Low incidence of toxoplasma infection during pregnancy and in newborns in Sweden

To estimate the burden of disease due to congenital toxoplasmosis in Sweden the incidence of primary infections during pregnancy and birth prevalence of congenital toxoplasmosis in 40978 children born in two regions in Sweden was determined. Women possibly infected during pregnancy were identified based on: 1, detection of specific IgG based on neonatal screening of the phenylketonuria (PKU) card blood spot followed by retrospective testing of stored prenatal samples to detect women who acquired infection during pregnancy and follow up of their children to 12 months; 2, detection of specific IgM on the PKU blood spot. The birth prevalence of congenital toxoplasmosis was 0·73/10000 (95% CI 0·15–2·14) (3/40978). The incidence of primary infection during pregnancy was 5·1/10000 (95% CI 2·6–8·9) susceptible pregnant women. The seroprevalence in the southern part was 25·7% and in the Stockholm area 14·0%. The incidence of infection during pregnancy was low, as the birth prevalence of congenital toxoplasmosis. Neonatal screening warrants consideration in view of the low cost and feasibility

The Application of Multispectral Techniques to Analytical Electron Microscopy

The York multispectral analytical electron microscope (MULSAM) was the first instrument specifically designed to acquire and process multiple Auger, X-ray, backscattered electron, elastically scattered electron, scanning electron microscopy (SEM) and specimen absorption current images simultaneously. Analyzing combinations of these signals with multispectral correlation techniques yields more information than would normally be obtained by treating each image separately. This paper reports some of the multispectral methods we have investigated at York which may be of use to other workers. Included are (1) a method that corrects for beam current fluctuations during long acquisition runs which is based on the anti-correlation between SEM and specimen current images, (2) the classification of topography for crystalline specimens by correlation partitioning of backscattered electron images and (3) the enhancement of surface state contrast in multi spectral scanning tunneling microscopy (STM) images using the Hotelling transform. The last example is intended to demonstrate that these techniques can also be applied to other fields in microscopy

Redundant Mechanisms for Regulation of Midline Crossing in Drosophila

During development, all neurons have to decide on whether to cross the longitudinal midline to project on the contralateral side of the body. In vertebrates and invertebrates regulation of crossing is achieved by interfering with Robo signalling either through sorting and degradation of the receptor, in flies, or through silencing of its repulsive activity, in vertebrates. Here I show that in Drosophila a second mechanism of regulation exists that is independent from sorting. Using in vitro and in vivo assays I mapped the region of Robo that is sufficient and required for its interaction with Comm, its sorting receptor. By modifying that region, I generated new forms of Robo that are insensitive to Comm sorting in vitro and in vivo, yet still able to normally translate repulsive activity in vivo. Using gene targeting by homologous recombination I created new conditional alleles of robo that are sorting defective (roboSD). Surprisingly, expression of these modified proteins results in phenotypically normal flies, unveiling a sorting independent mechanism of regulation

Systematic Conservation Planning in the Face of Climate Change: Bet-Hedging on the Columbia Plateau

Systematic conservation planning efforts typically focus on protecting current patterns of biodiversity. Climate change is poised to shift species distributions, reshuffle communities, and alter ecosystem functioning. In such a dynamic environment, lands selected to protect today's biodiversity may fail to do so in the future. One proposed approach to designing reserve networks that are robust to climate change involves protecting the diversity of abiotic conditions that in part determine species distributions and ecological processes. A set of abiotically diverse areas will likely support a diversity of ecological systems both today and into the future, although those two sets of systems might be dramatically different. Here, we demonstrate a conservation planning approach based on representing unique combinations of abiotic factors. We prioritize sites that represent the diversity of soils, topographies, and current climates of the Columbia Plateau. We then compare these sites to sites prioritized to protect current biodiversity. This comparison highlights places that are important for protecting both today's biodiversity and the diversity of abiotic factors that will likely determine biodiversity patterns in the future. It also highlights places where a reserve network designed solely to protect today's biodiversity would fail to capture the diversity of abiotic conditions and where such a network could be augmented to be more robust to climate-change impacts

Repeat Detector: versatile sizing of expanded tandem repeats and identification of interrupted alleles from targeted DNA sequencing

Targeted DNA sequencing approaches will improve how the size of short tandem repeats is measured for diagnostic tests and preclinical studies. The expansion of these sequences causes dozens of disorders, with longer tracts generally leading to a more severe disease. Interrupted alleles are sometimes present within repeats and can alter disease manifestation. Determining repeat size mosaicism and identifying interruptions in targeted sequencing datasets remains a major challenge. This is in part because standard alignment tools are ill-suited for repetitive and unstable sequences. To address this, we have developed Repeat Detector (RD), a deterministic profile weighting algorithm for counting repeats in targeted sequencing data. We tested RD using blood-derived DNA samples from Huntington’s disease and Fuchs endothelial corneal dystrophy patients sequenced using either Illumina MiSeq or Pacific Biosciences single-molecule, real-time sequencing platforms. RD was highly accurate in determining repeat sizes of 609 blood-derived samples from Huntington’s disease individuals and did not require prior knowledge of the flanking sequences. Furthermore, RD can be used to identify alleles with interruptions and provide a measure of repeat instability within an individual. RD is therefore highly versatile and may find applications in the diagnosis of expanded repeat disorders and in the development of novel therapies

CRISPR/Cas9-targeted enrichment and long-read sequencing of the Fuchs endothelial corneal dystrophy–associated TCF4 triplet repeat

PURPOSE: To demonstrate the utility of an amplification-free long-read sequencing method to characterize the Fuchs endothelial corneal dystrophy (FECD)-associated intronic TCF4 triplet repeat (CTG18.1). METHODS: We applied an amplification-free method, utilizing the CRISPR/Cas9 system, in combination with PacBio single-molecule real-time (SMRT) long-read sequencing, to study CTG18.1. FECD patient samples displaying a diverse range of CTG18.1 allele lengths and zygosity status (n = 11) were analyzed. A robust data analysis pipeline was developed to effectively filter, align, and interrogate CTG18.1-specific reads. All results were compared with conventional polymerase chain reaction (PCR)-based fragment analysis. RESULTS: CRISPR-guided SMRT sequencing of CTG18.1 provided accurate genotyping information for all samples and phasing was possible for 18/22 alleles sequenced. Repeat length instability was observed for all expanded (≥50 repeats) phased CTG18.1 alleles analyzed. Furthermore, higher levels of repeat instability were associated with increased CTG18.1 allele length (mode length ≥91 repeats) indicating that expanded alleles behave dynamically. CONCLUSION: CRISPR-guided SMRT sequencing of CTG18.1 has revealed novel insights into CTG18.1 length instability. Furthermore, this study provides a framework to improve the molecular diagnostic accuracy for CTG18.1-mediated FECD, which we anticipate will become increasingly important as gene-directed therapies are developed for this common age-related and sight threatening disease

Anthropogenic modification of forests means only 40% of remaining forests have high ecosystem integrity

Many global environmental agendas, including halting biodiversity loss, reversing land degradation, and limiting climate change, depend upon retaining forests with high ecological integrity, yet the scale and degree of forest modification remain poorly quantified and mapped. By integrating data on observed and inferred human pressures and an index of lost connectivity, we generate a globally consistent, continuous index of forest condition as determined by the degree of anthropogenic modification. Globally, only 17.4 million km2 of forest (40.5%) has high landscape-level integrity (mostly found in Canada, Russia, the Amazon, Central Africa, and New Guinea) and only 27% of this area is found in nationally designated protected areas. Of the forest inside protected areas, only 56% has high landscape-level integrity. Ambitious policies that prioritize the retention of forest integrity, especially in the most intact areas, are now urgently needed alongside current efforts aimed at halting deforestation and restoring the integrity of forests globally

Many Labs 2: Investigating Variation in Replicability Across Samples and Settings

We conducted preregistered replications of 28 classic and contemporary published findings, with protocols that were peer reviewed in advance, to examine variation in effect magnitudes across samples and settings. Each protocol was administered to approximately half of 125 samples that comprised 15,305 participants from 36 countries and territories. Using the conventional criterion of statistical significance (p < .05), we found that 15 (54%) of the replications provided evidence of a statistically significant effect in the same direction as the original finding. With a strict significance criterion (p < .0001), 14 (50%) of the replications still provided such evidence, a reflection of the extremely highpowered design. Seven (25%) of the replications yielded effect sizes larger than the original ones, and 21 (75%) yielded effect sizes smaller than the original ones. The median comparable Cohen’s ds were 0.60 for the original findings and 0.15 for the replications. The effect sizes were small (< 0.20) in 16 of the replications (57%), and 9 effects (32%) were in the direction opposite the direction of the original effect. Across settings, the Q statistic indicated significant heterogeneity in 11 (39%) of the replication effects, and most of those were among the findings with the largest overall effect sizes; only 1 effect that was near zero in the aggregate showed significant heterogeneity according to this measure. Only 1 effect had a tau value greater than .20, an indication of moderate heterogeneity. Eight others had tau values near or slightly above .10, an indication of slight heterogeneity. Moderation tests indicated that very little heterogeneity was attributable to the order in which the tasks were performed or whether the tasks were administered in lab versus online. Exploratory comparisons revealed little heterogeneity between Western, educated, industrialized, rich, and democratic (WEIRD) cultures and less WEIRD cultures (i.e., cultures with relatively high and low WEIRDness scores, respectively). Cumulatively, variability in the observed effect sizes was attributable more to the effect being studied than to the sample or setting in which it was studied.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Instituto de Investigaciones Psicológicas (IIP