High-Fat Diet Leads to Reduced Protein O-GlcNAcylation and Mitochondrial Defects Promoting the Development of Alzheimer’s Disease Signatures

The disturbance of protein O-GlcNAcylation is emerging as a possible link between altered brain metabolism and the progression of neurodegeneration. As observed in brains with Alzheimer’s disease (AD), flaws of the cerebral glucose uptake translate into reduced protein O-GlcNAcylation, which promote the formation of pathological hallmarks. A high-fat diet (HFD) is known to foster metabolic dysregulation and insulin resistance in the brain and such effects have been associated with the reduction of cognitive performances. Remarkably, a significant role in HFD-related cognitive decline might be played by aberrant protein O-GlcNAcylation by triggering the development of AD signature and mitochondrial impairment. Our data support the impairment of total protein O-GlcNAcylation profile both in the brain of mice subjected to a 6-week high-fat-diet (HFD) and in our in vitro transposition on SH-SY5Y cells. The reduction of protein O-GlcNAcylation was associated with the development of insulin resistance, induced by overfeeding (i.e., defective insulin signaling and reduced mitochondrial activity), which promoted the dysregulation of the hexosamine biosynthetic pathway (HBP) flux, through the AMPK-driven reduction of GFAT1 activation. Further, we observed that a HFD induced the selective impairment of O-GlcNAcylated-tau and of O-GlcNAcylated-Complex I subunit NDUFB8, thus resulting in tau toxicity and reduced respiratory chain functionality respectively, highlighting the involvement of this posttranslational modification in the neurodegenerative process.     

Structural Investigation and Molecular Modeling Studies of Strobilurin-Based Fungicides Active against the Rice Blast Pathogen Pyricularia oryzae

The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen.     

Anonymity preserving sequential pattern mining

The increasing availability of personal data of a sequential nature, such as time-stamped transaction or location data, enables increasingly sophisticated sequential pattern mining techniques. However, privacy is at risk if it is possible to reconstruct the identity of individuals from sequential data. Therefore, it is important to develop privacy-preserving techniques that support publishing of really anonymous data, without altering the analysis results significantly. In this paper we propose to apply the Privacy-by-design paradigm for designing a technological framework to counter the threats of undesirable, unlawful effects of privacy violation on sequence data, without obstructing the knowledge discovery opportunities of data mining technologies. First, we introduce a k-anonymity framework for sequence data, by defining the sequence linking attack model and its associated countermeasure, a k-anonymity notion for sequence datasets, which provides a formal protection against the attack. Second, we instantiate this framework and provide a specific method for constructing the k-anonymous version of a sequence dataset, which preserves the results of sequential pattern mining, together with several basic statistics and other analytical properties of the original data, including the clustering structure. A comprehensive experimental study on realistic datasets of process-logs, web-logs and GPS tracks is carried out, which empirically shows how, in our proposed method, the protection of privacy meets analytical utility.     

Guanine and plasmid DNA binding of mono- and trinuclear fac-[Re(CO)3]+ complexes with amino acid ligands

We have synthesized and fully characterized four new complexes comprising the fac-[Re(CO)3]+ moiety and the ligands NH3, L-proline (Pro), or N,N-dimethylglycine (dmGly). The reaction of [Re(H2O)3(CO)3]+ with the two amino acids gives trinuclear complexes of general formula [Re(L)(CO)3]3 (where L = amino acid). We have studied the in vitro behavior of these compounds with guanine and DNA in order to understand whether the cytotoxicity exhibited by certain rhenium complexes based on the fac-[Re(CO)3]+ core is due to the formation of nucleobase complexes and inter- or intrastrand links between DNA bases. We have performed model studies with guanine and studied the structural effects induced by different rhenium(I) tricarbonyl complexes on PhiX174 plasmid DNA by electrophoretic methods. Our results show that rhenium complexes with two available coordination sites interact with plasmid DNA to form a stable adduct that is likely to involve two bases.     

EDT Method for Multiple Labelled Objects Subject to Tied Distances

Machine Intelligence Research - The success of new scientific areas can be assessed by their potential for contributing to new theoretical approaches aligned with real-world applications. The...     

Antistatic packaging based on PTT/PTT-g-MA/ABS/MWCNT nanocomposites: Effect of the chemical functionalization of MWCNTs

Polymer/carbon nanotube nanocomposites have attracted high interest for a wide spectrum of applications, including antistatic packaging used to protect electronic devices against electrostatic discharge. Polytrimethylene terephthalate (PTT)/maleic-anhydride-grafted PTT (PTT-g-MA)/acrylonitrile butadiene styrene (ABS) blend-based multiwall carbon nanotubes (MWCNTs) nanocomposites were prepared through extrusion. It was conducted chemical functionalization on the MWCNTs by oxidation using nitric acid to introduce functional groups. The effect of the amount (0.5 or 1.0 wt%) and functionalization of MWCNTs on the nanocomposites was investigated. Despite the poor barrier properties of PTT/PTT-g-MA/ABS/MWCNT nanocomposites due to the presence of voids confirmed by scanning electron microscopy (SEM), the nanocomposites with functionalized MWCNT (MWCNTf) showed excellent barrier properties, indicating that the functionalization process improved the interaction between the MWCNTs and the matrix. The addition of MWCNTs into PTT/PTT-g-MA/ABS blend decreased the electrical resistivity by eight orders of magnitude. The use of MWCNTf may still disrupt the electrical network pathway and slightly decreasing the electrical resistivity, but the nanocomposites present the desired properties required for antistatic packaging.     

Assessing the impact of real-time machine translation on multilingual meetings in global software projects

Communication in global software development is hindered by language differences in countries with a lack of English speaking professionals. Machine translation is a technology that uses software to translate from one natural language to another. The progress of machine translation systems has been steady in the last decade. As for now, machine translation technology is particularly appealing because it might be used, in the form of cross-language chat services, in countries that are entering into global software projects. However, despite the recent progress of the technology, we still lack a thorough understanding of how real-time machine translation affects communication. In this paper, we present a set of empirical studies with the goal of assessing to what extent real-time machine translation can be used in distributed, multilingual requirements meetings instead of English. Results suggest that, despite far from 100 % accurate, real-time machine translation is not disruptive of the conversation flow and, therefore, is accepted with favor by participants. However, stronger effects can be expected to emerge when language barriers are more critical. Our findings add to the evidence about the recent advances of machine translation technology and provide some guidance to global software engineering practitioners in regarding the losses and gains of using English as a lingua franca in multilingual group communication, as in the case of computer-mediated requirements meetings.     

SOA-enabled compliance management: instrumenting, assessing, and analyzing service-based business processes

Facilitating compliance management, that is, assisting a company’s management in conforming to laws, regulations, standards, contracts, and policies, is a hot but non-trivial task. The service-oriented architecture (SOA) has evolved traditional, manual business practices into modern, service-based IT practices that ease part of the problem: the systematic definition and execution of business processes. This, in turn, facilitates the online monitoring of system behaviors and the enforcement of allowed behaviors—all ingredients that can be used to assist compliance management on the fly during process execution. In this paper, instead of focusing on monitoring and runtime enforcement of rules or constraints, we strive for an alternative approach to compliance management in SOAs that aims at assessing and improving compliance. We propose two ingredients: (i) a model and tool to design compliant service-based processes and to instrument them in order to generate evidence of how they are executed and (ii) a reporting and analysis suite to create awareness of a company’s compliance state and to enable understanding why and where compliance violations have occurred. Together, these ingredients result in an approach that is close to how the real stakeholders—compliance experts and auditors—actually assess the state of compliance in practice and that is less intrusive than enforcing compliance.