The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3

Proteins related to the ubiquitin-proteasome system play an important role during the differentiation and ciliogenesis of photoreceptor cells. Mutations in several genes involved in ubiquitination and proteostasis have been identified as causative of inherited retinal dystrophies (IRDs) and ciliopathies. USP48 is a deubiquitinating enzyme whose role in the retina is still unexplored although previous studies indicate its relevance for neurosensory organs. In this work, we describe that a pool of endogenous USP48 localises to the basal body in retinal cells and provide data that supports the function of USP48 in the photoreceptor cilium. We also demonstrate that USP48 interacts with the IRD-associated proteins ARL3 and UNC119a, and stabilise their protein levels using different mechanisms. Our results suggest that USP48 may act in the regulation/stabilisation of key ciliary proteins for photoreceptor function, in the modulation of intracellular protein transport, and in ciliary trafficking to the photoreceptor outer segment.     

Structure and stability of edible oleogels prepared with different unsaturated oils and hydrocolloids

Edible oleogels, with three oil types (olive, sunflower and flaxseed), hydroxypropylmethylcellulose (HPMC) and xanthan gum (XG), as structuring agents, were developed using the emulsion-template approach, and subsequent drying of the emulsions using conventional or vacuum drying. Our results showed that for both drying methods, well-structured oleogels were obtained using olive and sunflower oils for the preparation. These oleogels showed oil losses ˂10% after 35 days of storage. However, unstructured non-homogeneous oleogels were obtained when using flaxseed oil and conventional drying, while it was not feasible to develop flaxseed oleogel with vacuum drying. Oleogels showed interesting rheological properties, including a high oleogel strength with an elastic modulus of the order 10⁴–10⁵ Pa, weak dependence on frequency, and good thermostability. Moreover, high oxidative stability was obtained for olive oil oleogels, using both conventional and vacuum drying, and for sunflower oleogels using vacuum drying. Still, the initial oxidation rates of sunflower oleogels using conventional drying should be improved in future studies.     

Implantable automatic cardioverter-defibrillator: anesthesia experience

To evaluate the anesthetic management and intraoperative events in patients benefiting from an automatic implantable cardioverter defibrillator. We retrospectively reviewed the charts of 12 male patients in whom we had placed automatic implantable defibrillators (AID). In particular we assessed anesthetic management, recording type of anesthetic and intraoperative monitoring, the technique used to implant the AID and complications during and after surgery. Arterial pressure and heart rate were also analyzed. All patients experienced tachyarrhythmia or ventricular fibrillation. Ten of the 12 patients presented left ventricular ejection fractions (LVEF) between 21 and 28%; LVEF in the other 2 patients exceeded 30% (45 and 62%). All experienced statistically significant decreases in arterial pressure coincident with fibrillation. Three patients required dobutamine for sustained hypotension. Six presented ventricular extrasystoles during surgery. Late complications included 1 sudden death after surgery and 1 infection which obliged removal of the AID. AID implantation is not risk-free, given that the patients involved have heart disease with considerable degrees of deterioration in myocardial function. Nevertheless, with extensive preoperative examination of the patient and proper anesthetic management, complications before and after surgery are rare.     

Previous Gestational Diabetes Increases Atherogenic Dyslipidemia in Subsequent Pregnancy and Postpartum

In a cohort of women with previous gestational diabetes mellitus (GDM), we aimed to ascertain whether women with abnormal glucose tolerance 1‐year postdelivery had a more atherogenic lipid profile during and after pregnancy than those with normal glucose tolerance. A prospective cohort study with longitudinal design between January 2004 and March 2016 was conducted. Three hundred and six (56.8%) of 537 women diagnosed with GDM during the studied period attended a control visit during the first year after delivery. Of these, 112 (36.6%) had prediabetes and 16 (5.2%) had type 2 diabetes mellitus. No significant differences during pregnancy were found in total, low‐density lipoprotein, high‐density lipoprotein (HDL) cholesterol, and triacylglycerol (TAG) concentrations among the three groups. Only HDL cholesterol and TAG levels differed significantly among groups at 2 and 12 months after delivery. Logistic regression analysis revealed pregnancy HDL and glucose metabolism status to be associated with the HDL cholesterol concentration 1‐year postdelivery. Furthermore, the only independent factor associated with TAG levels 1 year after delivery was the gestational TAG concentration. In summary, an overweight multiethnic group of women with prior GDM presented a high incidence of postpartum dysglycemia (41.8%). HDL‐cholesterol and TAG levels, both components of the metabolic syndrome, differed significantly among the three study groups in the glucose‐metabolism status at 2 and 12 months after delivery. Women with previous GDM must be followed up in the postpartum period for early detection and management of lipid and glucose disorders.     

Development of Potent Inhibitors of the Mycobacterium tuberculosis Virulence Factor Zmp1 and Evaluation of Their Effect on Mycobacterial Survival inside Macrophages

The enzyme Zmp1 is a zinc‐containing peptidase that plays a critical role in the pathogenicity of Mycobacterium tuberculosis. Herein we describe the identification of a small set of Zmp1 inhibitors based on a novel 8‐hydroxyquinoline‐2‐hydroxamate scaffold. Among the synthesized compounds, N‐(benzyloxy)‐8‐hydroxyquinoline‐2‐carboxamide ( 1 c ) was found to be the most potent Zmp1 inhibitor known to date, and its binding mode was analyzed both by kinetics studies and molecular modeling, identifying critical interactions of 1 c with the zinc ion and residues in the active site. The effect of 1 c on intracellular Mycobacterium survival was assayed in J774 murine macrophages infected with M. tuberculosis H37Rv or M. bovis BCG and human monocyte‐derived macrophages infected with M. tuberculosis H37Rv. Cytotoxicity and genotoxicity were also assessed. Overall, inhibitor 1 c displays interesting in vitro antitubercular properties worthy of further investigation.     

Cytotoxicity of modified glass ionomer cement on odontoblast cells

Recently a modified glass ionomer cement (GIC) with enhanced bioactivity due to the incorporation of wollastonite or mineral trioxide aggregate (MTA) has been reported. The aim of this study was to evaluate the cytotoxic effect of the modified GIC on odontoblast-like cells. The cytotoxicity of a conventional GIC, wollastonite modified GIC (W-mGIC), MTA modified GIC (M-mGIC) and MTA cement has been evaluated using cement extracts, a culture media modified by the cement. Ion concentration and pH of each material in the culture media were measured and correlated to the results of the cytotoxicity study. Among the four groups, conventional GIC showed the most cytotoxicity effect, followed by W-mGIC and M-mGIC. MTA showed the least toxic effect. GIC showed the lowest pH (6.36) while MTA showed the highest (8.62). In terms of ion concentration, MTA showed the largest Ca²⁺ concentration (467.3 mg/L) while GIC showed the highest concentration of Si⁴⁺ (19.9 mg/L), Al³⁺ (7.2 mg/L) and Sr²⁺ (100.3 mg/L). Concentration of F^? was under the detection limit (0.02 mg/L) for all samples. However the concentrations of these ions are considered too low to be toxic. Our study showed that the cytotoxicity of conventional GIC can be moderated by incorporating calcium silicate based ceramics. The modified GIC might be promising as novel dental restorative cements.     

When paradigms collide at the road rail interface: evaluation of a sociotechnical systems theory design toolkit for cognitive work analysis

The Cognitive Work Analysis Design Toolkit (CWA-DT) is a recently developed approach that provides guidance and tools to assist in applying the outputs of CWA to design processes to incorporate the values and principles of sociotechnical systems theory. In this paper, the CWA-DT is evaluated based on an application to improve safety at rail level crossings. The evaluation considered the extent to which the CWA-DT met pre-defined methodological criteria and aligned with sociotechnical values and principles. Both process and outcome measures were taken based on the ratings of workshop participants and human factors experts. Overall, workshop participants were positive about the process and indicated that it met the methodological criteria and sociotechnical values. However, expert ratings suggested that the CWA-DT achieved only limited success in producing RLX designs that fully aligned with the sociotechnical approach. Discussion about the appropriateness of the sociotechnical approach in a public safety context is provided.

Practitioner Summary: Human factors and ergonomics practitioners need evidence of the effectiveness of methods. A design toolkit for cognitive work analysis, incorporating values and principles from sociotechnical systems theory, was applied to create innovative designs for rail level crossings. Evaluation results based on the application are provided and discussed.     

Optimization of <Emphasis Type="Italic">Brassica carinata</Emphasis> oil methanolysis for biodiesel production

Synthesis of FAME from Brassica carinata oil to produce biodiesel was accomplished using potassium hydroxide as the catalyst. A factorial design of experiments and a central composite design were used. The variables chosen were: type of Brassica carinata oil, initial catalyst concentration, and temperature; and the responses were FAME purity and yield. The type of B. carinata oil included high-erucic B. carinata (HEBC) and lowerucic B. carinata (LEBC) varieties. The results show that the type of B. carinata oil does not affect the purity and yield of FAME. However, HEBC oil is more suitable for biodiesel production because its iodine value is lower and within the European Union specifications. The initial catalyst concentration is the most important factor, having a positive influence on FAME purity but a negative effect on FAME yield. The temperature has a significant positive effect on FAME purity and a significant negative influence on FAME yield. Second-order models were obtained to predict FAME purity and yield as a function of catalyst concentration and temperature for HEBC oil methanolysis. The best conditions for this process are 25°C, and 1.2–1.5 wt% for the catalyst concentration.     

Mining closed patterns in relational,graph and network data

Recent theoretical insights have led to the introduction of efficient algorithms for mining closed item-sets. This paper investigates potential generalizations of this paradigm to mine closed patterns in relational, graph and network databases. Several semantics and associated definitions for closed patterns in relational data have been introduced in previous work, but the differences among these and the implications of the choice of semantics was not clear. The paper investigates these implications in the context of generalizing the LCM algorithm, an algorithm for enumerating closed item-sets. LCM is attractive since its run time is linear in the number of closed patterns and since it does not need to store the patterns output in order to avoid duplicates, further reducing memory signature and run time. Our investigation shows that the choice of semantics has a dramatic effect on the properties of closed patterns and as a result, in some settings a generalization of the LCM algorithm is not possible. On the other hand, we provide a full generalization of LCM for the semantic setting that has been previously used by the Claudien system.