Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9.

Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting that many are directly phosphorylated by these enzymes. Interestingly, when inhibiting Ypk1 we not only detected several hypo-phosphorylated sites in the previously reported RxRxxS/T-, but also in an RRxS/T-motif. Validation experiments revealed that neutral trehalase Nth1, a known PKA target, is additionally phosphorylated and activated downstream of Ypk1. Signaling through Ypk1 is therefore more closely related to PKA- and Sch9-signaling than previously appreciated and may perform functions previously only attributed to the latter kinases

A hybrid-capture approach to reconstruct the phylogeny of Scleractinia (Cnidaria: Hexacorallia)

A well-supported evolutionary tree representing most major lineages of scleractinian corals is in sight with the development and application of phylogenomic approaches. Specifically, hybrid-capture techniques are shedding light on the evolution and systematics of corals. Here, we reconstructed a broad phylogeny of Scleractinia to test previous phylogenetic hypotheses inferred from a few molecular markers, in particular, the relationships among major scleractinian families and genera, and to identify clades that require further research. We analysed 449 nuclear loci from 422 corals, comprising 266 species spanning 26 families, combining data across whole genomes, transcriptomes, hybrid capture and low-coverage sequencing to reconstruct the largest phylogenomic tree of scleractinians to date. Due to the large number of loci and data completeness (less than 38% missing data), node supports were high across shallow and deep nodes with incongruences observed in only a few shallow nodes. The “Robust” and “Complex” clades were recovered unequivocally, and our analyses confirmed that Micrabaciidae Vaughan, 1905 is sister to the “Robust” clade, transforming our understanding of the “Basal” clade. Several families remain polyphyletic in our phylogeny, including Deltocyathiidae Kitahara, Cairns, Stolarski & Miller, 2012, Caryophylliidae Dana, 1846, and Coscinaraeidae Benzoni, Arrigoni, Stefani & Stolarski, 2012, and we hereby formally proposed the family name Pachyseridae Benzoni & Hoeksema to accommodate Pachyseris Milne Edwards & Haime, 1849, which is phylogenetically distinct from Agariciidae Gray, 1847. Results also revealed species misidentifications and inconsistencies within morphologically complex clades, such as Acropora Oken, 1815 and Platygyra Ehrenberg, 1834, underscoring the need for reference skeletal material and topotypes, as well as the importance of detailed taxonomic work. The approach and findings here provide much promise for further stabilising the topology of the scleractinian tree of life and advancing our understanding of coral evolution

Id4 promotes the elimination of the pro-activation factor ascl1 to maintain quiescence of adult hippocampal stem cells

Quiescence is essential for the long-term maintenance of adult stem cells but how stem cells maintain quiescence is poorly understood. Here we show that neural stem cells in the adult mouse hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activated or quiescent states. We found that the inhibitor of DNA binding protein Id4 is enriched in quiescent neural stem cells and that elimination of Id4 results in abnormal accumulation of Ascl1 protein and premature stem cell activation. Accordingly, Id4 and other Id proteins promote elimination of Ascl1 protein in neural stem cell cultures. Id4 sequesters Ascl1 heterodimerisation partner E47, promoting Ascl1 protein degradation and stem cell quiescence. Our results highlight the importance of non-transcriptional mechanisms for the maintenance of neural stem cell quiescence and reveal a role for Id4 as a quiescence-inducing factor, in contrast with its role of promoting the proliferation of embryonic neural progenitors

Effect of pathology type and severity on the distribution of MRI signal intensities within the degenerated nucleus pulposus: application to idiopathic scoliosis and spondylolisthesis

<p>Abstract</p> <p>Background</p> <p>Disc degeneration is characterized by a loss of cellularity, degradation of the extracellular matrix, and, as a result, morphological changes and biomechanical alterations. We hypothesized that the distribution of the MR signal intensity within the nucleus zone of the intervertebral disc was modified according to the pathology and the severity of the pathology. The objective of this study was to propose new parameters characterizing the distribution of the signal intensity within the nucleus zone of lumbar intervertebral discs, and to quantify these changes in patients suffering from spondylolisthesis or idiopathic scoliosis.</p> <p>Methods</p> <p>A retrospective study had been performed on T2-weighted MR images of twenty nine patients suffering from spondylolisthesis and/or scoliosis. The high intensity zone of the nucleus pulposus was semi-automatically detected. The distance "DX" between the center weighted by the signal intensity and the geometrical center was quantified. The sum of the signal intensity on the axis perpendicular to the longitudinal axis of the disc was plotted for each position of the longitudinal axis allowing defining the maximum sum "SM" and its position "PSM".</p> <p>Results</p> <p>"SM" was clearly higher and "PSM" was more shifted for scoliosis than for spondylolisthesis. A two-way analysis of variance showed that the differences observed on "DX" were not attributed to the pathology nor its severity, the differences observed on "SM" were attributed to the pathology but not to its severity, and the differences observed on "PSM" were attributed to both the pathology and its severity.</p> <p>Conclusions</p> <p>The technique proposed in this study showed significant differences in the distribution of the MR signal intensity within the nucleus zone of intervertebral discs due to the pathology and its severity. The dependence of the "PSM" parameter to the severity of the pathology suggests this parameter as a predictive factor of the pathology progression. This new technique should be useful for the early diagnosis of intervertebral disc pathologies as it highlights abnormal patterns in the MRI signal for low severity of the pathology.</p

ZIO: The Ultimate Linux I/O Framework

ZIO (with Z standing for “The Ultimate I/O” Framework) was developed for CERN with the specific needs of physics labs in mind, which are poorly addressed in the mainstream Linux kernel. ZIO provides a framework for industrial, high-bandwith, high-channel count I/O device drivers (digitizers, function generators, timing devices like TDCs) with performance, generality and scalability as design goals. Among its features, it offers abstractions for • both input and output channels, and channel sets • run-time selection of trigger types • run-time selection of buffer types • sysfs-based configuration • char devices for data and metadata • a socket interface (PF ZIO) as alternative to char devices In this paper, we discuss the design and implementation of ZIO, and describe representative cases of driver development for typical and exotic applications: drivers for the FMC (FPGAMezzanine Card, see [1]) boards developed at CERN like the FMC ADC 100Msps digitizer, FMC TDC timestamp counter, and FMC DEL fine delay

Delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) for the quantification of glycosaminoglycan depletion and regeneration in human intervertebral discs.

none5S. Vaga; M. T. Raimondi; E. G. Caiani; F. Perona; M. FornariS., Vaga; Raimondi, MANUELA TERESA; Caiani, ENRICO GIANLUCA; F., Perona; M., Fornar

Mid-term evaluation of the effects of dynamic neutralization system on lumbar intervertebral discs using quantitative molecular MR imaging

Purpose: To evaluate the mid-term effects of implant of dynamic neutralization system (Dynesys) on disc tissue in patients with lumbar discopathy, through the quantifica- tion of glycosaminoglycans (GAG) concentration, both in treated and adjacent levels, by analysis of delayed gado- linium-enhanced MRI contrast (dGEMRIC) images. Materials and Methods: Ten patients with low back pain, underwent the dGEMRIC diagnostic protocol before, 6- months and after 2 years from surgery. Each patient was also evaluated with visual analog (VAS), Oswestry, and Prolo scales both at presurgery and during follow-up. From dGEMRIC images, a DT1 parametric map was obtained for each disc, as quantitative indicator of its GAG concentration, and divided in 13 sectors, which were classified at presurgery as normal or abnormal, based on a 70-ms threshold. Evolution of DT1 was studied during the follow-up. Results: Nine of ten patients completed the follow-up. VAS, Oswestry, and Prolo grades showed an improve- ment. This was accompanied by a reduction of DT1 in abnormal segments while normal segments showed a pat- tern of initial worsening at 6 months, followed by an improvement after 2 years. Conclusion: Our study confirmed the improvement in clinical evaluation, and for the first time related this to the changes in discs GAG concentration