Alzheimer\u27s Disease Genetics and \u3cem\u3eABCA7\u3c/em\u3e Splicing

Both common and rare polymorphisms within ABCA7 have been associated with Alzheimer’s disease (AD). In particular, the rare AD associated polymorphism rs200538373 was associated with altered ABCA7 exon 41 splicing and an AD risk odds ratio of ∼1.9. To probe the role of this polymorphism in ABCA7 splicing, we used minigene studies and qPCR of human brain RNA. We report aberrant ABCA7 exon 41 splicing in the brain of a carrier of the rs200538373 minor C allele. Moreover, minigene studies show that rs200538373 acts as a robust functional variant in vitro. Lastly, although the ABCA7 isoform with an extended exon 41 is predicted to undergo nonsense mediated RNA decay, this was not supported by qPCR analyses, which showed relatively normal ABCA7 mRNA levels in the carrier of the rs200538373 minor C allele. In summary, rs200538373 is a functional polymorphism that alters ABCA7 exon 41 splicing without grossly altering the level of ABCA7 mRNA

Comparing Maps of Mean Monthly Surface Temperature and Precipitation for Alaska and Adjacent Areas of Canada Produced by Two Different Methods

Maps of mean monthly surface temperature and precipitation for Alaska and adjacent areas of Canada, produced by Oregon State University’s Spatial Climate Analysis Service (SCAS) and the Alaska Geospatial Data Clearinghouse (AGDC), were analyzed. Because both sets of maps are generally available and in use by the community, there is a need to document differences between the processes and input data sets used by the two groups to produce their respective set of maps and to identify similarities and differences between the two sets of maps and possible reasons for the differences. These differences do not affect the observed large-scale patterns of seasonal and annual variability. Alaska is divided into interior and coastal zones, with consistent but different variability, separated by a transition region. The transition region has high interannual variability but low long-term mean variability. Both data sets support the four major ecosystems and ecosystem transition zone identified in our earlier work. Differences between the two sets of maps do occur, however, on the regional scale; they reflect differences in physiographic domains and in the treatment of these domains by the two groups (AGDC, SCAS). These differences also provide guidance for an improved observational network for Alaska. On the basis of validation with independent in situ data, we conclude that the data set produced by SCAS provides the best spatial coverage of Alaskan long-term mean monthly surface temperature and precipitation currently available.On a analysé des cartes représentant les moyennes mensuelles des précipitations et des températures de l’air en surface pour l’Alaska et les zones contiguës du Canada. Ces cartes avaient été établies par le service d’analyse du climat spatial (SCAS) de l’université de l’Oregon et le centre d’échange de données géospatiales de l’Alaska (AGDC). Vu qu’en général le public peut se procurer les deux ensembles de cartes et qu’il les utilise, il est nécessaire de documenter les différences entre les processus et les jeux de données d’entrée utilisés par les deux groupes pour créer leur propre ensemble de cartes, ainsi que de dégager les similarités et les différences entre les deux ensembles de cartes et les raisons possibles de ces différences. Ces dernières n’affectent pas les schémas de variabilité saisonnière et annuelle observés à grande échelle. L’Alaska est divisé en zones intérieures et zones côtières, possédant une variabilité constante mais différente, séparées par une région de transition. Celle-ci possède une grande variabilité interannuelle mais une faible variabilité à long terme de la moyenne. Les deux jeux de données sont compatibles avec les quatre grands écosystèmes et leurs zones de transition que nous avions identifiés dans nos travaux antérieurs. Il y a cependant des différences à l’échelle régionale entre les deux ensembles de cartes; elles témoignent de différences dans les domaines physiographiques et dans le traitement que font les deux groupes (AGDC et SCAS) de ces domaines. Ces différences offrent également une piste pour l’établissement d’un réseau d’observation amélioré pour l’Alaska. En nous basant sur une validation fondée sur des données indépendantes recueillies in situ, nous concluons que le jeu de données produit par SCAS représente actuellement la meilleure couverture spatiale disponible pour les moyennes mensuelles à long terme des précipitations et des températures de l’air en surface en Alaska

Belief in divine moral authority:validation of a shortened scale with implications for social attitudes and moral cognition

Religion and morality have been deeply interwoven throughout human history. Although much research has investigated the role of religiosity (e.g., belief in God, prayer, religious attendance) in shaping moral concerns, only recently has research in psychology begun to delve deeper into the meta-ethical beliefs theists hold about the spiritual foundations of morality. The present research builds on moral–philosophical discourse on Divine Command Theory and recent work by Piazza and Landy (2013), who developed the 20-item Morality Founded on Divine Authority (MFDA) scale to measure Divine Command beliefs. We sought primarily to reduce the MFDA scale to increase its pragmatic utility; Confirmatory Factor Analysis revealed an optimal 5-item scale. Across four studies, this scale yielded levels of construct, convergent, and incremental validity equivalent to those of the 20-item scale. Compared with several other measures of religiosity and conservative thinking, the short MFDA was the strongest predictor of anti-atheist prejudice among U.S. religious believers and Indian Hindus (Studies 1a–1b) and largely explained religiosity's relationship with attitudes toward science (Study 1a) and moral cognitive outcomes including deontological reasoning (Study 2a) and prohibitive morality (Study 2b). We conclude with discussion about the practical utility of this scale in ongoing research into religion and moral cognition

Capturing the dynamics of genome replication on individual ultra-long nanopore sequence reads.

Replication of eukaryotic genomes is highly stochastic, making it difficult to determine the replication dynamics of individual molecules with existing methods. We report a sequencing method for the measurement of replication fork movement on single molecules by detecting nucleotide analog signal currents on extremely long nanopore traces (D-NAscent). Using this method, we detect 5-bromodeoxyuridine (BrdU) incorporated by Saccharomyces cerevisiae to reveal, at a genomic scale and on single molecules, the DNA sequences replicated during a pulse-labeling period. Under conditions of limiting BrdU concentration, D-NAscent detects the differences in BrdU incorporation frequency across individual molecules to reveal the location of active replication origins, fork direction, termination sites, and fork pausing/stalling events. We used sequencing reads of 20-160 kilobases to generate a whole-genome single-molecule map of DNA replication dynamics and discover a class of low-frequency stochastic origins in budding yeast. The D-NAscent software is available at https://github.com/MBoemo/DNAscent.git

Using reference-free compressed data structures to analyze sequencing reads from thousands of human genomes.

We are rapidly approaching the point where we have sequenced millions of human genomes. There is a pressing need for new data structures to store raw sequencing data and efficient algorithms for population scale analysis. Current reference-based data formats do not fully exploit the redundancy in population sequencing nor take advantage of shared genetic variation. In recent years, the Burrows-Wheeler transform (BWT) and FM-index have been widely employed as a full-text searchable index for read alignment and de novo assembly. We introduce the concept of a population BWT and use it to store and index the sequencing reads of 2705 samples from the 1000 Genomes Project. A key feature is that, as more genomes are added, identical read sequences are increasingly observed, and compression becomes more efficient. We assess the support in the 1000 Genomes read data for every base position of two human reference assembly versions, identifying that 3.2 Mbp with population support was lost in the transition from GRCh37 with 13.7 Mbp added to GRCh38. We show that the vast majority of variant alleles can be uniquely described by overlapping 31-mers and show how rapid and accurate SNP and indel genotyping can be carried out across the genomes in the population BWT. We use the population BWT to carry out nonreference queries to search for the presence of all known viral genomes and discover human T-lymphotropic virus 1 integrations in six samples in a recognized epidemiological distribution

MinION Analysis and Reference Consortium: Phase 1 data release and analysis

The advent of a miniaturized DNA sequencing device with a high-throughput contextual sequencing capability embodies the next generation of large scale sequencing tools. The MinION™ Access Programme (MAP) was initiated by Oxford Nanopore Technologies™ in April 2014, giving public access to their USB-attached miniature sequencing device. The MinION Analysis and Reference Consortium (MARC) was formed by a subset of MAP participants, with the aim of evaluating and providing standard protocols and reference data to the community. Envisaged as a multi-phased project, this study provides the global community with the Phase 1 data from MARC, where the reproducibility of the performance of the MinION was evaluated at multiple sites. Five laboratories on two continents generated data using a control strain of Escherichia coli K-12, preparing and sequencing samples according to a revised ONT protocol. Here, we provide the details of the protocol used, along with a preliminary analysis of the characteristics of typical runs including the consistency, rate, volume and quality of data produced. Further analysis of the Phase 1 data presented here, and additional experiments in Phase 2 of E. coli from MARC are already underway to identify ways to improve and enhance MinION performance

Gender gap in surgery: Can integrated surgical programs increase the number of women in surgery?

Objective: To determine if the creation of integrated surgical programs has increased the recruitment of women into surgical residencies.Summary Background Data: Historically, there have been disproportionately lower numbers of women entering surgical residency programs compared to the percentage of women physicians. Per the ACGME, in 2017, women comprised 45.8% of all residents in training but just 29.9% of surgical residents. We sought to determine if certain factors, specifically integrated surgical programs, have made an impact on the number of women in surgical specialties.Methods: Data regarding surgical residents and physicians was extracted from the Accreditation Council of Graduate Medical Education (ACGME) Data Resource Books and ACGME Association of American Medical Colleges (AAMC) Physician Specialty Data Reports from 2007-2018.Results: Overall, integrated surgical programs consistently report increased percentages of women compared to non- integrated surgical programs.Conclusions: The creation of integrated surgical programs has increased and will likely continue to increase the proportion of women in surgical residencies

Deep short-read sequencing of chromosome 17 from the mouse strains A/J and CAST/Ei identifies significant germline variation and candidate genes that regulate liver triglyceride levels

Methods for accurate identification of nucleotide and structural variation using de novo short read sequencing of mouse chromosomes are described