Case report: A novel patient presenting TRIM32-related limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy autosomal recessive 8 (LGMDR8) is a rare clinical manifestation caused by the presence of biallelic variants in the TRIM32 gene. We present the clinical, molecular, histopathological, and muscle magnetic resonance findings of a novel 63-years-old LGMDR8 patient of Italian origins, who went undiagnosed for 24 years. Clinical exome sequencing identified two TRIM32 missense variants, c.1181G > A p.(Arg394His) and c.1781G > A p.(Ser594Asp), located in the NHL1 and NHL4 structural domains, respectively, of the TRIM32 protein. We conducted a literature review of the clinical and instrumental data associated to the so far known 26 TRIM32 variants, carried biallelically by 53 LGMDR8 patients reported to date in 20 papers. Our proband's variants were previously identified only in three independent LGMDR8 patients in homozygosis, therefore our case is the first in literature to be described as compound heterozygous for such variants. Our report also provides additional data in support of their pathogenicity, since p.(Arg394His) is currently classified as a variant of uncertain significance, while p.(Ser594Asp) as likely pathogenic. Taken together, these findings might be useful to improve both the genetic counseling and the diagnostic accuracy of this rare neuromuscular condition

Charting the NF-κB Pathway Interactome Map

Inflammation is part of a complex physiological response to harmful stimuli and pathogenic stress. The five components of the Nuclear Factor κB (NF-κB) family are prominent mediators of inflammation, acting as key transcriptional regulators of hundreds of genes. Several signaling pathways activated by diverse stimuli converge on NF-κB activation, resulting in a regulatory system characterized by high complexity. It is increasingly recognized that the number of components that impinges upon phenotypic outcomes of signal transduction pathways may be higher than those taken into consideration from canonical pathway representations. Scope of the present analysis is to provide a wider, systemic picture of the NF-κB signaling system. Data from different sources such as literature, functional enrichment web resources, protein-protein interaction and pathway databases have been gathered, curated, integrated and analyzed in order to reconstruct a single, comprehensive picture of the proteins that interact with, and participate to the NF-κB activation system. Such a reconstruction shows that the NF-κB interactome is substantially different in quantity and quality of components with respect to canonical representations. The analysis highlights that several neglected but topologically central proteins may play a role in the activation of NF-κB mediated responses. Moreover the interactome structure fits with the characteristics of a bow tie architecture. This interactome is intended as an open network resource available for further development, refinement and analysis

Pilot scale biofilm reactor for heterotrophic denitrification of groundwater: the Milan city case study

A pilot scale biofilm reactor has been applied to study the efficacy of an heterotrophic denitrification process for the removal of 40 mgNO3/L from Milan city groundwater, characterized by contextual pollution of VOCs and pesticides. The biological submerged filter (Biofor, Degrémont) with expanded clay as biomass support (Biolite, Degrémont) was fed with a constant water inflow of 0.6 m3/h, and the effluent was subjected to an aeration step (3 min HRT) and a GAC filtration (8 min EBCT). Tracer tests using LiCl were performed before and after bacterial colonization, revealing a mean residence time of 22 min and suggesting a PFR with axial dispersion (increasing with the colonizing degree), as the best interpretative model. A continuous dosage of sodium acetate (CH3COONa) and potassium phosphate (KH2PO4) was assured, with a variable organic carbon dosage, obtained fixing the C/DO ratio (0.94 gC/gDO for a concentration of 6.2 ± 0.55 mgDO/L) and varying the C/N ratio. Data observed during 70 days of stationary phase have shown that an applied C/N ratio equal to the stoichiometric value of 1.46 gC/gN led to a stable removal efficiency higher than 88.5%, while lower applied C/N values presented a significant occurrence of nitrite in the effluent. Stoichiometry was used to verify the aerobic and anoxic organic carbon consumption along the biofilter, since a concomitant removal of nitrogen and dissolved oxygen was observed, and suggested that no biomass stratification was present. The observed removal efficiencies did not highlight any inhibition mechanism associated to influent micro-pollutants, and any co-metabolic removal of VOCs or other organic pollutant could be inferred

Lead waste glasses management: Chemical pretreatment for use in cementitious composites

This article investigates the effect of a low-impact chemical treatment based on a nitrilotriacetic acid chelating agent on the reactivity of funnel glass derived from discarded cathode ray tubes. Treated and untreated glass has been recycled either as a supplementary cementing material or as a fine aggregate in cementitious mortars. The effect of the treatment on the chemical and morphological properties of cullets, as well as on the solubility in an alkaline environment has been evaluated. Data so far collected underline a change in glass cullets characteristics that consequently affects their behaviour in cementitious mortars, reducing the pozzolanic activity as supplementary cementing material, but strongly decreasing the tendency towards alkali silica reactions when added as a fine aggregate. The leaching behaviour of lead on treated and untreated glass and on derived composites has been determined to verify the sustainability of the prepared materials

Knowledge-based planning of groundwater treatment trains for an efficient drinking water supply system in urban areas

A knowledge-based planning of the proper treatment trains was applied to the drinking water supply system of Milan city, involving the application of statistical tools and experimental tests. As first step, multivariate statistical techniques were applied to groundwater monitoring data in order to identify specific contaminations of the captured groundwater and their spatial distribution. Starting from 88 quality parameters, 16 significant factors were extracted by Factor Analysis, identifying different kinds of groundwater contamination in the studied area. Then, Cluster Analysis allowed to recognize 8 typical compositions of captured groundwater and their distribution in DWS units. According to these results, different treatment processes were chosen to be adopted in DWS units and their performances were experimentally evaluated on specifically selected water samples. Heterotrophic denitrification has been tested at pilot-scale to treat water affected by nitrate contamination: results allowed to obtain the optimal operating parameters, such as organic carbon supply and volumetric loads, in order to comply with regulation limits. Activated carbon adsorption was tested at lab-scale for the removal of various VOCs (volatile organic carbon) and pesticides in different water mixtures: variable removal efficiencies were obtained towards different contaminants, depending on their physical-chemical properties and the occurrence of competition phenomena (as in the case of perchloroethylene, PCE, and trichloroethylene, TCE, simultaneous adsorption). Air stripping was tested at pilot-scale and it was found to be a suitable solution for removing the most volatile organic compounds (i.e. PCE). According to observed results, an air stripping step before adsorption phase could be a valid solution to increase the lifetime of GAC bed

Chelating Agent Treatment on Leaded Residuals from Glass Separated Urban Collection to Be Used in Cement Mortars

A mild chelating agent treatment was performed on the residuals of the sorting processes of separately collected urban glass, which is currently landfilled. This fraction, that represents about the 10 wt% of the overall collected glass, has a very heterogeneous composition and contains relatively high amounts of lead and barium and consequently cannot be used to produce new glass containers. This contaminated material shows, when used as fine aggregate in Portland Cement based composites, an expansive behaviour due to the alkali silica reactions. The expansion can only be partially reduced by using finely ground soda lime glass, showing pozzolanic activity. However, after the chelating agent treatment, because of heavy atoms surface depletion, the synergic effect of pozzolan addition leads to a suppressed expansion, thus allowing the use of waste in the formulation of cement composites

Effect of chemical composition of different types of recycled glass used as aggregates on the ASR performance of cement mortars

Glass with different chemical compositions, deriving from separate collection, has been used as fine aggregate to formulate cementitious mortars, substituting natural sand. Glass coming from cathode-ray tube monitors, fluorescent lamps, and crystal glass (from production of home d\ue9cor items) along with glass deriving from soda-lime glass containers, which has been taken as a reference, have been investigated. Glass solubility has been determined in alkaline environment similar to the one inside the cementitious composites. Alkali silica reaction has been tested on glass modified cement mortar in different accelerated conditions. The obtained results highlight an expansion behaviour of mortar samples containing glass with chemical composition different with respect to soda-lime glass. This behaviour is largely dependent on the ratio among modifier and stabilizer oxides in the glass and affects its solubility and consequently the gels composition when alkali silica reactions take place

Managing and controlling processes in product-based service networks

The increasing importance of the service provision within manufacturing companies calls for the introduction of a proper system of governance and control along the overall product-based service chain. The literature dealing with product support services is highly fragmented and contributions considering the whole supply chain or network are very scarce. This paper aims at filling this gap by proposing a conceptual performance measurement model for a product-based service network. Different set of performance indicators are developed depending on the type of assistance process (passive, collaborative and â??turn-keyâ??). The management perspective is extended from one company to a whole service network and a brief application case allows to clarify how the model can be applied to different actors. A higher number of case studies would be useful to further develop and complete the model

Synthesis of new 5,6-dihydrobenzo[h]quinazoline 2,4-diamino substituted and antiplatelet/antiphlogistic activities evaluation

In pursuing our research on some 2,4-diamino-benzopyranopyrimidines and 2-amino-5,6-dihydrobenzo[ h]quinazolines, previously reported as antiplatelet and analgesic/anti-inflammatory agents respectively, we designed and synthesized a new series of 5,6-dihydrobenzo[h]quinazoline 2,4-diamino substituted. The insertion of amino substituents at positions 2 and 4 of the benzoquinazoline scaffold resulted in compounds endowed with a potent ASA-like antiplatelet activity, combined with an antiinflammatory activity comparable, in some cases, to that of indomethacin, used as a reference drug