Anesthesiology Posters - 2019

Anesthesiology Postershttps://scholarlycommons.libraryinfo.bhs.org/research_education/1000/thumbnail.jp

Single-nucleus multi-omics of human stem cell-derived islets identifies deficiencies in lineage specification

Insulin-producing β cells created from human pluripotent stem cells have potential as a therapy for insulin-dependent diabetes, but human pluripotent stem cell-derived islets (SC-islets) still differ from their in vivo counterparts. To better understand the state of cell types within SC-islets and identify lineage specification deficiencies, we used single-nucleus multi-omic sequencing to analyse chromatin accessibility and transcriptional profiles of SC-islets and primary human islets. Here we provide an analysis that enabled the derivation of gene lists and activity for identifying each SC-islet cell type compared with primary islets. Within SC-islets, we found that the difference between β cells and awry enterochromaffin-like cells is a gradient of cell states rather than a stark difference in identity. Furthermore, transplantation of SC-islets in vivo improved cellular identities overtime, while long-term in vitro culture did not. Collectively, our results highlight the importance of chromatin and transcriptional landscapes during islet cell specification and maturation

Collaborative fisheries research reveals reserve size and age determine efficacy across a network of marine protected areas

A variety of criteria may influence the efficacy of networks of marine protected areas (MPA) designed to enhance biodiversity conservation and provide fisheries benefits. Meta-analyses have evaluated the influence of MPA attributes on abundance, biomass, and size structure of harvested species, reporting that MPA size, age, depth, and connectivity influence the strength of MPA responses. However, few empirical MPA evaluation studies have used consistent sampling methodology across multiple MPAs and years. Our collaborative fisheries research program systematically sampled 12 no-take or highly protective limited-take MPAs and paired fished reference areas across a network spanning 1100 km of coastline to evaluate the factors driving MPA efficacy across a large geographic region. We found that increased size and age consistently contributed to increased fish catch, biomass, and positive species responses inside MPAs, while accounting for factors such as latitude, primary productivity, and distance to the nearest MPA. Our study provides a model framework to collaboratively engage diverse stakeholders in fisheries research and provide high-quality data to assess the success of conservation strategies

The TESS-Keck Survey II: An Ultra-Short Period Rocky Planet and its Siblings Transiting the Galactic Thick-Disk Star TOI-561

We report the discovery of TOI-561, a multi-planet system in the galactic thick disk that contains a rocky, ultra-short period planet (USP). This bright ($V=10.2$) star hosts three small transiting planets identified in photometry from the NASA TESS mission: TOI-561 b (TOI-561.02, P=0.44 days, $R_b = 1.45\pm0.11\,R_\oplus$), c (TOI-561.01, P=10.8 days, $R_c=2.90\pm0.13\,R_\oplus$), and d (TOI-561.03, P=16.3 days, $R_d=2.32\pm0.16\,R_\oplus$). The star is chemically ([Fe/H]$=-0.41\pm0.05$, [$\alpha$/H]$=+0.23\pm0.05$) and kinematically consistent with the galactic thick disk population, making TOI-561 one of the oldest ($10\pm3\,$Gyr) and most metal-poor planetary systems discovered yet. We dynamically confirm planets b and c with radial velocities from the W. M. Keck Observatory High Resolution Echelle Spectrometer. Planet b has a mass and density of $3.2\pm0.8\,M_\oplus$ and $5.5^{+2.0}_{-1.6}\,$g$\,$cm$^{-3}$, consistent with a rocky composition. Its lower-than-average density is consistent with an iron-poor composition, although an Earth-like iron-to-silicates ratio is not ruled out. Planet c is $7.0\pm2.3\,M_\oplus$ and $1.6\pm0.6\,$g$\,$cm$^{-3}$, consistent with an interior rocky core overlaid with a low-mass volatile envelope. Several attributes of the photometry for planet d (which we did not detect dynamically) complicate the analysis, but we vet the planet with high-contrast imaging, ground-based photometric follow-up and radial velocities. TOI-561 b is the first rocky world around a galactic thick-disk star confirmed with radial velocities and one of the best rocky planets for thermal emission studies.Comment: Accepted at The Astronomical Journal; 25 pages, 10 figure

The TESS-Keck Survey. XI. Mass Measurements for Four Transiting sub-Neptunes orbiting K dwarf TOI-1246

Multi-planet systems are valuable arenas for investigating exoplanet architectures and comparing planetary siblings. TOI-1246 is one such system, with a moderately bright K dwarf (V=11.6, K=9.9) and four transiting sub-Neptunes identified by TESS with orbital periods of 4.31 d, 5.90 d, 18.66 d, and 37.92 d. We collected 130 radial velocity observations with Keck/HIRES and TNG/HARPS-N to measure planet masses. We refit the 14 sectors of TESS photometry to refine planet radii (2.97±0.06 R⊕,2.47±0.08 R⊕,3.46±0.09 R⊕, 3.72±0.16 R⊕), and confirm the four planets. We find that TOI-1246 e is substantially more massive than the three inner planets (8.1±1.1M⊕, 8.8±1.2M⊕, 5.3±1.7M⊕, 14.8±2.3M⊕). The two outer planets, TOI-1246 d and TOI-1246 e, lie near to the 2:1 resonance (Pe/Pd=2.03) and exhibit transit timing variations. TOI-1246 is one of the brightest four-planet systems, making it amenable for continued observations. It is one of only six systems with measured masses and radii for all four transiting planets. The planet densities range from 0.70±0.24 to 3.21±0.44g/cm3, implying a range of bulk and atmospheric compositions. We also report a fifth planet candidate found in the RV data with a minimum mass of 25.6 ± 3.6 M⊕. This planet candidate is exterior to TOI-1246 e with a candidate period of 93.8 d, and we discuss the implications if it is confirmed to be planetary in nature

The TESS-Keck Survey. XI. Mass Measurements for Four Transiting Sub-Neptunes Orbiting K Dwarf TOI-1246

Multiplanet systems are valuable arenas for investigating exoplanet architectures and comparing planetary siblings. TOI-1246 is one such system, with a moderately bright K dwarf (V = 11.6, K = 9.9) and four transiting sub-Neptunes identified by TESS with orbital periods of 4.31, 5.90, 18.66, and 37.92 days. We collected 130 radial velocity observations with Keck/HIRES and TNG/HARPS-N to measure planet masses. We refit the 14 sectors of TESS photometry to refine planet radii (2.97 +/- 0.06 R (circle plus), 2.47 +/- 0.08 R (circle plus), 3.46 +/- 0.09 R (circle plus), and 3.72 +/- 0.16 R (circle plus)) and confirm the four planets. We find that TOI-1246 e is substantially more massive than the three inner planets (8.1 +/- 1.1 M (circle plus), 8.8 +/- 1.2 M (circle plus), 5.3 +/- 1.7 M (circle plus), and 14.8 +/- 2.3 M (circle plus)). The two outer planets, TOI-1246 d and TOI-1246 e, lie near to the 2:1 resonance (P (e)/P ( d ) = 2.03) and exhibit transit-timing variations. TOI-1246 is one of the brightest four-planet systems, making it amenable for continued observations. It is one of only five systems with measured masses and radii for all four transiting planets. The planet densities range from 0.70 +/- 0.24 to 3.21 +/- 0.44 g cm(-3), implying a range of bulk and atmospheric compositions. We also report a fifth planet candidate found in the RV data with a minimum mass of 25.6 +/- 3.6 M (circle plus). This planet candidate is exterior to TOI-1246 e, with a candidate period of 93.8 days, and we discuss the implications if it is confirmed to be planetary in nature

The Psychological Science Accelerator: Advancing Psychology Through a Distributed Collaborative Network

Source at https://doi.org/10.1177/2515245918797607.Concerns about the veracity of psychological research have been growing. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions or replicate prior research in large, diverse samples. The PSA’s mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time limited), efficient (in that structures and principles are reused for different projects), decentralized, diverse (in both subjects and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside the network). The PSA and other approaches to crowdsourced psychological science will advance understanding of mental processes and behaviors by enabling rigorous research and systematic examination of its generalizability

Participation in collaborative fisheries research improves the perceptions of recreational anglers towards marine protected areas

Collaborative fisheries research programs engage stakeholders in data collection efforts, often with the benefit of increasing transparency about the status and management of natural resources. These programs are particularly important in marine systems, where management of recreational and commercial fisheries have historically been contentious. One such program is the California Collaborative Fisheries Research Program (CCFRP), which was designed in 2006 to engage recreational anglers in the scientific process and evaluate the efficacy of California’s network of marine protected areas. CCFRP began on the Central Coast of California and expanded statewide in 2017 to include six partner institutions in three regions: Northern, Central, and Southern California. To date, over 2,000 volunteer anglers have participated in the program, with many anglers volunteering for multiple years. However, the impacts of outreach, education, and collaborative research on those anglers at the statewide scale are currently unknown. Thus, the objective of the current study was to survey the statewide pool of volunteer anglers to assess the degree to which participation in CCFRP has influenced angler perceptions of MPAs, fisheries management, and conservation. We received 259 completed surveys out of a pool of 1,386 active anglers, equating to an 18.7% response rate. Participation in CCFRP resulted in a significant, positive impact on anglers’ attitudes towards MPAs in California across all regions. Anglers who participated in six or more CCFRP fishing trips had a more positive perception of MPAs than those who participated in fewer trips. Volunteer anglers across all regions perceived that they caught larger fishes, a higher abundance of fishes, and a greater diversity of species inside MPAs, consistent with the ecological findings of the program. These results highlight the benefits of involving community members in collaborative scientific research. Collaboration between researchers and the broader community increases transparency and trust between stakeholders, and results in greater understanding of natural resource dynamics, ultimately producing better management outcomes

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead