A common ontology for multi-dimensional shapes

In recent years, digital shapes have become more and more widespread and have been made available in a plethora of online repositories. A systematic and formal approach for capturing and representing shape-related information is needed to facilitate its reuse and enable the demonstration of useful cross-domain usage scenarios. In this paper we present an ontology for digital shapes, called the Common Shape Ontology (CSO). We discuss the rationale, the requirements and the scope of this ontology, we present in detail its structure and describe the most relevant choices related to its development. Finally, we show how the CSO conceptualization is used in domain-specific application scenarios

DNA-binding protects p53 from interactions with cofactors involved in transcription-independent functions

Binding-induced conformational changes of a protein at regions distant from the binding site may play crucial roles in protein function and regulation. The p53 tumour suppressor is an example of such an allosterically regulated protein. Little is known, however, about how DNA binding can affect distal sites for transcription factors. Furthermore, the molecular details of how a local perturbation is transmitted through a protein structure are generally elusive and occur on timescales hard to explore by simulations. Thus, we employed state-of-the-art enhanced sampling atomistic simulations to unveil DNA-induced effects on p53 structure and dynamics that modulate the recruitment of cofactors and the impact of phosphorylation at Ser215. We show that DNA interaction promotes a conformational change in a region 3 nm away from the DNA binding site. Specifically, binding to DNA increases the population of an occluded minor state at this distal site by more than 4-fold, whereas phosphorylation traps the protein in its major state. In the minor conformation, the interface of p53 that binds biological partners related to p53 transcription-independent functions is not accessible. Significantly, our study reveals a mechanism of DNA-mediated protection of p53 from interactions with partners involved in the p53 transcription-independent signalling. This also suggests that conformational dynamics is tightly related to p53 signalling

LTE Adaptation for Mobile Broadband Satellite Networks

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Kidins220/ARMS modulates brain morphology and anxiety-like traits in adult mice

open11: Kinase D interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is a transmembrane scaffold protein that participates in fundamental aspects of neuronal physiology including cell survival, differentiation, and synaptic plasticity. The Kidins220 constitutive knockout line displays developmental defects in the nervous and cardiovascular systems that lead to embryonic lethality, which has so far precluded the study of this protein in the adult. Moreover, Kidins220 mRNA is tightly regulated by alternative splicing, whose impact on nervous system physiology has not yet been addressed in vivo. Here, we have asked to what extent the absence of Kidins220 splicing and the selective knockout of Kidins220 impact on adult brain homeostasis. To answer this question, we used a floxed line that expresses only the full-length, non-spliced Kidins220 mRNA, and a forebrain-specific, CaMKII-Cre driven Kidins220 conditional knockout (cKO) line. Kidins220 cKO brains are characterized by enlarged ventricles in the absence of cell death, and by deficient dendritic arborization in several cortical regions. The deletion of Kidins220 leads to behavioral changes, such as reduced anxiety-like traits linked to alterations in TrkB-BDNF signaling and sex-dependent alterations of hippocampal-dependent spatial memory. Kidins220 floxed mice present similarly enlarged brain ventricles and increased associative memory. Thus, both the absolute levels of Kidins220 expression and its splicing pattern are required for the correct brain development and related expression of behavioral phenotypes. These findings are relevant in light of the increasing evidence linking mutations in the human KIDINS220 gene to the onset of severe neurodevelopmental disorders.openAlmacellas-Barbanoj, Amanda; Albini, Martina; Satapathy, Annyesha; Jaudon, Fanny; Michetti, Caterina; Krawczun-Rygmaczewska, Alicja; Huang, Huiping; Manago, Francesca; Papaleo, Francesco; Benfenati, Fabio; Cesca, FabriziaAlmacellas-Barbanoj, Amanda; Albini, Martina; Satapathy, Annyesha; Jaudon, Fanny; Michetti, Caterina; Krawczun-Rygmaczewska, Alicja; Huang, Huiping; Manago, Francesca; Papaleo, Francesco; Benfenati, Fabio; Cesca, Fabrizi

SINEUP Non-coding RNA Targeting GDNF Rescues Motor Deficits and Neurodegeneration in a Mouse Model of Parkinson's Disease.

International audience; Glial cell-derived neurotrophic factor (GDNF) has a potent action in promoting the survival of dopamine (DA) neurons. Several studies indicate that increasing GDNF levels may be beneficial for the treatment of Parkinson's disease (PD) by reducing neurodegeneration of DA neurons. Despite a plethora of preclinical studies showing GDNF efficacy in PD animal models, its application in humans remains questionable for its poor efficacy and side effects due to its uncontrolled, ectopic expression. Here we took advantage of SINEUPs, a new class of antisense long non-coding RNA, that promote translation of partially overlapping sense protein-coding mRNAs with no effects on their mRNA levels. By synthesizing a SINEUP targeting Gdnf mRNA, we were able to increase endogenous GDNF protein levels by about 2-fold. Adeno-associated virus (AAV)9-mediated delivery in the striatum of wild-type (WT) mice led to an increase of endogenous GDNF protein for at least 6 months and the potentiation of the DA system's functions while showing no side effects. Furthermore, SINEUP-GDNF was able to ameliorate motor deficits and neurodegeneration of DA neurons in a PD neurochemical mouse model. Our data indicate that SINEUP-GDNF could represent a new strategy to increase endogenous GDNF protein levels in a more physiological manner for therapeutic treatments of PD

Recombinant FSH improves sperm DNA damage in male infertility: A phase II clinical trial

Background and objectives: Male infertility is a global health dilemma and Follicle-Stimulating Hormone (FSH) administration has shown promising results. Several studies showed that infertile men with normal semen parameters have low levels of DNA damage while infertile men with abnormal semen parameters have more damage at the DNA level. Sperm DNA damage may affect the reproductive outcome and has been associated with failure in the achievement of competent embryos and pregnancy fulfillment. The aim of this study was to evaluate whether the administration of recombinant FSH (Gonal-f® PEN 900 IU) could improve sperm DNA fragmentation in men with infertility. The secondary endpoints of this study were to evaluate the FSH effects on sperm parameters and hormonal assets. Methods: A longitudinal, prospective, multicenter, open-label clinical trial was carried out. Infertile couples were recruited from six Italian Reproductive Medical Centers and 115 infertile men were enrolled for this study. All participants were treated with subcutaneous injections of Gonal-f® 150 IU every other day, within a 3 month-time frame. The semen samples were examined in accordance to the 2010 World Health Organization criteria. Sperm DNA Fragmentation (DFI) was determined by fluorescence microscopy using terminal deoxynucleotidyl transferase-mediated d-UTP Nick-end Labeling (TUNEL) assay. Statistical analysis was performed using both the t-test for paired samples and the Wilcoxon signed-rank test. Results: FSH administration improved DFI in 67% of patients, with an average decrease of 35.4% compared to the baseline. This improvement is more evident in men with basal DFI lower than 17% and in those with FSH basal levels between 2.16 and 4.27 IU/L. In addition, FSH enhanced the gonadal function, increasing the hormones AMH and Inhibin B and semen parameters. Limitation of these results are represented by the absence of a placebo group and of FSHR genotype stratification sub-analysis. Conclusion: Recombinant FSH 150 IU is well tolerated and effective in eliciting a significant DFI reduction as well as in improving gonadal function

NEMO-SN1 Abyssal Cabled Observatory in the Western Ionian Sea

The NEutrinoMediterranean Observatory—Submarine Network 1 (NEMO-SN1) seafloor observatory is located in the central Mediterranean Sea, Western Ionian Sea, off Eastern Sicily (Southern Italy) at 2100-m water depth, 25 km from the harbor of the city of Catania. It is a prototype of a cabled deep-sea multiparameter observatory and the first one operating with real-time data transmission in Europe since 2005. NEMO-SN1 is also the first-established node of the European Multidisciplinary Seafloor Observatory (EMSO), one of the incoming European large-scale research infrastructures included in the Roadmap of the European Strategy Forum on Research Infrastructures (ESFRI) since 2006. EMSO will specifically address long-term monitoring of environmental processes related to marine ecosystems, marine mammals, climate change, and geohazards