A targeted sequencing panel identifies rare damaging variants in multiple genes in the cranial neural tube defect, anencephaly

Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to life-long neurological handicap. Collectively NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n=85 anencephaly and n=5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N=509), we identified 397 rare variants (MAF<1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly

Modeling the interactions between river morphodynamics and riparian vegetation

The study of river-riparian vegetation interactions is an important and intriguing research field in geophysics. Vegetation is an active element of the ecological dynamics of a floodplain which interacts with the fluvial processes and affects the flow field, sediment transport, and the morphology of the river. In turn, the river provides water, sediments, nutrients, and seeds to the nearby riparian vegetation, depending on the hydrological, hydraulic, and geomorphological characteristic of the stream. In the past, the study of this complex theme was approached in two different ways. On the one hand, the subject was faced from a mainly qualitative point of view by ecologists and biogeographers. Riparian vegetation dynamics and its spatial patterns have been described and demonstrated in detail, and the key role of several fluvial processes has been shown, but no mathematical models have been proposed. On the other hand, the quantitative approach to fluvial processes, which is typical of engineers, has led to the development of several morphodynamic models. However, the biological aspect has usually been neglected, and vegetation has only been considered as a static element. In recent years, different scientific communities (ranging from ecologists to biogeographers and from geomorphologists to hydrologists and fluvial engineers) have begun to collaborate and have proposed both semiquantitative and quantitative models of river-vegetation interconnections. These models demonstrate the importance of linking fluvial morphodynamics and riparian vegetation dynamics to understand the key processes that regulate a riparian environment in order to foresee the impact of anthropogenic actions and to carefully manage and rehabilitate riparian areas. In the first part of this work, we review the main interactions between rivers and riparian vegetation, and their possible modeling. In the second part, we discuss the semiquantitative and quantitative models which have been proposed to date, considering both multi- and single-thread river

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

Fringe effects: detecting bull trout (Salvelinus confluentus) at distributional boundaries in a montane watershed

Robust assessment and monitoring programs are critical for effective conservation, yet for many taxa we fail to understand how trade-offs in sampling design affect power to detect population trends and describe spatial patterns. We tested an occupancy-based sampling approach to evaluate design considerations for detecting watershed-scale population trends associated with juvenile bull trout (Salvelinus confluentus) distributions. Electrofishing surveys were conducted across 275 stream sites from the Prairie Creek watershed, Northwest Territories, Canada. Site-level detectability of juvenile bull trout was not uniform, and imperfect detection affected modelled occupancy probabilities most in fringe habitats near distributional boundaries in steep reaches and large streams. We show that detecting a 30% change in watershed-level occupancy ≥78% of the time as conservation guidelines suggest, may require three repeat surveys (i.e., temporal replicates) and increased spatial sampling intensity of fringe habitats. Additional sampling effort in fringe sites could be offset by sampling fewer sites in core habitats to optimize designs for detecting demographic shifts in bull trout, while still minimizing risk of non-detection for this cryptic species.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Pico-litre sample introduction and acoustic levitation systems for time resolved protein crystallography experiments at XFELS

The system described in this work is a variant from traditional acoustic levitation first described by, Marzo et al [1]. It uses multiple transducers eliminating the requirement for a mirror surface, allowing for an open geometry as the sound from multiple transducers combines to generate the acoustic trap which is configured to catch pico litres of crystal slurries. These acoustic traps also have the significant benefit of eliminating potential beam attenuation due to support structures or microfluidic devices. Additionally they meet the need to eliminate sample environments when experiments are carried out using an X-ray Free Electron Lasers (XFEL) such as the Linac Coherent Light Source (LCLS) as any sample environment would not survive the exposure to the X-Ray beam. XFELs generate Light a billion times brighter than the sun. The application for this system will be to examine turn over in Beta lactamase proteins which is responsible for bacteria developing antibiotic resistance and therefore of significant importance to future world health. The system will allow for diffraction data to be collected before and after turnover allowing for a better understanding of the underling processes. The authors first described this work at Nanotech 2017 [2]