MPV17 does not control cancer cell proliferation

MPV17 is described as a mitochondrial inner membrane channel. Although its function remains elusive, mutations in the MPV17 gene result in hepato-cerebral mitochondrial DNA depletion syndrome in humans. In this study, we show that MPV17 silencing does not induce depletion in mitochondrial DNA content in cancer cells. We also show that MPV17 does not control cancer cell proliferation despite the fact that we initially observed a reduced proliferation rate in five MPV17-silenced cancer cell lines with two different shRNAs. However, shRNA-mediated MPV17 knockdown performed in this work provided misguiding results regarding the resulting proliferation phenotype and only a rescue experiment was able to shed definitive light on the implication of MPV17 in cancer cell proliferation. Our results therefore emphasize the caution that is required when scientific conclusions are drawn from a work based on lentiviral vector-based gene silencing and clearly demonstrate the need to systematically perform a rescue experiment in order to ascertain the specific nature of the experimental results

The impact of a radiologist-led workshop on MRI target volume delineation for radiotherapy

Introduction: Magnetic resonance imaging (MRI) is increasingly used for target volume delineation in radiotherapy due to its superior soft tissue visualisation compared to computed tomography (CT). The aim of this study was to assess the impact of a radiologist-led workshop on inter-observer variability in volume delineation on MRI. Methods: Data from three separate studies evaluating the impact of MRI in lung, breast and cervix were collated. At pre-workshop evaluation, observers involved in each clinical site were instructed to delineate specified volumes. Radiologists specialising in each cancer site conducted an interactive workshop on interpretation of images and anatomy for each clinical site. At post-workshop evaluation, observers repeated delineation a minimum of 2 weeks after the workshops. Inter-observer variability was evaluated using dice similarity coefficient (DSC) and volume similarity (VOLSIM) index comparing reference and observer volumes. Results: Post-workshop primary gross tumour volumes (GTV) were smaller than pre-workshop volumes for lung with a mean percentage reduction of 10.4%. Breast clinical target volumes (CTV) were similar but seroma volumes were smaller post-workshop on both supine (65% reduction) and prone MRI (73% reduction). Based on DSC scores, improvement in inter-observer variability was seen for the seroma cavity volume on prone MRI with a reduction in DSC score range from 0.4-0.8 to 0.7-0.9. Breast CTV demonstrated good inter-observer variability scores (mean DSC 0.9) for both pre- and post-workshop. Post-workshop observer delineated cervix GTV was smaller than pre-workshop by 26.9%. Conclusion: A radiologist-led workshop did not significantly reduce inter-observer variability in volume delineation for the three clinical sites. However, some improvement was noted in delineation of breast CTV, seroma volumes and cervix GTV

defective mitochondrial trna taurine modification activates global proteostress and leads to mitochondrial disease

Summary: A subset of mitochondrial tRNAs (mt-tRNAs) contains taurine-derived modifications at 34U of the anticodon. Loss of taurine modification has been linked to the development of mitochondrial diseases, but the molecular mechanism is still unclear. Here, we showed that taurine modification is catalyzed by mitochondrial optimization 1 (Mto1) in mammals. Mto1 deficiency severely impaired mitochondrial translation and respiratory activity. Moreover, Mto1-deficient cells exhibited abnormal mitochondrial morphology owing to aberrant trafficking of nuclear DNA-encoded mitochondrial proteins, including Opa1. The mistargeted proteins were aggregated and misfolded in the cytoplasm, which induced cytotoxic unfolded protein response. Importantly, application of chemical chaperones successfully suppressed cytotoxicity by reducing protein misfolding and increasing functional mitochondrial proteins in Mto1-deficient cells and mice. Thus, our results demonstrate the essential role of taurine modification in mitochondrial translation and reveal an intrinsic protein homeostasis network between the mitochondria and cytosol, which has therapeutic potential for mitochondrial diseases. : Taurine modification of mitochondrial tRNA is associated with mitochondrial disease. Fakruddin et al. find that taurine modification is indispensable for mitochondrial protein translation. The authors also find that deficiency of taurine modification impairs a mitochondrial-cytosolic proteostatic network through an Opa1-dependent mechanism and demonstrate the therapeutic potential of chemical chaperones. Keywords: tRNA, modification, taurine, mitochondria, Opa

An approach to identify, from DCE MRI, significant subvolumes of tumors related to outcomes in advanced head‐and‐neck cancera)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134885/1/mp7022.pd

miR-212/132 expression and functions: within and beyond the neuronal compartment

During the last two decades, microRNAs (miRNAs) emerged as critical regulators of gene expression. By modulating the expression of numerous target mRNAs mainly at the post-transcriptional level, these small non-coding RNAs have been involved in most, if not all, biological processes as well as in the pathogenesis of a number of diseases. miR-132 and miR-212 are tandem miRNAs whose expression is necessary for the proper development, maturation and function of neurons and whose deregulation is associated with several neurological disorders, such as Alzheimer's disease and tauopathies (neurodegenerative diseases resulting from the pathological aggregation of tau protein in the human brain). Although their involvement in neuronal functions is the most described, evidences point towards a role of these miRNAs in many other biological processes, including inflammation and immune functions. Incidentally, miR-132 was recently classified as a ‘neurimmiR’, a class of miRNAs operating within and between the neural and immune compartments. In this review, we propose an outline of the current knowledge about miR-132 and miR-212 functions in neurons and immune cells, by describing the signalling pathways and transcription factors regulating their expression as well as their putative or demonstrated roles and validated mRNA targets

Auditory spatial representations of the world are compressed in blind humans

Compared to sighted listeners, blind listeners often display enhanced auditory spatial abilities such as localization in azimuth. However, less is known about whether blind humans can accurately judge distance in extrapersonal space using auditory cues alone. Using virtualization techniques, we show that auditory spatial representations of the world beyond the peripersonal space of blind listeners are compressed compared to those for normally sighted controls. Blind participants overestimated the distance to nearby sources, and underestimated the distance to remote sound sources, in both reverberant and anechoic environments, and for speech, music and noise signals. Functions relating judged and actual virtual distance were well fitted by compressive power functions, indicating that the absence of visual information regarding the distance of sound sources may prevent accurate calibration of the distance information provided by auditory signals