Discovery of an Allosteric Ligand Binding Site in SMYD3 Lysine Methyltransferase

SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (K_D=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (K_D=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action.     

Computing optical flow across multiple scales: An adaptive coarse-to-fine strategy

Single-scale approaches to the determination of the optical flow field from the time-varying brightness pattern assume that spatio-temporal discretization is adequate for representing the patterns and motions in a scene. However, the choice of an appropriate spatial resolution is subject to conflicting, scene-dependent, constraints. In intensity-base methods for recovering optical flow, derivative estimation is more accurate for long wavelengths and slow velocities (with respect to the spatial and temporal discretization steps). On the contrary, short wavelengths and fast motions are required in order to reduce the errors caused by noise in the image acquisition and quantization process.Estimating motion across different spatial scales should ameliorate this problem. However, homogeneous multiscale approaches, such as the standard multigrid algorithm, do not improve this situation, because an optimal velocity estimate at a given spatial scale is likely to be corrupted at a finer scale. We propose an adaptive multiscale method, where the discretization scale is chosen locally according to an estimate of the relative error in the velocity estimation, based on image properties.Results for synthetic and video-acquired images show that our coarse-to-fine method, fully parallel at each scale, provides substantially better estimates of optical flow than do conventional algorithms, while adding little computational cost.     

Zeolite filled siloxane composite foams: Compression property

In this article, mechanical behavior under compression loads of an innovative adsorbent material, based on silicone composite foams filled with SAPO 34 zeolite, is presented. The innovative composite foams were obtained profiting by the dehydrogenative coupling of siloxane constituents. These new adsorbent systems have been proposed to overcome to the low mechanical stability of conventional SAPO‐34 coating for adsorption chiller. In this concern, static and cyclic compressive tests at room temperature have been carried out. Samples at increasing content of SAPO 34 zeolite were tested to evaluate the influence of the filler content on the mechanical behavior of the composite foam. The results showed that the presence of zeolite reduces the elastic limit of the foam and increases the strength. The foams evidenced also acceptable mechanical stability to cyclic compressive loads. The encouraging results confirm the possible use of these new composite foams as adsorbent materials for cyclic adsorption heat pumps. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46145.     

Lung Microbiome in Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases

Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host–microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.     

Probiotics Function in Preventing Atopic Dermatitis in Children

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by relapsing eczematous injuries and severe pruritus. In the last few years, the AD prevalence has been increasing, reaching 20% in children and 10% in adults in high-income countries. Recently, the potential role of probiotics in AD prevention has generated considerable interest. As many clinical studies show, the gut microbiota is able to modulate systemic inflammatory and immune responses influencing the development of sensitization and allergy. Probiotics are used increasingly against AD. However, the molecular mechanisms underlying the probiotics mediated anti-allergic effect remain unclear and there is controversy about their efficacy. In this narrative review, we examine the actual evidence on the effect of probiotic supplementation for AD prevention in the pediatric population, discussing also the potential biological mechanisms of action in this regard.     

Comparison and optimization of different methods of evaluation of displacements in cracked reinforced concrete beams

The evaluation of deflections of reinforced concrete beams is strongly affected by the cracking of concrete; in order to develop a correct calculation of deflections, it is necessary to define an adequate tension stiffening model and exact, prediction of the values of cracking moment and of Young's modulus of elasticity. In this paper, the different models of tension stiffening and the semi-empirical correlations for evaluating the modulus of rupture and the Young's modulus are synthetically described and compared with each other. The analytical deflections computed by means of different models are compared with the experimental results obtained by different authors, and an optimization analysis is developed in order to improve the CEB and ACI models.     

Lipid oxidation promotes acrylamide formation in fat-rich model systems

Lipid oxidation is one of the major chemical reactions occurring during food processing or storage and may have a strong impact on the final quality of foods. A significant role of carbonyl compounds derived from lipid oxidation in acrylamide formation has been recently proposed. In this work, the effect of lipid oxidation level on acrylamide formation was investigated by thermal treatment of differently formulated fat-rich model systems. Results showed that lipid oxidation positively influenced the formation of acrylamide. The effect was more evident in sugar-free system where lipid become the main sources of carbonyls. Catechins reduced acrylamide formation presumably by trapping carbohydrates and/or preventing lipid oxidation. More acrylamide was formed in model systems composed with sunflower oil than in those containing palm oil which is less susceptible to oxidation.In systems containing higher amount of water, acrylamide formation was delayed due to evaporative cooling. In these systems, the effect of catechin was more pronounced and the effect of lipid oxidation became detectable only after a prolonged reaction time.These findings suggested that lipid oxidation could become a relevant factor for acrylamide formation, particularly for dry foods with low carbohydrate content.     

High-resolution multi-bit second-order incremental converter with 1.5-μV residual offset and 94-dB SFDR

This paper describes an incremental converter based on a second order ???? modulator. The scheme uses a 3-bit DAC with inherent linearity, an optimal reset of integrators, and gives rise to an effective offset cancellation with a novel technique based on single or double chopping. The circuit, fabricated in a mixed 0.18-0.6???m CMOS technology, obtains 1.5-??V residual offset with 2V_PP fully differential range. The measured resolution is 19 bit obtained with 512 clock periods.