The effects of valid and invalid expectations about stimulus valence on behavioural and electrophysiological responses to emotional pictures

Previous studies have shown that uncertainty about the expected valence of an upcoming stimulus modulates behavioural and neural responses to the stimulus. However, relatively little is known about how invalid emotion expectations (i.e. expecting a positive picture but seeing a negative picture) affect neural and behavioural responses. To investigate this, two experiments were conducted where participants viewed and rated the pleasantness of emotional pictures that were preceded by a cue. In Experiment 1, there were three cue conditions: uncertain, valid and invalid. The uncertain cue did not indicate the valence of the upcoming picture, whereas cues in the valid condition (70% of positive and negative cues) correctly indicated the valence of the upcoming picture. The remaining trials were invalid, where the valence of the picture differed from the expected valence. Behavioural results showed that invalidly cued negative pictures elicited more neutral valence ratings compared to validly cued pictures. In Experiment 2 we replicated the findings of Experiment 1, and in addition found an increased amplitude for the early (400 – 600 ms) portion of the late positive potential (LPP) for invalidly compared to validly cued pictures. Together, these results show that invalid expectations influence the neural and behavioural processing of subsequently presented emotional pictures, where invalidly cued pictures led to attenuated (i.e., more neutral) emotional responses, and enhanced early LPP amplitude, compared to validly cued pictures

Biological mechanisms of aging predict age-related disease multimorbidities in patients

Genetic, environmental and pharmacological interventions into the aging process can confer resistance to a multiple age-related diseases in laboratory animals, including rhesus monkeys. These findings imply that mechanisms of aging might contribute to patterns of multimorbidity in humans, and hence could be targeted to prevent multiple conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation, and found strong, non-random associations between age-related diseases and aging mechanisms, confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age-related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signalling pathway and activity of the ERK1/2 pathway played a significant role across multiple aging mechanisms and multiple, diverse age-related diseases. Mechanisms of aging therefore contribute to multiple age-related diseases and to patterns of human age-related multimorbidity, and could potentially be targeted to prevent more than one age-related condition in the same patient

Assessment of mRNA and microRNA Stabilization in Peripheral Human Blood for Multicenter Studies and Biobanks

In this study we evaluate the suitability of two methods of RNA conservation in blood samples, PAXgene and RNAlater, in combination with variable shipping conditions for their application in multicenter studies and biobanking. RNA yield, integrity, and purity as well as levels of selected mRNA and microRNA species were analyzed in peripheral human blood samples stabilized by PAXgene or RNAlater and shipped on dry ice or at ambient temperatures from the study centers to the central analysis laboratory. Both examined systems were clearly appropriate for RNA stabilization in human blood independently of the shipping conditions. The isolated RNA is characterized by good quantity and quality and well suited for downstream applications like quantitative RT-PCR analysis of mRNA and microRNA. Superior yield and integrity values were received using RNAlater. It would be reasonable to consider the production and approval of blood collection tubes prefilled with RNAlater to facilitate the use of this excellent RNA stabilization system in large studies

Self-stabilizing algorithms for Connected Vertex Cover and Clique decomposition problems

In many wireless networks, there is no fixed physical backbone nor centralized network management. The nodes of such a network have to self-organize in order to maintain a virtual backbone used to route messages. Moreover, any node of the network can be a priori at the origin of a malicious attack. Thus, in one hand the backbone must be fault-tolerant and in other hand it can be useful to monitor all network communications to identify an attack as soon as possible. We are interested in the minimum \emph{Connected Vertex Cover} problem, a generalization of the classical minimum Vertex Cover problem, which allows to obtain a connected backbone. Recently, Delbot et al.~\cite{DelbotLP13} proposed a new centralized algorithm with a constant approximation ratio of $2$ for this problem. In this paper, we propose a distributed and self-stabilizing version of their algorithm with the same approximation guarantee. To the best knowledge of the authors, it is the first distributed and fault-tolerant algorithm for this problem. The approach followed to solve the considered problem is based on the construction of a connected minimal clique partition. Therefore, we also design the first distributed self-stabilizing algorithm for this problem, which is of independent interest

TGF-b Superfamily Cytokine MIC-1/GDF15 Is a Physiological Appetite and Body Weight Regulator

The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1−/−) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1−/− mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1−/− mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage

The ERP correlates of self-knowledge in ageing

Self-knowledge is a type of personal semantic knowledge that concerns one’s self-image and personal identity. It has most often been operationalized as the summary of one’s personality traits (“I am a stubborn person”). Interestingly, recent studies have revealed that the neural correlates of self-knowledge can be dissociated from those of general semantic and episodic memory in young adults. However, studies of “dedifferentiation” or loss of distinctiveness of neural representations in ageing suggest that the neural correlates of self-knowledge might be less distinct from those of semantic and episodic memory in older adults. We investigated this question in an event-related potential (ERP) study with 28 young and 26 older adults while they categorised personality traits for their self-relevance (self-knowledge conditions), and their relevance to certain groups of people (general semantic condition). Participants then performed a recognition test for previously seen traits (episodic condition). The amplitude of the late positive component (LPC), associated with episodic recollection processes, differentiated the self-knowledge, general semantic, and episodic conditions in young adults, but not in older adults. However, in older adults, participants with higher composite episodic memory scores had more differentiated LPC amplitudes across experimental conditions. Moreover, consistent with the fact that age-related neural dedifferentiation may be material and region specific, in both age groups some differences between memory types were observed for the N400 component, associated with semantic processing. Taken together, these findings suggest that declarative memory subtypes are less distinct in ageing, but that the amount of differentiation varies with episodic memory function

Macrophage Inhibitory Cytokine 1 (MIC-1/GDF15) Decreases Food Intake, Body Weight and Improves Glucose Tolerance in Mice on Normal & Obesogenic Diets

Food intake and body weight are controlled by a variety of central and peripheral factors, but the exact mechanisms behind these processes are still not fully understood. Here we show that that macrophage inhibitory cytokine-1 (MIC-1/GDF15), known to have anorexigenic effects particularly in cancer, provides protection against the development of obesity. Both under a normal chow diet and an obesogenic diet, the transgenic overexpression of MIC-1/GDF15 in mice leads to decreased body weight and fat mass. This lean phenotype was associated with decreased spontaneous but not fasting-induced food intake, on a background of unaltered energy expenditure and reduced physical activity. Importantly, the overexpression of MIC-1/GDF15 improved glucose tolerance, both under normal and high fat-fed conditions. Altogether, this work shows that the molecule MIC-1/GDF15 might be beneficial for the treatment of obesity as well as perturbations in glucose homeostasis

GMP-grade manufacturing and quality control of a non-virally engineered advanced therapy medicinal product for personalized treatment of age-related macular degeneration

The introduction of new therapeutics requires validation of Good Manufacturing Practice (GMP)-grade manufacturing including suitable quality controls. This is challenging for Advanced Therapy Medicinal Products (ATMP) with personalized batches. We have developed a person-alized, cell-based gene therapy to treat age-related macular degeneration and established a vali-dation strategy of the GMP-grade manufacture for the ATMP; manufacturing and quality control were challenging due to a low cell number, batch-to-batch variability and short production duration. Instead of patient iris pigment epithelial cells, human donor tissue was used to produce the transfected cell product ("tIPE"). We implemented an extended validation of 104 tIPE productions. Procedure, operators and devices have been validated and qualified by determining cell number, viability, extracellular DNA, sterility, duration, temperature and volume. Transfected autologous cells were transplanted to rabbits verifying feasibility of the treatment. A container has been engineered to ensure a safe transport from the production to the surgery site. Criteria for successful validation and qualification were based on tIPE's Critical Quality Attributes and Process Parameters, its manufacture and release criteria. The validated process and qualified operators are essential to bring the ATMP into clinic and offer a general strategy for the transfer to other manufacture centers and personalized ATMPs

Semiochemical-based alternatives to synthetic toxicant insecticides for pollen beetle management

There is an urgent need to develop sustainable pest management systems to protect arable crops in order to replace the current over-reliance on synthetic insecticides. Semiochemicals are insect- or plant-derived chemicals that are used by organisms as information signals. Integrated pest management tools are currently in development that utilise semiochemicals to manipulate the behaviour of pest insects and their natural enemies to provide effective control of pests within the crop. These innovative tools usually require fewer inputs and can involve multiple elements therefore reducing the likelihood of resistance developing compared with use of synthetic toxicants. We review here the life cycle of the pollen beetle Brassicogethes aeneus (previously known as Meligethes aeneus) which is a pest insect of oilseed rape (Brassica napus) and describe the current knowledge of any behaviour mediated by semiochemicals in this species. We discuss the behavioural processes where semiochemical-based control approaches may be appropriate and consider how these approaches could be integrated into an integrated pest management strategy for this important arable crop