Secretion-Positive LGI1 Mutations Linked to Lateral Temporal Epilepsy Impair Binding to ADAM22 and ADAM23 Receptors

Autosomal dominant lateral temporal epilepsy (ADTLE) is a focal epilepsy syndrome caused by mutations in the LGI1 gene, which encodes a secreted protein. Most ADLTE-causing mutations inhibit LGI1 protein secretion, and only a few secretion-positive missense mutations have been reported. Here we describe the effects of four disease-causing nonsynonymous LGI1 mutations, T380A, R407C, S473L, and R474Q, on protein secretion and extracellular interactions. Expression of LGI1 mutant proteins in cultured cells shows that these mutations do not inhibit protein secretion. This finding likely results from the lack of effects of these mutations on LGI1 protein folding, as suggested by 3D protein modelling. In addition, immunofluorescence and co-immunoprecipitation experiments reveal that all four mutations significantly impair interaction of LGI1 with the ADAM22 and ADAM23 receptors on the cell surface. These results support the existence of a second mechanism, alternative to inhibition of protein secretion, by which ADLTE-causing LGI1 mutations exert their loss-of-function effect extracellularly, and suggest that interactions of LGI1 with both ADAM22 and ADAM23 play an important role in the molecular mechanisms leading to ADLTE

Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family.

Fiesta de Tosantos (1101001

PET and PVC separation with hyperspectral Imagery

Traditional plants for plastic separation in homogeneous products employ material physical properties (for instance density). Due to the small intervals of variability of different polymer properties, the output quality may not be adequate. Sensing technologies based on hyperspectral imaging have been introduced in order to classify materials and to increase the quality of recycled products, which have to comply with specific standards determined by industrial applications. This paper presents the results of the characterization of two different plastic polymers—polyethylene terephthalate (PET) and polyvinyl chloride (PVC)—in different phases of their life cycle (primary raw materials, urban and urban-assimilated waste and secondary raw materials) to show the contribution of hyperspectral sensors in the field of material recycling. This is accomplished via near-infrared (900–1700 nm) reflectance spectra extracted from hyperspectral images acquired with a two-linear-spectrometer apparatus. Results have shown that a rapid and reliable identification of PET and PVC can be achieved by using a simple two near-infrared wavelength operator coupled to an analysis of reflectance spectra. This resulted in 100% classification accuracy. A sensor based on this identification method appears suitable and inexpensive to build and provides the necessary speed and performance required by the recycling industry

The role of storage in emerging country scenarios

AbstractDespite the electrical energy scenarios are quite different between industrialized countries and emerging and developing ones, for both contexts, energy storage systems could play a key role in the next future. Specifically, in emerging and developing countries, energy storage systems may allow a cost-effective exploitation of renewable sources in order to cope with energy security for centralized energy systems, but mainly to become a building block of rural electrification by off-grid power systems. In this paper a short overview of energy storage systems within the emerging and developing countries scenarios is reported. Specifically the paper provides a description of the typical configuration for batteries within off-grid systems and an overview of the typical economic models for batteries applications and the regulatory frameworks when off-grid applications are introduced. Finally the description of an experimental project in rural area of Tanzania points out the peculiar characteristics of batteries application in off-grid applications

A Population Survey in Italy Based on the ICF Classification: Recognizing Persons with Severe Disability

Aim of this paper is to describe functioning of subjects with “severe disability” collected with a protocol based on the International Classification of Functioning, Disability, and Health. It included sections on body functions and structures (BF and BS), activities and participation (A&P), and environmental factors (EF). In A&P, performance without personal support (WPS) was added to standard capacity and performance. Persons with severe disability were those reporting a number of very severe/complete problems in BF or in A&P-capacity superior to mean + 1SD. Correlations between BF and A&P and differences between capacity, performance-WPS, and performance were assessed with Spearman's coefficient. Out of 1051, 200 subjects were considered as severely disabled. Mild to moderate correlations between BF and A&P were reported (between 0.148 and 0.394 when the full range of impairments/limitations was taken into account; between 0.198 and 0.285 when only the severe impairments/limitations were taken into account); performance-WPS was less similar to performance than to capacity. Our approach enabled identifying subjects with “severe disability” and separating the effect of personal support from that of devices, policies, and service provision

The International Classification of Functioning Disability and Health, version for children and youth as a roadmap for projecting and programming rehabilitation in a neuropaediatric hospital unit.

Objective To test the impact of introducing a format based on the International Classification of Functioning Disability and Health, version for children and youth (ICF-CY) as a road-map for in-hospital paediatric neuro-rehabilitation on target definition, intra-team communication and workload as perceived by involved professionals. Design Single-centre pilot testing with impact assessment. Patients Team members of a tertiary care paediatric neurorehabilitation unit included 15 consecutive patients with severe neurological conditions. Methods An ICF-CY based format for rehabilitation projection and programming was constructed and tested for 12 months. The format comprises 3 sections: project, programme, and follow-up. Impact on the rehabilitation team was assessed with a questionnaire. Results All cases were described according to their specific needs with appropriate ICF-CY codes, and the interventions were linked to needs and targets. ICF-CY was judged an efficient tool in providing a road-map for rehabilitation in this setting, although concern was voiced about timing and workload. Conclusion ICF-CY may work as a road-map for in-hospital paediatric neuro-rehabilitation. Its implementation results in perceived improvements in the process. Training requirements and accurate evaluation of timing, workload and organizational context are critical issues that should be addressed before results from the present experience are generalized

Best practices for the manual curation of Intrinsically Disordered Proteins in DisProt

The DisProt database is a significant resource containing manually curated data on experimentally validated intrinsically disordered proteins (IDPs) and regions (IDRs) from the literature. Developed in 2005, its primary goal was to collect structural and functional information into proteins that lack a fixed three-dimensional (3D) structure. Today, DisProt has evolved into a major repository that not only collects experimental data but also contributes significantly to our understanding of the IDPs/IDRs roles in various biological processes, such as autophagy or the life cycle mechanisms in viruses, or their involvement in diseases (such as cancer and neurodevelopmental disorders). DisProt offers detailed information on the structural states of IDPs/IDRs, including state transitions, interactions, and their functions, all provided as curated annotations. One of the central activities of DisProt is the meticulous curation of experimental data from the literature. For this reason, to ensure that every expert and volunteer curator possesses the requisite knowledge for data evaluation, collection, and integration, training courses and curation materials are available. However, biocuration guidelines concur on the importance of developing robust guidelines that not only provide critical information about data consistency but also ensure data acquisition.This guideline aims to provide both biocurators and external users with best practices for manually curating IDPs and IDRs in DisProt. It describes every step of the literature curation process and provides use cases of IDP curation within DisProt. Database URL: https://disprot.org

Developmental and oncogenic effects of Insulin-like Growth Factor-I in Ptc1+/- mouse cerebellum

<p>Abstract</p> <p>Background</p> <p>Medulloblastoma is amongst the most common malignant brain tumors in childhood, arising from neoplastic transformation of granule neuron precursors (GNPs) of the cerebellum <it>via </it>deregulation of pathways involved in cerebellar development. Deregulation of the Sonic hedgehog/Patched1 (Shh/Ptc1) signaling pathway predisposes humans and mice to medulloblastoma. In the brain, insulin-like growth factor (IGF-I) plays a critical role during development as a neurotrophic and neuroprotective factor, and in tumorigenesis, as IGF-I receptor is often activated in medulloblastomas.</p> <p>Results</p> <p>To investigate the mechanisms of genetic interactions between Shh and IGF signaling in the cerebellum, we crossed nestin/IGF-I transgenic (IGF-I Tg) mice, in which transgene expression occurs in neuron precursors, with <it>Ptc1</it>^{<it>+/- </it>}knockout mice, a model of medulloblastoma in which cancer develops in a multistage process. The IGF-I transgene produced a marked brain overgrowth, and significantly accelerated tumor development, increasing the frequency of pre-neoplastic lesions as well as full medulloblastomas in <it>Ptc1</it>^<it>+/-</it>/IGF-I Tg mice. Mechanistically, tumor promotion by IGF-I mainly affected preneoplastic stages through <it>de novo </it>formation of lesions, while not influencing progression rate to full tumors. We also identified a marked increase in survival and proliferation, and a strong suppression of differentiation in neural precursors.</p> <p>Conclusions</p> <p>As a whole, our findings indicate that IGF-I overexpression in neural precursors leads to brain overgrowth and fosters external granular layer (EGL) proliferative lesions through a mechanism favoring proliferation over terminal differentiation, acting as a landscape for tumor growth. Understanding the molecular events responsible for cerebellum development and their alterations in tumorigenesis is critical for the identification of potential therapeutic targets.</p

PARP-1 cooperates with Ptc1 to suppress medulloblastoma and basal cell carcinoma

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