bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Continuous Video-EEG in Patients With Altered Consciousness Improve Patient Outcome? Current Evidence and Randomized Controlled Trial Design
Authors: Rossetti Andrea O. , Schindler Kaspar , Alvarez Vincent , Sutter Raoul , Novy Jan , Oddo Mauro , Warpelin-Decrausaz Loane , Rüegg Stephan
Published: March 2018

Continuous video-EEG is recommended for patients with altered consciousness; as compared to routine EEG (lasting <30 minutes), it improves seizure detection, but is time- and resource-consuming. Although North American centers increasingly implement continuous video-EEG, most other (including European) hospitals have insufficient resources. Only one study suggested that continuous video-EEG could improve outcome in adults, and recent assessments challenge this view. This article reviews current evidence on the added value for continuous video-EEG in clinical terms and describes a design for a prospective study.

In a multicenter randomized clinical trial (NCT03129438), adults with a Glasgow Coma Scale ≤11 will be randomized 1:1 to continuous video-EEG (cEEG) for 30 to 48 hours or 2 routine EEG (rEEG), assessed through standardized American Clinical Neurophysiology Society (ACNS) guidelines. The primary outcome will be mortality at 6 months, assessed blindly. Secondary outcomes will explore functional status at 4 weeks and 6 months, intensive care unit (ICU) length of stay, infection rates, and hospitalization costs. Using a 2-sided approach with power of 0.8 and a error of 0.05, 2 × 174 patients are needed to detect an absolute survival difference of 14%, suggested by the single available study on the topic.

This study should help clarifying whether cEEG has a significant impact on outcome and define its cost effectiveness. If the trial will result positive, it will encourage broader implementation of cEEG with consecutive substantial impact on health care and resource allocations. If not, it may offer a rationale to design a larger trial, and – at least for smaller centers – to avoid widespread implementation of cEEG, rationalizing personnel and device costs.
Resource-driven changes to host population stability alter the evolution of virulence and transmission
Authors: Hite Jessica L. , Cressler Clayton E.
Published: March 2018

What drives the evolution of parasite life-history traits? Recent studies suggest that linking within- and between-host processes can provide key insight into both disease dynamics and parasite evolution. Still, it remains difficult to understand how to pinpoint the critical factors connecting these cross-scale feedbacks, particularly under non-equilibrium conditions; many natural host populations inherently fluctuate and parasites themselves can strongly alter the stability of host populations. Here, we develop a general model framework that mechanistically links resources to parasite evolution across a gradient of stable and unstable conditions. First, we dynamically link resources and between-host processes (host density, stability, transmission) to virulence evolution, using a ‘non-nested’ model. Then, we consider a ‘nested’ model where population-level processes (transmission and virulence) depend on resource-driven changes to individual-level (within-host) processes (energetics, immune function, parasite production). Contrary to ‘non-nested’ model predictions, the ‘nested’ model reveals complex effects of host population dynamics on parasite evolution, including regions of evolutionary bistability; evolution can push parasites towards strongly or weakly stabilizing strategies. This bistability results from dynamic feedbacks between resource-driven changes to host density, host immune function and parasite production. Together, these results highlight how cross-scale feedbacks can provide key insights into the structuring role of parasites and parasite evolution.

This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
Livestock abundance predicts vampire bat demography, immune profiles and bacterial infection risk
Authors: Becker Daniel J. , Czirják Gábor Á. , Volokhov Dmitriy V. , Bentz Alexandra B. , Carrera Jorge E. , Camus Melinda S. , Navara Kristen J. , Chizhikov Vladimir E. , Fenton M. Brock , Simmons Nancy B. , Recuenco Sergio E. , Gilbert Amy T. , Altizer Sonia , Streicker Daniel G.
Published: March 2018

Human activities create novel food resources that can alter wildlife–pathogen interactions. If resources amplify or dampen, pathogen transmission probably depends on both host ecology and pathogen biology, but studies that measure responses to provisioning across both scales are rare. We tested these relationships with a 4-year study of 369 common vampire bats across 10 sites in Peru and Belize that differ in the abundance of livestock, an important anthropogenic food source. We quantified innate and adaptive immunity from bats and assessed infection with two common bacteria. We predicted that abundant livestock could reduce starvation and foraging effort, allowing for greater investments in immunity. Bats from high-livestock sites had higher microbicidal activity and proportions of neutrophils but lower immunoglobulin G and proportions of lymphocytes, suggesting more investment in innate relative to adaptive immunity and either greater chronic stress or pathogen exposure. This relationship was most pronounced in reproductive bats, which were also more common in high-livestock sites, suggesting feedbacks between demographic correlates of provisioning and immunity. Infection with both
Bartonella
and haemoplasmas were correlated with similar immune profiles, and both pathogens tended to be less prevalent in high-livestock sites, although effects were weaker for haemoplasmas. These differing responses to provisioning might therefore reflect distinct transmission processes. Predicting how provisioning alters host–pathogen interactions requires considering how both within-host processes and transmission modes respond to resource shifts.

This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
Human–nature interactions and the consequences and drivers of provisioning wildlife
Authors: Cox Daniel T. C. , Gaston Kevin J.
Published: March 2018

Many human populations are undergoing an extinction of experience, with a progressive decline in interactions with nature. This is a consequence both of a loss of opportunity for, and orientation towards, such experiences. The trend is of concern in part because interactions with nature can be good for human health and wellbeing. One potential means of redressing these losses is through the intentional provision of resources to increase wildlife populations in close proximity to people, thereby increasing the potential for positive human–nature experiences, and thence the array of benefits that can result. In this paper, we review the evidence that these resource subsidies have such a cascade of effects. In some Westernized countries, the scale of provision is extraordinarily high, and doubtless leads to both positive and negative impacts for wildlife. In turn, these impacts often lead to more frequent, reliable and closer human–nature interactions, with a greater variety of species. The consequences for human wellbeing remain poorly understood, although benefits documented in the context of human–nature interactions more broadly seem likely to apply. There are also some important feedback loops that need to be better characterized if resource provisioning is to contribute effectively towards averting the extinction of experience.

This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
Optimal foraging in seasonal environments: implications for residency of Australian flying foxes in food-subsidized urban landscapes
Authors: Páez David J. , Restif Olivier , Eby Peggy , Plowright Raina K.
Published: March 2018

Bats provide important ecosystem services such as pollination of native forests; they are also a source of zoonotic pathogens for humans and domestic animals. Human-induced changes to native habitats may have created more opportunities for bats to reside in urban settings, thus decreasing pollination services to native forests and increasing opportunities for zoonotic transmission. In Australia, fruit bats (
Pteropus
spp. flying foxes) are increasingly inhabiting urban areas where they feed on anthropogenic food sources with nutritional characteristics and phenology that differ from native habitats. We use optimal foraging theory to investigate the relationship between bat residence time in a patch, the time it takes to search for a new patch (simulating loss of native habitat) and seasonal resource production. We show that it can be beneficial to reside in a patch, even when food productivity is low, as long as foraging intensity is low and the expected searching time is high. A small increase in the expected patch searching time greatly increases the residence time, suggesting nonlinear associations between patch residence and loss of seasonal native resources. We also found that sudden increases in resource consumption due to an influx of new bats has complex effects on patch departure times that again depend on expected searching times and seasonality. Our results suggest that the increased use of urban landscapes by bats may be a response to new spatial and temporal configurations of foraging opportunities. Given that bats are reservoir hosts of zoonotic diseases, our results provide a framework to study the effects of foraging ecology on disease dynamics.

One contribution of 14 to a theme isssue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
From wetland specialist to hand-fed generalist: shifts in diet and condition with provisioning for a recently urbanized wading bird
Authors: Murray Maureen H. , Kidd Anjelika D. , Curry Shannon E. , Hepinstall-Cymerman Jeffrey , Yabsley Michael J. , Adams Henry C. , Ellison Taylor , Welch Catharine N. , Hernandez Sonia M.
Published: March 2018

Many wildlife species shift their diets to use novel resources in urban areas. The consequences of these shifts are not well known, and consumption of reliable—but low quality—anthropogenic food may present important trade-offs for wildlife health. This may be especially true for carnivorous species such as the American white ibis (
Eudocimus albus
), a nomadic wading bird which has been increasingly observed in urban parks in South Florida, USA. We tested the effects of anthropogenic provisioning on consumer nutrition (i.e. dietary protein), body condition and ectoparasite burdens along an urban gradient using stable isotope analysis, scaled mass index values and GPS transmitter data. Ibises that assimilated more provisioned food were captured at more urban sites, used more urban habitat, had lower mass–length residuals, lower ectoparasite scores, assimilated less
δ
15N and had smaller dietary isotopic ellipses. Our results suggest that ibises in urban areas are heavily provisioned with anthropogenic food, which appears to offer a trade-off by providing low-quality, but easily accessible, calories that may not support high mass but may increase time available for anti-parasite behaviours such as preening. Understanding such trade-offs is important for investigating the effects of provisioning on infection risk and the conservation of wildlife in human-modified habitats.

This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’.
Azotobacter vinelandii: the source of 100 years of discoveries and many more to come
Authors: Noar Jesse D. , Bruno-Bárcena Jose M.
Published: March 2018

Azotobacter vinelandii has been studied for over 100 years since its discovery as an aerobic nitrogen-fixing organism. This species has proved useful for the study of many different biological systems, including enzyme kinetics and the genetic code. It has been especially useful in working out the structures and mechanisms of different nitrogenase enzymes, how they can function in oxic environments and the interactions of nitrogen fixation with other aspects of metabolism. Interest in studying A. vinelandii has waned in recent decades, but this bacterium still possesses great potential for new discoveries in many fields and commercial applications. The species is of interest for research because of its genetic pliability and natural competence. Its features of particular interest to industry are its ability to produce multiple valuable polymers – bioplastic and alginate in particular; its nitrogen-fixing prowess, which could reduce the need for synthetic fertilizer in agriculture and industrial fermentations, via coculture; its production of potentially useful enzymes and metabolic pathways; and even its biofuel production abilities. This review summarizes the history and potential for future research using this versatile microbe.
Comparative Transcriptomic and Metabolomic Analyses in Response to Cold in Tartary Buckwheat (Fagopyrum tataricum)
Authors: Jeon Jin , Kim Jae Kwang , Wu Qi , Park Sang Un
Published: March 2018

Plants recognize multiple environmental signals that lead to substantial changes in the regulation of primary and secondary metabolism in order to adapt to environmental stresses. In this study, we investigate the effects of cold on the metabolome and transcriptome of tartary buckwheat, focusing on the phenylpropanoid biosynthetic pathway. Using RNA-sequencing analysis of the cold-regulated transcriptome of buckwheat, we identified several phenylpropanoid biosynthetic transcripts that accumulated in response to cold. To confirm the transcriptome data, we analyzed the expression of the phenylpropanoid biosynthetic transcripts in cold-treated buckwheat and showed that all the phenylpropanoid biosynthetic transcripts were upregulated in coldtreated buckwheat seedlings with the exception of FtDFR. From the metabolic profiling based on the GC-TOF-MS analysis, we show that most of the sugars and their derivatives significantly increase in response to cold, while some of amino acids and their derivatives decrease in cold-treated plants. Some organic acids derived from the tricarboxylic acid (TCA) cycle increased in the cold-treated plants compared with in the plants grown at 25°C. In particular, the contents of anthocyanins and proanthocyanidins were significantly increased by cold treatment. In summary, these results indicate that the metabolome and transcriptome of tartary buckwheat are extensively affected by cold stresses.

Highlight

Using the RNA-sequencing data and the metabolic profiling analysis, we identified the changes that occur in the transcriptome and metabolome of tartary buckwheat in response to cold, focusing on the flavonoid biosynthetic pathway.

Abbreviations

ANR

anthocyanidin reductase

ANS

Anthocyanin synthase

C4H

cinnamate 4-hydroxylase

CHI

chalcone isomerase

CHS

chalcone synthase

4CL

4-coumarate:CoA ligase

DFR

dihydroflavonol reductase

DPPH

2,2-diphenyl-1-picrylhydrazyl

F3H

flavanone 3-hydroxylase

F3’H

flavonoid 3’-hydroxylase

FLS

flavonol synthase

GC-TOFMS

gas chromatography-time of flight mass spectrometry

3GT

flavonoid 3-O-glucosyltransferase

HPLC

high-performance l iquid chromatography

LAR

leucoanthocyanidin

PA

proanthocyanidin

PAL

phenylalanine ammonia-lyase

RT

3-O-rhamnosyltransferase

TCA

tricarboxylic acid.
Capturing diverse microbial sequence with comprehensive and scalable probe design
Authors: Metsky Hayden C. , Siddle Katherine J. , Gladden-Young Adrianne , Qu James , Yang David K. , Brehio Patrick , Goldfarb Andrew , Piantadosi Anne , Wohl Shirlee , Carter Amber , Lin Aaron E. , Barnes Kayla G. , Tully Damien C. , Corleis Björn , Hennigan Scott , Barbosa-Lima Giselle , Vieira Yasmine R. , Paul Lauren M. , Tan Amanda L. , Garcia Kimberly F. , Parham Leda A. , Odia Ikponmwonsa , Eromon Philomena , Folarin Onikepe A. , Goba Augustine ,   Viral Hemorrhagic Fever Consortium, Simon-Lorière Etienne , Hensley Lisa , Balmaseda Angel , Harris Eva , Kwon Douglas , Allen Todd M. , Runstadler Jonathan A. , Smole Sandra , Bozza Fernando A. , Souza Thiago M. L. , Isern Sharon , Michael Scott F. , Lorenzana Ivette , Gehrke Lee , Bosch Irene , Ebel Gregory , Grant Donald , Happi Christian , Park Daniel J. , Gnirke Andreas , Sabeti Pardis C. , Matranga Christian B.
Published: March 2018

Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. We developed CATCH (Compact Aggregation of Targets for Comprehensive Hybridization), a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs compact probe sets that achieve full coverage of known sequence diversity and that scale well with this diversity. To illustrate applications of CATCH, we focused on capturing viral genomes. We designed, synthesized, and validated multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriched unique viral content on average 18× and allowed us to assemble genomes that we could not otherwise recover, while accurately preserving within-sample diversity. We used this approach to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of viral infections in samples with unknown content. Together, this work demonstrates a path toward more sensitive, cost-effective metagenomic sequencing.
Dysregulation of the engulfment pathway in the gut fuels Inflammatory Bowel Disease
Authors: Suarez Katherine , Lim Eileen , Singh Sujay , Pereira Matheus , Joosen Linda Petronella , Ibeawuchi Stella-Rita , Dunkel Ying , Mittal Yash , Ho Samuel B. , Chattopadhyay Ranajoy , Guma Monica , Boland Brigid S. , Dulai Parambir S. , Sandborn William J. , Ghosh Pradipta , Das Soumita
Published: March 2018

BACKGROUND & AIMS

Luminal dysbiosis is ubiquitous in inflammatory bowel disease (IBD), but how the microbes trigger pro-inflammatory cascades in the epithelial and phagocytic cells remains unknown. Here we investigated the role of the microbial sensor ELMO1 (Engulfment and Cell Motility Protein-1) in sensing and responding to IBD-associated microbes in the gut epithelium and in macrophages.

METHODS

A stem cell-based technique is used to grow enteroids from WT and ELMO1−/−mice and from colonic biopsies of patients with IBD and subsequently differentiate them into enteroid-derived monolayers (EDMs) that mimic the gut epithelium/Gut in a dish. EDMs infected with IBD-associated invasiveE. coli-LF82 were analyzed for bacterial internalization, cytokine production and monocyte-recruitment when co-cultured with monocytes.

RESULTS

Expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria in IBD, higher expression correlated with elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. ELMO1-/-murine EDMs displayed a significant reduction of bacterial internalization through epithelial tight junctions and in MCP-1 production compared to WT mice. MCP-1 that is released from the epithelium recruited monocytes. Once recruited, macrophages required ELMO1 to engulf the bacteria and propagate a robust pro-inflammatory cytokine storm (TNF-α).

CONCLUSIONS

ELMO1 couples microbial-sensing to inflammation in both phagocytic and non-phagocytic host cells; it is required for the production of MCP-1 in the epithelium and TNF-α in macrophages. Findings raise the possibility that upregulation of epithelial ELMO1 and the epithelial ELMO1→MCP-1 axis may serve as an early biomarker and therapeutic target, respectively, in IBD and other disorders of inflammation.
Dynamic integration of conceptual information during learning
Authors: Inhoff Marika C. , Libby Laura A. , Noguchi Takao , Love Bradley C. , Ranganath Charan
Published: March 2018

The development and application of concepts is a critical component of cognition. Although concepts can be formed on the basis of simple perceptual or semantic features, conceptual representations can also capitalize on similarities across feature relationships. By representing these types of higher-order relationships, concepts can simplify the learning problem and facilitate decisions. Despite this, little is known about the neural mechanisms that support the construction and deployment of these kinds of higher-order concepts during learning. To address this question, we combined a carefully designed associative learning task with computational model-based functional magnetic resonance imaging (fMRI). Participants were scanned as they learned and made decisions about sixteen pairs of cues and associated outcomes. Associations were structured such that individual cues shared feature relationships, operationalized as shared patterns of cue pair-outcome associations. In order to capture the large number of possible conceptual representational structures that participants might employ and to evaluate how conceptual representations are used during learning, we leveraged a well-specified Bayesian computational model of category learning [1]. Behavioral and model-based results revealed that participants who displayed a tendency to link experiences in memory benefitted from faster learning rates, suggesting that the use of the conceptual structure in the task facilitated decisions about cue pair-outcome associations. Model-based fMRI analyses revealed that trial-by-trial integration of cue information into higher-order conceptual representations was supported by an anterior temporal (AT) network of regions previously implicated in representing complex conjunctions of features and meaning-based information.
A genome-wide innateness gradient defines the functional state of human innate T cells
Authors: Gutierrez-Arcelus M. , Teslovich N. , Mola A. R. , Kim H. , Hannes S. , Slowikowski K. , Watts G. F. M. , Brenner M. , Raychaudhuri S. , Brennan P. J.
Published: March 2018

Innate T cells (ITCs), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cell populations, use conserved antigen receptors generated by somatic recombination to respond to non-peptide antigens in an innate-like manner. Understanding where these cells fit in the scheme of immunity has been a puzzle since their discovery. Here, immunophenotyping of 101 individuals revealed that these populations account for as much as 25% of peripheral human T cells. To better understand these cells, we generated detailed gene expression profiles using low-input RNA-seq and confirmed key findings through protein-level and functional validation. Unbiased transcriptomic analyses revealed a continuous ‘innateness gradient’ with adaptive T cells at one end followed by MAIT, iNKT, Vδ1+T, Vδ2+T, and natural killer cells at the other end. Innateness was characterized by decreased expression of translational machinery genes and reduced proliferative potential, which allowed for prioritization of effector functions, including rapid cytokine and chemokine production, and cytotoxicity. Thus, global transcriptional programs uncovered rapid proliferation and rapid effector functions as competing goals that respectively define adaptive and innate states.

One Sentence Summary

Adaptive and innate T cells align along a continuous innateness gradient, reflecting a trade-off between effector function and proliferative capacity.
Mosaic Patterns of B-vitamin Synthesis and Utilization in a Natural Marine Microbial Community
Authors: Gómez-Consarnau Laura , Sachdeva Rohan , Gifford Scott M. , Cutter Lynda S. , Fuhrman Jed A. , Sañudo-Wilhelmy Sergio A. , Moran Mary Ann
Published: March 2018

Aquatic environments contain diverse microbial communities whose complex interactions mediate the cycling of major and trace nutrients such as vitamins. B-vitamins are essential coenzymes that many organisms cannot synthesize. Thus their exchange among de-novo synthesizers and auxotrophs is expected to play an important role in the microbial consortia and explain some of the temporal and spatial changes observed in diversity. In this study, we analyzed metatranscriptomes of a natural coastal microbial community, diel sampled-quarterly over one year to try to identify the potential major B-vitamin synthesizers and consumers. Our transcriptomic data show that the best-represented taxa dominated the expression of synthesis genes for some B-vitamins but lacked transcripts for others. For instance, Rhodobacterales dominated the expression of vitamin-B12synthesis, but not of vitamin-B7, whose synthesis transcripts were mainly represented by Flavobacteria.In contrast, bacterial groups that constituted less than 4% of the community (e.g., Verrucomicrobia) accounted for most of the vitamin-B1synthesis transcripts. Furthermore, ambient vitamin-B1concentrations were higher in samples collected during the day, and were positively correlated with chlorophyll-aconcentration. Our analysis supports the hypothesis that the mosaic of metabolic interdependencies through B-vitamin synthesis and exchange are key processes that contribute to shaping microbial communities in nature.
Passenger mutations in 2500 cancer genomes: Overall molecular functional impact and consequences
Authors: Kumar Sushant , Warrell Jonathan , Li Shantao , McGillivray Patrick D. , Meyerson William , Salichos Leonidas , Harmanci Arif , Martinez-Fundichely Alexander , Chan Calvin W.Y. , Nielsen Morten Muhlig , Lochovsky Lucas , Zhang Yan , Li Xiaotong , Pedersen Jakob Skou , Herrmann Carl , Getz Gad , Khurana Ekta , Gerstein Mark B.
Published: March 2018

The Pan-cancer Analysis of Whole Genomes (PCAWG) project provides an unprecedented opportunity to comprehensively characterize a vast set of uniformly annotated coding and non-coding mutations present in thousands of cancer genomes. Classical models of cancer progression posit that only a small number of these mutations strongly drive tumor progression and that the remaining ones (termed “putative passengers”) are inconsequential for tumorigenesis. In this study, we leveraged the comprehensive variant data from PCAWG to ascertain the molecular functional impact of each variant. The impact distribution of PCAWG mutations shows that, in addition to high- and low-impact mutations, there is a group of medium-impact putative passengers predicted to influence gene activity. Moreover, the predicted impact relates to the underlying mutational signature: different signatures confer divergent impact, differentially affecting distinct regulatory subsystems and gene categories. We also find that impact varies based on subclonal architecture (i.e., early vs. late mutations) and can be related to patient survival. Finally, we note that insufficient power due to limited cohort sizes precludes identification of weak drivers using standard recurrence-based approaches. To address this, we adapted an additive effects model derived from complex trait studies to show that aggregating the impact of putative passenger variants (i.e. including yet undetected weak drivers) provides significant predictability for cancer phenotypes beyond the PCAWG identified driver mutations (12.5% additive variance). Furthermore, this framework allowed us to estimate the frequency of potential weak driver mutations in the subset of PCAWG samples lacking well-characterized driver alterations.
From proteins to polysaccharides: lifestyle and genetic evolution ofCoprothermobacter proteolyticus
Authors: Kunath B. J. , Delogu F. , Naas A.E. , Arntzen M.Ø. , Eijsink V.G.H. , Henrissat B. , Hvidsten T.R. , Pope P.B.
Published: March 2018

Microbial communities that degrade lignocellulosic biomass are typified by high levels of species- and strain-level complexity as well as synergistic interactions between both cellulolytic and non-cellulolytic microorganisms.Coprothermobacter proteolyticusfrequently dominates thermophilic, lignocellulose-degrading communities with wide geographical distribution, which is in contrast to reports that it ferments proteinaceous substrates and is incapable of polysaccharide hydrolysis. Here we deconvolute a highly efficient cellulose-degrading consortium (SEM1b) that is co-dominated byClostridium (Ruminiclostridium) thermocellum- and multiple heterogenic strains affiliated toC. proteolyticus. Metagenomic analysis of SEM1b recovered metagenome-assembled genomes (MAGs) for each constituent population, whilst in parallel two novel strains ofC. proteolyticuswere successfully isolated and sequenced. Annotation of allC. proteolyticusgenotypes (two strains and one MAG) revealed their genetic acquisition of carbohydrate-active enzymes (CAZymes), presumably derived from horizontal gene transfer (HGT) events involving polysaccharide-degrading Firmicutes or Thermotogae-affiliated populations that are historically co-located. HGT material included a saccharolytic operon, from which a CAZyme was biochemically characterized and demonstrated hydrolysis of multiple hemicellulose polysaccharides. Finally, temporal genome-resolved metatranscriptomic analysis of SEM1b revealed expression ofC. proteolyticusCAZymes at different SEM1b life-stages as well as co-expression of CAZymes from multiple SEM1b populations, inferring deeper microbial interactions that are dedicated towards community degradation of cellulose and hemicellulose. We show thatC. proteolyticus, a ubiquitous keystone population, consists of closely related strains that have adapted via HGT to presumably degrade both oligo- and longer polysaccharides present in decaying plants and microbial cell walls, thus explaining its dominance in thermophilic anaerobic digesters on a global scale.
The contribution of mitochondrial metagenomics to large-scale data mining and phylogenetic analysis of Coleoptera
Authors: Linard Benjamin , Crampton-Platt Alex , Moriniere Jérome , Timmermans Martijn J.T.N. , Andujar Carmelo , Arribas Paula , Miller Kirsten E. , Lipecki Julia , Favreau Emeline , Hunter Amie , Gómez-Rodríguez Carola , Barton Christopher , Nie Ruie , Gillett Conrad P.D.T. , Breeschoten Thijmen , Bocak Ladislav , Vogler Alfried P.
Published: March 2018

A phylogenetic tree at the species level is still far off for highly diverse insect orders, including the Coleoptera, but the taxonomic breadth of public sequence databases is growing. In addition, new types of data may contribute to increasing taxon coverage, such as metagenomic shotgun sequencing for assembly of mitogenomes from bulk specimen samples. The current study explores the application of these techniques for large-scale efforts to build the tree of Coleoptera. We used shotgun data from 17 different ecological and taxonomic datasets (5 unpublished) to assemble a total of 1942 mitogenome contigs of >3000 bp. These sequences were combined into a single dataset together with all mitochondrial data available at GenBank, in addition to nuclear markers widely used in molecular phylogenetics. The resulting matrix of nearly 16000 species with two or more loci produced trees (RAxML) showing overall congruence with the Linnaean taxonomy at hierarchical levels from suborders to genera. We tested the role of full-length mitogenomes in stabilizing the tree from GenBank data, as mitogenomes might link terminals with non-overlapping gene representation. However, the mitogenome data were only partly useful in this respect, presumably because of the purely automated approach to assembly and gene delimitation, but improvements in future may be possible by using multiple assemblers and manual curation. In conclusion, the combination of data mining and metagenomic sequencing of bulk samples provided the largest phylogenetic tree of Coleoptera to date, which represents a summary of existing phylogenetic knowledge and a defensible tree of great utility, in particular for studies at the intra-familial level, despite some shortcomings for resolving basal nodes.
The tumor suppressor BRCA1/BARD1 complex localizes to the synaptonemal complex and regulates recombination under meiotic dysfunction inCaenorhabditis elegans
Authors: Li Qianyan , Saito Takamune T. , Deshong Alison J. , Garcia Marina Martinez , Nadarajan Saravanapriah , Lawrence Katherine S. , Checchi Paula M. , Colaiacovo Monica P. , Engebrecht JoAnne
Published: March 2018

Breast cancer susceptibility gene 1(BRCA1) and binding partner BRCA1-associated RING domain protein 1 (BARD1) form an essential E3 ubiquitin ligase important for DNA damage repair and homologous recombination. InCaenorhabditis elegansBRCA1/BRC-1 and BARD1/BRD-1 orthologs are not essential, but function in DNA damage repair and homologous recombination, as well as in meiosis. In proliferating germ cells and in early meiotic prophase, BRC-1 and BRD-1 are nucleoplasmic, with enrichment at foci that partially overlap with the recombinase RAD-51. In mid-pachytene, BRC-1 and BRD-1 are observed on tracks, before concentrating to the short arms of bivalents, co-localizing with a central region component of the synaptonemal complex. We found that BRD-1 is essential for BRC-1 to associate with chromatin and the synaptonemal complex, but BRC-1 is not required for BRD-1 localization; the complex fails to properly localize in the absence of either meiotic recombination or chromosome synapsis. Inactivation of BRC-1/BRD-1 enhances the embryonic lethality of mutants that perturb chromosome synapsis and crossover recombination, suggesting that BRC-1/BRD-1 plays an important role in monitoring recombination in the context of the synaptonemal complex. We discovered that BRC-1/BRD-1 stabilizes the RAD51 filament when the formation of a crossover-intermediate is disrupted. Further, in the absence of BRC-1/BRD-1 crossover distribution is altered, and under meiotic dysfunction, crossover numbers are perturbed. Together, our studies indicate that BRC-1/BRD-1 localizes to the synaptonemal complex where it serves a checkpoint function to monitor and modulate meiotic recombination.

Project Summary

Our genomes are passed down from one generation to the next through the specialized cell division program of meiosis. Meiosis is highly regulated to coordinate both the large scale chromosomal and fine scale DNA events to ensure fidelity. We analyzed the role of the tumor suppressor BRCA1/BARD1 complex in meiosis in the worm,Caenorhabditis elegans. We find that BRCA1/BARD1 localizes dynamically to the proteinaeous structure that aligns maternal and paternal chromosomes, where it regulates crossover recombination. Although BRCA1/BARD1 mutants have only subtle meiotic defects, we show that this complex plays a critical role in meiotic recombination when meiosis is perturbed. These results highlight the complexity of ensuring accurate transmission of the genome and uncover the requirement for this conserved complex in meiosis. As women carrying BRCA1 mutations with no indication of cancer have fertility defects, our results provide insight into why BRCA1 mutations impact reproductive success.
Mitigation of coral bleaching by antioxidants
Authors: Yudowski Guillermo , Roberson Loretta , Marty-Rivera Michael
Published: March 2018

Coral bleaching, loss of symbiotic dinoflagellate algae from the coral holobiont, is a complex phenomenon that can result in coral death and reef degradation. Reactive oxygen species (ROS) have been suggested as a possible mechanism underlying this event. To determine if antioxidants can be used to reduce ROS production and coral bleaching, we tested the effects of thermal stress in Aiptasia pallida a model system for coral bleaching studies, and the scleractinian coral, Porites astreoides. We analyzed host ROS levels, symbiont dark-adapted quantum yield of photosystem II, and symbiont loss in the presence or absence of antioxidants. We found that a single dose of the antioxidant catechin, significantly reduced ROS levels in the hosts, mitigated the degradation of the symbionts quantum yield and reduced the loss of symbionts from thermally stressed P. astreoides but not from A. pallida. Taken together, these results support a key role of ROS and that antioxidants can prevent symbiont degradation and loss during thermally-induced bleaching in P. astreoides.
Detection and classification of hard and soft sweeps from unphased genotypes by multilocus genotype identity
Authors: Harris Alexandre M. , Garud Nandita R. , DeGiorgio Michael
Published: March 2018

Positive natural selection can lead to a decrease in genomic diversity at the selected site and at linked sites, producing a characteristic signature of elevated expected haplotype homozygosity. These selective sweeps can be hard or soft. In the case of a hard selective sweep, a single adaptive haplotype rises to high population frequency, whereas multiple adaptive haplotypes sweep through the population simultaneously in a soft sweep, producing distinct patterns of genetic variation in the vicinity of the selected site. Measures of expected haplotype homozygosity have previously been used to detect sweeps in multiple study systems. However, these methods are formulated for phased haplotype data, typically unavailable for nonmodel organisms, and may have reduced power to detect soft sweeps due to their increased genetic diversity relative to hard sweeps. To address these limitations, we applied the H12 and H2/H1 statistics of Garud et al. [2015] to unphased multilocus genotypes, denoting them as G12 and G2/G1. G12 (and the more direct expected homozygosity analogue to H12, denoted G123) has comparable power to H12 for detecting both hard and soft sweeps. G2/G1 can be used to classify hard and soft sweeps analogously to H2/H1, conditional on a genomic region having high G12 or G123 values. The reason for this power is that under random mating, the most frequent haplotypes will yield the most frequent multilocus genotypes. Simulations based on parameters compatible with our recent understanding of human demographic history suggest that expected homozygosity methods are best suited for detecting recent sweeps, and increase in power under recent population expansions. Finally, we find candidates for selective sweeps within the 1000 Genomes CEU, YRI, GIH, and CHB populations, which corroborate and complement existing studies.
Cooperative recruitment of Yan via a high-affinity ETS supersite organizes repression to confer specificity and robustness to cardiac cell fate specification
Authors: Boisclair Lachance Jean-François , Webber Jemma L. , Hong Lu , Dinner Aaron R. , Rebay Ilaria
Published: March 2018

Cis-regulatory modules (CRMs) are defined by unique combinations of transcription factor-binding sites. Emerging evidence suggests that the number, affinity, and organization of sites play important roles in regulating enhancer output and, ultimately, gene expression. Here, we investigate how the cis-regulatory logic of a tissue-specific CRM responsible for even-skipped (eve) induction during cardiogenesis organizes the competing inputs of two E-twenty-six (ETS) members: the activator Pointed (Pnt) and the repressor Yan. Using a combination of reporter gene assays and CRISPR–Cas9 gene editing, we suggest that Yan and Pnt have distinct syntax preferences. Not only does Yan prefer high-affinity sites, but an overlapping pair of such sites is necessary and sufficient for Yan to tune Eve expression levels in newly specified cardioblasts and block ectopic Eve induction and cell fate specification in surrounding progenitors. Mechanistically, the efficient Yan recruitment promoted by this high-affinity ETS supersite not only biases Yan–Pnt competition at the specific CRM but also organizes Yan-repressive complexes in three dimensions across the eve locus. Taken together, our results uncover a novel mechanism by which differential interpretation of CRM syntax by a competing repressor–activator pair can confer both specificity and robustness to developmental transitions.
SvABA: genome-wide detection of structural variants and indels by local assembly
Authors: Wala Jeremiah A. , Bandopadhayay Pratiti , Greenwald Noah F. , O'Rourke Ryan , Sharpe Ted , Stewart Chip , Schumacher Steve , Li Yilong , Weischenfeldt Joachim , Yao Xiaotong , Nusbaum Chad , Campbell Peter , Getz Gad , Meyerson Matthew , Zhang Cheng-Zhong , Imielinski Marcin , Beroukhim Rameen
Published: March 2018

Structural variants (SVs), including small insertion and deletion variants (indels), are challenging to detect through standard alignment-based variant calling methods. Sequence assembly offers a powerful approach to identifying SVs, but is difficult to apply at scale genome-wide for SV detection due to its computational complexity and the difficulty of extracting SVs from assembly contigs. We describe SvABA, an efficient and accurate method for detecting SVs from short-read sequencing data using genome-wide local assembly with low memory and computing requirements. We evaluated SvABA's performance on the NA12878 human genome and in simulated and real cancer genomes. SvABA demonstrates superior sensitivity and specificity across a large spectrum of SVs and substantially improves detection performance for variants in the 20–300 bp range, compared with existing methods. SvABA also identifies complex somatic rearrangements with chains of short (<1000 bp) templated-sequence insertions copied from distant genomic regions. We applied SvABA to 344 cancer genomes from 11 cancer types and found that short templated-sequence insertions occur in ∼4% of all somatic rearrangements. Finally, we demonstrate that SvABA can identify sites of viral integration and cancer driver alterations containing medium-sized (50–300 bp) SVs.
Hit count estimate variability for website-specific queries in search engines
Authors: Font-Julian Cristina I. , Ontalba-Ruipérez José-Antonio , Orduña-Malea Enrique
Published: March 2018

Purpose

The purpose of this paper is to determine the effect of the chosen search engine results page (SERP) on the website-specific hit count estimation indicator.

Design/methodology/approach

A sample of 100 Spanish rare disease association websites is analysed, obtaining the website-specific hit count estimation for the first and last SERPs in two search engines (Google and Bing) at two different periods in time (2016 and 2017).

Findings

It has been empirically demonstrated that there are differences between the number of hits returned on the first and last SERP in both Google and Bing. These differences are significant when they exceed a threshold value on the first SERP.

Research limitations/implications

Future studies considering other samples, more SERPs and generating different queries other than website page count () would be desirable to draw more general conclusions on the nature of quantitative data provided by general search engines.

Practical implications

Selecting a wrong SERP to calculate some metrics (in this case, website-specific hit count estimation) might provide misleading results, comparisons and performance rankings. The empirical data suggest that the first SERP captures the differences between websites better because it has a greater discriminating power and is more appropriate for webometric longitudinal studies.

Social implications

The findings allow improving future quantitative webometric analyses based on website-specific hit count estimation metrics in general search engines.

Originality/value

The website-specific hit count estimation variability between SERPs has been empirically analysed, considering two different search engines (Google and Bing), a set of 100 websites focussed on a similar market (Spanish rare diseases associations), and two annual samples, making this study the most exhaustive on this issue to date.
Analysis of the behaviour of the clients assisted and sales variables in the different phases of the product life cycle
Authors: Galiano Aida , Rodríguez Vicente , Saco Manuela
Published: March 2018

Purpose

The Bass model was created to analyse the product life cycle (PLC) in order to help sales and marketing departments in their business decision making. The purpose of this paper is to analyse the diferences between the clients assisted and sales variables, to discover which of the two variables is the more useful for the estimation of the PLC phases through the Bass model, thus aiding the managers of company sales and marketing departments.

Design/methodology/approach

In this research, the authors analysed the 223,577 clients assisted by a nationwide network of car dealerships, who acquired 36,819 vehicles, during a 24-month period. In the analysis, the Bass model was applied to define the PLC phases; and nonlinear regression models were used to carry out the estimations.

Findings

The results show that more consistent estimates of the PLC phases are obtained from the clients assisted variable. This work has theoretical and practical implications that can help business management.

Research limitations/implications

The most remarkable thing about this research is that we have shown that the functionality of the clients assisted variable is greater than the sales variable for the Bass model and, therefore, for PLC estimation.

Practical implications

The results of this research are very useful, since they allow marketing decision makers to obtain more consistent estimations of the PLC phases using the Bass model and the clients assisted variable. This is based on the fact that the use of this variable helps to detect if there is any deficiency in the design of the marketing strategy when the client does not make the purchase.

Social implications

The data on clients assisted are as easily available to companies as sales data. However, the use of this variable improves PLC analysis and this allows an improvement in company forecasting. Thus, making the clients assisted variable a tool to strategically plan investments in innovation and marketing would reduce uncertainty in business management.

Originality/value

The purpose of this paper is to analyse the diferences between the clients assisted and sales variables, to discover which of the two variables is the more useful for the estimation of the PLC phases through the Bass model, thus aiding the managers of company sales and marketing departments.
Trends and directions in service triads research
Authors: Sengupta Sourav , Niranjan Tarikere T. , Krishnamoorthy Mohan
Published: March 2018

Purpose

Service triads refer to tripartite relationships in which client firms serve their customers through third-party service providers. The purpose of this paper is to systematically review the nascent but fast-growing literature on service triads to explore the broad themes along which the literature has grown, and to identify the gaps and future research opportunities.

Design/methodology/approach

Systematic literature review (SLR) approach is adopted to retrieve, select, and synthesise relevant service triads studies. A citation network analysis on the corpus resulting from the SLR identified the core articles of the literature.

Findings

The SLR uncovered ten themes of research along the articles’ objectives, theories and methodologies. The classification framework of service triads, the roles of customers and providers, the size of the provider, triadic risks, controlling service delivery and service quality, regulated triads, the stability of the triads, and cross-country, cross-culture triads emerged as significant under-researched areas.

Originality/value

The paper illustrates research trends and provides insights into the neglected and under-researched problems of service triads. This is the first SLR on service triads.