397 research outputs found
When the mask comes off:Mothers’ experiences of parenting a daughter with autism spectrum condition
Homophily and Contagion Are Generically Confounded in Observational Social Network Studies
We consider processes on social networks that can potentially involve three
factors: homophily, or the formation of social ties due to matching individual
traits; social contagion, also known as social influence; and the causal effect
of an individual's covariates on their behavior or other measurable responses.
We show that, generically, all of these are confounded with each other.
Distinguishing them from one another requires strong assumptions on the
parametrization of the social process or on the adequacy of the covariates used
(or both). In particular we demonstrate, with simple examples, that asymmetries
in regression coefficients cannot identify causal effects, and that very simple
models of imitation (a form of social contagion) can produce substantial
correlations between an individual's enduring traits and their choices, even
when there is no intrinsic affinity between them. We also suggest some possible
constructive responses to these results.Comment: 27 pages, 9 figures. V2: Revised in response to referees. V3: Ditt
Spontaneous allelic variant in deafness–blindness gene \u3ci\u3eUsh1g\u3c/i\u3e resulting in an expanded phenotype
Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target-specific, directed mutagenesis or phenotypic selection following chemical mutagenesis. An alternative approach is to exploit deficiencies in DNA repair pathways that maintain genetic integrity in response to spontaneously induced damage. Mice deficient in the DNA glycosylase NEIL1 show elevated spontaneous mutations, which arise from translesion DNA synthesis past oxidatively induced base damage. Several litters of Neil1 knockout mice included animals that were distinguished by their backwards-walking behavior in open-field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting and circling. Mapping of the mutation that conferred these behaviors showed the introduction of a stop codon at amino acid 4 of the Ush1g gene. Ush1gbw/bwnull mice displayed auditory and vestibular defects that are commonly seen with mutations affecting inner-ear hair-cell function, including a complete lack of auditory brainstem responses and vestibular-evoked potentials. As in other Usher syndrome type I mutant mouse lines, hair cell phenotypes included disorganized and split hair bundles, as well as altered distribution of proteins for stereocilia that localize to the tips of
row 1 or row 2. Disruption to the bundle and kinocilium displacement suggested that USH1G is essential for forming the hair cell\u27s kinocilial links. Consistent with other Usher type 1 models, Ush1gbw/bw mice had no substantial retinal degeneration compared with Ush1gbw/+ controls. In contrast to previously described Ush1g alleles, this new allele provides the first knockout model for this gene
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International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations
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Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.
Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures
Effects of Transmitters and Amyloid-Beta Peptide on Calcium Signals in Rat Cortical Astrocytes: Fura-2AM Measurements and Stochastic Model Simulations
BACKGROUND: To better understand the complex molecular level interactions seen in the pathogenesis of Alzheimer's disease, the results of the wet-lab and clinical studies can be complemented by mathematical models. Astrocytes are known to become reactive in Alzheimer's disease and their ionic equilibrium can be disturbed by interaction of the released and accumulated transmitters, such as serotonin, and peptides, including amyloid- peptides (A). We have here studied the effects of small amounts of A25-35 fragments on the transmitter-induced calcium signals in astrocytes by Fura-2AM fluorescence measurements and running simulations of the detected calcium signals. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular calcium signals were measured in cultured rat cortical astrocytes following additions of serotonin and glutamate, or either of these transmitters together with A25-35. A25-35 increased the number of astrocytes responding to glutamate and exceedingly increased the magnitude of the serotonin-induced calcium signals. In addition to A25-35-induced effects, the contribution of intracellular calcium stores to calcium signaling was tested. When using higher stimulus frequency, the subsequent calcium peaks after the initial peak were of lower amplitude. This may indicate inadequate filling of the intracellular calcium stores between the stimuli. In order to reproduce the experimental findings, a stochastic computational model was introduced. The model takes into account the major mechanisms known to be involved in calcium signaling in astrocytes. Model simulations confirm the principal experimental findings and show the variability typical for experimental measurements. CONCLUSIONS/SIGNIFICANCE: Nanomolar A25-35 alone does not cause persistent change in the basal level of calcium in astrocytes. However, even small amounts of A25-35, together with transmitters, can have substantial synergistic effects on intracellular calcium signals. Computational modeling further helps in understanding the mechanisms associated with intracellular calcium oscillations. Modeling the mechanisms is important, as astrocytes have an essential role in regulating the neuronal microenvironment of the central nervous system
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Bomb-produced radiocarbon validation of growth-increment crossdating allows marine paleoclimate reconstruction
The bivalve Pacific geoduck (Panopea generosa) has been used in the eastern North Pacific Ocean to create proxies for environmental factors such as temperature and oceanographic conditions. This type of research depends upon accurate age determination of Pacific geoducks, which historically was based on shell growth-increment counts. A recent study comparing age estimates generated by the dendrochronology (tree-ring science) procedure of crossdating to those estimated from growth-increment counts found a significant difference between the methods for geoduck older than 30 years. Compared to the traditional age determination method of counting growth increments, the crossdating method estimates a greater longevity in this species, with some individuals living in excess of 150 years. In the present study, the accuracy of each method was independently assessed using bomb-produced radiocarbon (C-14) techniques. Specimens whose birth years were estimated to be within the era of the bomb-produced marine C-14 increase and where the differences between ages estimated by the two methods were greatest were selected for C-14 analysis. The difference between age estimates from traditional growth-increment counts and those from crossdating was evaluated using their respective C-14 chronologies in comparisons to a reference chronology as a standard. The comparisons relied on Bayesian nonlinear models using Markov Chain Monte Carlo simulation. This method of analysis showed that with a 50% probability geoducks were aged correctly when using the crossdating method, compared to the growth increment counts which had a 50% probability of underestimating the age by 4 years. Therefore, the crossdated age estimates were found to be more accurate than increment counts. Furthermore, these results provide new confidence in using Pacific geoduck biochronologies for paleoclimate and paleoenvironmental reconstruction. Published by Elsevier B.V.Keywords: Age determination, Pacific geoduck, Bomb-produced radiocarbon, Bayesian models, Shell growth-increment counts, Crossdating, Panopea generos
The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment
The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in
operation since July 2014. This paper describes the second data release from
this phase, and the fourteenth from SDSS overall (making this, Data Release
Fourteen or DR14). This release makes public data taken by SDSS-IV in its first
two years of operation (July 2014-2016). Like all previous SDSS releases, DR14
is cumulative, including the most recent reductions and calibrations of all
data taken by SDSS since the first phase began operations in 2000. New in DR14
is the first public release of data from the extended Baryon Oscillation
Spectroscopic Survey (eBOSS); the first data from the second phase of the
Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2),
including stellar parameter estimates from an innovative data driven machine
learning algorithm known as "The Cannon"; and almost twice as many data cubes
from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous
release (N = 2812 in total). This paper describes the location and format of
the publicly available data from SDSS-IV surveys. We provide references to the
important technical papers describing how these data have been taken (both
targeting and observation details) and processed for scientific use. The SDSS
website (www.sdss.org) has been updated for this release, and provides links to
data downloads, as well as tutorials and examples of data use. SDSS-IV is
planning to continue to collect astronomical data until 2020, and will be
followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14
happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov
2017 (this is the "post-print" and "post-proofs" version; minor corrections
only from v1, and most of errors found in proofs corrected
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