bluuebunny/crossref_metadata_2025 huggingface dataset:
To eat and not be eaten: diurnal mass gain and foraging strategies in wintering great tits
Authors: Moiron Maria , Mathot Kimberley J. , Dingemanse Niels J.
Published: March 2018

Adaptive theory predicts that the fundamental trade-off between starvation and predation risk shapes diurnal patterns in foraging activity and mass gain in wintering passerine birds. Foragers mitigating both types of risk should exhibit a bimodal distribution (increased foraging and mass gain early and late in the day), whereas both foraging and mass gains early (versus late) during the day are expected when the risk of starvation (versus predation) is greatest. Finally, relatively constant rates of foraging and mass gain should occur when the starvation–predation risk trade-off is independent of body mass. Using automated feeders with integrated digital balances, we estimated diurnal patterns in foraging and body mass gain to test which ecological scenario was best supported in wintering great titsParus major. Based on data of 40 consecutive winter days recording over 12 000 body masses of 28 individuals, we concluded that birds foraged and gained mass early during the day, as predicted by theory when the starvation–predation risk trade-off is mass-dependent and starvation risk outweighs predation risk. Slower explorers visited the feeders more often, and decreased their activity along the day more strongly, compared with faster explorers, thereby explaining a major portion of the individual differences in diurnal patterning of foraging activity detected using random regression analyses. Birds did not differ in body mass gain trajectories, implying both that individuals differed in the usage of feeders, and that unbiased conclusions regarding how birds resolve starvation–predation risk trade-off require the simultaneous recording of foraging activity and body mass gain trajectories. Our study thereby provides the first unambiguous demonstration that individual birds are capable of adjusting their diurnal foraging and mass gain trajectories in response to ecological predictors of starvation risk as predicted by starvation–predation risk trade-off theory.
Parental and embryonic experiences with predation risk affect prey offspring behaviour and performance
Authors: Donelan Sarah C. , Trussell Geoffrey C.
Published: March 2018

Because phenotypic plasticity can operate both within and between generations, phenotypic outcomes are often shaped by a complex history of environmental signals. For example, parental and embryonic experiences with predation risk can both independently and interactively influence prey offspring traits early in their life. Parental and embryonic risk experiences can also independently shape offspring phenotypes throughout an offspring's ontogeny, but the persistence of their interactive effects throughout offspring ontogeny is unknown. We examined the effects of parental and embryonic experiences with predation risk on the response of 1-year-old prey (the carnivorous snail,Nucella lapillus) offspring to current predation risk. We found that parental and embryonic risk experiences had largely independent effects on offspring performance and that these effects were context dependent. Parental experience with risk had strong impacts on multiple offspring traits in the presence of current risk that generally improved offspring performance under risk, but embryonic risk experience had relatively weaker effects and only operated in the absence of current risk to reduce offspring growth. These results illustrate that past environmental experiences can dynamically shape organism phenotypes across ontogeny and that attention to these effects is key to a better understanding of predator/prey dynamics in natural systems.
Cryopreservation of human mucosal tissues
Authors: Hughes Sean M. , Ferre April L. , Yandura Sarah E. , Shetler Cory , Baker Chris A. R. , Calienes Fernanda , Levy Claire N. , Astronomo Rena D. , Shu Zhiquan , Lentz Gretchen M. , Fialkow Michael , Kirby Anna C. , Juliana McElrath M. , Sinclair Elizabeth , Rohan Lisa C. , Anderson Peter L. , Shacklett Barbara L. , Dezzutti Charlene S. , Gao Dayong , Hladik Florian
Published: March 2018

BACKGROUND

Cryopreservation of leukocytes isolated from the cervicovaginal and colorectal mucosa is useful for the study of cellular immunity (see Hughes SM et al. PLOS ONE 2016). However, some questions about mucosal biology and sexually transmitted infections are better addressed with intact mucosal tissue, for which there is no standard cryopreservation protocol.

METHODS AND FINDINGS

To find an optimal preservation protocol for mucosal tissues, we tested slow cooling (1%C/min) with 10% dimethylsulfoxide (designated “cryopreservation”) and fast cooling (plunge in liquid nitrogen) with 20% dimethylsulfoxide and 20% ethylene glycol (“vitrification”). We compared fresh and preserved human cervicovaginal and colorectal tissues in a range of assays, including metabolic activity, human immunodeficiency virus infection, cell phenotype, tissue structure by hematoxylin-and-eosin staining, cell number and viability, production of cytokines, and microbicide drug concentrations. Metabolic activity, HIV infectability, and tissue structure were similar in cryopreserved and vitrified vaginal tissues. However, vitrification led to poor cell recovery from the colorectal mucosa, with 90% fewer cells recovered after isolation from vitrified colorectal tissues than from cryopreserved. HIV infection rates were similar for fresh and cryopreserved ectocervical tissues, whereas cryopreserved colorectal tissues were less easily infected than fresh tissues (hazard ratio 0.7 [95% confidence interval 0.4, 1.2]). Finally, we compared isolation of cells before and after cryopreservation. Cell recoveries were higher when cells were isolated after freezing and thawing (71% [59-84%]) than before (50% [38-62%]). Cellular function was similar to fresh tissue in both cases. Microbicide drug concentrations were lower in cryopreserved explants compared to fresh ones.

CONCLUSIONS

Cryopreservation of intact cervicovaginal and colorectal tissues with dimethylsulfoxide works well in a range of assays, while the utility of vitrification is more limited. Cell yields are higher from cryopreserved intact tissue pieces than from thawed cryopreserved single cell suspensions isolated before freezing, but T cell functions are similar.
A combinatorial lipid code shapes the electrostatic landscape of plant endomembranes
Authors: Platre Matthieu Pierre , Doumane Mehdi , Bayle Vincent , Simon Mathilde Laetitia Audrey , Maneta-Peyret Lilly , Fouillen Laetitia , Stanislas Thomas , Armengot Laia , Pejchar Přemysl , Caillaud Marie-Cécile , Potocký Martin , Čopič Alenka , Moreau Patrick , Jaillais Yvon
Published: March 2018

Membrane surface charge is critical for the transient, yet specific recruitment of proteins with polybasic regions to certain organelles. In all eukaryotes, the plasma membrane (PM) is the most electronegative compartment of the cell, which specifies its identity. As such, membrane electrostatics is a central parameter in signaling, intracellular trafficking and polarity. Here, we explore which are the lipids that control membrane electrostatics using plants as a model. We show that phosphatidic acidic (PA), phosphatidylserine (PS) and phosphatidylinositol-4-phosphate (PI4P) are separately required to generate the electrostatic signature of the plant PM. In addition, we reveal the existence of an electrostatic territory that is organized as a gradient along the endocytic pathway and is controlled by PS/PI4P combination. Altogether, we propose that combinatorial lipid composition of the cytosolic leaflet of cellular organelles not only defines the plant electrostatic territory but also distinguishes different compartments within this territory by specifying their varying surface charges.
Flexible top-down modulation in human ventral temporal cortex
Authors: Zhang Ruyuan , Kay Kendrick
Published: March 2018

Visual neuroscientists have long characterized attention as inducing a scaling or additive effect on fixed parametric functions describing neural responses (e.g., contrast response functions). Here, we instead propose that top-down effects are more complex and manifest in ways that depend not only on attention but also other cognitive processes involved in executing a task. To substantiate this theory, we analyze fMRI responses in human ventral temporal cortex (VTC) in a study where stimulus eccentricity and cognitive task are varied. We find that as stimuli are presented farther into the periphery, bottom-up stimulus-driven responses decline but top-down attentional enhancement increases substantially. This disproportionate enhancement of weak responses cannot be easily explained by conventional models of attention. Furthermore, we find that attentional effects depend on the specific cognitive task performed by the subject, indicating the influence of additional cognitive processes other than attention (e.g., decision-making). The effects we observe replicate in an independent experiment from the same study, and also generalize to a separate study involving different stimulus manipulations (contrast and phase coherence). Our results suggest that a quantitative understanding of top-down modulation requires more nuanced and more precise characterization of multiple cognitive factors involved in completing a perceptual task.
Changes in Acceptance of Evolution and Associated Factors during a Year of Introductory Biology: The Shifting Impacts of Biology Knowledge, Politics, Religion, Demographics, and Understandings of the Nature of Science
Authors: Dunk Ryan D.P. , Wiles Jason R.
Published: March 2018

Recent research has identified many factors influencing student acceptance of biological evolution, but few of these factors have been measured in a longitudinal context of changing knowledge and acceptance of evolution over a period of instruction. This study investigates factors previously associated with evolution acceptance as well as other potential factors among students over the course of a year-long majors and non-majors introductory biology sequence at a private, research-intensive university in the northeastern United States. Acceptance of evolution was measured using the Measure of Acceptance of the Theory of Evolution (MATE) instrument, and other factors were measured using well-established instruments and a demographic survey. As expected given the context, evolution was widely accepted among the population (71% of our sample scored in the “high” or “very high” acceptance range), but 160 students were in the very low to moderate acceptance range. Over the course of the academic year, regressions on measures of normalized change revealed that as knowledge of the Nature of Science (NOS) increased, evolution acceptance increased (R2= .378,p<< 0.001). Increasing levels of genetic literacy (R2= .214,p<< 0.001) and Evolutionary Knowledge (R2= .177,p<< 0.001) were also significantly associated with increases in acceptance of evolution. We also examined the longitudinal effect of combining various factors into unified working models of acceptance of evolution, and this is the first study by our knowledge to do so. From fall to spring, the influence of student knowledge of NOS on evolution acceptance increased, as did the influence of genetic literacy. Conversely, the influence of religious variables decreased, as did the influence of political inclinations and race/ethnicity. Our results indicate that as students learn more about the nature of science, they may rely more on scientific explanations for natural phenomena. This study also underscores the importance of using longitudinal, multifactorial analyses to understand acceptance of evolution.
4D imaging reveals stage dependent random and directed cell motion during somite morphogenesis
Authors: McColl James , Mok Gi Fay , Lippert Anna H , Ponjavic Aleks , Muresan Leila , Münsterberg Andrea
Published: March 2018

Somites are paired embryonic segments that form in a regular sequence from unsegmented mesoderm during vertebrate development. Of fundamental importance, they are transient structures that generate cell lineages of the musculoskeletal system in the trunk such as cartilage, tendon, bone, endothelial cells and skeletal muscle. Surprisingly, very little is known about the morphological transition and cellular dynamics during somite differentiation. Here, we address this by examining cellular rearrangements and morphogenesis in differentiating somites using live multi photon imaging of GFP-transgenic chick embryos. We specifically focussed on the dynamic changes in two principle regions within the somite (the medial and lateral domains) to investigate extensive morphological changes. Furthermore, by using quantitative analysis and cell tracking, we were able to capture for the first time a progenitor cell bulk movement towards the rostral-medial domain of the myotome, where skeletal muscle formation first initiates.
Parietal representations of stimulus features are amplified during memory retrieval and flexibly aligned with top-down goals
Authors: Favila Serra E. , Samide Rosalie , Sweigart Sarah C. , Kuhl Brice A.
Published: March 2018

In studies of human episodic memory, the phenomenon of reactivation has traditionally been observed in regions of occipitotemporal cortex (OTC) involved in sensory experience. However, reactivation also occurs in lateral parietal cortex (LPC), and recent evidence indicates that reactivation of stimulus-specific information may be stronger in LPC than in OTC. These observations raise a number of questions about the nature of memory representations in LPC and their relation to representations in OTC. Here, we report two fMRI experiments that quantify stimulus feature information (color and object category) within LPC and OTC, separately during perception and memory retrieval, in male and female human subjects. Across both experiments, we show a clear dissociation between OTC and LPC: while feature information in OTC is relatively stronger during perception than memory, feature information in LPC is relatively stronger during memory than perception. Thus, while OTC and LPC represent common stimulus features, they preferentially represent this information during different stages. We show that this transformation of feature information across regions co-occurs with stimulus-level reinstatement within LPC and high-level OTC. In Experiment 2, we consider whether feature information in LPC during memory retrieval is flexibly and dynamically shaped by top-down goals. Indeed, we find that dorsal LPC preferentially represents retrieved feature information that addresses current goals. In contrast, ventral LPC represents retrieved features independent of current goals. Collectively, these findings provide insight into the nature and significance of mnemonic representations in LPC and constitute an important bridge between putative mnemonic and control functions of parietal cortex.
Haemoproteus paraortalidum n. sp. in captive Black-fronted Piping-guans Aburria jacutinga (Galliformes, Cracidae): high prevalence in a population reintroduced into the wild
Authors: Ferreira-Junior Francisco C. , Angeli Dutra Daniela de , Martins Nelson R.S , Valkiūnas Gediminas , Braga Érika M.
Published: March 2018

Haemosporidian parasites of the genus Haemoproteus are widespread and can cause disease and even mortality in birds under natural and captive conditions. The Black-fronted Piping-guan (Aburria jacutinga) is an endangered Neotropical bird of the Cracidae (Galliformes) going through a reintroduction program to avoid extinction. We used microscopic examination and partial cytochrome b DNA sequencing to describe a new Haemoproteus species infecting Black-fronted Piping-guans bred and raised in captivity that were reintroduced into the Atlantic rainforest. Haemoproteus (Parahaemoproteus) paraortalidum n. sp. was detected in the blood of 19 out of 29 examined birds. The new species is distinguished from other haemoproteids due to the shape of gametocytes, which have pointed ends in young stages, and due to the presence of vacuole-like unstained spaces in macrogametocytes and numerous volutin granules both in macro- and microgametocytes. Illustrations of the new species are provided. Phylogenetic inference positioned this parasite in the Parahaemoproteus subgenus clade together with the other two Haemoproteus genetic lineages detected in cracids up to date. We discuss possible implications of the reintroduction of birds infected with haemosporidian parasites into de wild. Treatment of Haemoproteus infections remains insufficiently studied, but should be considered for infected birds before reintroduction to improve host reproductive and survival rates after release.
Rapid, raw-read reference and identification (R4IDs): A flexible platform for rapid generic species ID using long-read sequencing technology
Authors: Parker Joe , Helmstetter Andrew , Crowe James , Iacona John , Devey Dion , Papadopulos Alexander S. T.
Published: March 2018

The versatility of the current DNA sequencing platforms and the development of portable, nanopore sequencers means that it has never been easier to collect genetic data for unknown sample ID. DNA barcoding and meta-barcoding have become increasingly popular and barcode databases continue to grow at an impressive rate. However, the number of canonical genome assemblies (reference or draft) that are publically available is relatively tiny, hindering the more widespread use of genome scale DNA sequencing technology for accurate species identification and discovery. Here, we show that rapid raw-read reference datasets, or R4IDs for short, generated in a matter of hours on the Oxford Nanopore MinION, can bridge this gap and accelerate the generation of useable reference sequence data. By exploiting the long read length of this technology, shotgun genomic sequencing of a small portion of an organism’s genome can act as a suitable reference database despite the low sequencing coverage. These R4IDs can then be used for accurate species identification with minimal amounts of re-sequencing effort (1000s of reads). We demonstrated the capabilities of this approach with six vascular plant species for which we created R4IDs in the laboratory and then re-sequenced, live at the Kew Science Festival 2016. We further validated our method using simulations to determine the broader applicability of the approach. Our data analysis pipeline has been made available as a Dockerised workflow for simple, scalable deployment for a range of uses.
Early-life social environment alters juvenile behavior and neuroendocrine function in a highly social cichlid fish
Authors: Solomon-Lane Tessa K. , Hofmann Hans A.
Published: March 2018

Early-life experiences can shape adult behavior, with consequences for fitness and health, yet fundamental questions remain unanswered about how early-life social experiences are translated into variation in brain and behavior. The African cichlid fish Astatotilapia burtoni, a model system in social neuroscience, is well known for its highly plastic social phenotypes in adulthood. Here, we rear juveniles in either social groups or pairs to investigate the effects of early-life social environments on behavior and neuroendocrine gene expression. We find that both juvenile behavior and neuroendocrine function are sensitive to early-life effects. Behavior robustly co-varies across multiple contexts (open field, social cue investigation, and dominance behavior assays) to form a behavioral syndrome, with pair-reared juveniles towards the end of syndrome that is less active and socially interactive. Pair-reared juveniles also submit more readily as subordinates. In a separate cohort, we measured whole brain expression of stress and sex hormone genes. Expression of glucocorticoid receptor (GR) 1a was elevated in group-reared juveniles, supporting a highly-conserved role for the stress axis mediating early-life effects. The effect of rearing environment on androgen receptor (AR) α and estrogen receptor (ER) α expression was mediated by treatment duration (1 vs. 5 weeks). Finally, expression of corticotropin-releasing factor (CRF) and GR2 decreased significantly over time. Rearing environment also caused striking differences in gene co-expression, such that expression was tightly integrated in pair-reared juveniles, but not group-reared or isolates. Together, this research demonstrates the important developmental origins of behavioral phenotypes and identifies potential behavioral and neuroendocrine mechanisms.
Barcoded oligonucleotides ligated on RNA amplified for multiplex and parallel in-situ analyses
Authors: Iyer Eswar P. R. , Punthambaker Sukanya , Liu Songlei , Jindal Kunal , Farrell Michael , Murn Jernej , Ferrante Thomas , Rudnicki Stewart , Kohman Richie E. , Wassie Asmamaw T. , Goodwin Daniel , Chen Fei , Alon Shahar , Sinha Anubhav , Milanova Denitsa , Aron Liviu , Camplisson Conor , Skrynnyk Alex , Reginato Paul Louis , Conway Nick , Aach John , Yankner Bruce , Boyden Edward S. , Church George M.
Published: March 2018

We present Barcoded Oligonucleotides Ligated On RNA Amplified for Multiplexed and parallel In-Situ analysis (BOLORAMIS), a reverse-transcription (RT)-free method for spatially-resolved, targeted, in-situ RNA identification of single or multiple targets. For this proof of concept, we have profiled 154 distinct coding and small non-coding transcripts ranging in sizes 18 nucleotides in length and upwards, from over 200, 000 individual human induced pluripotent stem cells (iPSC) and demonstrated compatibility with multiplexed detection, enabled by fluorescent in-situ sequencing. We use BOLORAMIS data to identify differences in spatial localization and cell-to-cell expression heterogeneity. Our results demonstrate BOLORAMIS to be a generalizable toolset for targeted, in-situ detection of coding and small non-coding RNA for single or multiplexed applications.
A Comparison of Temporal Response Function Estimation Methods for Auditory Attention Decoding
Authors: Wong Daniel D.E. , Fuglsang Søren A. , Hjortkjær Jens , Ceolini Enea , Slaney Malcolm , Cheveigné Alain de
Published: March 2018

The decoding of selective auditory attention from noninvasive electroencephalogram (EEG) data is of interest in brain computer interface and auditory perception research. The current state-of-the-art approaches for decoding the attentional selection of listeners are based on temporal response functions (TRFs). In the current context, a TRF is a function that facilitates a mapping between features of sound streams and EEG responses. It has been shown that when the envelope of attended speech and EEG responses are used to derive TRF mapping functions, the TRF model predictions can be used to discriminate between attended and unattended talkers. However, the predictive performance of the TRF models is dependent on how the TRF model parameters are estimated. There exist a number of TRF estimation methods that have been published, along with a variety of datasets. It is currently unclear if any of these methods perform better than others, as they have not yet been compared side by side on a single standardized dataset in a controlled fashion. Here, we present a comparative study of the ability of different TRF estimation methods to classify attended speakers from multi-channel EEG data. The performance of the TRF estimation methods is evaluated using different performance metrics on a set of labeled EEG data from 18 subjects listening to mixtures of two speech streams.
Simultaneous B and T cell acute lymphoblastic leukemias in zebrafish driven by transgenic MYC: implications for oncogenesis and lymphopoiesis
Authors: Borga Chiara , Park Gilseung , Foster Clay , Burroughs-Garcia Jessica , Marchesin Matteo , Ahmed Syed T. , Bresolin Silvia , Batchelor Lance , Scordino Teresa , Miles Rodney R. , Kronnie Geertruy te , Regens James L. , Frazer J. Kimble
Published: March 2018

Precursor-B cell acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer, but there are no useful zebrafish pre-B ALL models. We describe the first highly-penetrant zebrafish pre-B ALL, driven by human MYC. Leukemias express B lymphoblast-specific genes and are distinct from T cell ALL (T-ALL)—which these fish also develop. Zebrafish pre-B ALL shares in vivo features and expression profiles with human pre-B ALL, and these profiles differ from zebrafish T-ALL or normal B and T cells. These animals also exhibit aberrant lymphocyte development. As the only robust zebrafish pre-B ALL model and only example where T-ALL also develops, this model can reveal differences between MYC-driven pre-B vs. T-ALL and be exploited to discover novel pre-B ALL therapies.

Statement of significance

We describe the first robust zebrafish pre-B ALL model in MYC-transgenic animals known to develop T-ALL, revealing the only animal model with both human ALL types. We also describe aberrant multi-lineage lymphopoiesis. This powerful system can be used to study MYC-driven leukemogenesis and discover new pre-B ALL targeted therapies.
Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency
Authors: Mulholland Christopher B. , Traube Franziska R. , Parsa Edris , Eckl Eva-Maria , Schönung Maximillian , Modic Miha , Bartoschek Michael D. , Stolz Paul , Ryan Joel , Carell Thomas , Leonhardt Heinrich , Bultmann Sebastian
Published: March 2018

The TET-oxidized cytosine derivatives, 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC), are considered DNA demethylation intermediates as well as stable epigenetic marks in mammals. We compared modified cytosine and enzyme levels in TET-knockout cells during naive pluripotency exit and found distinct and differentiation-dependent contributions of TET1 and TET2 to 5hmC and 5fC formation. The divergent modified cytosine levels argue for independent consecutive oxidation steps in vivo with broad implications for epigenetic regulation.
Detection of race-specific resistance against Puccinia coronata f. sp. avenae in Brachypodium species
Authors: Omidvar Vahid , Dugyala Sheshanka , Li Feng , Rottschaefer Susan , Miller Marisa E. , Ayliffe Mick , Moscou Matthew J. , Kianian Shahryar F. , Figueroa Melania
Published: March 2018

Oat crown rust caused by Puccinia coronata f. sp. avenae is the most destructive foliar disease of cultivated oat. Characterization of genetic factors controlling resistance responses to Puccinia coronata f. sp. avenae in non-host species could provide new resources for developing disease protection strategies in oat. We examined symptom development and fungal colonization levels of a collection of Brachypodium distachyon and B. hybridum accessions infected with three North American P. coronata f. sp. avenae isolates. Our results demonstrated that colonization phenotypes are dependent on both host and pathogen genotypes, indicating a role for race-specific responses in these interactions. These responses were independent of the accumulation of reactive oxygen species. Expression analysis of several defense-related genes suggested that salicylic acid and ethylene-mediated signaling, but not jasmonic acid are components of resistance reaction to P. coronata f. sp. avenae. Our findings provide the basis to conduct a genetic inheritance study to examine if effector-triggered immunity contributes to non-host resistance to P. coronata f. sp. avenae in Brachypodium species.
Accounting for location uncertainty in azimuthal telemetry data improves ecological inference
Authors: Gerber Brian D. , Hooten Mevin B. , Peck Christopher P. , Rice Mindy B. , Gammonley James H. , Apa Anthony D. , Davis Amy J.
Published: March 2018

Characterizing animal space use is critical to understand ecological relationships. Despite many decades of using radio-telemetry to track animals and make spatial inference, there are few statistical options to handle these unique data and no synthetic framework for modeling animal location uncertainty and accounting for it in ecological models. We describe a novel azimuthal telemetry model (ATM) to account for azimuthal uncertainty with covariates and propagate location uncertainty into ecological models. We evaluate the ATM with commonly used estimators in several study design scenarios using simulation. We also provide illustra-tive empirical examples, demonstrating the impact of ignoring location uncertainty within home range and resource selection analyses. We found the ATM to have good performance and the only model that has appropriate measures of coverage. Ignoring animal location un-certainty when estimating resource selection or home ranges can have pernicious effects on ecological inference. We demonstrate that home range estimates can be overly confident and conservative when ignoring location uncertainty and resource selection coefficients can lead to incorrect inference and over confidence in the magnitude of selection. Our findings and model development have important implications for interpreting historical analyses using this type of data and the future design of radio-telemetry studies.
Pan-cancer deconvolution of cellular composition identifies molecular correlates of antitumour immunity and checkpoint blockade response
Authors: Chakravarthy Ankur , Furness Andrew , Joshi Kroopa , Ghorani Ehsan , Ford Kirsty , Ward Matthew J , King Emma V , Lechner Matt , Marafioti Teresa , Quezada Sergio , Thomas Gareth J , Feber Andrew , Fenton Tim R
Published: March 2018

The nature and extent of immune cell infiltration into solid tumours are key determinants of therapeutic response. Here, using a novel DNA methylation-based approach to tumour cell fraction deconvolution, we report the integrated analysis of tumour composition and genomics across a wide spectrum of solid cancers. Initially studying head and neck squamous cell carcinoma, we identify two distinct tumour subgroups: ‘immune hot’ and ‘immune cold’, which display differing prognosis, mutation burden, cytokine signalling, cytolytic activity, and oncogenic driver events. We demonstrate the existence of such tumour subgroups pan-cancer, link clonal-neoantigen burden to hot tumours, and show that transcriptional signatures of hot tumours are selectively engaged in immunotherapy responders. We also find that treatment-naive hot tumours are markedly enriched for known immune-resistance genomic alterations and define a catalogue of novel and known mediators of active antitumour immunity, deriving biomarkers and potential targets for precision immunotherapy.
All-optical electrophysiology reveals brain-state dependent changes in hippocampal subthreshold dynamics and excitability
Authors: Adam Yoav , Kim Jeong J. , Lou Shan , Zhao Yongxin , Brinks Daan , Wu Hao , Mostajo-Radji Mohammed A. , Kheifets Simon , Parot Vicente , Chettih Selmaan , Williams Katherine J. , Farhi Samouil L. , Madisen Linda , Harvey Christopher D. , Zeng Hongkui , Arlotta Paola , Campbell Robert E. , Cohen Adam E.
Published: March 2018

A technology to record membrane potential from multiple neurons, simultaneously, in behaving animals will have a transformative impact on neuroscience research1. Parallel recordings could reveal the subthreshold potentials and intercellular correlations that underlie network behavior2. Paired stimulation and recording can further reveal the input-output properties of individual cells or networks in the context of different brain states3. Genetically encoded voltage indicators are a promising tool for these purposes, but were so far limited to single-cell recordings with marginal signal to noise ratio (SNR) in vivo4-6. We developed improved near infrared voltage indicators, high speed microscopes and targeted gene expression schemes which enabled recordings of supra- and subthreshold voltage dynamics from multiple neurons simultaneously in mouse hippocampus, in vivo. The reporters revealed sub-cellular details of back-propagating action potentials, correlations in sub-threshold voltage between multiple cells, and changes in dynamics associated with transitions from resting to locomotion. In combination with optogenetic stimulation, the reporters revealed brain state-dependent changes in neuronal excitability, reflecting the interplay of excitatory and inhibitory synaptic inputs. These tools open the possibility for detailed explorations of network dynamics in the context of behavior.
A sexually dimorphic neuroendocrine cascade acts through shared sensory neurons to regulate behavior inC. elegans
Authors: Hilbert Zoë A. , Kim Dennis H.
Published: March 2018

ABSTRACT

Sexually dimorphic behaviors are observed in species across the animal kingdom, however the relative contributions of sex-specific and sex-shared nervous systems to such behaviors are not fully understood. Building on our previous work which described the sexually dimorphic expression of a neuroendocrine ligand, DAF-7, and its role in behavioral decision-making inC. elegans(Hilbert and Kim, 2017), we show here that sex-specific expression ofdaf-7is regulated by another neuroendocrine ligand, Pigment Dispersing Factor (PDF-1), which has previously been implicated in regulating male-specific behavior (Barrios et al., 2012). Our analysis revealed that PDF-1 acts sex- and cell-specifically in the ASJ neurons to regulate the expression ofdaf-7and we show that differences in the expression of the PDFR-1 receptor account for the sex-specific effects of this pathway. Our data suggest that modulation of the sex-shared nervous system by neuroendocrine signaling pathways can play a role in shaping sexually dimorphic behaviors.
Automated high-quality reconstruction of metabolic networks from high-throughput data
Authors: Hartleb Daniel , Fritzemeier C. Jonathan , Lercher Martin J.
Published: March 2018

While new genomes are sequenced at ever increasing rates, their phenotypic analysis remains a major bottleneck of biomedical research. The generation of genome-scale metabolic models capable of accurate phenotypic predictions is a labor-intensive endeavor; accordingly, such models are available for only a small percentage of sequenced species. The standard metabolic reconstruction process starts from a (semi-)automatically generated draft model, which is then refined through extensive manual curation. Here, we present a novel strategy suitable for full automation, which exploits high-throughput gene knockout or nutritional growth data. We test this strategy by reconstructing accurate genome-scale metabolic models for three strains ofStreptococcus, a major human pathogen. The resulting models contain a lower proportion of reactions unsupported by genomic evidence than the most widely usedE. colimodel, but reach the same accuracy in terms of knockout prediction. We confirm the models’ predictive power by analyzing experimental data for auxotrophy, additional nutritional environments, and double gene knockouts, and we generate a list of potential drug targets. Our results demonstrate the feasibility of reconstructing high-quality genome-scale metabolic models from high-throughput data, a strategy that promises to massively accelerate the exploration of metabolic phenotypes.

Significance statement

Reading bacterial genomes has become a cheap, standard laboratory procedure. A genome by itself, however, is of little information value – we need a way to translate its abstract letter sequence into a model that describes the capabilities of its carrier. Until now, this endeavor required months of manual work by experts. Here, we show how this process can be automated by utilizing high-throughput experimental data. We use our novel strategy to generate highly accurate metabolic models for three strains ofStreptococcus, a major threat to human health.
Site-Specific Labelling of Multidomain Proteins by Amber Codon Suppression
Authors: Heil Christina S. , Rittner Alexander , Goebel Bjarne , Beyer Daniel , Grininger Martin
Published: March 2018

Amber codon suppression is a powerful tool to site-specifically modify proteins to generate novel biophysical probes. Yet, its application on large and complex multidomain proteins is challenging, leading to difficulties during structural and conformational characterization using spectroscopic methods. The animal fatty acid synthase type I is a 540 kDa homodimer displaying large conformational variability. As the key enzyme ofde novofatty acid synthesis, it attracts interest in the fields of obesity, diabetes and cancer treatment. Substrates and intermediates remain covalently bound to the enzyme during biosynthesis and are shuttled to all catalytic domains by the acyl carrier protein domain. Thus, conformational variability of animal FAS is an essential aspect for fatty acid biosynthesis. We investigate this multidomain protein as a model system for probing amber codon suppression by genetic encoding of non-canonical amino acids. The systematic approach relies on a microplate-based reporter assay of low complexity, that was used for quick screening of suppression conditions. Furthermore, the applicability of the reporter assay is demonstrated by successful upscaling to both full-length constructs and increased expression scale. The obtained fluorescent probes of murine FAS type I could be subjected readily to a conformational analysis using single-molecule fluorescence resonance energy transfer.
Electrical transient laws in neuronal microdomains based on electro-diffusion
Authors: Cartailler J. , Holcman D.
Published: March 2018

The current-voltage (I-V) conversion characterizes the physiology of cellular microdomains and reflects cellular communication, excitability, and electrical transduction. Yet deriving such I-V laws remains a major challenge in most cellular microdomains due to their small sizes and the difficulty of accessing voltage with a high nanometer precision. We present here novel analytical relations derived for different numbers of ionic species inside a neuronal micro/nano-domains, such as dendritic spines. When a steady-state current is injected, we find a large deviation from the classical Ohm’s law, showing that the spine neck resistance is insuficent to characterize electrical properties. For a constricted spine neck, modeled by a hyperboloid, we obtain a new I-V law that illustrates the consequences of narrow passages on electrical conduction. Finally, during a fast current transient, the local voltage is modulated by the distance between activated voltage-gated channels. To conclude, electro-diffusion laws can now be used to interpret voltage distribution in neuronal microdomains.
Autism Diagnostic Observation Schedule (ADOS) scores in males and females diagnosed with autism: a naturalistic study
Authors: Adamou Marios , Johnson Maria , Alty Bronwen
Published: March 2018

Purpose

Many tools are available for assessing autism in an adult population; however, few have been studied for the effects of gender on diagnostic scores. The purpose of this paper is to evaluate the Autism Diagnostic Observation Schedule (ADOS) assessment for gender bias in a clinical population, specifically whether the ADOS favours a “male-type” of autism.

Design/methodology/approach

The ADOS scores of patients referred to an NHS specialist autism assessment service were retrospectively examined for significant gender differences. The combined ADOS scores and diagnostic outcome were grouped by gender for each participant. The data were analysed in SPSS using independentt-tests to look for significant gender differences between combined ADOS scores and diagnostic outcomes.

Findings

A significant difference was observed in the mean combined ADOS scores for those participants who later received an autism diagnosis (male=10, female=6,t(13)=3.34,p=10; 0.005). However, no significant difference was observed between mean scores of those who did not receive an autism diagnosis (t(26)=1.21,p=0.237).

Originality/value

The ADOS is a popular assessment used for autism diagnosis. These results provide support for a male gender bias. This could have clinical implications for autism assessment services, whereby lower diagnostic thresholds could be considered for female patients. This could allow more females with autism to receive a diagnosis, and access support services.
Consumer preferences regarding national and EU quality labels for cheese, ham and honey
Authors: Kos Skubic Mira , Erjavec Karmen , Klopčič Marija
Published: March 2018

Purpose

The purpose of this paper is to investigate consumer preferences in the Slovenian context with regard to cheese, ham and honey labelled with the national and EU protected designation of origin (PDO) indication and the protected geographical indication (PGI) associated with price and origin.

Design/methodology/approach

An online survey with a representative sample of the Slovenian population of 650 consumers was conducted. Consumer preferences were estimated using choice-based conjoint analysis.

Findings

The findings show that price is the most powerful driver of consumer preferences for cheese and honey, whereas it is origin for ham, which proved to be the most strongly desired “Slovenian” food product of all items analysed. Label is the least preferable attribute for all three products considered. Cheese, ham and honey bearing the national PDO and PGI labels were more desired than products carrying the EU PDO and PGI labels. The study findings also show the main statistically significant differences in the age and gender of consumers.

Research limitations/implications

The biggest limitation is that the study focused on certain labels only, related to quality, and origin in particular.

Practical implications

This result highlights the need to extend and intensify promotional and communication activities to increase consumer preferences for the national and EU PDO- and PGI-labelled cheeses, ham and honey.

Originality/value

This study contributes to relevant literature by presenting the results regarding consumer preferences for the EU and national quality labels for different food categories in Slovenia, which has no tradition in using the EU quality labels.
Teleological sales and purchase approaches in complex business relationships – customers’ expectations before and perceptions after purchase
Authors: Rodríguez Rocío , Svensson Göran , Román Sergio , Wood Greg
Published: March 2018

Purpose

The purpose of this study is to examine the actions and interactions that take place before and after purchase between a service provider (service seller) and its customers (service buyers) in complex business relationships. Specifically, it is to examine customers’ expectations of the service provider’s service offer before purchase and the same customers’ perceptions of the service solution offered after purchase in a business-to-business (B2B) context.

Design/methodology/approach

This study adopted a mixed methods design, which combined data generated through in-depth interviews (both with service buyers and key informants from the service company), an online customer survey, analysis of textual documents and structured observations of buyer–seller interactions and actions. Both objective and subjective points of view at different stages of the investigation were collected.

Findings

The authors’ results show that, contrary to previous evidence in B2C service research, the customers’ perceptions of the service performance were not significantly related to their previous expectations. In this context, characterized by dynamic and constantly evolving processes and many parties (both from the buyer and the seller company) involved in the implementation process, service complexity may cause a lack of well-formed expectations regarding how the service will perform and its relevant performance attributes.

Research limitations/implications

This study suggests that the service models traditionally used to describe and explain customer service expectations and perceptions in relatively simple service contexts with final consumers are difficult to apply in B2B complex business relationships. Rather, scholars need to take a holistic, continuously evolving and adapted perspective when examining the formation of customer service expectations and their perceptions in B2B complex services.

Practical implications

There should be a teleological balance between sales and purchase approaches in B2B contexts to optimize the outcome of complex business relationships between service providers and service receivers. The authors suggest several recommendations to service providers to ensure that their salespeople do not create unrealistic and unachievable expectations in the minds of the service receivers. Service providers are also encouraged to develop formal cross functional teams (e.g. consisting of salespeople, service technicians and service support) based on mutual understanding and information sharing.

Originality/value

This study provides an alternative time-oriented understanding of the way customer expectations before purchase and their perceptions after purchasing a complex software solution in industrial markets formed through the lens of teleological framework. As such, this is the first empirical inquiry with this specific framework in B2B contexts making a relevant contribution to literature.
Entrepreneurial motivation as a key salesperson competence: trait antecedents and performance consequences
Authors: Rajabi Reza , Brashear-Alejandro Thomas , Chelariu Cristian
Published: March 2018

Purpose

This study aims to explore the effects of three competency layers of personality on salesperson effort and performance: self-efficacy, competitiveness and entrepreneurial motivation.

Design/methodology/approach

A two-study approach with data from 285 business-to-business (B2B) salespeople in the USA and 342 B2B/business-to-consumer salespeople in Poland is used. This study has also used structural equation modelling with partial least squares, common method assessment and mediation testing.

Findings

The findings show that across both studies, entrepreneurial motivation relates directly and positively to effort: salespeople with a greater entrepreneurial motivation exert more effort to perform their sales-related tasks. In addition, competitiveness and self-efficacy are two antecedents of entrepreneurial motivation in a sales context.

Originality/value

This study introduces the concept of entrepreneurial motivation as a goal orientation.
Do hostels play a role in pleasing Millennial travellers? The Portuguese case
Authors: Veríssimo Medéia , Costa Carlos
Published: March 2018

Purpose

The purpose of this paper is to identify the best hostel practices and trends, and to evaluate and discuss how they are keeping up with the present demand created by the Millennials market.

Design/methodology/approach

Methodological approach is based on two complementary qualitative methods: ethnographic participant observation and netnography. Portuguese hostels are the target of this study, as they are considered some of the best in the world. First, a fieldwork was conducted in three top-rated hostels in Lisbon, aiming to immerse in hostel’s environment. Then, 300 online reviews were analysed to identify what customers value the most in those services. Data interpretation was done through a content analysis crossing supply-demand perspectives.

Findings

Results indicate that, while staying in a hostel, the Millennials want to: meet people, engage in activities and events, have local experiences, feel comfortable/at home, get good value for money and enjoy the convenience. In return, hostels play an important role in hospitality industry by pleasing the Millennials, by offering: central location, an interactive atmosphere, functional facilities, well-planned design and decoration, a set of activities and events and personal treatment.

Originality/value

This paper is one of the few to describe Millennials’ travel behaviour towards hostels’ services.