A Novel Genetic Screen Identifies Modifiers of Age-Dependent Amyloid β Toxicity in the Drosophila Brain

The accumulation of amyloid β peptide (Aβ) in the brain of Alzheimer's disease (AD) patients begins many years before clinical onset. Such process has been proposed to be pathogenic through the toxicity of Aβ soluble oligomers leading to synaptic dysfunction, phospho-tau aggregation and neuronal loss. Yet, a massive accumulation of Aβ can be found in approximately 30% of aged individuals with preserved cognitive function. Therefore, within the frame of the "amyloid hypothesis", compensatory mechanisms and/or additional neurotoxic or protective factors need to be considered and investigated. Here we describe a modifier genetic screen in Drosophila designed to identify genes that modulate toxicity of Aβ42 in the CNS. The expression of Aβ42 led to its accumulation in the brain and a moderate impairment of negative geotaxis at 18 days post-eclosion (d.p.e) as compared with genetic or parental controls. These flies were mated with a collection of lines carrying chromosomal deletions and negative geotaxis was assessed at 5 and 18 d.p.e. Our screen is the first to take into account all of the following features, relevant to sporadic AD: (1) pan-neuronal expression of wild-type Aβ42; (2) a quantifiable complex behavior; (3) Aβ neurotoxicity associated with progressive accumulation of the peptide; and (4) improvement or worsening of climbing ability only evident in aged animals. One hundred and ninety-nine deficiency (Df) lines accounting for ~6300 genes were analyzed. Six lines, including the deletion of 52 Drosophila genes with human orthologs, significantly modified Aβ42 neurotoxicity in 18-day-old flies. So far, we have validated CG11796 and identified CG17249 as a strong candidate (whose human orthologs are HPD and PRCC, respectively) by using RNAi or mutant hemizygous lines. PRCC encodes proline-rich protein PRCC (ppPRCC) of unknown function associated with papillary renal cell carcinoma. HPD encodes 4-hydroxyphenylpyruvate dioxygenase (HPPD), a key enzyme in tyrosine degradation whose Df causes autosomal recessive Tyrosinemia type 3, characterized by mental retardation. Interestingly, lines with a partial Df of HPD ortholog showed increased intraneuronal accumulation of Aβ42 that coincided with geotaxis impairment. These previously undetected modifiers of Aβ42 neurotoxicity in Drosophila warrant further study to validate their possible role and significance in the pathogenesis of sporadic AD.Fil: Belfiori Carrasco, Lautaro Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Marcora, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Bocai, Nadia Irina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ceriani, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Crime prediction and monitoring in Porto, Portugal, using machine learning, spatial and text analytics

Crimes are a common societal concern impacting quality of life and economic growth. Despite the global decrease in crime statistics, specific types of crime and feelings of insecurity, have often increased, leading safety and security agencies with the need to apply novel approaches and advanced systems to better predict and prevent occurrences. The use of geospatial technologies, combined with data mining and machine learning techniques allows for significant advances in the criminology of place. In this study, official police data from Porto, in Portugal, between 2016 and 2018, was georeferenced and treated using spatial analysis methods, which allowed the identification of spatial patterns and relevant hotspots. Then, machine learning processes were applied for space-time pattern mining. Using lasso regression analysis, significance for crime variables were found, with random forest and decision tree supporting the important variable selection. Lastly, tweets related to insecurity were collected and topic modeling and sentiment analysis was performed. Together, these methods assist interpretation of patterns, prediction and ultimately, performance of both police and planning professionals

The Rhizobium etli σ(70) (SigA) factor recognizes a lax consensus promoter

A collection of Rhizobium etli promoters was isolated from a genomic DNA library constructed in the promoter-trap vector pBBMCS53, by their ability to drive the expression of a gusA reporter gene. Thirty-seven clones were selected, and their transcriptional start-sites were determined. The upstream sequence of these 37 start-sites, and the sequences of seven previously identified promoters were compared. On the basis of sequence conservation and mutational analysis, a consensus sequence CTTGACN(16–23)TATNNT was obtained. In this consensus sequence, nine on of twelve bases are identical to the canonical Escherichia coli σ(70) promoter, however the R.etli promoters only contain 6.4 conserved bases on average. We show that the R.etli sigma factor SigA recognizes all R.etli promoters studied in this work, and that E.coli RpoD is incapable of recognizing them. The comparison of the predicted structure of SigA with the known structure of RpoD indicated that regions 2.4 and 4.2, responsible for promoter recognition, are different only by a single amino acid, whereas the region 1 of SigA contains 72 extra residues, suggesting that the differences contained in this region could be related to the lax promoter recognition of SigA

Recent advances in the theory and practice of logical analysis of data

Logical Analysis of Data (LAD) is a data analysis methodology introduced by Peter L. Hammer in 1986. LAD distinguishes itself from other classification and machine learning methods by the fact that it analyzes a significant subset of combinations of variables to describe the positive or negative nature of an observation and uses combinatorial techniques to extract models defined in terms of patterns. In recent years, the methodology has tremendously advanced through numerous theoretical developments and practical applications. In the present paper, we review the methodology and its recent advances, describe novel applications in engineering, finance, health care, and algorithmic techniques for some stochastic optimization problems, and provide a comparative description of LAD with well-known classification methods

Electron–phonon coupling and superconductivity in a 2D Tl–Pb compound on Si(111)

[EN] Electron-phonon interaction in a single-layer Tl-Pb compound on Si(111) is investigated within the density-functional theory and linear-response approach in the mixed-basis pseudopotential representation. It is found that phonon-induced scattering of electrons at the Fermi level is primarily determined by surface electronic states responsible for bonding at the interface and by low-energy, predominantly shear-vertical vibrations of adatoms. The contribution of substrate-localized vibrations involved in the electron-phonon scattering turns out to be small. We have also estimated the superconducting transition temperature T-c by solving the linearized gap equation of the Eliashberg theory. An analysis of phonon-mediated transitions for a number of electronic states in the Tl-Pb surface bands showed that the strength of the coupling varies with the binding energy, increasing as it approaches the Fermi level, and significantly depends on the surface band to which the state belongs.This work was supported by the University of the Basque Country (Grants no. GIC07-IT-366-07 and No. IT-756-13) and the Spanish Ministry of Science and Innovation (Grant no. FIS2016-75862-P). The authors acknowledge support by the state of Baden-Wurttemberg through bwHPC

Identification of groundwater patterns based on remote sensing. Case study: fractured hard rock aquifers in Wako Kungo, Angola

Groundwater is considered the major portion of the world´s freshwater resources. Groundwater in Angola is utilised for several urban centres on the coast and in the arid southern provinces and is a major source for rural supply. The main objective of the present work was to process and analyse optical and radar images that cover the study area and combine them in a GIS to identify groundwater patterns in fractured hard rock aquifers and sedimentary basins in the valleys. Field observations and the geological data allowed to distinguish two main aquifer types in the study are: one detritic and other fractured that is the object of this study. The results from the study show that, integration and interpretation of different thematic layers such as lineament, drainage, vegetation index and on field data is useful to predict the recharge and discharge areas. Concerning to water quality, hydrogeochemistry analysis shows that, to the physical-chemical parameters analysed, groundwater in the study area can be evaluated as good quality water; Identificação de padrões de água subterrânea com base em detecção remota. Estudo de caso: aquíferos em rochas duras fracturadas no Wako Kungo, Angola Resumo: A água subterrânea é considerada a maior porção dos recursos de água doce do mundo. A água subterrânea é utilizada em vários centros urbanos das províncias do litoral de Angola e nas províncias áridas do Sul é uma das principais fontes de abastecimento nas zonas rurais. O presente trabalho tem como objetivo principal processar e analisar imagens ópticas e de radar que cobrem a área de estudo e combiná-las em um SIG para identificar padrões de águas subterrâneas em aquíferos fracturados e bacias sedimentares nos vales. As observações de campo e os dados geológicos permitiram distinguir dois principais tipos de aquíferos na área de estudo, um de tipo detrítico e outro fracturado, que é o objecto deste estudo. Os resultados mostram que a integração e interpretação de diferentes camadas temáticas tais como lineamentos, drenagem, índice de vegetação e dados de campo, é útil para prever áreas de recarga e descarga. No que diz respeito à qualidade da água, o estudo hidrogeoquímico mostrou que para os parâmetros físico-químicos analisados, as águas subterrâneas da área de estudo podem ser avaliadas como águas de boa qualidade

Estudo de aquíferos fraturados e porosos com base em deteção remota em Wako Kungo, Angola

A água subterrânea em Angola é usada como água de abastecimento para várias áreas urbanas e é também uma importante fonte de abastecimento de água rural e para a agricultura. Com a crescente procura de água, estudos anteriores relacionados com o uso de deteção remota e SIGs no mapeamento de águas subterrâneas podem mostrar-se altamente úteis no desenvolvimento e gestão eficiente e controlada dos recursos hídricos subterrâneos

Quick Wins Workshop and Companies Profiling to Analyze Industrial Symbiosis Potential. Valenciaport's Cluster as Case Study

[EN] Industrial symbiosis (IS) improves resource efficiency and creates sustainable opportunities by encouraging synergies between industries. However, managers still have difficulties in promoting IS, given the lack of appropriate managerial tools to efficiently obtain an overview of IS potential. In this paper, a procedure merging the Quick Wins Workshop format with clustering techniques is proposed, in order to both identify IS opportunities and support IS creation in the industrial cluster of Valenciaport. A total of 18 stakeholders took part in the study. As a result, 79 different resources classified into eight categories-materials (16), goods (14), space (11), expertise (11), energy (9), services (8), hydrocarbons (7), and water (3)-were derived and a total of 78 possible matchings were found. The creation of IS was supported by the clustering methods, which allow for the definition of common symbiotic features among stakeholders, classifying them into groups with similar IS potential. Three IS profiles were identified (high, medium, and low IS potential) and two strategic projects were devised, accordingly. It can be concluded that the proposed procedure provides useful managerial tools to identify resource flows, uncover patterns of exchange, identify possible matchings, and devise projects in communities interested in fostering IS from scratch.This research was funded by the Valencian Institute of Business Competitiveness (IVACE), grant number IMAMCA/2019/1.Artacho Ramírez, MÁ.; Pacheco-Blanco, B.; Cloquell Ballester, VA.; Vicent, M.; Celades, I. (2020). Quick Wins Workshop and Companies Profiling to Analyze Industrial Symbiosis Potential. Valenciaport's Cluster as Case Study. 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