Comprehensive transcriptomic analysis of cell lines as models of primary tumors across 22 tumor types.

Cancer cell lines are a cornerstone of cancer research but previous studies have shown that not all cell lines are equal in their ability to model primary tumors. Here we present a comprehensive pan-cancer analysis utilizing transcriptomic profiles from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia to evaluate cell lines as models of primary tumors across 22 tumor types. We perform correlation analysis and gene set enrichment analysis to understand the differences between cell lines and primary tumors. Additionally, we classify cell lines into tumor subtypes in 9 tumor types. We present our pancreatic cancer results as a case study and find that the commonly used cell line MIA PaCa-2 is transcriptionally unrepresentative of primary pancreatic adenocarcinomas. Lastly, we propose a new cell line panel, the TCGA-110-CL, for pan-cancer studies. This study provides a resource to help researchers select more representative cell line models

Feminist foreign policy in Israel and Germany? The Women, Peace, and Security agenda, development policy, and female representation

This paper explores the relationship between feminist foreign policy (FFP) and a country’s national role conception (NRC). Specifically, it asks whether countries with ‘masculine’ NRCs are opposed to the pursuit of FFP while countries with a more ‘feminine’ national role conception are advocates of FFP. To this end, the paper conducts a comparative analysis of ‘masculine’ Israel and ‘feminine’ Germany along three domains: normative (with a focus on the Women, Peace, and Security [WPS] agenda), material (in relation to development policy), and institutional (with reference to female representation). Generally speaking, Germany has indeed undertaken broader and more substantive activities in pursuit of FFP goals than Israel. At the same time, Israel has clearly been more active than its ‘masculine’ role would suggest, and Germany less active and vocal than its ‘civilian power’ role would imply. Overall, the discussion suggests that whether countries pursue FFP goals is strongly influenced by the latter’s compatibility with the countries’ overarching NRCs, with party ideology, institutional autonomy, and intersection between gender policy and state interests playing a greater role regarding the specific levels of commitment and intensity shown in the pursuit of those goals

Effects of frequency-dependent spatial variation in soundscape settlement cues for reef fish larvae

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Salas, A. K., Ballard, M. S., Mooney, T. A., & Wilson, P. S. Effects of frequency-dependent spatial variation in soundscape settlement cues for reef fish larvae. Marine Ecology Progress Series, 687, (2022): 1-21, https://doi.org/10.3354/meps14012.The mechanisms that link reef soundscapes to larval fish settlement behaviors are poorly understood, yet the management of threatened reef communities requires we maintain the recruitment processes that recover and sustain populations. Using a field-calibrated sound propagation model, we predicted the transmission loss in the relevant frequency band as a function of range, depth, and azimuth to estimate the spatial heterogeneity in the acoustic cuescape. The model highlighted the frequency- and depth-dependence of the sound fields fishes may encounter, and we predict these complex spatial patterns influence how sounds function as settlement cues. Both modeling and field measurements supported a non-monotonic decline in amplitude with distance from the reef. We modeled acoustic fields created by sounds at frequencies from 2 common soniferous reef-based animals (snapping shrimps and toadfish) and estimated detection spaces of these sounds for larvae of 2 reef fish species. Results demonstrated that larval depth will influence cue availability and amplitude, and these spatial patterns of detection depend on cue frequency and the larval receiver’s auditory sensitivity. Estimated spatial scales of detection coupled with field measurements suggest cue amplitudes might allow some larvae to detect reef-based sounds at a range exposing them to the predicted spatial variation in the acoustic cuescape. In an individual-based model, cues available to even the shortest modeled distances improved settlement success. Our results emphasize the need to consider the frequency- and depth-dependence of the acoustic cues larval fishes encounter to increase understanding of the role of soundscapes in larval settlement.We thank the following funding sources for partial support: The University of Texas at Austin Integrative Biology Department’s Zoology Scholarship Endowment for Excellence award (A.K.S.), Smithsonian Tropical Research Institute (STRI) Short-term Fellowship (A.K.S.), Office of Naval Research (P.S.W. and M.S.B), and National Science Foundation (OCE-15-36782; T.A.M). We thank P. Gondola for support through the STRI Bocas del Toro Research Station and Dr. Andrew Altieri for assistance in site selection and knowledge of local ecosystem

Heterogeneity in HIV and cellular transcription profiles in cell line models of latent and productive infection: implications for HIV latency.

BackgroundHIV-infected cell lines are widely used to study latent HIV infection, which is considered the main barrier to HIV cure. We hypothesized that these cell lines differ from each other and from cells from HIV-infected individuals in the mechanisms underlying latency.ResultsTo quantify the degree to which HIV expression is inhibited by blocks at different stages of HIV transcription, we employed a recently-described panel of RT-ddPCR assays to measure levels of 7 HIV transcripts ("read-through," initiated, 5' elongated, mid-transcribed/unspliced [Pol], distal-transcribed [Nef], polyadenylated, and multiply-sliced [Tat-Rev]) in bulk populations of latently-infected (U1, ACH-2, J-Lat) and productively-infected (8E5, activated J-Lat) cell lines. To assess single-cell variation and investigate cellular genes associated with HIV transcriptional blocks, we developed a novel multiplex qPCR panel and quantified single cell levels of 7 HIV targets and 89 cellular transcripts in latently- and productively-infected cell lines. The bulk cell HIV transcription profile differed dramatically between cell lines and cells from ART-suppressed individuals. Compared to cells from ART-suppressed individuals, latent cell lines showed lower levels of HIV transcriptional initiation and higher levels of polyadenylation and splicing. ACH-2 and J-Lat cells showed different forms of transcriptional interference, while U1 cells showed a block to elongation. Single-cell studies revealed marked variation between/within cell lines in expression of HIV transcripts, T cell phenotypic markers, antiviral factors, and genes implicated in latency. Expression of multiply-spliced HIV Tat-Rev was associated with expression of cellular genes involved in activation, tissue retention, T cell transcription, and apoptosis/survival.ConclusionsHIV-infected cell lines differ from each other and from cells from ART-treated individuals in the mechanisms governing latent HIV infection. These differences in viral and cellular gene expression must be considered when gauging the suitability of a given cell line for future research on HIV. At the same time, some features were shared across cell lines, such as low expression of antiviral defense genes and a relationship between productive infection and genes involved in survival. These features may contribute to HIV latency or persistence in vivo, and deserve further study using novel single cell assays such as those described in this manuscript

ITAG : an eco-sensor for fine-scale behavioral measurements of soft-bodied marine invertebrates

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Animal Biotelemetry 3 (2015): 31, doi:10.1186/s40317-015-0076-1.Soft-bodied marine invertebrates comprise a keystone component of ocean ecosystems; however, we know little of their behaviors and physiological responses within their natural habitat. Quantifying ocean conditions and measuring organismal responses to the physical environment is vital to understanding the species or ecosystem-level influences of a changing ocean. Here we describe a novel, soft-bodied invertebrate eco-sensor tag (the ITAG), its trial attachments to squid and jellyfish, and the fine-scale behavioral measurements recorded on captive animals. Tags were deployed on five jellyfish (Aurelia aurita) and eight squid (Loligo forbesi) in laboratory conditions for up to 24 h. Using concurrent video and tag data, movement signatures for specific behaviors were identified. These behaviors included straight swimming (for jellyfish), and finning, jetting, direction reversal and turning (for squid). Overall activity levels were quantified using the root-mean-squared magnitude of acceleration, and finning was found to be the dominant squid swimming gait during captive squid experiments. External light sensors on the ITAG were used to compare squid swimming activity relative to ambient light across a ca. 20-h trial. The deployments revealed that while swimming was continuous for captive squid, energetically costly swimming behaviors (i.e., jetting and rapid direction reversals) occurred infrequently. These data reflect the usefulness of the ITAG to study trade-offs between behavior and energy expenditure in captive and wild animals. These data demonstrate that eco-sensors with sufficiently high sampling rates can be applied to quantify behavior of soft-bodied taxa and changes in behavior due to interactions with the surrounding environment. The methods and tool described here open the door for substantial lab and field-based measurements of fine-scale behavior, physiology, and concurrent environmental parameters that will inform fisheries management, and elucidate the ecology of these important keystone taxa.This work was supported by WHOI’s Ocean Life Institute and the Innovative Technology Program, Hopkins Marine Station’s Marine Life Observatory (to KK), as well as the National Science Foundation’s Ocean Acidification Program (to TAM) and NSF’s Program for Innovative Development of Biological Research (to TAM, KK and KAS)

Augmenting biologging with supervised machine learning to study in situ behavior of the medusa Chrysaora fuscescens

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Fannjiang, C., Mooney, T. A., Cones, S., Mann, D., Shorter, K. A., & Katija, K. Augmenting biologging with supervised machine learning to study in situ behavior of the medusa Chrysaora fuscescens. Journal of Experimental Biology, 222, (2019): jeb.207654, doi:10.1242/jeb.207654.Zooplankton play critical roles in marine ecosystems, yet their fine-scale behavior remains poorly understood because of the difficulty in studying individuals in situ. Here, we combine biologging with supervised machine learning (ML) to propose a pipeline for studying in situ behavior of larger zooplankton such as jellyfish. We deployed the ITAG, a biologging package with high-resolution motion sensors designed for soft-bodied invertebrates, on eight Chrysaora fuscescens in Monterey Bay, using the tether method for retrieval. By analyzing simultaneous video footage of the tagged jellyfish, we developed ML methods to: (1) identify periods of tag data corrupted by the tether method, which may have compromised prior research findings, and (2) classify jellyfish behaviors. Our tools yield characterizations of fine-scale jellyfish activity and orientation over long durations, and we conclude that it is essential to develop behavioral classifiers on in situ rather than laboratory data.This work was supported by the David and Lucile Packard Foundation (to K.K.), the Woods Hole Oceanographic Institution (WHOI) Green Innovation Award (to T.A.M., K.K. and K.A.S.) and National Science Foundation (NSF) DBI collaborative awards (1455593 to T.A.M. and K.A.S.; 1455501 to K.K.). Deposited in PMC for immediate release

Solvent exposure of Tyr10 as a probe of structural differences between monomeric and aggregated forms of the amyloid-β peptide.

Aggregation of amyloid-β (Aβ) peptides is a characteristic pathological feature of Alzheimer's disease. We have exploited the relationship between solvent exposure and intrinsic fluorescence of a single tyrosine residue, Tyr10, in the Aβ sequence to probe structural features of the monomeric, oligomeric and fibrillar forms of the 42-residue Aβ1-42. By monitoring the quenching of Tyr10 fluorescence upon addition of water-soluble acrylamide, we show that in Aβ1-42 oligomers this residue is solvent-exposed to a similar extent to that found in the unfolded monomer. By contrast, Tyr10 is significantly shielded from acrylamide quenching in Aβ1-42 fibrils, consistent with its proximity to the fibrillar cross-β core. Furthermore, circular dichroism measurements reveal that Aβ1-42 oligomers have a considerably lower β-sheet content than the Aβ1-42 fibrils, indicative of a less ordered molecular arrangement in the former. Taken together these findings suggest significant differences in the structural assembly of oligomers and fibrils that are consistent with differences in their biological effects.This work was funded by grants to E.K.E from the Wenner-Gren Foundations, the Hasselblad Foundation, and the Swedish Innovation Agency (Vinnova) and to C.M.D from the Wellcome Trust. The TEM imaging was carried out in the Multi-Imaging Unit in the Department of Physiology, Development and Neuroscience, University of Cambridge, UK and quantitative amino acid analysis was carried out at the Protein and Nucleic Acid Chemistry Facility, Department of Biochemistry, University of Cambridge, UK.This is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.bbrc.2015.11.01

Soundscapes influence the settlement of the common caribbean coral porites astreoides irrespective of light conditions

Author Posting. © Royal Society, 2018. This article is posted here by permission of Royal Society for personal use, not for redistribution. The definitive version was published in Proceedings of the Royal Society Open Science 5(12) (2018): 181358. doi: 10.1098/rsos.181358.The settlement of reef-building corals is critical to the survival and recovery of reefs. Recent evidence indicates that coral larvae orient towards reef sound, yet the components of the acoustic environment that may attract coral larvae and induce settlement are unknown. Here we investigated the effects of ambient soundscapes on settlement of Porites astreoides coral larvae using in situ chambers on reefs differing in habitat quality (coral and fish abundance). Mean larval settlement was twice as high in an acoustic environment with high levels of low-frequency sounds, typical of a high-quality, healthy reef; this result was observed in both natural light and dark treatments. Overall, the enhancement of coral settlement by soundscapes typical of healthy reefs suggests a positive feedback where soundscape properties of reefs with elevated coral and fish abundance may facilitate coral recruitment.This study is funded by NSF Biological Oceanography award 15-36782 which supported all authors

Microbial and nutrient dynamics in mangrove, reef, and seagrass waters over tidal and diurnal time scales

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Becker, C. C., Weber, L., Suca, J. J., Llopiz, J. K., Mooney, T. A., & Apprill, A. Microbial and nutrient dynamics in mangrove, reef, and seagrass waters over tidal and diurnal time scales. Aquatic Microbial Ecology, 85, (2020): 101-119, https://doi.org/10.3354/ame01944.In coral reefs and adjacent seagrass meadow and mangrove environments, short temporal scales (i.e. tidal, diurnal) may have important influences on ecosystem processes and community structure, but these scales are rarely investigated. This study examines how tidal and diurnal forcings influence pelagic microorganisms and nutrient dynamics in 3 important and adjacent coastal biomes: mangroves, coral reefs, and seagrass meadows. We sampled for microbial (Bacteria and Archaea) community composition, cell abundances and environmental parameters at 9 coastal sites on St. John, US Virgin Islands that spanned 4 km in distance (4 coral reefs, 2 seagrass meadows and 3 mangrove locations within 2 larger bays). Eight samplings occurred over a 48 h period, capturing day and night microbial dynamics over 2 tidal cycles. The seagrass and reef biomes exhibited relatively consistent environmental conditions and microbial community structure but were dominated by shifts in picocyanobacterial abundances that were most likely attributed to diel dynamics. In contrast, mangrove ecosystems exhibited substantial daily shifts in environmental parameters, heterotrophic cell abundances and microbial community structure that were consistent with the tidal cycle. Differential abundance analysis of mangrove-associated microorganisms revealed enrichment of pelagic oligotrophic taxa during high tide and enrichment of putative sediment-associated microbes during low tide. Our study underpins the importance of tidal and diurnal time scales in structuring coastal microbial and nutrient dynamics, with diel and tidal cycles contributing to a highly dynamic microbial environment in mangroves, and time of day likely contributing to microbial dynamics in seagrass and reef biomes.This research was supported by NSF awards OCE-1536782 to T.A.M., J.K.L., and A.A. and OCE-1736288 to A.A., NOAA Cooperative Institutes award NA19O AR 4320074 to A.A. and E. Kujawinski and the Andrew W. Mellon Foundation Endowed Fund for Innovative Research to A.A