Prion expression is activated by Adenovirus 5 infection and affects the adenoviral cycle in human cells

The prion protein is a cell surface glycoprotein whose physiological role remains elusive, while its implication in transmissible spongiform encephalopathies (TSEs) has been demonstrated. Multiple interactions between the prion protein and viruses have been described: viruses can act as co-factors in TSEs and life cycles of different viruses have been found to be controlled by prion modulation. We present data showing that human Adenovirus 5 induces prion expression. Inactivated Adenovirus did not alter prion transcription, while variants encoding for early products did, suggesting that the prion is stimulated by an early adenoviral function. Down-regulation of the prion through RNA interference showed that the prion controls adenovirus replication and expression. These data suggest that the prion protein could play a role in the defense strategy mounted by the host during viral infection, in a cell autonomous manner. These results have implications for the study of the prion protein and of associated TSEs

A novel application method for wearable bend sensors

Bend sensors fundamental characteristic is to furnish an electrical resistance value related to the angle they are bent. This feature can be successfully exploited to realize wearable systems capable to measure human static and dynamic postures. In particular some efforts have been made to determine finger joint movements of human hands and it has been demonstrated the feasibility of using the so called data glove system as a goniometric device. The repeatability of such system is quite good for general purposes but it is still not sufficient for specific applications (for instance in virtual surgery). So here we introduce a novel application method of bend sensors and demonstrate how it can be useful to improve the system repeatabilit

In vitro analysis of pyrogenicity and cytotoxicity profiles of flex sensors to be used to sense human joint postures

Flex sensors can be usefully adopted as mechanical-electrical transducers to measure human joint movements, since their electrical resistance varies proportionally to the angle assumed by the joint under measure. Over time, these sensors have been investigated in terms of mechanical and electrical behavior, but no reports have detailed the possibility of their adoption not just on top but under the human skin of the joint. To this aim, our work investigated in vitro the pyrogenic potential and cytotoxicity of some commercially available flex sensors as a first step toward the necessary requirements regarding their biocompatibility, to predict possible foreign body reactions when used in vivo. Results demonstrated that some specific flex sensors satisfy such requirement

Interplay of the nuclear envelope with chromatin in physiology and pathology

The nuclear envelope compartmentalizes chromatin in eukaryotic cells. The main nuclear envelope components are lamins that associate with a panoply of factors, including the LEM domain proteins. The nuclear envelope of mammalian cells opens up during cell division. It is reassembled and associated with chromatin at the end of mitosis when telomeres tether to the nuclear periphery. Lamins, LEM domain proteins, and DNA binding factors, as BAF, contribute to the reorganization of chromatin. In this context, an emerging role is that of the ESCRT complex, a machinery operating in multiple membrane assembly pathways, including nuclear envelope reformation. Research in this area is unraveling how, mechanistically, ESCRTs link to nuclear envelope associated factors as LEM domain proteins. Importantly, ESCRTs work also during interphase for repairing nuclear envelope ruptures. Altogether the advances in this field are giving new clues for the interpretation of diseases implicating nuclear envelope fragility, as laminopathies and cancer

Support vector machines to detect physiological patterns for EEG and EMG-based human-computer interaction:a review

Support vector machines (SVMs) are widely used classifiers for detecting physiological patterns in human-computer interaction (HCI). Their success is due to their versatility, robustness and large availability of free dedicated toolboxes. Frequently in the literature, insufficient details about the SVM implementation and/or parameters selection are reported, making it impossible to reproduce study analysis and results. In order to perform an optimized classification and report a proper description of the results, it is necessary to have a comprehensive critical overview of the applications of SVM. The aim of this paper is to provide a review of the usage of SVM in the determination of brain and muscle patterns for HCI, by focusing on electroencephalography (EEG) and electromyography (EMG) techniques. In particular, an overview of the basic principles of SVM theory is outlined, together with a description of several relevant literature implementations. Furthermore, details concerning reviewed papers are listed in tables and statistics of SVM use in the literature are presented. Suitability of SVM for HCI is discussed and critical comparisons with other classifiers are reported

Robust and language-independent acoustic features in Parkinson's disease

Introduction: The analysis of vocal samples from patients with Parkinson's disease (PDP) can be relevant in supporting early diagnosis and disease monitoring. Intriguingly, speech analysis embeds several complexities influenced by speaker characteristics (e.g., gender and language) and recording conditions (e.g., professional microphones or smartphones, supervised, or non-supervised data collection). Moreover, the set of vocal tasks performed, such as sustained phonation, reading text, or monologue, strongly affects the speech dimension investigated, the feature extracted, and, as a consequence, the performance of the overall algorithm. Methods: We employed six datasets, including a cohort of 176 Healthy Control (HC) participants and 178 PDP from different nationalities (i.e., Italian, Spanish, Czech), recorded in variable scenarios through various devices (i.e., professional microphones and smartphones), and performing several speech exercises (i.e., vowel phonation, sentence repetition). Aiming to identify the effectiveness of different vocal tasks and the trustworthiness of features independent of external co-factors such as language, gender, and data collection modality, we performed several intra- and inter-corpora statistical analyses. In addition, we compared the performance of different feature selection and classification models to evaluate the most robust and performing pipeline. Results: According to our results, the combined use of sustained phonation and sentence repetition should be preferred over a single exercise. As for the set of features, the Mel Frequency Cepstral Coefficients demonstrated to be among the most effective parameters in discriminating between HC and PDP, also in the presence of heterogeneous languages and acquisition techniques. Conclusion: Even though preliminary, the results of this work can be exploited to define a speech protocol that can effectively capture vocal alterations while minimizing the effort required to the patient. Moreover, the statistical analysis identified a set of features minimally dependent on gender, language, and recording modalities. This discloses the feasibility of extensive cross-corpora tests to develop robust and reliable tools for disease monitoring and staging and PDP follow-up

Changes in gene expression in human skeletal stem cells transduced with constitutively active Gs\u3b1 correlates with hallmark histopathological changes seen in fibrous dysplastic bone

Fibrous dysplasia (FD) of bone is a complex disease of the skeleton caused by dominant activating mutations of the GNAS locus encoding for the \u3b1 subunit of the G protein-coupled receptor complex (Gs\u3b1). The mutation involves a substitution of arginine at position 201 by histidine or cysteine (Gs\u3b1R201H or R201C), which leads to overproduction of cAMP. Several signaling pathways are implicated downstream of excess cAMP in the manifestation of disease. However, the pathogenesis of FD remains largely unknown. The overall FD phenotype can be attributed to alterations of skeletal stem/progenitor cells which normally develop into osteogenic or adipogenic cells (in cis), and are also known to provide support to angiogenesis, hematopoiesis, and osteoclastogenesis (in trans). In order to dissect the molecular pathways rooted in skeletal stem/progenitor cells by FD mutations, we engineered human skeletal stem/progenitor cells with the Gs\u3b1R201C mutation and performed transcriptomic analysis. Our data suggest that this FD mutation profoundly alters the properties of skeletal stem/progenitor cells by pushing them towards formation of disorganized bone with a concomitant alteration of adipogenic differentiation. In addition, the mutation creates an altered in trans environment that induces neovascularization, cytokine/chemokine changes and osteoclastogenesis. In silico comparison of our data with the signature of FD craniofacial samples highlighted common traits, such as the upregulation of ADAM (A Disintegrin and Metalloprotease) proteins and other matrix-related factors, and of PDE7B (Phosphodiesterase 7B), which can be considered as a buffering process, activated to compensate for excess cAMP. We also observed high levels of CEBPs (CCAAT-Enhancer Binding Proteins) in both data sets, factors related to browning of white fat. This is the first analysis of the reaction of human skeletal stem/progenitor cells to the introduction of the FD mutation and we believe it provides a useful background for further studies on the molecular basis of the disease and for the identification of novel potential therapeutic targets

Class 1, 2, and 3 BRAF-mutated metastatic colorectal cancer: A detailed clinical, pathologic, and molecular characterization

Purpose: BRAF mutations are grouped in activating RASindependent signaling as monomers (class 1-V600E) or as dimers (class 2-codons 597/601), and RAS-dependent with impaired kinase activity (class 3-codons 594/596). Although clinical, pathologic, and molecular features of V600EBRAFmutated metastatic colorectal cancer (mCRC) are well known, limited data are available from the two other classes. Experimental Design: Data from 117 patients with BRAF (92 class 1, 12 class 2, and 13 class 3)-mutated mCRC were collected. A total of 540 BRAF wt mCRCs were included as control. IHC profiling was performed to determine the consensus molecular subtypes (CMS), cytokeratin 7/20 profiles, tumor-infiltrating lymphocyte infiltration, and BM1/BM2 categorization. Overall survival (OS) and progression-free survival were evaluated by Kaplan-Meier and log-rank test. Results: Class 3 BRAF-mutated mCRC was more frequently left sided (P = 0.0028), pN0 (P = 0.0159), and without peritoneal metastases (P = 0.0176) compared with class 1, whereas class 2 cases were similar to class 1. Hazard ratio for OS, as compared with BRAF wt, was 2.38 [95% confidence interval (CI), 1.61-3.54] for class 1, 1.90 (95% CI, 0.85-4.26) for class 2, and 0.93 (95% CI, 0.51-1.69) for class 3 (P < 0.0001). Class 2 and 3 tumors were all assigned to CMS2-3. A higher median CD3/CD8-positive lymphocyte infiltration was observed in BRAF-mutated class 2 (P = 0.033) compared with class 3 cases. Conclusions: For the first time, different clinical and pathologic features and outcome data were reported according to the three BRAF mutation classes in mCRC. Specific targeted treatment strategies should be identified in the near future for such patients

Study of the B +→ J / ψ Λ ¯ p decay in proton-proton collisions at √s = 8 TeV

A study of the B +→ J / ψ Λ ¯ p decay using proton-proton collision data collected at s = 8 TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 19.6 fb−1, is presented. The ratio of branching fractions B(B+→J/ψΛ¯p)/B(B+→J/ψK∗(892)+) is measured to be (1.054 ± 0.057(stat) ± 0.035(syst) ± 0.011(B))%, where the last uncertainty reflects the uncertainties in the world-average branching fractions of Λ ¯ and K*(892) + decays to reconstructed final states. The invariant mass distributions of the J / ψ Λ ¯ , J/ψp, and Λ ¯ p systems produced in the B +→ J / ψ Λ¯ p decay are investigated and found to be inconsistent with the pure phase space hypothesis. The analysis is extended by using a model-independent angular amplitude analysis, which shows that the observed invariant mass distributions are consistent with the contributions from excited kaons decaying to the Λ ¯ p system. [Figure not available: see fulltext.