Ancient Amazonian populations left lasting impacts on forest structure

Amazonia contains a vast expanse of contiguous tropical forest and is influential in global carbon and hydrological cycles. Whether ancient Amazonia was highly disturbed or modestly impacted, and how ancient disturbances have shaped current forest ecosystem processes, is still under debate. Amazonian Dark Earths (ADEs), which are anthropic soil types with enriched nutrient levels, are one of the primary lines of evidence for ancient human presence and landscape modifications in settings that mostly lack stone structures and which are today covered by vegetation. We assessed the potential of using moderate spatial resolution optical satellite imagery to predict ADEs across the Amazon Basin. Maximum entropy modeling was used to develop a predictive model using locations of ADEs across the basin and satellite‐derived remotely sensed indices. Amazonian Dark Earth sites were predicted to be primarily along the main rivers and in eastern Amazonia. Amazonian Dark Earth sites, when compared with randomly selected forested sites located within 50 km of ADE sites, were less green canopies (lower normalized difference vegetation index) and had lower canopy water content. This difference was accentuated in two drought years, 2005 and 2010. This is contrary to our expectation that ADE sites would have nutrient‐rich soils that support trees with greener canopies and forests on ADE soils being more resilient to drought. Biomass and tree height were lower on ADE sites in comparison with randomly selected adjacent sites. Our results suggested that ADE‐related ancient human impact on the forest is measurable across the entirety of the 6 million km2 of Amazon Basin using remotely sensed data

Evaluation of methods for detecting human reads in microbial sequencing datasets

Sequencing data from host-associated microbes can often be contaminated by the body of the investigator or research subject. Human DNA is typically removed from microbial reads either by subtractive alignment (dropping all reads that map to the human genome) or by using a read classification tool to predict those of human origin, and then discarding them. To inform best practice guidelines, we benchmarked eight alignment-based and two classification-based methods of human read detection using simulated data from 10 clinically prevalent bacteria and three viruses, into which contaminating human reads had been added. While the majority of methods successfully detected >99 % of the human reads, they were distinguishable by variance. The most precise methods, with negligible variance, were Bowtie2 and SNAP, both of which misidentified few, if any, bacterial reads (and no viral reads) as human. While correctly detecting a similar number of human reads, methods based on taxonomic classification, such as Kraken2 and Centrifuge, could misclassify bacterial reads as human, although the extent of this was species-specific. Among the most sensitive methods of human read detection was BWA, although this also made the greatest number of false positive classifications. Across all methods, the set of human reads not identified as such, although often representing 300 bp) bacterial reads, the highest performing approaches were classification-based, using Kraken2 or Centrifuge. For shorter (c. 150 bp) bacterial reads, combining multiple methods of human read detection maximized the recovery of human reads from contaminated short read datasets without being compromised by false positives. A particularly high-performance approach with shorter bacterial reads was a two-stage classification using Bowtie2 followed by SNAP. Using this approach, we re-examined 11 577 publicly archived bacterial read sets for hitherto undetected human contamination. We were able to extract a sufficient number of reads to call known human SNPs, including those with clinical significance, in 6 % of the samples. These results show that phenotypically distinct human sequence is detectable in publicly archived microbial read datasets

Early frontotemporal dementia targets neurons unique to apes and humans

Objective: Frontotemporal dementia (FTD) is a neurodegenerative disease that erodes uniquely human aspects of social behavior and emotion. The illness features a characteristic pattern of early injury to anterior cingulate and frontoinsular cortex. These regions, though often considered ancient in phylogeny, are the exclusive homes to the von Economo neuron (VEN), a large bipolar projection neuron found only in great apes and humans. Despite progress toward understanding the genetic and molecular bases of FTD, no class of selectively vulnerable neurons has been identified. Methods: Using unbiased stereology, we quantified anterior cingulate VENs and neighboring Layer 5 neurons in FTD (n = 7), Alzheimer's disease (n = 5), and age‐matched nonneurological control subjects (n = 7). Neuronal morphology and immunohistochemical staining patterns provided further information about VEN susceptibility. Results: FTD was associated with early, severe, and selective VEN losses, including a 74% reduction in VENs per section compared with control subjects. VEN dropout was not attributable to general neuronal loss and was seen across FTD pathological subtypes. Surviving VENs were often dysmorphic, with pathological tau protein accumulation in Pick's disease. In contrast, patients with Alzheimer's disease showed normal VEN counts and morphology despite extensive local neurofibrillary pathology. Interpretation: VEN loss links FTD to its signature regional pattern. The findings suggest a new framework for understanding how evolution may have rendered the human brain vulnerable to specific forms of degenerative illness

Genomic diversity affects the accuracy of bacterial single-nucleotide polymorphism-calling pipelines

Background: Accurately identifying SNPs from bacterial sequencing data is an essential requirement for using genomics to track transmission and predict important phenotypes such as antimicrobial resistance. However, most previous performance evaluations of SNP calling have been restricted to eukaryotic (human) data. Additionally, bacterial SNP calling requires choosing an appropriate reference genome to align reads to, which, together with the bioinformatic pipeline, affects the accuracy and completeness of a set of SNP calls obtained. This study evaluates the performance of 209 SNP calling pipelines using a combination of simulated data from 254 strains of 10 clinically common bacteria and real data from environmentally-sourced and genomically diverse isolates within the genera Citrobacter, Enterobacter, Escherichia and Klebsiella. Results: We evaluated the performance of 209 SNP calling pipelines, aligning reads to genomes of the same or a divergent strain. Irrespective of pipeline, a principal determinant of reliable SNP calling was reference genome selection. Across multiple taxa, there was a strong inverse relationship between pipeline sensitivity and precision, and the Mash distance (a proxy for average nucleotide divergence) between reads and reference genome. The effect was especially pronounced for diverse, recombinogenic, bacteria such as Escherichia coli, but less dominant for clonal species such as Mycobacterium tuberculosis. Conclusions: The accuracy of SNP calling for a given species is compromised by increasing intra-species diversity. When reads were aligned to the same genome from which they were sequenced, among the highest performing pipelines was Novoalign/GATK. By contrast, when reads were aligned to particularly divergent genomes, the highest-performing pipelines often employed the aligners NextGenMap or SMALT, and/or the variant callers LoFreq, mpileup or Strelka

A Lithium Depletion Age for the Carina Association

The dispersed remnants of stellar nurseries, stellar associations provide unparalleled samples of coeval stars critical for studies of stellar and planetary formation and evolution. The Carina Stellar Association is one of the closest stellar associations to Earth, and yet measurements of its age have varied from 13 to 45 Myr. We aim to update the age of Carina using the Lithium Depletion Boundary method. We obtain new measurements of the Li 6708 Angstrom, absorption feature in likely members using optical spectra from the Goodman HTS on SOAR and NRES on LCO. We detect the depletion boundary at M_K ~= 6.8 (M5), which corresponds to an age of 41(+3,-5) Myr. The age is consistent within uncertainties across six different models, including those that account for magnetic fields and spots. We also estimate the age through analysis of the group's overall variability, and by comparing the association members' CMD to stellar evolutionary models using a Gaussian Mixture Model, recovering ages consistent with the LDB. The resulting age agrees with the older end of previous age measurements and is consistent with the lithium depletion age for the neighboring Tucana-Horologium Moving Group.Comment: 9 pages, 6 figures, accepted to AJ on 10/17/202

Use of ipratropium bromide in asthma: Results of a multi-clinic study

A multi-center, double-blind, 90-day study compared an ipratropium bromide metered-dose inhaler (40 [mu]g four times a day) with a metaproterenol metered-dose inhaler (1,500 [mu]g four times a day) in 164 patients with asthma; of the 144 patients who completed the study, 71 received ipratropium and 73 received metaproterenol. Our results suggest that both drugs were equally effective bronchodilators. Although the shape of the pulmonary function response curves suggested that ipratropium has different bronchodilator kinetics than metaproterenol (in that it has a slower onset of action and a more prolonged duration), comparison of the areas under the curves for the two drugs showed that there was no statistical difference between ipratropium or metaproterenol. The only significant side effects noted with ipratropium were cough and exacerbation of symptoms; no anticholinergic side effects were noted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25980/1/0000046.pd

Convergence towards a European strategic culture? A constructivist framework for explaining changing norms.

The article contributes to the debate about the emergence of a European strategic culture to underpin a European Security and Defence Policy. Noting both conceptual and empirical weaknesses in the literature, the article disaggregates the concept of strategic culture and focuses on four types of norms concerning the means and ends for the use of force. The study argues that national strategic cultures are less resistant to change than commonly thought and that they have been subject to three types of learning pressures since 1989: changing threat perceptions, institutional socialization, and mediatized crisis learning. The combined effect of these mechanisms would be a process of convergence with regard to strategic norms prevalent in current EU countries. If the outlined hypotheses can be substantiated by further research the implications for ESDP are positive, especially if the EU acts cautiously in those cases which involve norms that are not yet sufficiently shared across countries

Comparison of F(ab') versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

BACKGROUND: Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. METHODS: We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm(3), fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. RESULTS: 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. CONCLUSIONS: In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation

Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

Following the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1–2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decreased below 0.1%, but increased owing to parental mixed mosaicism for 5 (9%)—that could be quantified in semen for paternal cases (recurrence risks of 5.6–12.1%). Implementation of this strategy offers the prospect of driving a major transformation in the practice of genetic counselling

Estimating cumulative pathway effects on risk for age-related macular degeneration using mixed linear models

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly in developed countries and typically affects more than 10 % of individuals over age 80. AMD has a large genetic component, with heritability estimated to be between 45 % and 70 %. Numerous variants have been identified and implicate various molecular mechanisms and pathways for AMD pathogenesis but those variants only explain a portion of AMD’s heritability. The goal of our study was to estimate the cumulative genetic contribution of common variants on AMD risk for multiple pathways related to the etiology of AMD, including angiogenesis, antioxidant activity, apoptotic signaling, complement activation, inflammatory response, response to nicotine, oxidative phosphorylation, and the tricarboxylic acid cycle. While these mechanisms have been associated with AMD in literature, the overall extent of the contribution to AMD risk for each is unknown. METHODS: In a case–control dataset with 1,813 individuals genotyped for over 600,000 SNPs we used Genome-wide Complex Trait Analysis (GCTA) to estimate the proportion of AMD risk explained by SNPs in genes associated with each pathway. SNPs within a 50 kb region flanking each gene were also assessed, as well as more distant, putatively regulatory SNPs, based on DNaseI hypersensitivity data from ocular tissue in the ENCODE project. RESULTS: We found that 19 previously associated AMD risk SNPs contributed to 13.3 % of the risk for AMD in our dataset, while the remaining genotyped SNPs contributed to 36.7 % of AMD risk. Adjusting for the 19 risk SNPs, the complement activation and inflammatory response pathways still explained a statistically significant proportion of additional risk for AMD (9.8 % and 17.9 %, respectively), with other pathways showing no significant effects (0.3 % – 4.4 %). DISCUSSION: Our results show that SNPs associated with complement activation and inflammation significantly contribute to AMD risk, separately from the risk explained by the 19 known risk SNPs. We found that SNPs within 50 kb regions flanking genes explained additional risk beyond genic SNPs, suggesting a potential regulatory role, but that more distant SNPs explained less than 0.5 % additional risk for each pathway. CONCLUSIONS: From these analyses we find that the impact of complement SNPs on risk for AMD extends beyond the established genome-wide significant SNPs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-015-0760-4) contains supplementary material, which is available to authorized users