Knockdown of Amyloid Precursor Protein in Zebrafish Causes Defects in Motor Axon Outgrowth

Amyloid precursor protein (APP) plays a pivotal role in Alzheimer’s disease (AD) pathogenesis, but its normal physiological functions are less clear. Combined deletion of the APP and APP-like protein 2 (APLP2) genes in mice results in post-natal lethality, suggesting that APP performs an essential, if redundant, function during embryogenesis. We previously showed that injection of antisense morpholino to reduce APP levels in zebrafish embryos caused convergent-extension defects. Here we report that a reduction in APP levels causes defective axonal outgrowth of facial branchiomotor and spinal motor neurons, which involves disorganized axonal cytoskeletal elements. The defective outgrowth is caused in a cell-autonomous manner and both extracellular and intracellular domains of human APP are required to rescue the defective phenotype. Interestingly, wild-type human APP rescues the defective phenotype but APPswe mutation, which causes familial AD, does not. Our results show that the zebrafish model provides a powerful system to delineate APP functions in vivo and to study the biological effects of APP mutations

The Comet Interceptor Mission

Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum ΔV capability of 600 ms−1. Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Analysis of Ergot Alkaloids

The principles and application of established and newer methods for the quantitative and semi-quantitative determination of ergot alkaloids in food, feed, plant materials and animal tissues are reviewed. The techniques of sampling, extraction, clean-up, detection, quantification and validation are described. The major procedures for ergot alkaloid analysis comprise liquid chromatography with tandem mass spectrometry (LC-MS/MS) and liquid chromatography with fluorescence detection (LC-FLD). Other methods based on immunoassays are under development and variations of these and minor techniques are available for specific purposes

Emerging Issues on Tropane Alkaloid Contamination of Food in Europe

The occurrence of tropane alkaloids (TAs), toxic plant metabolites, in food in Europe was studied to identify those TAs in food most relevant for human health. Information was extracted from the literature and the 2016 study from the European Food Safety Authority. Calystegines were identified as being inherent TAs in foods common in Europe, such as Solanum tuberosum (potato), S. melongena (eggplant, aubergine), Capsicum annuum (bell pepper) and Brassica oleracea (broccoli, Brussels sprouts). In addition, some low-molecular-weight tropanes and Convolvulaceae-type TAs were found inherent to bell pepper. On the other hand, atropine, scopolamine, convolvine, pseudotropine and tropine were identified as emerging TAs resulting from the presence of associated weeds in food. The most relevant food products in this respect are unprocessed and processed cereal-based foods for infants, young children or adults, dry (herbal) teas and canned or frozen vegetables. Overall, the occurrence data on both inherent as well as on associated TAs in foods are still scarce, highlighting the need for monitoring data. It also indicates the urge for food safety authorities to work with farmers, plant breeders and food business operators to prevent the spreading of invasive weeds and to increase awareness

Emerging Issues on Tropane Alkaloid Contamination of Food in Europe

The occurrence of tropane alkaloids (TAs), toxic plant metabolites, in food in Europe was studied to identify those TAs in food most relevant for human health. Information was extracted from the literature and the 2016 study from the European Food Safety Authority. Calystegines were identified as being inherent TAs in foods common in Europe, such as Solanum tuberosum (potato), S. melongena (eggplant, aubergine), Capsicum annuum (bell pepper) and Brassica oleracea (broccoli, Brussels sprouts). In addition, some low-molecular-weight tropanes and Convolvulaceae-type TAs were found inherent to bell pepper. On the other hand, atropine, scopolamine, convolvine, pseudotropine and tropine were identified as emerging TAs resulting from the presence of associated weeds in food. The most relevant food products in this respect are unprocessed and processed cereal-based foods for infants, young children or adults, dry (herbal) teas and canned or frozen vegetables. Overall, the occurrence data on both inherent as well as on associated TAs in foods are still scarce, highlighting the need for monitoring data. It also indicates the urge for food safety authorities to work with farmers, plant breeders and food business operators to prevent the spreading of invasive weeds and to increase awareness

A Team of Humanoid Game Commentators

Abstract — We present our work on creating a team of two humanoid robot commentators for soccer games of teams of four AIBO robots. The two humanoids stand on the side lines of the field, autonomously observe the game, wirelessly listen to a “game computer controller, ” and coordinate their annoucements with each other. Given the large degree of uncertainty and dynamics of the robot soccer games, we further introduce a “puppet master” system that allows humans to intervene in a sliding autonomy manner, prompting the robots to commentate on an event if undetected. The robots process then input from these three sources, namely own and shared vision, game controller, and occasional puppet master, to recognize events which they translate into a varied set of predefined annoucements. We present the behavioral architecture, the vision-based event recognition, and the game-based adaptive criteria for the selection of comments. We exemplify our development with multiple illustrative cases corresponding to different game situations. In summary, our work contributes a team of two humanoids fully executing a challenging observation, modeling, coordination, and reporting task