understanding of diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's Disease (HD), and amyotrophic lateral sclerosis (ALS), there are still no disease-modifying therapeutics. The discrepancy between the number of lead compounds and approved drugs may partially be a result of the methods used to generate the leads and highlights the need for new technology to obtain more detailed and physiologically relevant information on cellular processes in normal and diseased states. We developed a high-throughput automated microscope system and primary neuron model of HD that allows us to monitor dynamic stress responses in intact, fully differentiated neurons. We are able to assay thousands of conditions, including millions of neurons, in a short period of time, which can reveal completely new aspects of biology and identify lead therapeutics in the span of a few months when conventional methods could take years or fail all together. We use this system to understand how neurons, a long-lived, postmitotic cell type, differ in their acute responses to proteotoxic insults including those associated with malformed protein. We show that neurons have a deficient acute stress response to multiple known stimuli, including thermal stress, Hsp90 inhibition, and proteasome inhibition. We find that neurons have low expression of the two major stress-responsive transcriptional activators in mammals, HSF1 and HSF2. We also find that neurons have high constitutive chaperoning capability through relatively high levels of Hsp90 and Hsc70. High Hsp90, however, decreases the acute stress response through negative regulation of HSF1. By increasing HSF1 levels, we were able to restore the response in neurons and protect them from the toxicity associated with malformed protein. We propose a mechanism for the attenuated acute stress response in neurons that implicates a high Hsp90 to HSF1 ratio, which results in an increased ability to cope with chronic stresses, but decreased ability to respond acutely when basal homeostatic responses are overwhelmed. We conclude that targeted therapies to bolster acute stress responses in neurons through increasing HSF1 expression or activation will therefore benefit HD and other neurodegenerative disorders of protein conformation

Publisher Correction: Deubiquitinase Usp12 functions noncatalytically to induce autophagy and confer neuroprotection in models of Huntington's disease.

The original version of this Article incorrectly gave a publication date of 8 October 2018; this should have been 28 September 2018. This has now been corrected in the PDF and HTML versions of the Article

Deubiquitinase Usp12 functions noncatalytically to induce autophagy and confer neuroprotection in models of Huntington's disease.

Huntington's disease is a progressive neurodegenerative disorder caused by polyglutamine-expanded mutant huntingtin (mHTT). Here, we show that the deubiquitinase Usp12 rescues mHTT-mediated neurodegeneration in Huntington's disease rodent and patient-derived human neurons, and in Drosophila. The neuroprotective role of Usp12 may be specific amongst related deubiquitinases, as the closely related homolog Usp46 does not suppress mHTT-mediated toxicity. Mechanistically, we identify Usp12 as a potent inducer of neuronal autophagy. Usp12 overexpression accelerates autophagic flux and induces an approximately sixfold increase in autophagic structures as determined by ultrastructural analyses, while suppression of endogenous Usp12 slows autophagy. Surprisingly, the catalytic activity of Usp12 is not required to protect against neurodegeneration or induce autophagy. These findings identify the deubiquitinase Usp12 as a regulator of neuronal proteostasis and mHTT-mediated neurodegeneration

Deubiquitinase Usp12 functions noncatalytically to induce autophagy and confer neuroprotection in models of Huntington's disease.

Huntington's disease is a progressive neurodegenerative disorder caused by polyglutamine-expanded mutant huntingtin (mHTT). Here, we show that the deubiquitinase Usp12 rescues mHTT-mediated neurodegeneration in Huntington's disease rodent and patient-derived human neurons, and in Drosophila. The neuroprotective role of Usp12 may be specific amongst related deubiquitinases, as the closely related homolog Usp46 does not suppress mHTT-mediated toxicity. Mechanistically, we identify Usp12 as a potent inducer of neuronal autophagy. Usp12 overexpression accelerates autophagic flux and induces an approximately sixfold increase in autophagic structures as determined by ultrastructural analyses, while suppression of endogenous Usp12 slows autophagy. Surprisingly, the catalytic activity of Usp12 is not required to protect against neurodegeneration or induce autophagy. These findings identify the deubiquitinase Usp12 as a regulator of neuronal proteostasis and mHTT-mediated neurodegeneration

Publisher Correction: Deubiquitinase Usp12 functions noncatalytically to induce autophagy and confer neuroprotection in models of Huntington's disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper