Punctuated chromatin states regulate Plasmodium falciparum antigenic variation at the intron and 2 kb upstream regions

2 kb upstream region FAIRE-Seq signal comparison between var genes and different gene families (P-value is calculated based on Wilcoxon-Rank-Sum test, FDR indicates false discovery rate). (XLSX 53 kb

A comparison of AC and HVDC options for the connection of offshore wind generation in Great Britain

This paper presents a comparison of two forms of cable connection of a distant offshore wind farm to a transmission system: AC and HVDC. The requirements of relevant industry standards in Great Britain (GB) that drive a connection design and, hence, its cost are highlighted along with an analysis of the ways in which AC cable connections might be made to comply while facilitating export of active power. Dynamic studies investigating responses to grid-side short circuit faults show that, in the particular scenarios studied, an AC connection of a wind farm in the place of a large synchronous generator is marginally detrimental while an HVDC connection is beneficial. A comparison of costs shows that the cross-over distance at which HVDC is cheaper than AC for wind farms of different sizes occurs at longer distances than have hitherto commonly been assumed, and AC connections benefit from reactive compensation not only at the point of common coupling and wind farm end but also at the connection mid-point

Ketamine administration in healthy volunteers reproduces aberrant agency experiences associated with schizophrenia

Introduction. Aberrant experience of agency is characteristic of schizophrenia. An understanding of the neurobiological basis of such experience is therefore of considerable importance for developing successful models of the disease. We aimed to characterise the effects of ketamine, a drug model for psychosis, on sense of agency (SoA). SoA is associated with a subjective compression of the temporal interval between an action and its effects: This is known as "intentional binding". This action-effect binding provides an indirect measure of SoA. Previous research has found that the magnitude of binding is exaggerated in patients with schizophrenia. We therefore investigated whether ketamine administration to otherwise healthy adults induced a similar pattern of binding. Methods. 14 right-handed healthy participants (8 female; mean age 22.4 years) were given low-dose ketamine (100 ng/mL plasma) and completed the binding task. They also underwent structured clinical interviews. Results. Ketamine mimicked the performance of schizophrenia patients on the intentional binding task, significantly increasing binding relative to placebo. The size of this effect also correlated with aberrant bodily experiences engendered by the drug. Conclusions. These data suggest that ketamine may be able to mimic certain aberrant agency experiences that characterise schizophrenia. The link to individual changes in bodily experience suggests that the fundamental change produced by the drug has wider consequences in terms of individuals' experiences of their bodies and movements

Malaria infected red blood cells release small regulatory RNAs through extracellular vesicles

The parasite Plasmodium falciparum causes the most severe form of malaria. Cell communication between parasites is an important mechanism to control population density and differentiation. The infected red blood cells (iRBCs) release small extracellular vesicles (EVs) that transfer cargoes between cells. The EVs synchronize the differentiation of the asexual parasites into gametocytes to initiate the transmission to the mosquito. Beside their role in parasite communication, EVs regulate vascular function. So far, the exact cargoes responsible for cellular communication remain unknown. We isolated EVs from cultured iRBCs to determine their small RNA content. We identified several types of human and plasmodial regulatory RNAs. While the miRNAs and tRNA-derived fragments were the most abundant human RNAs, we also found Y-RNAs, vault RNAs, snoRNAs and piRNAs. Interestingly, we found about 120 plasmodial RNAs, including mRNAs coding for exported proteins and proteins involved in drug resistance, as well as non-coding RNAs, such as rRNAs, small nuclear (snRNAs) and tRNAs. These data show, that iRBC-EVs carry small regulatory RNAs. A role in cellular communication is possible since the RNAs were transferred to endothelial cells. Furthermore, the presence of Plasmodium RNAs, in EVs suggests that they may be used as biomarker to track and detect disease

Changes in resting neural connectivity during propofol sedation.

BACKGROUND: The default mode network consists of a set of functionally connected brain regions (posterior cingulate, medial prefrontal cortex and bilateral parietal cortex) maximally active in functional imaging studies under "no task" conditions. It has been argued that the posterior cingulate is important in consciousness/awareness, but previous investigations of resting interactions between the posterior cingulate cortex and other brain regions during sedation and anesthesia have produced inconsistent results. METHODOLOGY/PRINCIPAL FINDINGS: We examined the connectivity of the posterior cingulate at different levels of consciousness. "No task" fMRI (BOLD) data were collected from healthy volunteers while awake and at low and moderate levels of sedation, induced by the anesthetic agent propofol. Our data show that connectivity of the posterior cingulate changes during sedation to include areas that are not traditionally considered to be part of the default mode network, such as the motor/somatosensory cortices, the anterior thalamic nuclei, and the reticular activating system. CONCLUSIONS/SIGNIFICANCE: This neuroanatomical signature resembles that of non-REM sleep, and may be evidence for a system that reduces its discriminable states and switches into more stereotypic patterns of firing under sedation

Confidence and psychosis: a neuro-computational account of contingency learning disruption by NMDA blockade.

A state of pathological uncertainty about environmental regularities might represent a key step in the pathway to psychotic illness. Early psychosis can be investigated in healthy volunteers under ketamine, an NMDA receptor antagonist. Here, we explored the effects of ketamine on contingency learning using a placebo-controlled, double-blind, crossover design. During functional magnetic resonance imaging, participants performed an instrumental learning task, in which cue-outcome contingencies were probabilistic and reversed between blocks. Bayesian model comparison indicated that in such an unstable environment, reinforcement learning parameters are downregulated depending on confidence level, an adaptive mechanism that was specifically disrupted by ketamine administration. Drug effects were underpinned by altered neural activity in a fronto-parietal network, which reflected the confidence-based shift to exploitation of learned contingencies. Our findings suggest that an early characteristic of psychosis lies in a persistent doubt that undermines the stabilization of behavioral policy resulting in a failure to exploit regularities in the environment.FV was supported by the Groupe Pasteur Mutualité. RG was supported by the Fondation pour la Recherche Médicale and the Fondation Bettencourt Schueller. SP is supported by a Marie Curie Intra-European fellowship (FP7-PEOPLE-2012-IEF). AF was supported by National Health and Medical Research Council grants (IDs : 1050504 and 1066779) and an Australian Research Council Future Fellowship (ID: FT130100589). This work was supported by the Wellcome Trust and the Bernard Wolfe Health Neuroscience Fund.This is the final version of the article. It first appeared from the Nature Publishing Group via http://dx.doi.org/10.1038/mp.2015.7

A supervised blood vessel segmentation technique for digital Fundus images using Zernike Moment based features

This paper proposes a new supervised method for blood vessel segmentation using Zernike moment-based shape descriptors. The method implements a pixel wise classification by computing a 11-D feature vector comprising of both statistical (gray-level) features and shape-based (Zernike moment) features. Also the feature set contains optimal coefficients of the Zernike Moments which were derived based on the maximum differentiability between the blood vessel and background pixels. A manually selected training points obtained from the training set of the DRIVE dataset, covering all possible manifestations were used for training the ANN-based binary classifier. The method was evaluated on unknown test samples of DRIVE and STARE databases and returned accuracies of 0.945 and 0.9486 respectively, outperforming other existing supervised learning methods. Further, the segmented outputs were able to cover thinner blood vessels better than previous methods, aiding in early detection of pathologies

Examining human interactions with smart retail technology : A hybrid SEM- fsQCA investigation

As technologies evolve, businesses have focused on enhancing human interactions beyond simple satisfaction. This new research builds on recent exploratory work, responding to calls for testing antecedents and consequences of Smart Retail Technology (SRT) interactions. An online survey was administered to 338 respondents. In addition to structural equation modelling (SEM), fuzzy set Qualitative Comparative Analysis (fsQCA) was employed to identify value outcomes. Results demonstrate that the more individuals perceive a business’s technologies to be distinctive, the more likely they are to interact with those technologies. Respondents’ innovativeness was positively associated with their intentions to interact with SRT. The fsQCA outcomes offer an understanding of the types of individuals who perceive value through SRT interaction. Findings offer managerial implications and extend current knowledge about adopting interactive technologies. This is the first study to contribute a comprehensive SRT model that examines the inter-relationships between antecedents and consequences of interacting with SRT