Failure to detect mutations in U2AF1 due to changes in the GRCh38 reference sequence

The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in myelodysplastic syndrome, acute myeloid leukemia, and other cancers. A change introduced in the GRCh38 version of the human reference build prevents detection of mutations in this gene, and others, by variant calling pipelines. This study describes the problem in detail and shows that a modified GRCh38 reference build with unchanged coordinates can be used to ameliorate the issue

Ribosome-associated vesicles: A dynamic subcompartment of the endoplasmic reticulum in secretory cells

The endoplasmic reticulum (ER) is a highly dynamic network of membranes. Here, we combine live-cell microscopy with in situ cryo–electron tomography to directly visualize ER dynamics in several secretory cell types including pancreatic β-cells and neurons under near-native conditions. Using these imaging approaches, we identify a novel, mobile form of ER, ribosome-associated vesicles (RAVs), found primarily in the cell periphery, which is conserved across different cell types and species. We show that RAVs exist as distinct, highly dynamic structures separate from the intact ER reticular architecture that interact with mitochondria via direct intermembrane contacts. These findings describe a new ER subcompartment within cells

The need for laboratory work to aid in the understanding of exoplanetary atmospheres

Advancements in our understanding of exoplanetary atmospheres, from massive gas giants down to rocky worlds, depend on the constructive challenges between observations and models. We are now on a clear trajectory for improvements in exoplanet observations that will revolutionize our ability to characterize the atmospheric structure, composition, and circulation of these worlds. These improvements stem from significant investments in new missions and facilities, such as JWST and the several planned ground-based extremely large telescopes. However, while exoplanet science currently has a wide range of sophisticated models that can be applied to the tide of forthcoming observations, the trajectory for preparing these models for the upcoming observational challenges is unclear. Thus, our ability to maximize the insights gained from the next generation of observatories is not certain. In many cases, uncertainties in a path towards model advancement stems from insufficiencies in the laboratory data that serve as critical inputs to atmospheric physical and chemical tools. We outline a number of areas where laboratory or ab initio investigations could fill critical gaps in our ability to model exoplanet atmospheric opacities, clouds, and chemistry. Specifically highlighted are needs for: (1) molecular opacity linelists with parameters for a diversity of broadening gases, (2) extended databases for collision-induced absorption and dimer opacities, (3) high spectral resolution opacity data for relevant molecular species, (4) laboratory studies of haze and condensate formation and optical properties, (5) significantly expanded databases of chemical reaction rates, and (6) measurements of gas photo-absorption cross sections at high temperatures. We hope that by meeting these needs, we can make the next two decades of exoplanet science as productive and insightful as the previous two decades.Publisher PD

Evaluating the Influence of Epidemiological Parameters and Host Ecology on the Spread of Phocine Distemper Virus through Populations of Harbour Seals

Catriona Harris was supported by a grant from the UK Natural Environment Research Council. The funders had no role in study design, data collections and analysis, decision to publish, or preparation of the manuscript.Background: Outbreaks of phocine distemper virus (PDV) in Europe during 1988 and 2002 were responsible for the death of around 23,000 and 30,000 harbour seals, respectively. These epidemics, particularly the one in 2002, provided an unusual opportunity to estimate epidemic parameters for a wildlife disease. There were marked regional differences in the values of some parameters both within and between epidemics. Methodology and Principal Findings: We used an individual-based model of seal movement that allowed us to incorporate realistic representations of space, time and animal behaviour into a traditional epidemiological modelling framework. We explored the potential influence of a range of ecological (foraging trip duration, time of epidemic onset, population size) and epidemiological (length of infectious period, contact rate between infectious and susceptible individuals, case mortality) parameters on four readily-measurable epidemic characteristics (number of dead individuals, duration of epidemic, peak mortality date and prevalence) and on the probability that an epidemic would occur in a particular region. We analysed the outputs as if they were the results of a series of virtual experiments, using Generalised Linear Modelling. All six variables had a significant effect on the probability that an epidemic would be recognised as an unusual mortality event by human observers. Conclusions: Regional and temporal variation in contact rate was the most likely cause of the observed differences between the two epidemics. This variation could be a consequence of differences in the way individuals divide their time between land and sea at different times of the year.Publisher PDFPeer reviewe

Re:Chicago

https://via.library.depaul.edu/museum-publications/1012/thumbnail.jp