Genetic Architecture and Molecular,Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art,Opportunities and Challenges

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdiagnosed. Moreover, its genetic etiology has been studied only recently due to the unavailability of large cohorts with a certain diagnosis and shows genetic heterogeneity with a rare contribution of pathogenic mutations and relatively common risk factors. The rapid increase in the reported cases of DLB highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods proposed by the International DLB consortium rely on a list of criteria that comprises both clinical observations and the use of biomarkers. Herein, we summarize the up-to-now reported knowledge on the genetic architecture of DLB and discuss the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.     

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.     

Nondeterministic, nonmonotonic logic databases

We consider an extension of Datalog with mechanisms for temporal, nonmonotonic, and nondeterministic reasoning, which we refer to as Datalog++. We show, by means of examples, its flexibility in expressing queries concerning aggregates and data cube. Also, we show how iterated fixpoint and stable model semantics can be combined to the purpose of clarifying the semantics of Datalog++ programs and supporting their efficient execution. Finally, we provide a more concrete implementation strategy on which basis the design of optimization techniques tailored for Datalog++ is addressed     

Sacha inchi (Plukenetia volubilis L.) shell: an alternative source of phenolic compounds and antioxidants

Sacha inchi seed (SI) is known as a rich source of oil with high content of polyunsaturared fatty acids of the ω‐3 and ω‐6 type (~85% of total fatty acids). However, few studies have focused on the use of by‐products from the seed. The aim of this study was to characterise the main phenolic families present in SI shell and to evaluate the best extraction solvent for the extraction of phenolic compounds (PC) and antioxidant capacity (AOXC). The PC content corresponded to 74.5 ± 5.1 mg g^?1 of which 93.1% were condensed tannins and the remaining compounds corresponded to free and bound phenolic acids, hydrolyzable tannins, flavonoids and flavanoids. Protocatechic and p‐coumaric acids but also hydroxycinammic acid derivatives of ferulic and o‐coumaric type and lignan derivatives were identified. Acetone containing solvents favoured the extraction of higher amounts of total PC and AOXC. This study highlights the potential use of SI shell as a novel and alternative source of PC antioxidants for the nutraceutical and/or functional food industries.     

Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long-term cannabis users: A secondary analysis of a case–control study

Cannabis is now legal in many countries and while numerous studies have reported on its impact on cognition and appetite regulation, none have examined fatty acid metabolism in young cannabis users. We conducted an exploratory analysis to evaluate cannabis impact on fatty acid metabolism in cannabis users (n = 21) and non-cannabis users (n = 16). Serum levels of some saturated and monounsaturated fatty acids, including palmitic, palmitoleic, and oleic acids were higher in cannabis users compared to nonusers. As palmitic acid can be derived from diet or lipogenesis from sugars, we evaluated lipogenesis using a de novo lipogenesis index (palmitate/linoleic acid) and carbon-specific isotope analysis, which allows for the determination of fatty acid ¹³C signature. The significantly higher de novo lipogenesis index in the cannabis users group along with a more enriched ¹³C signature of palmitic acid suggested an increase in lipogenesis. In addition, while serum glucose concentration did not differ between groups, pyruvate and lactate were lower in the cannabis user group, with pyruvate negatively correlating with palmitic acid. Furthermore, the endocannabinoid 2-arachidonoylglycerol was elevated in cannabis users and could contribute to lipogenesis by activating the cannabinoid receptor 1. Because palmitic acid has been suggested to increase inflammation, we measured peripheral cytokines and observed no changes in inflammatory cytokines. Finally, an anti-inflammatory metabolite of palmitic acid, palmitoylethanolamide was elevated in cannabis users. Our results suggest that lipogenic activity is increased in cannabis users; however, future studies, including prospective studies that control dietary intake are required.     

Synthetic Activity of Recombinant Whole Cell Biocatalysts Containing 2-Deoxy-D-ribose-5-phosphate Aldolase from Pectobacterium atrosepticum

In nature 2-deoxy-D-ribose-5-phosphate aldolase (DERA) catalyses the reversible formation of 2-deoxyribose 5-phosphate from D-glyceraldehyde 3-phosphate and acetaldehyde. In addition, this enzyme can use acetaldehyde as the sole substrate, resulting in a tandem aldol reaction, yielding 2,4,6-trideoxy-D-erythro-hexapyranose, which spontaneously cyclizes. This reaction is very useful for the synthesis of the side chain of statin-type drugs used to decrease cholesterol levels in blood. One of the main challenges in the use of DERA in industrial processes, where high substrate loads are needed to achieve the desired productivity, is its inactivation by high acetaldehyde concentration. In this work, the utility of different variants of Pectobacterium atrosepticum DERA (PaDERA) as whole cell biocatalysts to synthesize 2-deoxyribose 5-phosphate and 2,4,6-trideoxy-D-erythro-hexapyranose was analysed. Under optimized conditions, E. coli BL21 (PaDERA C-His AA C49M) whole cells yields 99 % of both products. Furthermore, this enzyme is able to tolerate 500 mM acetaldehyde in a whole-cell experiment which makes it suitable for industrial applications.     

School principals at their lonely work: Recording workday practices through ESM logs

This study used portable technology based on Experience Sampling Methodology (ESM log) to register workday practices of school principals and heads from Chilean schools who were implementing school improvement plans aimed at developing a culture of organizational learning. For a week, Smartphone devices which beeped seven times a day were given to School Principals and Heads of Technical-Pedagogical Units, who then answered closed questions about their current agenda. Six municipal schools in a district of the V Region of Chile participated in the study. The main results support the notion that, at the time of data collection, most school Principals and Heads of Technical-Pedagogical Units were working alone, and if they were interacting with other people, they were always in command. Following underlying assumed roles, most school principals reported performing administrative tasks, while Heads of Technical-Pedagogical Units mainly addressed instructional issues, fostering a rigid framework for the assignment of tasks. Follow-up semi-structured interviews confirmed that participants were not working as a team but rather alone on important issues and urgent matters. Participants regarded the use of the device as a very practical and useful tool to analyze their daily practices. Results are discussed focusing on the use of portable technology to address methodological issues faced when approaching research on educational leadership from a distributed leadership perspective.     

Phenolic profiles of Andean purple corn (Zea mays L.)

Qualitative and quantitative high performance liquid chromatography with diode array detection (HPLC-DAD) was performed to characterize the presence of phenolic compounds in Andean purple corn. Phenolic compounds were analyzed by separating them in two main fractions: a water fraction (WF) and an ethyl acetate fraction (EAF). The WF rich in anthocyanins revealed the presence of cyanidin-3-glucoside, pelargonidin-3-glucoside and peonidin-3-glucoside. The respective acylated anthocyanin glucoside forms of these compounds were also detected following alkaline hydrolysis. The EAF was composed of phenolic acids such as p-coumaric, vanillic acid, protocatechuic acid, flavonoids such quercetin derivatives and a hesperitin derivative. Alkaline and acid hydrolysis of the EAF revealed the presence of p-coumaric and ferulic acid as main components in four bound hydroxycinnamic acid forms present in the ethyl acetate fraction.     

End fixity in cold-formed steel sections using press joining

Connections in cold formed steel structures using multiple press joins can develop moment resistance. This paper describes and presents the results of a series of tests on cold formed steel C sections with multiple press joined connections. The experimental results are compared with similar tests on simply supported and pinned end connected beams and the degree of partial fixity is assessed. The failure load can be predicted using plastic analysis techniques.