Survey of pickup ion signatures in the vicinity of Titan using CAPS/IMS

Pickup ion detection at Titan is challenging because ion cyclotron waves are rarely detected in the vicinity of the moon. In this work, signatures left by freshly produced pickup heavy ions (m/q ∼ 16 to m/q ∼ 28) as detected in the plasma data by the Cassini Plasma Spectrometer/Ion Mass Spectrometer (CAPS/IMS) instrument on board Cassini are analyzed. In order to discern whether these correspond to ions of exospheric origin, one of the flybys during which the reported signatures were observed is investigated in detail. For this purpose, ion composition data from time-of-flight measurements and test particle simulations to constrain the ions' origin are used. After being validated, the detection method is applied to all the flybys for which the CAPS/IMS instrument gathered valid data, constraining the region around the moon where the signatures are observed. The results reveal an escape region located in the anti-Saturn direction as expected from the nominal corotation electric field direction. These findings provide new constraints for the area of freshly produced pickup ion escape, giving an approximate escape rate of inline image ions· s−1

Long-standing Small-scale Reconnection Processes at Saturn Revealed by Cassini

The internal mass source from the icy moon Enceladus in Saturn’s rapidly rotating magnetosphere drives electromagnetic dynamics in multiple spatial and temporal scales. The distribution and circulation of the internal plasma and associated energy are thus crucial in understanding Saturn’s magnetospheric environment. Magnetic reconnection is one of the key processes in driving plasma and energy transport in the magnetosphere, and also a fundamental plasma process in energizing charged particles. Recent works suggested that reconnection driven by Saturn’s rapid rotation might appear as a chain of microscale structures, named drizzle-like reconnection. The drizzle-like reconnection could exist not only in the nightside magnetodisk, but also in the dayside magnetodisk. Here, using in situ measurements from the Cassini spacecraft, we report multiple reconnection sites that were successively detected during a time interval longer than one rotation period. The time separation between two adjacently detected reconnection sites can be much less than one rotation period, implying that the reconnection processes are likely small-scale, or frequently repetitive. The spatial distribution of the identified long-standing multiple small reconnection site sequences shows no significant preference on local times. We propose that the small reconnection sites discussed in this Letter are rotationally driven and rotate with the magnetosphere. Since the reconnection process on Saturn can be long-durational, the rotational regime can cause these smallscale reconnection sites to spread to all local times, resulting in global release of energy and mass from the magnetosphere

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

Pramipexole effects on startle gating in rats and normal men

Dopamine D3 receptors regulate sensorimotor gating in rats, as evidenced by changes in prepulse inhibition (PPI) of startle after acute administration of D3 agonists and antagonists. In this study, we tested the effects of the D3-preferential agonist, pramipexole, on PPI in normal men and Sprague–Dawley rats. Acoustic startle and PPI were tested in clinically normal men, comparing the effects of placebo vs. 0.125 mg (n = 20) or placebo vs. 0.1875 mg (n = 20) pramipexole, in double blind, crossover designs. These measures were also tested in male Sprague–Dawley rats using a parallel design [vehicle vs. 0.1 mg/kg (n = 8), vehicle vs. 0.3 mg/kg (n = 8) or vehicle vs. 1.0 mg/kg pramipexole (n = 8)]. Autonomic and subjective measures of pramipexole effects and several personality instruments were also measured in humans. Pramipexole increased drowsiness and significantly increased PPI at 120-ms intervals in humans; the latter effect was not moderated by baseline PPI or personality scale scores. In rats, pramipexole causes a dose-dependent reduction in long-interval (120 ms) PPI, while low doses actually increased short-interval (10–20 ms) PPI. Effects of pramipexole on PPI in rats were independent of baseline PPI and changes in startle magnitude. The preferential D3 agonist pramipexole modifies PPI in humans and rats. Unlike indirect DA agonists and mixed D2/D3 agonists, pramipexole increases long-interval PPI in humans, in a manner that is independent of baseline PPI and personality measures. These findings are consistent with preclinical evidence for differences in the D2- and D3-mediated regulation of sensorimotor gating

Reconnection Acceleration in Saturn's Dayside Magnetodisk: A Multicase Study with Cassini

Recently, rotationally driven magnetic reconnection was first discovered in Saturn's dayside magnetosphere. This newly confirmed process could potentially drive bursty phenomena at Saturn, i.e., pulsating energetic particles and auroral emissions. Using Cassini's measurements of magnetic fields and charged particles, we investigate particle acceleration features during three magnetic reconnection events observed in Saturn's dayside magnetodisk. The results suggest that the rotationally driven reconnection process plays a key role in producing energetic electrons (up to 100 keV) and ions (several hundreds of kiloelectron volts). In particular, we find that energetic oxygen ions are locally accelerated at all three reconnection sites. Isolated, multiple reconnection sites were recorded in succession during an interval lasting for much less than one Saturn rotation period. Moreover, a secondary magnetic island is reported for the first time at the dayside, collectively suggesting that the reconnection process is not steady and could be "drizzle-like." This study demonstrates the fundamental importance of internally driven magnetic reconnection in accelerating particles in Saturn's dayside magnetosphere, and likewise in the rapidly rotating Jovian magnetosphere and beyond

Post-traumatic stress disorder in children and adolescents one year after a super-cyclone in Orissa, India: exploring cross-cultural validity and vulnerability factors

BACKGROUND: It has been asserted that psychological responses to disasters in children and adolescents vary widely across cultures, but this has rarely been investigated. The objectives of the study were to clinically evaluate the construct of traumatic stress symptoms and disorder in children and adolescents after a super-cyclone in Orissa, India; to find out the prevalence at one year; compare the effect in high and low exposure areas and study the factors associated with it. METHODS: Clinical examination of children and adolescents (n = 447) was done, supplemented by a symptoms checklist based on International Classification of Mental and Behavioural Disorders, Diagnostic Criteria for Research and a semi-structured questionnaire for disaster related experiences. RESULTS: A majority of children had post-traumatic symptoms. Post-traumatic stress disorder (PTSD) was present in 30.6% (95% confidence interval: 26.4 to 34.9), and an additional 13.6% had sub-syndromal PTSD. Parents or teachers reported mental health concerns in 7.2% subjects, who were a minor proportion (12.8%) of subjects with any syndromal diagnosis (n = 196). Significantly more (43.7%) children in high exposure areas had PTSD than that (11.2%) in low exposure areas (p < 0.001). Depression was significantly associated with PTSD. Binary logistic regression analysis indicated that high exposure, lower educational level and middle socioeconomic status significantly predicted the outcome of PTSD. Extreme fear and perceived threat to life during the disaster, death in family, damage to home, or staying in shelters were not significantly associated with PTSD. CONCLUSION: Following natural disaster PTSD is a valid clinical construct in children and adolescents in Indian set up; and though highly prevalent it may be missed without clinical screening. Its manifestation and associated factors resembled those in other cultures

Study of the chemotactic response of multicellular spheroids in a microfluidic device

YesWe report the first application of a microfluidic device to observe chemotactic migration in multicellular spheroids. A microfluidic device was designed comprising a central microchamber and two lateral channels through which reagents can be introduced. Multicellular spheroids were embedded in collagen and introduced to the microchamber. A gradient of fetal bovine serum (FBS) was established across the central chamber by addition of growth media containing serum into one of the lateral channels. We observe that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS. This invasion is more directional and aggressive than that observed for individual cells in the same experimental setup. In contrast to spheroids of OSC–19, U87-MG multicellular spheroids migrate as individual cells. A study of the exposure of spheroids to the chemoattractant shows that the rate of diffusion into the spheroid is slow and thus, the chemoattractant wave engulfs the spheroid before diffusing through it.This work has been supported by National Research Program of Spain (DPI2011-28262-c04-01) and by the project "MICROANGIOTHECAN" (CIBERBBN, IMIBIC and SEOM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing