344 research outputs found
Spinal Cord Stimulation Paradigms and Pain Relief:A Preclinical Systematic Review on Modulation of the Central Inflammatory Response in Neuropathic Pain
Optical Spectroscopy of the Surface Population of the rho Ophiuchi Molecular Cloud: The First Wave of Star Formation
We present the results of optical spectroscopy of 139 stars obtained with the
Hydra multi-object spectrograph. The objects extend over a 1.3 square degree
area surrounding the main cloud of the rho Oph complex. The objects were
selected from narrowband images to have H alpha in emission. Using the presence
of strong H alpha emission, lithium absorption, location in the
Hertzsprung-Russell diagram, or previously reported x-ray emission, we were
able to identify 88 objects as young stars associated with the cloud. Strong H
alpha emission was confirmed in 39 objects with line widths consistent with
their origin in magnetospheric accretion columns. Two of the strongest
emission-line objects are young, x-ray emitting brown dwarf candidates with M8
spectral types. Comparisons of the bolometric luminosities and effective
temperatures with theoretical models suggest a medianage for this population of
2.1 Myr which is signifcantly older than the ages derived for objects in the
cloud core. It appears that these stars formed contemporaneously with low mass
stars in the Upper Scorpius subgroup, likely triggered by massive stars in the
Upper-Centaurus subgroup.Comment: 35 pages of postscript which includes seven figures (some of which
are multi-panel) and four postscript tables. Astronomical Journal (in press
Very Low-Mass Objects in the Coronet Cluster: The Realm of the Transition Disks
We present optical and IR spectra of a set of low-mass stars and brown dwarfs
in the Coronet cluster (aged ~1Myr), obtained with the multifiber spectrograph
FLAMES/VLT and IRS/Spitzer. The optical spectra reveal spectral types between
M1 and M7.5, confirm the youth of the objects (via Li 6708 A absorption), and
show the presence of accretion (via Halpha) and shocks (via forbidden line
emission). The IRS spectra, together with IR photometry from the IRAC/MIPS
instruments on Spitzer and 2MASS, confirm the presence of IR excesses
characteristic of disks around ~70% of the objects. Half of the disks do not
exhibit any silicate emission, or present flat features characteristic of large
grains. The rest of the disks show silicate emission typical of amorphous and
crystalline silicate grains a few microns in size. About 50% of the objects
with disks do not show near-IR excess emission, having "transitional" disks,
according to their classical definition. This is a very high fraction for such
a young cluster. The large number of "transitional" disks suggests lifetimes
comparable to the lifetimes of typical optically thick disks. Therefore, these
disks may not be in a short-lived phase, intermediate between Class II and
Class III objects. The median spectral energy distribution of the disks in the
Coronet cluster is also closer to a flat disk than observed for the disks
around solar-type stars in regions with similar age. The differences in the
disk morphology and evolution in the Coronet cluster could be related to fact
that these objects have very late spectral types compared to the solar-type
stars in other cluster studies. Finally, the optical spectroscopy reveals that
one of the X-ray sources is produced by a Herbig Haro object in the cloud.Comment: 51 pages, 13 figures, 10 table
A very brief description of LOFAR - the Low Frequency Array
LOFAR (Low Frequency Array) is an innovative radio telescope optimized for
the frequency range 30-240 MHz. The telescope is realized as a phased aperture
array without any moving parts. Digital beam forming allows the telescope to
point to any part of the sky within a second. Transient buffering makes
retrospective imaging of explosive short-term events possible. The scientific
focus of LOFAR will initially be on four key science projects (KSPs): 1)
detection of the formation of the very first stars and galaxies in the universe
during the so-called epoch of reionization by measuring the power spectrum of
the neutral hydrogen 21-cm line (Shaver et al. 1999) on the ~5' scale; 2)
low-frequency surveys of the sky with of order expected new sources; 3)
all-sky monitoring and detection of transient radio sources such as gamma-ray
bursts, x-ray binaries, and exo-planets (Farrell et al. 2004); and 4) radio
detection of ultra-high energy cosmic rays and neutrinos (Falcke & Gorham 2003)
allowing for the first time access to particles beyond 10^21 eV (Scholten et
al. 2006). Apart from the KSPs open access for smaller projects is also
planned. Here we give a brief description of the telescope.Comment: 2 pages, IAU GA 2006, Highlights of Astronomy, Volume 14, K.A. van
der Hucht, e
Amygdala responses to emotional faces in twins discordant or concordant for the risk for anxiety and depression.
Background: Functional brain imaging studies have shown deviant amygdala responses to emotional stimuli in subjects suffering from anxiety and depressive disorder, but both hyperactivity and hypoactivity compared to healthy controls have been reported. To account for these discrepant findings, we hypothesize that genetic and environmental risk factors differently impact on amygdala functioning. Methods: To test this hypothesis, we assessed amygdala responses to an emotional faces paradigm during functional magnetic resonance imaging in monozygotic twin pairs discordant for the risk of anxiety and depression (n = 10 pairs) and in monozygotic twin pairs concordant for high (n = 7 pairs) or low (n = 15 pairs) risk for anxiety and depression. Results: Main effects (all faces vs. baseline) revealed robust bilateral amygdala activity across groups. In discordant twins, increased amygdala responses were found for negatively valenced stimuli (angry/anxious faces) in high-risk twins compared to their low-risk co-twins. In contrast, concordant high-risk pairs revealed blunted amygdala reactivity to both positive and negative faces compared with concordant low-risk pairs. Post-hoc analyses showed that these findings were independent of 5-HTTLPR genotype. Conclusions: Our findings indicate amygdala hyperactivity in subjects who are at high risk for anxiety and depression through environmental factors and amygdala hypoactivity in those at risk mainly through genetic factors. We suggest that this result reflects a difference in baseline amygdala activation in these groups. Future imaging studies on anxiety and depression should aim to avoid admixture of subjects who are at genetic risk with those at risk due to environmental factors. © 2008 Elsevier Inc. All rights reserved
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.
Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes
Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2 Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup
Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes
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