Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Rilievo fotogrammetrico e visualizzazione in autostereoscopia di piccole sculture. La Venere di Frasassi come pilot-case per i Musei Archeologici

La valorizzazione dell’archeologia necessita di nuovi strumenti per l’acquisizione 3D. L’articolo presenta un workflow per la digitalizzazione di piccoli reperti archeologici finalizzati al contesto museale. La principale novità è costituita dall’impiego di un monitor 3D autostereoscopico. Ricerche come queste mirano a superare alcune difficoltà proprie dei musei archeologici nel coinvolgimento dei visitatori, attraverso l’uso di repliche virtuali

Functional Analysis for Habitat Mapping in a Special Area of Conservation Using Sentinel-2 Time-Series Data

The mapping and monitoring of natural and semi-natural habitats are crucial activities and are regulated by European policies and regulations, such as the 92/43/EEC. In the Mediterranean area, which is characterized by high vegetational and environmental diversity, the mapping and monitoring of habitats are particularly difficult and often exclusively based on in situ observations. In this scenario, it is necessary to automate the generation of updated maps to support the decisions of policy makers. At present, the availability of high spatiotemporal resolution data provides new possibilities for improving the mapping and monitoring of habitats. In this work, we present a methodology that, starting from remotely sensed time-series data, generates habitat maps using supervised classification supported by Functional Data Analysis. We constructed the methodology using Sentinel-2 data in the Mediterranean Special Area of Conservation &ldquo;Gola di Frasassi&rdquo; (Code: IT5320003). In particular, the training set uses 308 field plots with 11 target classes (five forests, two shrubs, one grassland, one mosaic, one extensive crop, and one urban land). Starting from vegetation index time-series data, Functional Principal Component Analysis was applied to derive FPCA scores and components. In particular, in the classification stage, the FPCA scores are considered as features. The obtained results out-performed a previous map derived from photo-interpretation by domain experts. We obtained an overall accuracy of 85.58% using vegetation index time-series, topography, and lithology data. The main advantages of the proposed approach are the capability to efficiently compress high dimensional data (dense remote-sensing time series) providing results in a compact way (e.g., FPCA scores and mean seasonal time profiles) that: (i) facilitate the link between remote sensing with habitat mapping and monitoring and their ecological interpretation and (ii) could be complementary to species-based approaches in plant community ecology and phytosociology

Virtualization and Vice Versa: A New Procedural Model of the Reverse Virtualization for the User Behavior Tracking in the Virtual Museums

In this paper we present a method of the user behavior (UB) tracking by capturing and measuring user activities through the defined procedural model of the reverse virtualization process, implementing a proof of concept on a real case scenario: the Civic Gallery of Ascoli. In order to define the universal model of such “vice versa” virtual reality (VR) experience, we assigned particular descriptive functions (descriptors) to each interactive feature of the virtual user space. In this virtualization phase we store user interaction information locally using the web-socket streams protocol, ensuring complete control and manipulation of monitored functions. Our algorithm firstly collects the user interaction data and extracts the descriptors’ arguments into the indexed vector of corresponding variables. The next step determines UB pattern by solving the inverse descriptive functions in combination with an appropriate statistical analysis of gathered data. The final result of the proposed method is the repository of salient data that is used in the further user experience improvement, as well as to enable the museums to distinguish the most important points of the visitor interest in the virtual web tours. Our approach also offers a potential benefit of obtained results in an automatic calculation and prediction of UB patterns using artificial intelligence (AI

RSV- and BPZE1-induced signaling pathways in MDDC.

<p><b>A</b>: Total cell lysates were prepared from MDDC treated with BPZE1 (100∶1), RSV (MOI of 1) or both at the indicated time-points. Mock-infected cells were added as control. Proteins were resolved by 10% SDS-PAGE and Western blot analysis was performed to detect the phosphorylation of STAT1, IkBα, ERK1/2 and p38. Human phosphorylated β actin was used to normalize the results. Data are from one representative of three independent experiments performed with MDDC obtained from different donors. <b>B</b>: Histograms represent means of the relative optical density of phosphorylated proteins from three independent experiments. Error bars represent SEM.</p

Impact of BPZE1 on RSV-induced T lymphocyte polarization.

<p>MDDC were treated with BPZE1 (bacteria/cell ratio of 100∶1), RSV (MOI of 1) or both. Mock-infected cells were added as control. After 48 h, treated MDDC were cultured with purified allogeneic CD3 T cells. On day12, supernatants were collected, and IFN-γ (Th1), IL-5 (Th2) and IL-17 (Th17) were measured by ELISA. Values are expressed as medians with interquartile range of 13 independent experiments performed with MDDC obtained from different donors and expressed as ng/ml (IFNγ) or pg/ml (IL-5 and IL-17). Statistical significant differences are indicated by * (<i>P</i>≤0.0083).</p

Impact of BPZE1 on phenotypic maturation of RSV-infected MDDC.

<p>MDDC were treated with BPZE1 (bacteria/cell ratio 100∶1), RSV (MOI of 1) or both. After 24 h, cells were analyzed for the indicated surface markers associated with a mature phenotype. Mock-infected cells were used as control. Fluorescence data are reported as median fluorescence intensity (MedFI) for CD80 and CD38, and as percentage of positive cells for CD83. Values are expressed as medians with interquartile range of seven independent experiments performed with MDDC obtained from different donors. Statistical significant differences are indicated by * (<i>P</i>≤0.0083).</p

RSV- and BPZE1-induced IL-6, IFNβ, CCL5, IL-12p40 and IL-12p35 gene expression in MDDC.

<p>MDDC were treated with BPZE1 (100∶1), RSV (MOI of 1) or both. Mock-infected cells were added as control. Total RNA was extracted at the indicated time points. Kinetics of mRNA expression for p40 and p35 subunits of IL-12p70, IL-6, IFNβ and CCL5 was evaluated by real-time quantitative RT-PCR. The mRNA transcripts were normalized with respect to the endogenous reference (human β actin) sample. Data were expressed as fold increase (mean ± SEM of four experiments) with respect to mock-treated cells at 5 h.</p