Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) together affect >10% of the children in the United States, but considerable behavioral overlaps between the two ...disorders can often complicate differential diagnosis. Currently, there is no screening test designed to differentiate between the two disorders, and with waiting times from initial suspicion to diagnosis upwards of a year, methods to quickly and accurately assess risk for these and other developmental disorders are desperately needed. In a previous study, we found that four machine-learning algorithms were able to accurately (area under the curve (AUC)>0.96) distinguish ASD from ADHD using only a small subset of items from the Social Responsiveness Scale (SRS). Here, we expand upon our prior work by including a novel crowdsourced data set of responses to our predefined top 15 SRS-derived questions from parents of children with ASD (n=248) or ADHD (n=174) to improve our model's capability to generalize to new, 'real-world' data. By mixing these novel survey data with our initial archival sample (n=3417) and performing repeated cross-validation with subsampling, we created a classification algorithm that performs with AUC=0.89±0.01 using only 15 questions.
For many bacteria with sequenced genomes, we do not understand how they synthesize some amino acids. This makes it challenging to reconstruct their metabolism, and has led to speculation that ...bacteria might be cross-feeding amino acids. We studied heterotrophic bacteria from 10 different genera that grow without added amino acids even though an automated tool predicts that the bacteria have gaps in their amino acid synthesis pathways. Across these bacteria, there were 11 gaps in their amino acid biosynthesis pathways that we could not fill using current knowledge. Using genome-wide mutant fitness data, we identified novel enzymes that fill 9 of the 11 gaps and hence explain the biosynthesis of methionine, threonine, serine, or histidine by bacteria from six genera. We also found that the sulfate-reducing bacterium Desulfovibrio vulgaris synthesizes homocysteine (which is a precursor to methionine) by using DUF39, NIL/ferredoxin, and COG2122 proteins, and that homoserine is not an intermediate in this pathway. Our results suggest that most free-living bacteria can likely make all 20 amino acids and illustrate how high-throughput genetics can uncover previously-unknown amino acid biosynthesis genes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective: The recent addition of the callous-unemotional (CU) traits specifier, "with Limited Prosocial Emotions (LPE)," to major classification systems has prompted the need for assessment tools ...that aid in the identification of elevations on these traits for diagnostic purposes. The goal of the current study was to use and evaluate multiple methods for establishing cutoff scores for the multi-informant questionnaire, the Inventory of Callous-Unemotional Traits (ICU).
Method: The present study compared the clinical utility of various proposed cutoff methods and scores (i.e., empirically derived cutoffs using receiver operating characteristic (ROC), normative cutoffs, and rational scoring approximations of LPE criteria) in both a longitudinal sample of justice-involved male adolescents (N = 1,216; M
age
= 15.29, SD = 1.29) and a cross-sectional sample of school children (N = 289; M
age
= 11.47 years; SD = 2.26).
Results: Methods resulted in a range of cutoff scores with substantial diagnostic overlap and validity. Specifically, they designated justice-involved adolescents at risk for later delinquency, aggression, and rearrests, and they designated school children more likely to be rated by parents and teacher as having conduct problems and rated by peers as being rejected and mean.
Conclusions: The results lead to ranges of ICU scores that have support for their validity and can help to guide clinical decisions about children and adolescents who may be elevated on CU traits.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, NUK, PILJ, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
24.
Genetic evidence for archaic admixture in Africa Hammer, Michael F; Woerner, August E; Mendez, Fernando L ...
Proceedings of the National Academy of Sciences - PNAS,
09/2011, Letnik:
108, Številka:
37
Journal Article
Recenzirano
Odprti dostop
A long-debated question concerns the fate of archaic forms of the genus HOMO: did they go extinct without interbreeding with anatomically modern humans, or are their genes present in contemporary ...populations? This question is typically focused on the genetic contribution of archaic forms outside of Africa. Here we use DNA sequence data gathered from 61 noncoding autosomal regions in a sample of three sub-Saharan African populations (Mandenka, Biaka, and San) to test models of African archaic admixture. We use two complementary approximate-likelihood approaches and a model of human evolution that involves recent population structure, with and without gene flow from an archaic population. Extensive simulation results reject the null model of no admixture and allow us to infer that contemporary African populations contain a small proportion of genetic material (≈2%) that introgressed ≈35 kya from an archaic population that split from the ancestors of anatomically modern humans ≈700 kya. Three candidate regions showing deep haplotype divergence, unusual patterns of linkage disequilibrium, and small basal clade size are identified and the distributions of introgressive haplotypes surveyed in a sample of populations from across sub-Saharan Africa. One candidate locus with an unusual segment of DNA that extends for >31 kb on chromosome 4 seems to have introgressed into modern Africans from a now-extinct taxon that may have lived in central Africa. Taken together our results suggest that polymorphisms present in extant populations introgressed via relatively recent interbreeding with hominin forms that diverged from the ancestors of modern humans in the Lower-Middle Pleistocene.
Neanderthals were a group of archaic hominins that occupied most of Europe and parts of Western Asia from ∼30,000 to 300,000 years ago (KYA). They coexisted with modern humans during part of this ...time. Previous genetic analyses that compared a draft sequence of the Neanderthal genome with genomes of several modern humans concluded that Neanderthals made a small (1-4%) contribution to the gene pools of all non-African populations. This observation was consistent with a single episode of admixture from Neanderthals into the ancestors of all non-Africans when the two groups coexisted in the Middle East 50-80 KYA. We examined the relationship between Neanderthals and modern humans in greater detail by applying two complementary methods to the published draft Neanderthal genome and an expanded set of high-coverage modern human genome sequences. We find that, consistent with the recent finding of Meyer et al. (2012), Neanderthals contributed more DNA to modern East Asians than to modern Europeans. Furthermore we find that the Maasai of East Africa have a small but significant fraction of Neanderthal DNA. Because our analysis is of several genomic samples from each modern human population considered, we are able to document the extent of variation in Neanderthal ancestry within and among populations. Our results combined with those previously published show that a more complex model of admixture between Neanderthals and modern humans is necessary to account for the different levels of Neanderthal ancestry among human populations. In particular, at least some Neanderthal-modern human admixture must postdate the separation of the ancestors of modern European and modern East Asian populations.
The stability of callous-unemotional (CU) traits and both individual and contextual factors that influence this stability have been studied in community adolescent samples but not to great extent in ...adolescents who have been arrested. We estimated the developmental changes in CU traits measured over the course of 36 months (6-month intervals) following the first arrest of male adolescents (N = 1,216). Using latent growth curve modeling and the multiple cohort multiple group method to account for the accelerated cohort study design, we were able to estimate the degree of change in these traits from ages 13 to 20 years. Overall in the sample, CU traits showed a moderate level of stability, similar to what has been reported in community samples, as well as an overall decline at older ages. Whether the adolescent was formally processed after first arrest (positively) and intelligence (negatively) was related to high levels of CU traits at arrest but unrelated to changes over time. Impulse control and maternal warmth showed consistent negative associations whereas self-reported offending, neighborhood disorganization, and association with delinquent peers showed consistent positive associations with CU traits over time. These findings support the importance of these variables for understanding the level and course of CU traits in justice-involved adolescents and provide potential targets for interventions implemented to reduce these traits in justice-involved adolescents.
Long-term observations of ecological communities are necessary for generating and testing predictions of ecosystem responses to climate change. We investigated temporal trends and spatial patterns of ...soil fauna along similar environmental gradients in three sites of the McMurdo Dry Valleys, Antarctica, spanning two distinct climatic phases: a decadal cooling trend from the early 1990s through the austral summer of February 2001, followed by a shift to the current trend of warming summers and more frequent discrete warming events. After February 2001, we observed a decline in the dominant species (the nematode Scottnema lindsayae) and increased abundance and expanded distribution of less common taxa (rotifers, tardigrades, and other nematode species). Such diverging responses have resulted in slightly greater evenness and spatial homogeneity of taxa. However, total abundance of soil fauna appears to be declining, as positive trends of the less common species so far have not compensated for the declining numbers of the dominant species. Interannual variation in the proportion of juveniles in the dominant species was consistent across sites, whereas trends in abundance varied more. Structural equation modeling supports the hypothesis that the observed biological trends arose from dissimilar responses by dominant and less common species to pulses of water availability resulting from enhanced ice melt. No direct effects of mean summer temperature were found, but there is evidence of indirect effects via its weak but significant positive relationship with soil moisture. Our findings show that combining an understanding of species responses to environmental change with long-term observations in the field can provide a context for validating and refining predictions of ecological trends in the abundance and diversity of soil fauna.
Exome and whole-genome sequencing studies are becoming increasingly common, but little is known about the accuracy of the genotype calls made by the commonly used platforms. Here we use replicate ...high-coverage sequencing of blood and saliva DNA samples from four European-American individuals to estimate lower bounds on the error rates of Complete Genomics and Illumina HiSeq whole-genome and whole-exome sequencing. Error rates for nonreference genotype calls range from 0.1% to 0.6%, depending on the platform and the depth of coverage. Additionally, we found (1) no difference in the error profiles or rates between blood and saliva samples; (2) Complete Genomics sequences had substantially higher error rates than Illumina sequences had; (3) error rates were higher (up to 6%) for rare or unique variants; (4) error rates generally declined with genotype quality (GQ) score, but in a nonlinear fashion for the Illumina data, likely due to loss of specificity of GQ scores greater than 60; and (5) error rates increased with increasing depth of coverage for the Illumina data. These findings, especially (3)-(5), suggest that caution should be taken in interpreting the results of next-generation sequencing-based association studies, and even more so in clinical application of this technology in the absence of validation by other more robust sequencing or genotyping methods.
There is great interest in the patterns and extent of linkage disequilibrium (LD) in humans and other species. Characterizing LD is of central importance for gene-mapping studies and can provide ...insights into the biology of recombination and human demographic history. Here, we review recent developments in this field, including the recently proposed 'haplotype-block' model of LD. We describe some of the recent data in detail and compare the observed patterns to those seen in simulations.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Saturn’s moon Titan has a methane cycle with clouds, rain, rivers, lakes, and seas; it is the only world known to presently have a volatile cycle akin to Earth’s tropospheric water cycle. ...Anomalously specular radar reflections (ASRR) from Titan’s tropical region were observed with the Arecibo Observatory (AO) and Green Bank Telescope (GBT) and interpreted as evidence for liquid surfaces. The Cassini spacecraft discovered lakes/seas on Titan, however, it did not observe lakes/seas at the AO/GBT anomalously specular locations. A satisfactory explanation for the ASRR has been elusive for more than a decade. Here we show that the ASRR originate from one terrain unit, likely paleolakes/paleoseas. Titan observations provide ground-truth in the search for oceans on exoearths and an important lesson is that identifying liquid surfaces by specular reflections requires a stringent definition of specular; we propose a definition for this purpose.
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