46 research outputs found
Integrating Preventive Law and Therapeutic Jurisprudence: A Law and Psychology Based Approach to Lawyering
Integrating Preventive Law and Therapeutic Jurisprudence: A Law and Psychology Based Approach to Lawyering
The genomes of two key bumblebee species with primitive eusocial organization
Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation
Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response
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Practicing therapeutic jurisprudence ::law as a helping profession /
Interpretation of Association Signals and Identification of Causal Variants from Genome-wide Association Studies
GWAS have been successful in identifying disease susceptibility loci, but it remains a challenge to pinpoint the causal variants in subsequent fine-mapping studies. A conventional fine-mapping effort starts by sequencing dozens of randomly selected samples at susceptibility loci to discover candidate variants, which are then placed on custom arrays or used in imputation algorithms to find the causal variants. We propose that one or several rare or low-frequency causal variants can hitchhike the same common tag SNP, so causal variants may not be easily unveiled by conventional efforts. Here, we first demonstrate that the true effect size and proportion of variance explained by a collection of rare causal variants can be underestimated by a common tag SNP, thereby accounting for some of the “missing heritability” in GWAS. We then describe a case-selection approach based on phasing long-range haplotypes and sequencing cases predicted to harbor causal variants. We compare this approach with conventional strategies on a simulated data set, and we demonstrate its advantages when multiple causal variants are present. We also evaluate this approach in a GWAS on hearing loss, where the most common causal variant has a minor allele frequency (MAF) of 1.3% in the general population and 8.2% in 329 cases. With our case-selection approach, it is present in 88% of the 32 selected cases (MAF = 66%), so sequencing a subset of these cases can readily reveal the causal allele. Our results suggest that thinking beyond common variants is essential in interpreting GWAS signals and identifying causal variants
At the Crossroads of Nanotoxicology<i>in vitro</i>: Past Achievements and Current Challenges
Copper Indium Gallium Selenide (CIGS) Photovoltaic Devices Made Using Multistep Selenization of Nanocrystal Films
The power conversion efficiency of
photovoltaic devices made with
ink-deposited Cu(In<sub><i>x</i></sub>Ga<sub>1–<i>x</i></sub>)Se<sub>2</sub> (CIGS) nanocrystal layers can be
enhanced by sintering the nanocrystals with a high temperature selenization
process. This process, however, can be challenging to control. Here,
we report that ink deposition followed by annealing under inert gas
and then selenization can provide better control over CIGS nanocrystal
sintering and yield generally improved device efficiency. Annealing
under argon at 525 °C removes organic ligands and diffuses sodium
from the underlying soda lime glass into the Mo back contact to improve
the rate and quality of nanocrystal sintering during selenization
at 500 °C. Shorter selenization time alleviates excessive MoSe<sub>2</sub> formation at the Mo back contact that leads to film delamination,
which in turn enables multiple cycles of nanocrystal deposition and
selenization to create thicker, more uniform absorber films. Devices
with power conversion efficiency greater than 7% are fabricated using
the multiple step nanocrystal deposition and sintering process
