A new targeted CFTR mutation panel based on next-generation sequencing technology

Searching for mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) is a key step in the diagnosis of and neonatal and carrier screening for cystic fibrosis (CF), and it has implications for prognosis and personalized therapy. The large number of mutations and genetic and phenotypic variability make this search a complex task. Herein, we developed, validated, and tested a laboratory assay for an extended search for mutations in CFTR using a next-generation sequencing based method, with a panel of 188 CFTR mutations customized for the Italian population. Overall, 1426 dried blood spots from neonatal screening, 402 genomic DNA samples from various origins, and 1138 genomic DNA samples from patients with CF were analyzed. The assay showed excellent analytical and diagnostic operative characteristics. We identified and experimentally validated 159 (of 188) CFTR mutations. The assay achieved detection rates of 95.0% and 95.6% in two large-scale case series of CF patients from central and northern Italy, respectively. These detection rates are among the highest reported so far with a genetic test for CF based on a mutation panel. This assay appears to be well suited for diagnostics, neonatal and carrier screening, and assisted reproduction, and it represents a considerable advantage in CF genetic counseling

Catalytic upgrading of clean biogas to synthesis gas

Clean biogas, produced by anaerobic digestion of biomasses or organic wastes, is one of the most promising substitutes for natural gas. After its purification, it can be valorized through different reforming processes that convert CH4 and CO2 into synthesis gas (a mixture of CO and H2). However, these processes have many issues related to the harsh conditions of reaction used, the high carbon formation rate and the remarkable endothermicity of the reforming reactions. In this context, the use of the appropriate catalyst is of paramount importance to avoid deactivation, to deal with heat issues and mild reaction conditions and to attain an exploitable syngas composition. The development of a catalyst with high activity and stability can be achieved using different active phases, catalytic supports, promoters, preparation methods and catalyst configurations. In this paper, a review of the recent findings in biogas reforming is presented. The different elements that compose the catalytic system are systematically reviewed with particular attention on the new findings that allow to obtain catalysts with high activity, stability, and resistance towards carbon formation

Evaluation of the Catalytic Activity of Metal Phosphates and Related Oxides in the Ketonization of Propionic Acid

In recent years, the upgrading of lignocellulose bio-oils from fast-pyrolysis by means of ketonization has emerged as a frontier research domain to produce a new generation of biofuels. Propionic acid (PA) ketonization is extensively investigated as a model reaction over metal oxides, but the activity of other materials, such as metal phosphates, is mostly unknown. Therefore, PA ketonization was preliminarily investigated in the gas phase over both phosphates and oxides of Al, Zr, and La. Their catalytic activity was correlated to the physicochemical properties of the materials characterized by means of XRD, XRF, BET N2 porosimetry, and CO2- and NH3-TPD. Noteworthy, monoclinic ZrO2 proved to be the most promising candidate for the target reaction, leading to a 3-pentanone productivity as high as 5.6 h 121 in the optimized conditions. This value is higher than most of those reported for the same reaction in both the academic and patent literature

Laser-Scribing Optimization for Sprayed SnO2-Based Perovskite Solar Modules on Flexible Plastic Substrates

Flexible perovskite solar cells (FPSCs) are prime candidates for applications requiring a highly efficient, low-cost, lightweight, thin, and even foldable power source. Despite record efficiencies of lab-scale flexible devices (19.5% on a 0.1 cm(2) area), scalability represents a critical factor toward commercialization of FPSCs. Large-area automized deposition techniques and efficient laser scribing procedures are required to enable a high-throughput production of flexible perovskite modules (FPSMs), with the latter being much more challenging compared to glass substrates. In this work, we introduce the combined concept of laser scribing optimization and automatized spray-coating of SnO2 layers. Based on a systematic variation of the incident laser power and a comprehensive morphological and electrical analysis of laser-based cell interconnections, optimal scribing parameters are identified. Furthermore, spray-coating is used to deposit uniform compact SnO2 films on large-area (>120 cm(2)) plastic substrates. FPSCs with spray-coated SnO2 show comparable performance as spin-coated cells, delivering up to 15.3% efficiency on small areas under 1 sun illumination. When upscaling to large areas, FPSMs deliver 12% power conversion efficiency (PCE) and negligible hysteresis on 16.8 cm(2) and 11.7% PCE on a 21.8 cm(2) active area. Our perovskite devices preserved 78% efficiency when the active area increased from 0.1 to 16.8 cm(2), demonstrating that our combined approach is an effective strategy for large-area manufacturing of perovskite devices on flexible substrates

d-mannose treatment neither affects uropathogenic Escherichia coli properties nor induces stable FimH modifications

Abstract: Urinary tract infections (UTIs) are mainly caused by uropathogenic Escherichia coli (UPEC). Acute and recurrent UTIs are commonly treated with antibiotics, the efficacy of which is limited by the emergence of antibiotic resistant strains. The natural sugar d-mannose is considered as an alternative to antibiotics due to its ability to mask the bacterial adhesin FimH, thereby preventing its binding to urothelial cells. Despite its extensive use, the possibility that d-mannose exerts “antibiotic-like” activity by altering bacterial growth and metabolism or selecting FimH variants has not been investigated yet. To this aim, main bacterial features of the prototype UPEC strain CFT073 treated with d-mannose were analyzed by standard microbiological methods. FimH functionality was analyzed by yeast agglutination and human bladder cell adhesion assays. Our results indicate that high d-mannose concentrations have no effect on bacterial growth and do not interfere with the activity of different antibiotics. d-mannose ranked as the least preferred carbon source to support bacterial metabolism and growth, in comparison with d-glucose, d-fructose, and l-arabinose. Since small glucose amounts are physiologically detectable in urine, we can conclude that the presence of d-mannose is irrelevant for bacterial metabolism. Moreover, d-mannose removal after long-term exposure did not alter FimH’s capacity to bind to mannosylated proteins. Overall, our data indicate that d-mannose is a good alternative in the prevention and treatment of UPEC-related UTIs

Amino Acid-based Formula in Cowʼs Milk Allergy: Long-term Effects on Body Growth and Protein Metabolism. A Randomized Trial

Objectives: The long-term effects of amino acid-based formula (AAF) in the treatment of cow's milk allergy (CMA) are largely unexplored. The present study comparatively evaluates body growth and protein metabolism in CMA children treated with AAF or with extensively hydrolyzed whey formula (eHWF), and healthy controls. Methods: A 12-month multicenter randomized control trial was conducted in outpatients with CMA (age 5-12 m) randomized in 2 groups, treated with AAF (group 1) and eHWF (group 2), and compared with healthy controls (group 3) fed with follow-on (if age 12 months). At enrolment (T0), after 3 (T3), 6 (T6), and 12 months (T12) a clinical evaluation was performed. At T0 and T3, in subjects with CMA serum levels of albumin, urea, total protein, retinol-binding protein, and insulin-like growth factor 1 were measured. Results: Twenty-one subjects in group 1 (61.9% boys, age 6.5\ub11.5 months), 19 in group 2 (57.9% boys, age 7\ub11.7 months) and 25 subjects in group 3 (48% boys, age 5.5\ub10.5 months) completed the study. At T0, the weight z score was similar in group 1 (-0.74) and 2 (-0.76), with differences compared to group 3 (-0.17, P<0.05). At T12, the weight z score value was similar between the 3 groups without significant differences. There were no significant changes in protein metabolism in children in groups 1 and 2. Conclusion: Long-term treatment with AAF is safe and allows adequate body growth in children with CMA

Metabolomic profiling for the identification of novel diagnostic markers in prostate cancer

Metabolomic profiling offers a powerful methodology for understanding the perturbations of biochemical systems occurring during a disease process. During neoplastic transformation, prostate cells undergo metabolic reprogramming to satisfy the demands of growth and proliferation. An early event in prostate cell transformation is the loss of capacity to accumulate zinc. This change is associated with a higher energy efficiency and increased lipid biosynthesis for cellular proliferation, membrane formation and cell signaling. Moreover, recent studies have shown that sarcosine, an N-methyl derivative of glycine, was significantly increased during disease progression from normal to localized to metastatic prostate cancer. Mapping the metabolomic profiles to their respective biochemical pathways showed an upregulation of androgen-induced protein synthesis, an increased amino acid metabolism and a perturbation of nitrogen breakdown pathways, along with high total choline-containing compounds and phosphocholine levels. In this review, the role of emerging biomarkers is summarized, based on the current understanding of the prostate cancer metabolome

Parameterization and solar radiation simulation for optimization of a modular canopy

This study perceives the developing process of a parameterization modeling in Grasshopper® for complex surfaces using building simulation, considering diffuse and beam radiation as the key-variables. The primary goal of this article is to create, simulate and optimize a modular, semi-opened canopy based in retro-studies of tree leaves as engineering structures. The method applied consisted of the definition of parameters and criteria for the optimization of the simulation process and was divided into three stages: a study of form, form parameterization, and simulation and optimization. Ladybug® for Grasshopper® plugin was used to carry out the simulations, and Octopus® was used as a motor for optimizing the final script. The object of study chosen was the process of creation of a canopy because, in hot and humid climates, such as in Brazil, the roofing areas are a critical part of the building envelopes that are highly susceptible to solar radiation and other environmental changes, thereby, influencing the indoor comfort conditions for the occupants. Although the final product was created for a specific climate zone, it can be applied to any other zones with a few changes in the parameters due to parameterization. As main results, the solar control devices contributed to a reduction of 86% of the annual average of hourly beam solar radiation while maintaining high levels of diffuse radiation

Tandem Hydrogenation/Hydrogenolysis of Furfural to 2-Methylfuran over a Fe/Mg/O Catalyst: Structure–Activity Relationship

The hydrodeoxygenation of furfural (FU) was investigated over Fe-containing MgO catalysts, on a continuous gas flow reactor, using methanol as a hydrogen donor. Catalysts were prepared either by coprecipitation or impregnation methods, with different Fe/Mg atomic ratios. The main product was 2-methylfuran (MFU), an important highly added value chemical, up to 92% selectivity. The catalyst design helped our understanding of the impact of acid/base properties and the nature of iron species in terms of catalytic performance. In particular, the addition of iron on the surface of the basic oxide led to (i) the increase of Lewis acid sites, (ii) the increase of the dehydrogenation capacity of the presented catalytic system, and (iii) to the significant enhancement of the FU conversion to MFU. FTIR studies, using methanol as the chosen probe molecule, indicated that, at the low temperature regime, the process follows the typical hydrogen transfer reduction, but at the high temperature regime, methanol dehydrogenation and methanol disproportionation were both presented, whereas iron oxide promoted methanol transfer. FTIR studies were performed using furfural and furfuryl alcohol as probe molecules. These studies indicated that furfuryl alcohol activation is the rate-determining step for methyl furan formation. Our experimental results clearly demonstrate that the nature of iron oxide is critical in the efficient hydrodeoxygenation of furfural to methyl furan and provides insights toward the rational design of catalysts toward C–O bonds' hydrodeoxygenation in the production of fuel components

A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia

NDUFB11, a component of mitochondrial complex I, is a relatively small integral membrane protein, belonging to the 'supernumerary' group of subunits, but proved to be absolutely essential for the assembly of an active complex I. Mutations in in the X-linked nuclear encoded NDUFB11 gene have recently been discovered in association with two distinct phenotypes, i.e. microphthalmia with linear skin defects and histiocytoid cardiomyopathy. We report on a male with complex I deficiency, caused by a de novo mutation in NDUFB11 and displaying early onset sideroblastic anemia as the unique feature. This is the third report that describes a mutation in NDUFB11 but all are associated to a different phenotype. Our results further expand the molecular spectrum and associated clinical phenotype of NDUFB11 defects