Common Muscle Metabolic Signatures Highlight Arginine and Lysine Metabolism as Potential Therapeutic Targets to Combat Unhealthy Aging

Biological aging research is expected to reveal modifiable molecular mechanisms that can be harnessed to slow or possibly reverse unhealthy trajectories. However, there is first an urgent need to define consensus molecular markers of healthy and unhealthy aging. Established aging hallmarks are all linked to metabolism, and a ‘rewired’ metabolic circuitry has been shown to accelerate or delay biological aging. To identify metabolic signatures distinguishing healthy from unhealthy aging trajectories, we performed nontargeted metabolomics on skeletal muscles from 2-month-old and 21-month-old mice, and after dietary and lifestyle interventions known to impact biological aging. We hypothesized that common metabolic signatures would highlight specific pathways and processes promoting healthy aging, while revealing the molecular underpinnings of unhealthy aging. Here, we report 50 metabolites that commonly distinguished aging trajectories in all cohorts, including 18 commonly reduced under unhealthy aging and 32 increased. We stratified these metabolites according to known relationships with various aging hallmarks and found the greatest associations with oxidative stress and nutrient sensing. Collectively, our data suggest interventions aimed at maintaining skeletal muscle arginine and lysine may be useful therapeutic strategies to minimize biological aging and maintain skeletal muscle health, function, and regenerative capacity in old age.     

De Novo Missense Mutations in TNNC1 and TNNI3 Causing Severe Infantile Cardiomyopathy Affect Myofilament Structure and Function and Are Modulated by Troponin Targeting Agents

Rare pediatric non-compaction and restrictive cardiomyopathy are usually associated with a rapid and severe disease progression. While the non-compaction phenotype is characterized by structural defects and is correlated with systolic dysfunction, the restrictive phenotype exhibits diastolic dysfunction. The molecular mechanisms are poorly understood. Target genes encode among others, the cardiac troponin subunits forming the main regulatory protein complex of the thin filament for muscle contraction. Here, we compare the molecular effects of two infantile de novo point mutations in TNNC1 (p.cTnC-G34S) and TNNI3 (p.cTnI-D127Y) leading to severe non-compaction and restrictive phenotypes, respectively. We used skinned cardiomyocytes, skinned fibers, and reconstituted thin filaments to measure the impact of the mutations on contractile function. We investigated the interaction of these troponin variants with actin and their inter-subunit interactions, as well as the structural integrity of reconstituted thin filaments. Both mutations exhibited similar functional and structural impairments, though the patients developed different phenotypes. Furthermore, the protein quality control system was affected, as shown for TnC-G34S using patient’s myocardial tissue samples. The two troponin targeting agents levosimendan and green tea extract (-)-epigallocatechin-3-gallate (EGCg) stabilized the structural integrity of reconstituted thin filaments and ameliorated contractile function in vitro in some, but not all, aspects to a similar degree for both mutations.     

A theoretically-based novel protocol for the analytic treatment of the glass failure stresses associated with coaxial double ring test method

With the aim of validating a new standardized Coaxial Double Ring testing procedure, without overpressure and with fixed geometry, an ad hoc theoretical approach has been proposed here to rearrange the laboratory outcomes accounting for the effects of the geometric non-linearities associated with such a testing configuration. By borrowing this idea, once the experimental values of the failure load have been determined, it has been possible to obtain an expression in closed form (fully defined by only two coefficients) of the maximum tensile stress (σ_max) in the core of the specimen. Following this, in order to make the laboratory outcomes comparable and homogeneous, the σ_max-values have been then re-scaled to a common reference condition (equibiaxial stress on a reference area, σ_eqbx), by means of the use of a correction coefficient (K) able to determine, under a condition of equal probability of failure, the effective area (A_eff) of the tested specimens. After being corrected to account for the effects of the stress corrosion cracking (static fatigue effect), all re-scaled data have been finally interpreted using a Weibull-type statistical distribution to determine the main fractile values of the glass strength. Doing so, despite some unavoidable approximations, this procedure furnished a highly effective means of determining the bending strength of float glass. Unlike the pure numerical approach proposed in codes and literature, which requires to correct the experimental data via FEM simulation, the rationale behind the proposed approach is in fact to elaborate the experimental data through an analytic treatment of the problem, which would greatly facilitate the interpretation of the data as well as the standardization of the testing procedure.     

The territorial and landscape impacts of photovoltaic systems: Definition of impacts and assessment of the glare risk

The installation and operation of systems that exploit solar energy through photovoltaic conversion, recently promoted in some European countries by new sell-back tariffs, is a relevant transformation of the territory for various reasons (land use, elimination of the existing vegetation, visual impact on the components of the landscape, microclimate change, glare from the reflection of the direct sunlight). The weak energy intensity of the solar source coupled with the low conversion efficiency of the photovoltaic cells, make the physical dimensions of such systems relevant and, with them, also the environmental, territorial and landscape impacts that basically depend on the physical extent of the system. If it is well known that an incentive to the exploitation of renewable sources is one of the features of the policy of land conservation, including the one of the protected areas, at the same time the concerns of local communities and governments about the environmental, territorial and landscape impacts of this technology are increasing rapidly.Given this picture, this work is intended to clarify the territorial impacts of the ground mounted photovoltaic systems. Later, the paper concentrates on a specific impact, which is the assessment of the risk of glare by reflection of direct sunlight from the surfaces of photovoltaic modules. The methodologies that can be used to assess this impact and the outcomes of an evaluation carried out for a 5000 m² PV system currently designed on a hilly territory in Italy are presented.     

Evaluation of the laboratory prediction of surface properties of bituminous mixtures

An experimental and analytical investigation was carried out both in laboratory and in situ on wearing courses. The approach presented in this paper aims to predict the in situ density and surface properties of bituminous layers, during the phase of mix design in laboratory. Therefore, the main attempt of this study is to identify, amongst the commonly available laboratory equipments, the most adequate for producing specimens that, used for carrying out simple and reliable laboratory test, allow the prediction of the surface characteristics of the mixture as laid on site.This is done by comparing the data collected from an experimental site with those calculated from laboratory specimens compacted with the superpave gyratory compactor (SGC).Typical laboratory tests (such as the sand patch method and the skid test) as well as the surface data obtained with a laser profilometer have been considered for characterizing the properties of a standard Italian wearing course, laid in two different final thicknesses and produced with the most common raw materials, according to the currently used techniques for mixtures production and laying process for maintenance work. An evaluation of the SGC ability to represent the density and surface properties of the mixture once on site is then discussed.     

The assessment of the damage probability of storage tanks in domino events triggered by fire

An approach aimed to the quantitative assessment of the risk caused by escalation scenarios triggered by fire was developed. Simplified models for the estimation of the vessel time to failure (ttf) with respect to the radiation intensity on the vessel shell were obtained using a multi-level approach to the analysis of vessel wall failure under different fire conditions. Each vessel “time to failure” calculated by this approach for the specific fire scenario of concern was compared to a reference time required for effective mitigation actions and related to the escalation probability. The failure probability of each vessel was correlated to the probability of scenarios involving multiple vessel failure as a consequence of the primary fire, thus allowing a comprehensive assessment of domino scenarios triggered by fire. The application of the methodology to the analysis of several case-studies allowed the estimation of the quantitative contribution of escalation events triggered by fire to the overall individual and societal risk indexes.     

Spatial resolution enhancement of ultrasound images using neural networks

Spatial resolution in modern ultrasound imaging systems is limited by the high cost of large aperture transducer arrays, which require a large number of transducer elements and electronic channels. A new technique to enhance the spatial resolution of pulse-echo imaging systems is presented. The method attempts to build an image that could be obtained with a transducer array aperture larger than that physically available. We consider two images of the same object obtained with two different apertures, the full aperture and a subaperture, of the same transducer. A suitable artificial neural network (ANN) is trained to reproduce the relationship between the image obtained with the transducer full aperture and the image obtained with a subaperture. The inputs of the neural network are portions of the image obtained with the subaperture (low resolution image), and the target outputs are the corresponding portions of the image produced by the full aperture (high resolution image). After the network is trained, it can produce images with almost the same resolution of the full aperture transducer, but using a reduced number of real transducer elements. All computations are carried out on envelope-detected decimated images; for this reason, the computational cost is low and the method is suitable for real-time applications. The proposed method was applied to experimental data obtained with the ultrasound synthetic aperture focusing technique (SAFT), giving quite promising results. Realtime implementation on a modern, full-digital echographic system is currently being developed.     

Absolute measurement of planarity with Fritz's method: uncertainty evaluation

Fritz's method [Opt. Eng. 23, 379 (1984)] of using Zernike polynomials to assess the absolute planarity of test plates is revisited. A refinement is described that takes into account the data decorrelation that appears in experiments. An uncertainty balance is defined by propagation of error contributions through the steps of the method. The resultant measuring procedure is demonstrated on a data set from experiments, and a nanometer level of uncertainty is achieved.     

Interaction between low-profile agents and glass fibres in polyester-based composites

Scanning electron microscope and differential scanning calorimetry studies were used to study the morphology and thermal properties of cured systems constituted of different unsaturated polyester formulations, two conventional low-shrink additives and one suitably synthetized additive. The aim was to clarify the influence of these low-profile agents on the resulting phase structure and on the thermal behaviour of the systems. Moreover, the influence was investigated of low-profile agents on the fibre/matrix adhesion in composite materials reinforced with glass fibres coated by silane coupling agents.