Gut physiology mediates a trade-off between adaptation to malnutrition and susceptibility to food-borne pathogens.

The animal gut plays a central role in tackling two common ecological challenges, nutrient shortage and food-borne parasites, the former by efficient digestion and nutrient absorption, the latter by acting as an immune organ and a barrier. It remains unknown whether these functions can be independently optimised by evolution, or whether they interfere with each other. We report that Drosophila melanogaster populations adapted during 160 generations of experimental evolution to chronic larval malnutrition became more susceptible to intestinal infection with the opportunistic bacterial pathogen Pseudomonas entomophila. However, they do not show suppressed immune response or higher bacterial loads. Rather, their increased susceptibility to P. entomophila is largely mediated by an elevated predisposition to loss of intestinal barrier integrity upon infection. These results may reflect a trade-off between the efficiency of nutrient extraction from poor food and the protective function of the gut, in particular its tolerance to pathogen-induced damage.

Rockfall susceptibility assessment and remote geological mapping with LiDAR point clouds

Characterizing the geological features and structures in three dimensions over inaccessible rock cliffs is needed to assess natural hazards such as rockfalls and rockslides and also to perform investigations aimed at mapping geological contacts and building stratigraphy and fold models. Indeed, the detailed 3D data, such as LiDAR point clouds, allow to study accurately the hazard processes and the structure of geologic features, in particular in vertical and overhanging rock slopes. Thus, 3D geological models have a great potential of being applied to a wide range of geological investigations both in research and applied geology projects, such as mines, tunnels and reservoirs. Recent development of ground-based remote sensing techniques (LiDAR, photogrammetry and multispectral / hyperspectral images) are revolutionizing the acquisition of morphological and geological information. As a consequence, there is a great potential for improving the modeling of geological bodies as well as failure mechanisms and stability conditions by integrating detailed remote data. During the past ten years several large rockfall events occurred along important transportation corridors where millions of people travel every year (Switzerland: Gotthard motorway and railway; Canada: Sea to sky highway between Vancouver and Whistler). These events show that there is still a lack of knowledge concerning the detection of potential rockfalls, making mountain residential settlements and roads highly risky. It is necessary to understand the main factors that destabilize rocky outcrops even if inventories are lacking and if no clear morphological evidences of rockfall activity are observed. In order to increase the possibilities of forecasting potential future landslides, it is crucial to understand the evolution of rock slope stability. Defining the areas theoretically most prone to rockfalls can be particularly useful to simulate trajectory profiles and to generate hazard maps, which are the basis for land use planning in mountainous regions. The most important questions to address in order to assess rockfall hazard are: Where are the most probable sources for future rockfalls located? What are the frequencies of occurrence of these rockfalls? I characterized the fracturing patterns in the field and with LiDAR point clouds. Afterwards, I developed a model to compute the failure mechanisms on terrestrial point clouds in order to assess the susceptibility to rockfalls at the cliff scale. Similar procedures were already available to evaluate the susceptibility to rockfalls based on aerial digital elevation models. This new model gives the possibility to detect the most susceptible rockfall sources with unprecented detail in the vertical and overhanging areas. The results of the computation of the most probable rockfall source areas in granitic cliffs of Yosemite Valley and Mont-Blanc massif were then compared to the inventoried rockfall events to validate the calculation methods. Yosemite Valley was chosen as a test area because it has a particularly strong rockfall activity (about one rockfall every week) which leads to a high rockfall hazard. The west face of the Dru was also chosen for the relevant rockfall activity and especially because it was affected by some of the largest rockfalls that occurred in the Alps during the last 10 years. Moreover, both areas were suitable because of their huge vertical and overhanging cliffs that are difficult to study with classical methods. Limit equilibrium models have been applied to several case studies to evaluate the effects of different parameters on the stability of rockslope areas. The impact of the degradation of rockbridges on the stability of large compartments in the west face of the Dru was assessed using finite element modeling. In particular I conducted a back-analysis of the large rockfall event of 2005 (265'000 m3) by integrating field observations of joint conditions, characteristics of fracturing pattern and results of geomechanical tests on the intact rock. These analyses improved our understanding of the factors that influence the stability of rock compartments and were used to define the most probable future rockfall volumes at the Dru. Terrestrial laser scanning point clouds were also successfully employed to perform geological mapping in 3D, using the intensity of the backscattered signal. Another technique to obtain vertical geological maps is combining triangulated TLS mesh with 2D geological maps. At El Capitan (Yosemite Valley) we built a georeferenced vertical map of the main plutonio rocks that was used to investigate the reasons for preferential rockwall retreat rate. Additional efforts to characterize the erosion rate were made at Monte Generoso (Ticino, southern Switzerland) where I attempted to improve the estimation of long term erosion by taking into account also the volumes of the unstable rock compartments. Eventually, the following points summarize the main out puts of my research: The new model to compute the failure mechanisms and the rockfall susceptibility with 3D point clouds allows to define accurately the most probable rockfall source areas at the cliff scale. The analysis of the rockbridges at the Dru shows the potential of integrating detailed measurements of the fractures in geomechanical models of rockmass stability. The correction of the LiDAR intensity signal gives the possibility to classify a point cloud according to the rock type and then use this information to model complex geologic structures. The integration of these results, on rockmass fracturing and composition, with existing methods can improve rockfall hazard assessments and enhance the interpretation of the evolution of steep rockslopes. -- La caractérisation de la géologie en 3D pour des parois rocheuses inaccessibles est une étape nécessaire pour évaluer les dangers naturels tels que chutes de blocs et glissements rocheux, mais aussi pour réaliser des modèles stratigraphiques ou de structures plissées. Les modèles géologiques 3D ont un grand potentiel pour être appliqués dans une vaste gamme de travaux géologiques dans le domaine de la recherche, mais aussi dans des projets appliqués comme les mines, les tunnels ou les réservoirs. Les développements récents des outils de télédétection terrestre (LiDAR, photogrammétrie et imagerie multispectrale / hyperspectrale) sont en train de révolutionner l'acquisition d'informations géomorphologiques et géologiques. Par conséquence, il y a un grand potentiel d'amélioration pour la modélisation d'objets géologiques, ainsi que des mécanismes de rupture et des conditions de stabilité, en intégrant des données détaillées acquises à distance. Pour augmenter les possibilités de prévoir les éboulements futurs, il est fondamental de comprendre l'évolution actuelle de la stabilité des parois rocheuses. Définir les zones qui sont théoriquement plus propices aux chutes de blocs peut être très utile pour simuler les trajectoires de propagation des blocs et pour réaliser des cartes de danger, qui constituent la base de l'aménagement du territoire dans les régions de montagne. Les questions plus importantes à résoudre pour estimer le danger de chutes de blocs sont : Où se situent les sources plus probables pour les chutes de blocs et éboulement futurs ? Avec quelle fréquence vont se produire ces événements ? Donc, j'ai caractérisé les réseaux de fractures sur le terrain et avec des nuages de points LiDAR. Ensuite, j'ai développé un modèle pour calculer les mécanismes de rupture directement sur les nuages de points pour pouvoir évaluer la susceptibilité au déclenchement de chutes de blocs à l'échelle de la paroi. Les zones sources de chutes de blocs les plus probables dans les parois granitiques de la vallée de Yosemite et du massif du Mont-Blanc ont été calculées et ensuite comparés aux inventaires des événements pour vérifier les méthodes. Des modèles d'équilibre limite ont été appliqués à plusieurs cas d'études pour évaluer les effets de différents paramètres sur la stabilité des parois. L'impact de la dégradation des ponts rocheux sur la stabilité de grands compartiments de roche dans la paroi ouest du Petit Dru a été évalué en utilisant la modélisation par éléments finis. En particulier j'ai analysé le grand éboulement de 2005 (265'000 m3), qui a emporté l'entier du pilier sud-ouest. Dans le modèle j'ai intégré des observations des conditions des joints, les caractéristiques du réseau de fractures et les résultats de tests géoméchaniques sur la roche intacte. Ces analyses ont amélioré l'estimation des paramètres qui influencent la stabilité des compartiments rocheux et ont servi pour définir des volumes probables pour des éboulements futurs. Les nuages de points obtenus avec le scanner laser terrestre ont été utilisés avec succès aussi pour produire des cartes géologiques en 3D, en utilisant l'intensité du signal réfléchi. Une autre technique pour obtenir des cartes géologiques des zones verticales consiste à combiner un maillage LiDAR avec une carte géologique en 2D. A El Capitan (Yosemite Valley) nous avons pu géoréferencer une carte verticale des principales roches plutoniques que j'ai utilisé ensuite pour étudier les raisons d'une érosion préférentielle de certaines zones de la paroi. D'autres efforts pour quantifier le taux d'érosion ont été effectués au Monte Generoso (Ticino, Suisse) où j'ai essayé d'améliorer l'estimation de l'érosion au long terme en prenant en compte les volumes des compartiments rocheux instables. L'intégration de ces résultats, sur la fracturation et la composition de l'amas rocheux, avec les méthodes existantes permet d'améliorer la prise en compte de l'aléa chute de pierres et éboulements et augmente les possibilités d'interprétation de l'évolution des parois rocheuses.

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci.

Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10(-3)), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10(-4)). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10(-4)) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other.

Antibiotic susceptibility of Neochlamydia hartmanellae and Parachlamydia acanthamoebae in amoebae.

Parachlamydia acanthamoebae and Neochlamydia hartmanellae are Chlamydia-related bacteria naturally infecting free-living amoebae. These strict intracellular bacteria might represent emerging pathogens. Recent studies report an association with lower respiratory tract infections, especially with pneumonia where they have been identified as a potential causative agent in 1-2% of cases. In this study, we defined the antibiotic susceptibility of N. hartmanellae, two strains of P. acanthamoebae and two yet unclassified Parachlamydiaceae strains using a quantitative approach. We confirmed the results obtained earlier for P. acanthamoebae strain Bn9 in an observational study. Macrolides (MICs < 0.06-0.5 μg/ml), rifampicin (MICs 0.25-2) and doxycycline (2-4 μg/ml) were active against P. acanthamoebae strains and Neochlamydia. All strains were resistant to amoxicillin, ceftriaxone and imipenem (MIC ≥32 μg/ml). Similarly to other Chlamydia-related bacteria, all investigated Parachlamydiaceae were resistant to quinolones (MICs ≥ 16 μg/ml). Therefore, we recommend a treatment with macrolides for Parachlamydia-associated pneumonia.

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

Effect of partial-thickness tear on loading capacities of the supraspinatus tendon: a finite element analysis.

Partial-thickness tears of the supraspinatus tendon frequently occur at its insertion on the greater tubercule of the humerus, causing pain and reduced strength and range of motion. The goal of this work was to quantify the loss of loading capacity due to tendon tears at the insertion area. A finite element model of the supraspinatus tendon was developed using in vivo magnetic resonance images data. The tendon was represented by an anisotropic hyperelastic constitutive law identified with experimental measurements. A failure criterion was proposed and calibrated with experimental data. A partial-thickness tear was gradually increased, starting from the deep articular-sided fibres. For different values of tendon tear thickness, the tendon was mechanically loaded up to failure. The numerical model predicted a loss in loading capacity of the tendon as the tear thickness progressed. Tendon failure was more likely when the tendon tear exceeded 20%. The predictions of the model were consistent with experimental studies. Partial-thickness tears below 40% tear are sufficiently stable to persist physiotherapeutic exercises. Above 60% tear surgery should be considered to restore shoulder strength.

El patrimoni educatiu, un element d'una pedagogia cultural i ciutadana

El present article desenvolupa els eixos de pensament que s’estan elaborant des de diferents angles sobre el patrimoni educatiu. Una revisió sobre la importància de les aportacions de les investigacions a l’entorn del patrimoni educatiu permet assenyalar els punts d’inflexió dels museus pedagògics en l’actualitat. Entre aquests destaca la influència que els museus pedagògics, a través de les seves activitats de recerca, difusió i formació, exerceixen en la conformació d’una pedagogia cultural i ciutadana. Amb la irrupció d’una pedagogia d’encuny culturalista, els museus pedagògics recuperen els fonaments i formes de creació de discurs de la pedagogia cultural sorgida a l’inici del segle XX, tot introduint les aproximacions etnogràfiques en les arrels dels estudis i investigacions. D’altra banda, també ressalta el fet que els museus pedagògics resignifiquen la seva acció a partir de les pedagogies ètiques que atorguen un paper principal als projectes de ciutadania. Així, doncs, ambdós aspectes, cultura i ciutadania, es perfilen com els trets diferencials dels museus pedagògics actuals. A més, aquesta caracterització requereix encara d’una reflexió sobre el sentit i amplitud dels canvis introduïts en els projectes museístics.

Development of a microprocessor controlled energy harvester using a Peltier element

Nowadays it is necessary to research other types of energy alternatives and find the way to supply and save the energy we waste. The aim of the project consist of programming a microprocessor to measure if an oven radiates heat to the exterior, for the measure It is used a Peltier element that generates a voltage depending of the temperature difference between the oven and the air of the place where the oven is situated; The energy generated by the oven will be recollected in a condensor. A sensor will be used to know the exact measure. The second part of the project the main propose, is the development of a harvester. The microprocessor will use the voltage produced by the Peltier element to supply the electricity that it needs to work. A low power circuit and the appropriate software are needed to save the voltage generated.

Etiology, antimicrobial susceptibility profile of Staphylococcus spp. and risk factors associated with bovine mastitis in the states of Bahia and Pernambuco

The purpose of this paper was to study the etiology of mastitis, determine the antimicrobial susceptibility profile of Staphylococcus spp. and to identify the risk factors associated with infection in dairy cows in the states of Bahia and Pernambuco, Brazil. From the 2,064 milk samples analyzed, 2.6% were associated with cases of clinical mastitis and 28.2% with subclinical mastitis. In the microbiological culture, Staphylococcus spp. (49.1%) and Corynebacterium spp. (35.3%) were the main agents found, followed by Prototheca spp. (4.6%) and Gram negative bacilli (3.6%). In the antimicrobial susceptibility testing, all 218 Staphylococcus spp. were susceptible to rifampicin and the least effective drug was amoxicillin (32.6%). Multidrug resistance to three or more drugs was observed in 65.6% of Staphylococcus spp. The risk factors identified for mastitis were the extensive production system, not providing feed supplements, teat drying process, not disinfecting the teats before and after milking, and inadequate hygiene habits of the milking workers. The presence of multiresistant isolates in bovine milk demonstrates the importance of the choice and appropriate use of antimicrobial agents. Prophylactic and control measures, including teat antisepsis and best practices for achieving hygienic milking should be established in order to prevent new cases of the disease in herds.

An Hp-Adaptive Hierarchical Formulation for the Boundary Element Method Applied to Elasticity in Two Dimensions

This paper presents an HP-Adaptive Procedure with Hierarchical formulation for the Boundary Element Method in 2-D Elasticity problems. Firstly, H, P and HP formulations are defined. Then, the hierarchical concept, which allows a substantial reduction in the dimension of equation system, is introduced. The error estimator used is based on the residual computation over each node inside an element. Finally, the HP strategy is defined and applied to two examples.

Mefenpyr-diethyl action on fenoxaprop-p-ethyl detoxification in wheat varieties

Safeners protect crops against herbicide injury. The aim of this study was to examine the differential susceptibility of five wheat (Triticum aestivum) varieties to the herbicide fenoxaprop-p-ethyl, as well as the performance of mefenpyr-diethyl on minimizing herbicide injury and on lipid contents. Varieties BRS 49, CD 104, CEP 24, IAPAR 78 and Rubi were sprayed with fenoxaprop-p-ethyl (69 g ha¹), fenoxaprop-p-ethyl + mefenpyr-diethyl (69 g + 18.75 g ha-1), or mefenpyr-diethyl (18.75 g ha-1). Plants were evaluated visually for injury at 7 and 14 days after treatment (DAT). Glutathione S-transferase (GST) activity was assayed in aerial parts at 7 DAT, and lipid content was measured at 14 DAT. Varieties CEP 24, IAPAR 78 and Rubi were more tolerant to fenoxaprop-p-ethyl than BRS 49, and CD 104 rapidly recovering from the slight phytotoxicity symptoms produced by the herbicide. Mefenpyr-diethyl prevented crop injury associated with the herbicide. GST activity did not correlate directly with fenoxaprop-p-ethyl detoxification. However, lipid content was related to the susceptibility of wheat to fenoxaprop-p-ethyl treatment.

Differential susceptibility of biotypes of conyza sumatrensis to Chlorimuron-ethyl herbicide

Horseweed (Conyza spp.) is an annual weed, infesting soybean crops in southern Brazil, with chlorimuron-ethyl being one of the most commonly used herbicides for its control. However, in recent soybean harvests, an unsatisfactory control of this weed using this herbicide was observed, generating suspicion regarding the selection of resistant biotypes. The objective of this study was to evaluate the susceptibility of horseweed biotypes to the herbicide chlorimuron-ethyl. Two experiments were conducted in a greenhouse; in the first one, the biotypes were selected selected, and the second experiment was arranged in a 5 x 5 factorial in a completely randomized design with four replications. The treatments used in the preparation of the dose response curves were doses of the herbicide chlorimuron-ethyl (0.0, 1.56, 3.13, 6.25, 12.5, and 25 g ha-1), applied on the five horseweed biotypes at the 3-4 leaf growth stage. The variables evaluated were visual control percentage and shoot dry weight, compared to the control without herbicide application, and plant acetolactate accumulation. It was concluded that there is a differential susceptibility among the biotypes at doses of less than 20 g ha-1 (dose response curves), which indicates low-level resistance. The practical consequences are the indications of chlorimuron-ethyl application at the maximum doses recomended and that the practice of rotating mechanisms of action must be used in the chemical weed management of these areas.