Modulations in resting state networks of subcortical structures linked to creativity

Creativity is a sine qua non ability for almost all aspects of everyday life. Although very profound behavioural models were provided by 21st century psychologists, the neural correlates of these personality features associated with creativity are largely unknown. Recent models suggest strong relationships between dopamine release and various creative skills. Herein, we employed functional connectivity analyses of resting-state functional magnetic imaging data in order to shed light on these neural underpinnings of creative aspects. For improved sensitivity, we performed the study at ultra-high magnetic field (7 T). Seed regions were defined based on subcortical (ventral tegmental area/substantia nigra, nucleus caudatus) activation foci of a remote associates task (RAT). In addition, bilateral PCC was used as seed region to examine the default-mode network. Network strength across subjects was regressed against a battery of psychological variables related to creativity. Dopaminergic network variations turned out to be indicative for individual differences in creative traits. In this regard, the caudate network showed stronger connectivity in individuals with higher extraversion measures, while connectivity with the midbrain network was found increased with higher ideational behaviour and emotional stability

Selection bias in dynamically measured supermassive black hole samples : its consequences and the quest for the most fundamental relation

We compare the set of local galaxies having dynamically measured black holes with a large, unbiased sample of galaxies extracted from the Sloan Digital Sky Survey. We confirm earlier work showing that the majority of black hole hosts have significantly higher velocity dispersions sigma than local galaxies of similar stellar mass. We use Monte Carlo simulations to illustrate the effect on black hole scaling relations if this bias arises from the requirement that the black hole sphere of influence must be resolved to measure black hole masses with spatially resolved kinematics. We find that this selection effect artificially increases the normalization of the M-bh-sigma relation by a factor of at least similar to 3; the bias for the M-bh-M-star relation is even larger. Our Monte Carlo simulations and analysis of the residuals from scaling relations both indicate that sigma is more fundamental than M-star or effective radius. In particular, the M-bh-M-star relation is mostly a consequence of the M-bh-sigma and sigma-M-star relations, and is heavily biased by up to a factor of 50 at small masses. This helps resolve the discrepancy between dynamically based black hole-galaxy scaling relations versus those of active galaxies. Our simulations also disfavour broad distributions of black hole masses at fixed sigma. Correcting for this bias suggests that the calibration factor used to estimate black hole masses in active galaxies should be reduced to values of f(vir) similar to 1. Black hole mass densities should also be proportionally smaller, perhaps implying significantly higher radiative efficiencies/black hole spins. Reducing black hole masses also reduces the gravitational wave signal expected from black hole mergers.Peer reviewe

Red Nuggets at z~1.5: Compact passive galaxies and the formation of the Kormendy Relation

We present the results of NICMOS imaging of a sample of 16 high mass passively evolving galaxies with 1.3<z<2, taken primarily from the Gemini Deep Deep Survey. Around 80% of galaxies in our sample have spectra dominated by stars with ages >1 Gyr. Our rest-frame R-band images show that most of these objects have compact regular morphologies which follow the classical R^1/4 law. These galaxies scatter along a tight sequence in the Kormendy relation. Around one-third of the massive red objects are extraordinarily compact, with effective radii under one kiloparsec. Our NICMOS observations allow the detection of such systems more robustly than is possible with optical (rest-frame UV) data, and while similar systems have been seen at z>2, this is the first time such systems have been detected in a rest-frame optical survey at 1.3<z<2. We refer to these compact galaxies as "red nuggets". Similarly compact massive galaxies are completely absent in the nearby Universe. We introduce a new "stellar mass Kormendy relation" (stellar mass density vs size) which isolates the effects of size evolution from those of luminosity and color evolution. The 1.1 < z < 2 passive galaxies have mass densities that are an order of magnitude larger then early type galaxies today and are comparable to the compact distant red galaxies at 2 < z < 3. We briefly consider mechanisms for size evolution in contemporary models focusing on equal-mass mergers and adiabatic expansion driven by stellar mass loss. Neither of these mechanisms appears able to transform the high-redshift Kormendy relation into its local counterpart. Comment: Accepted version (to appear in ApJ

Ultra-high-field fMRI insights on insight: Neural correlates of 2 the Aha!-moment

Finding creative solutions to difficult problems is a fundamental aspect of human culture and a skill highly needed. However, the exact neural processes underlying creative problem solving remain unclear. Insightful problem solving tasks were shown to be a valid method for investigating one subcomponent of creativity: the Aha!-Moment. Finding insightful solutions during a remote associates task (RAT) was found to elicit specific cortical activity changes. Considering the strong affective components of Aha!-Moments, as manifested in the subjectively experienced feeling of relief following the sudden emergence of the solution of the problem without any conscious forewarning, we hypothesized the subcortical dopaminergic reward network to be critically engaged during Aha. To investigate those subcortical contributions to insight, we employed ultra-high field 7-Tesla fMRI during a German Version of the RAT. During this task subjects were exposed to word triplets and instructed to find a solution word being associated with all of the three given words. They were supposed to press a button as soon as they felt confident about their solution without further revision, allowing us to capture the exact event of Aha!-Moment. Besides the finding on cortical involvement of the left anterior middle temporal gyrus (aMTG), here we showed for the first time robust subcortical activity changes related to insightful problem solving in the bilateral thalamus, hippocampus and the dopaminergic midbrain comprising ventral tegmental area (VTA), nucleus accumbens (NAcc) and caudate nucleus. These results shed new light on the affective neural mechanisms underlying insightful problem solving

Real-time imaging of density ducts between the plasmasphere and ionosphere

Ionization of the Earth's atmosphere by sunlight forms a complex, multilayered plasma environment within the Earth's magnetosphere, the innermost layers being the ionosphere and plasmasphere. The plasmasphere is believed to be embedded with cylindrical density structures (ducts) aligned along the Earth's magnetic field, but direct evidence for these remains scarce. Here we report the first direct wide-angle observation of an extensive array of field-aligned ducts bridging the upper ionosphere and inner plasmasphere, using a novel ground-based imaging technique. We establish their heights and motions by feature tracking and parallax analysis. The structures are strikingly organized, appearing as regularly spaced, alternating tubes of overdensities and underdensities strongly aligned with the Earth's magnetic field. These findings represent the first direct visual evidence for the existence of such structures

Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy

Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. As novel and improved immunotherapies may fill this need, we dissected the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 25 tumors (10 pre- and 15 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas were infiltrated by NK, T and B cells, and immunosuppressive myeloid populations. NK cells showed reduced cytotoxicity and T cells had a dysfunctional profile. Interaction analysis revealed a vast immunoregulatory network and identified NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduced neuroblastoma growth, with complete responses in vivo. Moreover, addition of TIGIT blockade to standard relapse treatment in a chemotherapy-resistant Th-ALKF1174L/MYCN 129/SvJ syngeneic model significantly improved survival. Concluding, our integrative analysis of neuroblastoma’s vast immunoregulatory network provides novel targets and a rationale for immunotherapeutic combination strategies

Zika Virus: Medical Countermeasure Development Challenges

Introduction: Reports of high rates of primary microcephaly and Guillain–Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment. Methods: Multiple information sources were employed to support the review. These included publically available literature, patents, official communications, English and Lusophone lay press. Online surveys were distributed to physicians in the US, Mexico and Argentina and responses analyzed. Computational epitope analysis as well as infectious disease outbreak modeling and forecasting were implemented. Field observations in Brazil were compiled and interviews conducted with public health officials

Development of a hypoallergenic recombinant parvalbumin for first-in-man subcutaneous immunotherapy of fish allergy.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1.Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c 1.Escherichia coli-produced mCyp c 1 was purified using standard chromatographic techniques. Physicochemical properties were investigated by gel electrophoresis, size exclusion chromatography, circular dichroism spectroscopy, reverse-phase high-performance liquid chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural and/or recombinant). GMP-compliant alum-adsorbed mCyp c 1 was tested for acute toxicity in mice and rabbits and for repeated-dose toxicity in mice. Accelerated and real-time protocols were used to evaluate stability of mCyp c 1 as drug substance and drug product.Purified mCyp c 1 behaves as a folded and stable molecule. Using sera of 26 double-blind placebo-controlled food-challenge-proven fish-allergic patients, reduction in allergenic activity ranged from 10- to 5,000-fold (1,000-fold on average), but with retained immunogenicity (immunization in mice/rabbits) and potency to stimulate human PBMCs. Toxicity studies revealed no toxic effects and real-time stability studies on the Al(OH)3-adsorbed drug product demonstrated at least 20 months of stability.The GMP drug product developed for treatment of fish allergy has the characteristics targeted for in FAST: i.e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine.info:eu-repo/grantAgreement/EC/FP7/20187

Serendipitous discovery of a dying Giant Radio Galaxy associated with NGC 1534, using the murchison widefield array

Recent observations with the Murchison Widefield Array at 185 MHz have serendipitously unveiled a heretofore unknown giant and relatively nearby (z=0.0178) radio galaxy associated with NGC 1534. The diffuse emission presented here is the first indication that NGC 1534 is one of a rare class of objects (along with NGC 5128 and NGC 612) in which a galaxy with a prominent dust lane hosts radio emission on scales of ~700 kpc. We present details of the radio emission along with a detailed comparison with other radio galaxies with discs. NGC 1534 is the lowest surface brightness radio galaxy known with an estimated scaled 1.4-GHz surface brightness of just 0.2 mJy arcmin-2. The radio lobes have one of the steepest spectral indices yet observed: α = -2.1 ± 0.1, and the core to lobe luminosity ratio is <0.1 per cent. We estimate the space density of this low brightness (dying) phase of radio galaxy evolution as 7 × 10-7 Mpc-3 and argue that normal AGN cannot spend more than 6 per cent of their lifetime in this phase if they all go through the same cycle