Nusinersen Modulates Proteomics Profiles of Cerebrospinal Fluid in Spinal Muscular Atrophy Type 1 Patients

Spinal muscular atrophy (SMA) type 1 is a severe infantile autosomal-recessive neuromuscular disorder caused by a survival motor neuron 1 gene (SMN1) mutation and characterized by progressive muscle weakness. Without supportive care, SMA type 1 is rapidly fatal. The antisense oligonucleotide nusinersen has recently improved the natural course of this disease. Here, we investigated, with a functional proteomic approach, cerebrospinal fluid (CSF) protein profiles from SMA type 1 patients who underwent nusinersen administration to clarify the biochemical response to the treatment and to monitor disease progression based on therapy. Six months after starting treatment (12 mg/5 mL × four doses of loading regimen administered at days 0, 14, 28, and 63), we observed a generalized reversion trend of the CSF protein pattern from our patient cohort to that of control donors. Notably, a marked up-regulation of apolipoprotein A1 and apolipoprotein E and a consistent variation in transthyretin proteoform occurrence were detected. Since these multifunctional proteins are critically active in biomolecular processes aberrant in SMA, i.e., synaptogenesis and neurite growth, neuronal survival and plasticity, inflammation, and oxidative stress control, their nusinersen induced modulation may support SMN improved-expression effects. Hence, these lipoproteins and transthyretin could represent valuable biomarkers to assess patient responsiveness and disease progression.     

Effect of Heat Treatment on the Electrochemical and Mechanical Behavior of the Ti6Al4V Alloy

Metallurgical and Materials Transactions A - The effects of heat treatment on the hardness and electrochemical behavior of the Ti6Al4V alloy were studied. Two heat treatments were performed: one...     

Energy Dissipation in Shape Memory Alloy Devices

A way of reasoning to reduce the response of a structural system under dynamic excitation is to think in terms of energy dissipation via plastic deformation devices. The concept of recoverable plastic deformation opens the way to the application of smart materials and, in particular, of shape memory alloys (SMAs). The characterization of the TiNi alloy structural component, with a complete definition of its mechanical properties and assembling features, is discussed.     

Focusing bistatic synthetic aperture radar using dip move out

The appearance of new synthetic aperture radar (SAR) acquisition techniques based on opportunity sources enhances interest in bistatic geometries. In seismic data acquisition, each source is currently accompanied by up to 10 000 receivers, and in the last two decades, the bistatic geometry has been carefully studied by scores of authors. Rather then introducing new focusing techniques, within the first-order Born approximation (no multiple reflections), seismic bistatic acquisitions are transformed into monostatic ones using a simple operator named "dip move out" (DMO). In essence, the elliptical locus of the reflectors corresponding to a spike in the bistatic survey is forward modeled as if observed in a monostatic one. The outcome of the model, the so-called smile, is a short operator, slowly time varying but space stationary. To transform a bistatic survey into a monostatic one, it is enough to convolve the initial dataset with this smile. Based on the well-known similarity between seismic and SAR surveys, DMO is first described in its simple geometric understanding and is then used in the SAR case. The same processing that is being used for movement compensation can be applied to the bistatic to monostatic survey transformation. Synthetic examples are also provided.     

Reaction of anti-phosphatidyl inositol antisera with neural membranes

Ca. 15% of the phosphatidyl inositol in myelin and microsomal membranes from rat brain was detectable by antiphosphatidyl inositol antibody. Antibody-detectable phosphatidyl inositol in myelin and microsomes readily increased when the membranes were incubated at 45 C with the antiserum. Synaptic membranes also had only a limited capacity to adsorb antibody. Quantitative binding studies with synaptic membranes and mitochondria were limited, because these membranes contain cardiolipin, which cross reacts with phosphatidyl inositol antisera. Moreover, highly purified synaptic and mitochondrial membranes contain appreciable amounts of other membrane fractions.     

Development and characterization of a microthermoelectric generator with plated copper/constantan thermocouples

This work reports the development and the characterization of a microthermoelectric generator (μTEG) based on planar technology using electrochemically deposited constantan and copper thermocouples on a micro machined silicon substrate with a SiO₂/Si₃N₄/SiO₂ thermally insulating membrane to create a thermal gradient. The μTEG has been designed and optimized by finite element simulation in order to exploit the different thermal conductivity of silicon and membrane in order to obtain the maximum temperature difference on the planar surface between the hot and cold junctions of the thermocouples. The temperature difference was dependent on the nitrogen (N₂) flow velocity applied to the upper part of the device. The fabricated thermoelectric generator presented maximum output voltage and power of 118 mV/cm² and of 1.1 μW/cm², respectively, for a device with 180 thermocouples, 3 kΩ of internal resistance, and under a N₂ flow velocity of 6 m/s. The maximum efficiency (performance) was 2 × 10^?3 μW/cm² K².     

Advances in decoherence control

Abstract

I address the current status of dynamical decoupling techniques in terms of required control resources and feasibility. Based on recent advances in both improving the theoretical design and assessing the control performance for specific noise models, I argue that significant progress may still be possible on the road to implementing decoupling under realistic constraints.     

Network Analysis of Gut Microbiome and Metabolome to Discover Microbiota-Linked Biomarkers in Patients Affected by Non-Small Cell Lung Cancer

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.     

Biochemical and sensorial evaluation of intact and boned broiler breast meat tenderness during ageing

Meat tenderness is the main characteristic demanded by consumers and is affected by rigor mortis development and proteolysis activities, both of which occur during carcass refrigeration. In this work, we demonstrate that broiler breast fillet tenderness can be further increased and its extension depends on whether or not meat is excised from the carcass. Post-harvest samples taken from 0 to 72 h after slaughtering and kept refrigerated at 2 ± 2 °C were evaluated for tenderness by myofibrillar fragmentation index determination, shear force analysis and sensorial testing. The 24 h post-harvested intact samples were 30.6% more tender than excised samples and 41.7% more tender than control samples (p ? 0.05). The myofibrillar fragments index was 13.2% higher in intact samples than in deboned fillet (p ? 0.05) and a sensory test showed that the 24 h intact samples were of major acceptability. Our results demonstrated that tenderness was best achieved with intact breast fillet samples stored at 2 ± 2 °C for 24 h.