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

Soil physical properties and root growth of radiata pine

Soil water potential decreased exponentially and soil strength increased logarithmically as the volumetric water content decreased in soils of contrasting texture at a range of bulk densities. Soil air-filled porosity was a linear function of volumetric water content. At constant soil strength and non-limiting soil air-filled porosity (≥ 0.16 cm³ cm-³ the root elongation rate of radiata pine seedlings decreased linearly with soil water potential in the range - 0.01 to - 0.20 MPa. The rate of decrease in elongation rate was reduced with increasing soil strength. When soil water potential was < - 0.20 MPa, the root elongation rate was linearly related to the log of negative soil water potential. The root elongation rate decreased exponentially with increase of soil strength at constant soil matric potential and non-limiting air-filled porosity. This relationship was independent of both soil water potential and soil texture. However the diameters of both root and root tip increased, but root biomass decreased with increase of soil strength. There was no significant osmotic regulation at water potentials in the rooting media of ≥ - 0.2 MPa. Osmotic regulation commenced at < - 0.20 MPa and this partially compensated for the turgor loss from water stress. The wall yielding coefficient decreased with loss of turgor. The reduction in the root elongation rate with decreased water potential was an integrated effect of both decreased turgor pressure and reduced wall yielding coefficient. Roots osmotically regulated against increasing soil strength. No significant relationship between yield turgor pressure and both water potential and soil strength was observed. When soil air-filled porosity was non-limiting, root elongation rate in soil (∆R) was determined by soil matric potential (Ψm) and soil strength (Q) and was best described by a non-linear model: ∆R = α e-βQ + γѰm. The effect of water potential in decreasing root growth was most pronounced at low soil strength. Roots of radiata pine are able to penetrate higher soil strength at higher soil matric potential, and root growth of radiate pine seedlings ceased at higher soil matric potential in compacted soil than in loose soil

Elaboration et étude de nouveaux matériaux de cathode, dérivés de LiCoO2, par un procédé de desintercalation chimique

This work is pointed to the study of cathode materials for lithium batteries based on LixCoO2 (x = 0.19-1.0), LixCo (1-y) FeyO2 (x <1, y = 0-0.5) and LixCo (1-y) NiyO2 (x <1, y = 0-1), by the use of a chemical deintercalation method of lithium. Chemical deintercalation produces stable materials in the range of x = 0.4-1. For x <0.4 a decomposition occurs with the formation of Co3O4. The materials are analyzed by X-ray diffraction, which shows that all the compounds have a hexagonal lattice, whose parameter c increases by the deintercalation, and the parameter a decreases to a certain limit. The CoO6 octahedras become more distorted by deintercalation, which increases the metastability of the phases. A progressive charge transfer is recorded between Co4 + and O2-, which leads to the appearance of gaps in the oxygen subnetwork, producing a progressive loss of oxygen. Substitution of Co by Fe induces an increase in the cation order., an increase in the distortion of Co (Fe) O6 octahedra, along with a widening of the van der Waals gap. The deintercalated compounds containing iron are analyzed by Mossbauer spectroscopy, which shows that the iron does not change to the oxidation state 4+. Substitution of Co with Ni leads to thermodynamically more stable compounds, which can generate higher rates of desintercalation (x minimum = 0.21). From an electrochemical point of view, chemical deintercalation induces structural modifications that make the materials more suitable for subsequent charge-discharge processes.Ce travail porte sur l'étude des nouveaux matériaux de cathode pour les batteries au lithium à base de LixCoO2 (x=0.19-1.0), LixCo(1-y)FeyO2 (x<1, y=0-0. 5) et LixCo(1-y)NiyO2 (x<1, y=0-1), par l'utilisation d'une méthode de desintercalation chimique du lithium. La desintercalation chimique produit des matériaux stables sur le domaine de x=0.4-1. Pour x<0.4 il se produit une décomposition avec la formation du Co3O4. Les matériaux sont analysés par diffraction RX, qui montre que tous les composés ont une maille hexagonale, dont le paramètre c augmente par la desintercalation, et le paramètre a diminue jusqu'a une limite. Les octaedres CoO6 deviennent plus distordus par desintercalation, ce qui augmente la métastabilité des phases. Un transfert progressif de charge est enregistré entre Co4+ et O2-, qui conduit à l'apparition des lacunes dans le sous-réseau oxygène, qui se manifestent sous la forme d'une perte progressive de l'oxygène. La substitution du Co par Fe induit une augmentation de l'ordre cationique, une augmentation de la distorsion des octaèdres Co(Fe)O6, en même temps qu'un élargissement du gap de van der Waals. Les composés desintercalés, contenant du fer sont analysés par spectroscopie Mossbauer, qui montre que le fer ne passe pas à l'état d'oxydation 4+. La substitution du Co par Ni conduit à des composés plus stables thermodynamiquement, qui peuvent conduire à des taux de desintercalation plus forts (x minimum = 0.21). De point de vue électrochimique, la desintercalation chimique induit des modifications structurales qui rendent les materiaux plus aptes pour les processus ulterieurs de charge-décharge

Research on Multiobjective Optimization Algorithm for Cooperative Harvesting Trajectory Optimization of an Intelligent Multiarm Straw-Rotting Fungus Harvesting Robot

In view of the difficulties of fruit cluster identification, the specific harvesting sequence constraints of aggregated fruits, and the balanced harvesting task assignment for the multiple arms with a series-increasing symmetric shared (SISS) region, this paper proposes a multi-objective optimization algorithm, which combines genetic algorithm (GA) and ant colony optimization (ACO) stepwise, to optimize the multiarm cooperative harvesting trajectory of straw-rotting fungus to effectively improve the harvesting efficiency and the success rate of non-destructive harvesting. In this approach, firstly, the multiarm trajectory optimization problem is abstracted as a multiple travelling salesman problem (MTSP). Secondly, an improved local density clustering algorithm is designed to identify the cluster fruits to prepare data for harvesting aggregated fruits in a specific order later. Thirdly, the MTSP has been decomposed into M independent TSP (traveling salesman problem) problems by using GA, in which a new DNA (deoxyribonucleic acid) assignment rule is designed to resolve the problem of the average distribution of multiarm harvesting tasks with the SISS region. Then, the improved ant colony algorithm, combined with the auction mechanism, is adopted to achieve the shortest trajectory of each arm, which settles the difficulty that the clustered mature fruits should be harvested in a specified order. The experiments show that it can search for a relatively stable optimal solution in a relatively short time. The average harvesting efficiency is up to 1183 pcs/h and the average harvesting success rate is about 97%. Therefore, the proposed algorithm can better plan the harvesting trajectory for multiarm intelligent harvesting, especially for areas with many aggregated fruits

Investigations into Gas-Pore Effects on Fatigue Strength with a Peridynamic Approach

Fatigue evaluations are one of the main challenges to applying additively manufactured primary structural elements onto aircraft, especially for the gas-pore effects on fatigue strength. In this work, a bond decomposition strategy (BDS) in peridynamics (PD) is proposed; combined with our previously proposed model for fatigue damage, numerical simulations were performed to study the effect of Gas Pore (GP) on fatigue strength. Compared with the strategies in original paradigm of peridynamics, BDS achieves more elaborate description for bond status, predicts deformation fields around discontinuities with improved accuracy, and makes the spacing of material points become independent of discontinuity geometries. Two initiation modes are found in PD simulations, which exert an obvious impact on the final fatigue lifetimes; furthermore, it is revealed that GP not only leads to lower fatigue strength but also results in dispersity of fatigue strength data, in which dispersity is more severe if the GP size is larger, and the decline of fatigue strength is the most severe if the GP is located at subsurface for the same GP size

Phosphorus Removal From Aqueous Solution By Adsorption Onto La-modified Clinoptilolite

A La-modified clinoptilolite adsorbent was developed for phosphorus removal from aqueous solution. The effects of operational parameters such as pH, adsorbent dosage, contact time and temperature on phosphorus adsorption were investigated. The results showed that the phosphorus removal ratio of modified clinoptilolite (99.45%) was significantly improved, which was over triple than that of natural ones (31.50%) under optimum conditions. The adsorption process was well described by the pseudo-second-order kinetic model. Moreover, the adsorption data closely fitted the Freundlich isotherm model. The proper pH for phosphorus removal ranged from 5 to 8. The adsorption process was appeared to be controlled by chemical precipitation. The mechanism might involve ion complexation during subsequent adsorption of phosphorus on lanthanum hydroxides. It cost modified clinoptilolite less time to reach equilibrium. The application of modified clinoptilolite is available in wastewater treatment

Phosphorus Removal From Aqueous Solution By Adsorption Onto La-modified Clinoptilolite

A La-modified clinoptilolite adsorbent was developed for phosphorus removal from aqueous solution. The effects of operational parameters such as pH, adsorbent dosage, contact time and temperature on phosphorus adsorption were investigated. The results showed that the phosphorus removal ratio of modified clinoptilolite (99.45%) was significantly improved, which was over triple than that of natural ones (31.50%) under optimum conditions. The adsorption process was well described by the pseudo-second-order kinetic model. Moreover, the adsorption data closely fitted the Freundlich isotherm model. The proper pH for phosphorus removal ranged from 5 to 8. The adsorption process was appeared to be controlled by chemical precipitation. The mechanism might involve ion complexation during subsequent adsorption of phosphorus on lanthanum hydroxides. It cost modified clinoptilolite less time to reach equilibrium. The application of modified clinoptilolite is available in wastewater treatment

Amyloid-β42 clearance and neuroprotection mediated by X-box binding protein 1 signaling decline with aging in the Drosophila brain

The unfolded protein response (UPR) may be pathogenically related to Alzheimer's disease. Yet, the effects of chronic amyloid-β42 (Aβ42) accumulation and UPR activation upon neurotoxicity remain unclear. Here, we show that neuronal Aβ42 expression in Drosophila activated the inositol-requiring protein-1/X-box binding protein 1 (XBP1) UPR branch before the onset of behavioral impairment and persisted with aging. Early upregulation of hsc3/BiP, a target of XBP1 and activating transcription factor 6 pathways, was also sustained in old animals. Downregulation of XBP1 enhanced neurotoxicity and the accumulation of Aβ42 and polyubiquitinated proteins. Consistently, overexpression of spliced XBP1 reduced Aβ42 and improved geotaxis in old flies. The activation of protein kinase RNA-like endoplasmic reticulum (ER) kinase contributed to the age-dependent geotaxis deficit. Spliced XBP1 gene targets ER degradation-enhancing mannosidase-like protein 1, ER degradation-enhancing mannosidase-like protein 2, and HRD1 were elevated in 5-day-old Aβ42-expressing flies as compared to controls but not in 18-day-old flies. Our results indicate that inositol-requiring protein-1/XBP1 activation is neuroprotective and enhances Aβ42 clearance. They also suggest that such response becomes inefficient with aging.Fil: 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: 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: 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: 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

A Lightweight Position-Enhanced Anchor-Free Algorithm for SAR Ship Detection

As an active microwave device, synthetic aperture radar (SAR) uses the backscatter of objects for imaging. SAR image ship targets are characterized by unclear contour information, a complex background and strong scattering. Existing deep learning detection algorithms derived from anchor-based methods mostly rely on expert experience to set a series of hyperparameters, and it is difficult to characterize the unique characteristics of SAR image ship targets, which greatly limits detection accuracy and speed. Therefore, this paper proposes a new lightweight position-enhanced anchor-free SAR ship detection algorithm called LPEDet. First, to resolve unclear SAR target contours and multiscale performance problems, we used YOLOX as the benchmark framework and redesigned the lightweight multiscale backbone, called NLCNet, which balances detection speed and accuracy. Second, for the strong scattering characteristics of the SAR target, we designed a new position-enhanced attention strategy, which suppresses background clutter by adding position information to the channel attention that highlights the target information to more accurately identify and locate the target. The experimental results for two large-scale SAR target detection datasets, SSDD and HRSID, show that our method achieves a higher detection accuracy and a faster detection speed than state-of-the-art SAR target detection methods

Endoplasmic Reticulum Stress in Tauopathies: Contrasting Human Brain Pathology with Cellular and Animal Models

The accumulation and spreading of protein tau in the human brain are major features of neurodegenerative disorders known as tauopathies. In addition to several subcellular abnormalities, tau aggregation within neurons seems capable of triggering endoplasmic reticulum (ER) stress and the consequent unfolded protein response (UPR). In metazoans, full activation of a complex ER-UPR network may restore proteostasis and ER function or, if stress cannot be solved, commit cells to apoptosis. Due to these alternative outcomes (survival or death), the pharmacological manipulation of ER-UPR has become the focus of potential therapies in many human diseases, including tauopathies. Here we update and analyze the experimental data from human brain, cellular, and animal models linking tau accumulation and ER-UPR. We further discuss mechanistic aspects and put the ER-UPR into perspective as a possible therapeutic target in this group of diseases.Fil: 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: 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: 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: 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