bluuebunny/crossref_metadata_2025 huggingface dataset:
Nascent transcript analysis of glucocorticoid crosstalk with TNF defines primary and cooperative inflammatory repression
Authors: Sasse Sarah K. , Gruca Margaret , Allen Mary A. , Kadiyala Vineela , Song Tengyao , Gally Fabienne , Gupta Arnav , Pufall Miles A. , Dowell Robin D. , Gerber Anthony N.
Published: January 2019

The glucocorticoid receptor (GR) binds to specific DNA sequences and directly induces transcription of anti-inflammatory genes that contribute to cytokine repression, frequently in cooperation with NF-kB. Whether inflammatory repression also occurs through local interactions between GR and inflammatory gene regulatory elements remains controversial. Here, using Global Run-on Sequencing (GRO-seq) in human airway epithelial cells, we show that glucocorticoid signaling represses transcription within 10 minutes. Many repressed regulatory regions reside within ‘hyper-ChIPable’ genomic regions that are subject to non-specific interactions with some antibodies. When this was accounted for, we determined that transcriptional repression occurs without local GR occupancy. Instead, widespread transcriptional induction through canonical GR binding sites is associated with reciprocal repression of distal TNF-regulated enhancers through a chromatin-dependent process, as evidenced by chromatin accessibility and enhancer-reporter assays. Simultaneously, transcriptional induction of key anti-inflammatory effectors is decoupled from primary repression through cooperation between GR and NF-kB at a subset of regulatory regions. Thus, glucocorticoids exert bimodal restraints on inflammation characterized by rapid primary transcriptional repression without local GR occupancy and secondary anti-inflammatory effects resulting from transcriptional cooperation between GR and NF-kB.
Brain Abnormalities Associated with Self-Injurious Thoughts and Behaviors: A Meta-Analysis of Neuroimaging Studies
Authors: Huang Xieyining , Rootes-Murdy Kelly , Bastidas Diana M. , Nee Derek E. , Franklin Joseph C.
Published: January 2019

Self-injurious thoughts and behaviors (SITBs) have long been believed to result in part from brain abnormalities. This meta-analysis aims to evaluate whether the extant literature justifies any definitive conclusions about whether and how SITBs may be associated with aberrant findings. Sixty studies published through June 1st, 2017 that compared individuals with and without SITBs were included, resulting in 734 coordinates. A pooled meta-analysis assessing for general risk for SITBs indicated a lack of convergence on structural abnormalities. Functional abnormalities in the precuneus/posterior cingulate cortex (PCC), temporal-parietal junction, and rostral-lateral prefrontal cortex were significant using multi-level kernel density analysis but nonsignificant using activation-likelihood estimation. Separate analyses for types of SITBs suggested that deliberate self-harm might be associated with abnormalities in the precuneus/PCC. Some moderator effects were detected. Overall, the meta-analytic evidence was not robust. More studies are needed to reach definitive conclusions about whether SITBs are associated with brain abnormalities.
Identification of the best index case significantly improves mutation detection rates in families with hereditary breast and ovarian cancer
Authors: Wyrwoll Margot J. , Fuchs Lea , Waschk Daniel E.J.
Published: January 2019

To date, a disease-causing mutation can be found in 15-30% of families with hereditary breast and ovarian cancer (HBOC) and it is believed that more than half of the cases still remain unsolved. Usually it is intended to perform genetic analyses in the family member with the most severe phenotype, which, however, may not always be possible. Moreover, no standard criteria have been established to define the person who is most suitable for genetic testing within a family: ‘the best index case’. We therefore established clinical criteria to identify the best index case in HBOC and analyzed the impact on genetic testing. 130 patients who presented at our department from 2016 to 2018 were divided into two groups. In group A (N = 98) genetic analyses were performed in the best index case based on our criteria. In group B (N = 32) at least one other family member was considered a better index case. The detection rate of expected mutations was significantly higher for group A (64.3% vs. 32.0%, p = 0.034) while there was no significant difference of calculated mutation carrier risks between these groups. We conclude that the mutation detection rate in families with HBOC is notably higher after identifying the best index case for genetic testing according to the clinical selection criteria reported here.
The visual system of the genetically tractable crustaceanParhyale hawaiensis: diversification of eyes and visual circuits associated with low-resolution vision
Authors: Ramos Ana Patricia , Gustafsson Ola , Labert Nicolas , Salecker Iris , Nilsson Dan-Eric , Averof Michalis
Published: January 2019

Background

Arthropod eyes have diversified during evolution to serve multiple needs, such as finding mates, hunting prey, and navigating in complex surroundings under varying light conditions. This diversity is reflected in the optical apparatus, photoreceptors and neural circuits that underpin vision. While this diversity has been extensively documented, our ability to genetically manipulate the visual system to investigate its function is largely limited to a single species, the fruitflyDrosophila melanogaster. Here, we describe the visual system ofParhyale hawaiensis, an amphipod crustacean for which we have established tailored genetic tools.

Results

AdultParhyalehave apposition-type compound eyes made up of ∼50 ommatidia. Each ommatidium contains four photoreceptor cells with large rhabdomeres (R1-4), expected to be sensitive to the polarisation of light, and one photoreceptor cell with a smaller rhabdomere (R5). The two types of photoreceptors express different opsins, belonging to families with distinct wavelength sensitivities. Using thecis.-regulatory regions of opsin genes, we established transgenic reporters expressed in each photoreceptor cell type. Based on these reporters, we show that R1-4 and R5 photoreceptors extend axons to the first optic lobe neuropil, revealing striking differences compared with the photoreceptor projections found in related crustaceans and insects. Investigating visual function, we show thatParhyalehas a positive phototactic response and is capable of adapting its eyes to different levels of light intensity.

Conclusions

We propose that the visual system ofParhyaleserves low-resolution visual tasks, such as orientation and navigation, based on broad gradients of light intensity and polarisation. Optic lobe structure and photoreceptor projections point to significant divergence from the conserved visual circuits found in other malacostracan crustaceans and insects, which could be associated with a shift to low-resolution vision. Our study provides the foundation for research in the visual system of this genetically tractable species.
New Asgard archaea capable of anaerobic hydrocarbon cycling
Authors: Seitz Kiley W. , Dombrowski Nina , Eme Laura , Spang Anja , Lombard Jonathan , Sieber Jessica R. , Teske Andreas P. , Ettema Thijs J.G. , Baker Brett J.
Published: January 2019

Large reservoirs of natural gas in the oceanic subsurface sustain a complex biosphere of anaerobic microbes, including recently characterized archaeal lineages that extend the potential to mediate hydrocarbon oxidation (methane and butane) beyond the Methanomicrobia. Here we describe a new archaeal phylum, Helarchaeota, belonging to the Asgard superphylum with the potential for hydrocarbon oxidation. We reconstructed Helarchaeota genomes from hydrothermal deep-sea sediment metagenomes in hydrocarbon-rich Guaymas Basin, and show that these encode novel methyl-CoM reductase-like enzymes that are similar to those found in butane-oxidizing archaea. Based on these results as well as the presence of several alkyl-CoA oxidation and Wood-Ljungdahl pathway genes in the Helarchaeota genomes, we suggest that members of the Helarchaeota have the potential to activate and subsequently anaerobically oxidize short-chain hydrocarbons. These findings link a new phylum of Asgard archaea to the microbial utilization of hydrothermally generated hydrocarbons, and extend this genomic blueprint further through the archaeal domain.
A novel thermostable aspartic protease fromTalaromyces leycettanusand its specific autocatalytic activation through an intermediate transition state
Authors: Guo Yujie , Tu Tao , Ren Yaxin , Wang Yaru , Bai Yingguo , Su Xiaoyun , Wang Yuan , Yao Bin , Huang Huoqing , Luo Huiying
Published: January 2019

Aspartic proteases exhibit optimum enzyme activity under acidic condition and have been extensively used in food, fermentation and leather industries. In this study, a novel aspartic protease precursor (proTlAPA1) fromTalaromyces leycettanuswas identified and successfully expressed inPichia pastoris. Subsequently, the auto-activation processing of the zymogen proTlAPA1 was studied by SDS-PAGE and N-terminal sequencing, under different processing conditions.TlAPA1 shared the highest identity of 70.3 % with the aspartic endopeptidase fromByssochlamys spectabilis(GAD91729) and was classified into a new subgroup of the aspartic protease A1 family, based on evolutionary analysis. MatureTlAPA1 protein displayed an optimal activity at 60 °C and remained stable at temperatures of 55 °C and below, indicating the thermostable nature ofTlAPA1 aspartic protease. During the auto-activation processing of proTlAPA1, a 45 kDa intermediate was identified that divided the processing mechanism into two steps: formation of intermediates, and activation of the mature protein (TlAPA1). The former step was completely induced by pH of the buffer, while the latter process depended on protease activity. The discovery of the novel aspartic proteaseTlAPA1 and study of its activation process will contribute to a better understanding of the mechanism of aspartic proteases auto-activation.

IMPORTANCE

The novel aspartic proteaseTlAPA1 was identified fromT. leycettanusand expressed as a zymogen (proTlAPA1) inP. pastoris. Enzymatic characteristics of the mature protein were studied and the specific pattern of zymogen conversion was described. The auto-activation processing of proTlAPA1 proceeded in two stages and an intermediate was identified in this process. These results describe a new subgroup of aspartic protease A1 family and provide insights into a novel mode of activation processing in aspartic proteases.
Modelling the role of dual specificity phosphatases in Herceptin resistant breast cancer cell lines
Authors: Buiga Petronela , Elson Ari , Tabernero Lydia , Schwartz Jean-Marc
Published: January 2019

Background

Breast cancer remains the most lethal type of cancer for women. A significant proportion of breast cancer cases are characterised by overexpression of the human epidermal growth factor receptor 2 protein (HER2). These cancers are commonly treated by Herceptin (Trastuzumab), but resistance to drug treatment frequently develops in tumour cells. Dual-specificity phosphatases (DUSPs) are thought to play a role in the mechanism of resistance, since some of them were reported to be overexpressed in tumours resistant to Herceptin.

Results

We used a systems biology approach to investigate how DUSP overexpression could favour cell proliferation and to predict how this mechanism could be reversed by targeted inhibition of selected DUSPs. We measured the expression of 20 DUSP genes in two breast cancer cell lines following long-term (6 months) exposure to Herceptin, after confirming that these cells had become resistant to the drug. We constructed several Boolean models including specific substrates of each DUSP, and showed that our models correctly account for resistance when overexpressed DUSPs were kept activated. We then simulated inhibition of both individual and combinations of DUSPs, and determined conditions under which the resistance could be reversed.

Conclusions

These results show how a combination of experimental analysis and modelling help to understand cell survival mechanisms in breast cancer tumours, and crucially enable us to generate testable predictions potentially leading to new treatments of resistant tumours.
Individuals’ expected genetic contributions to future generations, reproductive value, and short-term metrics of fitness in free-living song sparrows (Melospiza melodia)
Authors: Reid Jane M. , Nietlisbach Pirmin , Wolak Matthew E. , Keller Lukas F. , Arcese Peter
Published: January 2019

Appropriately defining and enumerating ‘fitness’ is fundamental to explaining and predicting evolutionary dynamics. Yet theoretical concepts of fitness are often hard to translate into quantities that can be quantified in wild populations experiencing complex environmental, demographic, genetic and selective variation. While the ‘fittest’ entities might be widely understood to be those that ultimately leave most descendants at some future time, such long-term legacies are hard to measure, impeding evaluation of how well more tractable short-term metrics of individual fitness directly predict longer-term outcomes. One opportunity for conceptual and empirical convergence stems from the principle of individual reproductive value (Vi), defined as the number of copies of each of an individual’s alleles that is expected to be present in future generations given the individual’s realised pedigree of descendants. Since Vi tightly predicts an individual’s longer-term genetic contribution, quantifying Vi provides a tractable route to quantifying what, to date, has been an abstract fitness concept. We used complete pedigree data from free-living song sparrows (Melospiza melodia) to demonstrate that individuals’ expected genetic contributions stabilise within an observed 20-year time period, allowing individual Vi to be evaluated. Considerable among-individual variation in Vi was evident in both sexes. However, standard short-term metrics of individual fitness, comprising lifespan, lifetime reproductive success and projected growth rate, typically explained less than half the variation. Given these results, we discuss what evolutionary inferences can and cannot be directly drawn from short-term versus longer-term fitness metrics observed on individuals, and highlight that analyses of pedigree structure may provide useful complementary insights into evolutionary processes and outcomes.
Dosage-sensitivity of human transcription factor genes
Authors: Ni Zhihua , Zhou Xiao-Yu , Aslam Sidra , Niu Deng-Ke
Published: January 2019

Changes in the copy number of protein-coding genes would lead to detrimental effects if the consequent changes in protein concentration disrupt essential cellular functions. Large-scale genomic studies have identified thousands of dosage-sensitive genes in human genome. We are interested in the dosage-sensitivity of transcription factor (TF) genes whose products are essential for the growth, division and differentiation of cells by regulating the expression of the genetic information encoded in the genome. We first surveyed the enrichment of human TF genes in four recently curated datasets of dosage-sensitive genes, including the haploinsufficient genes identified by a large-scale genomic study, the haploinsufficient genes predicted by a machine learning approach, the genes with conserved copy number across mammals, and the ohnologs. Then we selected the dosage-sensitive genes that are present in all the four dataset and regarded them as the most reliable dosage-sensitive genes, and the genes that are absent from any one of the four datasets as the most reliable dosage-insensitive genes, and surveyed the enrichments of TFs genes in these two datasets. A large number of TF genes were found to be dosage-insensitive, which is beyond the expectation based on the role of TFs. In spite of this, the likeness of TF genes to be dosage-sensitive were supported by five datasets, with the conserved-copy-number genes as the exception. The nuclear receptors are the only one family of TFs whose dosage-sensitivity was consistently supported by all the six datasets. In addition, we found that TF families with very few members are also more likely to be dosage-sensitive while the largest TF family, C2H2-ZF, are most likely dosage-insensitive. The most extensively studied TFs, p53, are not special in dosage-sensitivity. They are significantly enriched in only three datasets. We also confirmed that dosage-sensitive genes generally have long coding sequences, high expression levels and experienced stronger selective pressure. Our results indicate some TFs function in a dose-dependent manner while some other not. Gene dosage changes in some TF families like nuclear receptor would result in disease phenotypes while the effects of such changes in some TFs like C2H2-ZF would be mild.
The role of genetic diversity in the evolution and maintenance of environmentally-cued, male alternative reproductive tactics
Authors: Stewart KA , Draaijer R , Kolasa MR , Smallegange IM
Published: January 2019

Background

Alternative reproductive tactics (ARTs) are taxonomically pervasive strategies adopted by individuals to maximize reproductive success within populations. Even for conditionally-dependent traits, consensus postulates most ARTs involve both genetic and environmental interactions (GEIs), but to date, quantifying genetic variation underlying the threshold disposing an individual to switch phenotypes in response to an environmental cue has been a difficult undertaking. Our study aims to investigate the origins and maintenance of ARTs within environmentally disparate populations of the microscopic bulb mite, Rhizoglyphus robini, that express ‘fighter’ and ‘scrambler’ male morphs mediated by a complex combination of environmental and genetic factors.

Results

Using never-before-published individual genetic profiling, we found all individuals across populations are highly inbred with the exception of scrambler males in stressed environments. In fact within the poor environment, scrambler males and females showed no significant difference in genetic differentiation (Fst) compared to all other comparisons, and although fighters were highly divergent from the rest of the population in both poor or rich environments (e.g., Fst, STRUCTURE), fighters demonstrated approximately three times less genetic divergence from the population in poor environments. AMOVA analyses further corroborated significant genetic differentiation across subpopulations, between morphs and sexes, and among subpopulations within each environment.

Conclusion

Our study provides new insights into the origin of ARTs in the bulb mite, highlighting the importance of GEIs: genetic correlations, epistatic interactions, and sex-specific inbreeding depression across environmental stressors. Asymmetric reproductive output, coupled with the purging of highly inbred individuals during environmental oscillations, also facilitates genetic variation within populations, despite evidence for strong directional selection. This cryptic genetic variation also conceivably facilitates stable population persistence even in the face of spatially or temporally unstable environmental challenges. Ultimately, understanding the genetic context that maintains thresholds, even for conditionally-dependent ARTs, will enhance our understanding of within population variation and our ability to predict responses to selection.
Mai1 protein acts between host recognition of pathogen effectors and MAPK signaling
Authors: Hind Sarah R. , Roberts Robyn , Pedley Kerry F. , Diner Benjamin A. , Szarzanowicz Matthew J. , Luciano-Rosario Dianiris , Majhi Bharat B. , Popov Georgy , Sessa Guido , Oh Chang-Sik , Martin Gregory B.
Published: January 2019

The molecular mechanisms acting between host recognition of pathogen effectors by NOD-like receptor (NLR) proteins and mitogen-activated protein kinase (MAPK) signaling cascades are unknown. MAPKKKα (M3Kα) activates MAPK signaling leading to programmed cell death (PCD) associated with NLR-triggered immunity. We identified a tomato M3Kα-interacting protein, SlMai1, that has 80% amino acid identity withArabidopsisbrassinosteroid kinase 1 (AtBsk1). SlMai1 has a protein kinase domain and a C-terminal tetratricopeptide repeat domain which interacts with the kinase domain of M3Kα. Virus-induced gene silencing ofMai1homologs inNicotiana benthamianaincreased susceptibility toPseudomonas syringaeand compromised PCD induced by four NLR proteins. PCD was restored by expression of a syntheticSlMai1gene that resists silencing. Expression of AtBsk1 did not restore PCD inMai1-silenced plants, suggesting SlMai1 is functionally divergent from AtBsk1. PCD caused by overexpression of M3Kα or MKK2 was unaffected byMai1silencing indicating Mai1 acts upstream of these proteins. Co-expression of Mai1 with M3Kα in leaves enhanced MAPK phosphorylation and accelerated PCD. These findings reveal Mai1 as a molecular link acting between host recognition of pathogens and MAPK signaling.

Author Summary

Plants use intracellular immune receptors to detect and respond to specific effector proteins which pathogens translocate into the host cell as part of their infection process. Localized programmed cell death (PCD) involving a mitogen-activated protein kinase (MAPK) cascade is an important host response associated with effector-triggered immunity, although the molecular connections between immune receptors and MAPK signaling is unknown. The Mai1 protein was found to act downstream of multiple immune receptors inNicotiana benthamianaand to physically interact with MAPKKKα. The Mai1-MAPKKKα interaction enhances MAPK phosphorylation, triggers PCD and promotes disease resistance.
Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis
Authors: Goodwin Leslie O. , Splinter Erik , Davis Tiffany L. , Urban Rachel , He Hao , Braun Robert E. , Chesler Elissa J. , Kumar Vivek , van Min Max , Ndukum Juliet , Philip Vivek M. , Reinholdt Laura G. , Svenson Karen , White Jacqueline K. , Sasner Michael , Lutz Cathleen , Murray Stephen A.
Published: January 2019

Transgenesis has been a mainstay of mouse genetics for over 30 yr, providing numerous models of human disease and critical genetic tools in widespread use today. Generated through the random integration of DNA fragments into the host genome, transgenesis can lead to insertional mutagenesis if a coding gene or an essential element is disrupted, and there is evidence that larger scale structural variation can accompany the integration. The insertion sites of only a tiny fraction of the thousands of transgenic lines in existence have been discovered and reported, due in part to limitations in the discovery tools. Targeted locus amplification (TLA) provides a robust and efficient means to identify both the insertion site and content of transgenes through deep sequencing of genomic loci linked to specific known transgene cassettes. Here, we report the first large-scale analysis of transgene insertion sites from 40 highly used transgenic mouse lines. We show that the transgenes disrupt the coding sequence of endogenous genes in half of the lines, frequently involving large deletions and/or structural variations at the insertion site. Furthermore, we identify a number of unexpected sequences in some of the transgenes, including undocumented cassettes and contaminating DNA fragments. We demonstrate that these transgene insertions can have phenotypic consequences, which could confound certain experiments, emphasizing the need for careful attention to control strategies. Together, these data show that transgenic alleles display a high rate of potentially confounding genetic events and highlight the need for careful characterization of each line to assure interpretable and reproducible experiments.
Co-movements between the British pound, the euro and the Japanese yen: the Brexit impact
Authors: Alvarez-Diez Susana , Baixauli-Soler J. Samuel , Belda-Ruiz Maria
Published: January 2019

Purpose

The purpose of this paper is to analyze the Brexit effect – pre-Brexit and post-Brexit referendum periods – on the co-movements between the British pound (GBP), the euro (EUR) and the yen (JPY) against the US dollar (USD).

Design/methodology/approach

To ascertain the asymmetric behavior of dynamic correlations, the authors use the dynamic conditional correlation (DCC) model, the asymmetric dynamic conditional correlation (A-DCC) model and the diagonal BEKK model assuming Gaussian and Student’stdistribution. Several dummy variables have been included in order to identify the main periods related to Brexit.

Findings

Findings show a negative impact of the pre-Brexit referendum period on the correlation between GBP and EUR, while there is no significant effect on GBP–JPY and EUR–JPY pairs. The loss of correlation in the GBP–EUR pairing has not recovered during the post-Brexit referendum period, which could be attributed to the uncertainty about the final impact of Brexit on British and Eurozone economies.

Practical implications

The loss of correlation in the GBP–EUR pair has important implications for individual investors, portfolio managers and traders with respect to hedging activities, international trading and investment strategies.

Originality/value

The results are the first to address how Brexit has impacted on the co-movements between exchange rates using different multivariate models that allow for correlations to change over time.
More than just characters in a story: effective and meaningful involvement of young people in mental health research
Authors: MacSweeney Niamh , Bowman Sarah , Kelly Clare
Published: January 2019

Purpose

The story of youth mental health remains poorly understood. To truly progress our understanding of youth mental health, we must shift our focus from one in which young people are the subjects, or “characters”, of research efforts to one in which they are active agents, or “authors”. This change in dynamic falls under the banner of public and patient involvement (PPI), a growing movement that emphasises the meaningful involvement of the public in health research. The paper aims to discuss these issues.

Design/methodology/approach

Here, the authors aim to stimulate this shift in focus by describing emerging practices of youth involvement in paediatric research and outlining how such practices can be extended to the domain of youth mental health. In particular, the authors highlight Young Persons’ Advisory Groups (YPAG), through which young people can be involved in an active, meaningful and mutually beneficial manner, at each step in the research life cycle.

Findings

A YPAG comprises young people who act as research partners, providing guidance on a range of activities. In the health domain, YPAGs have provided fresh perspectives, generated valuable knowledge and changed attitudes about youth involvement in research. Moreover, they provide young people with genuine opportunities to shape research so that it addresses issues they encounter in their everyday lives.

Originality/value

The establishment of youth mental health YPAGs will enhance the authors’ research questions, design, delivery and impact. The authors outline how researchers can embrace PPI and work together with young people to tell a different story of youth mental health.
Size‐mediated priority and temperature effects on intra‐cohort competition and cannibalism in a damselfly
Authors: Sniegula Szymon , Golab Maria J. , Johansson Frank
Published: January 2019

A shift in the relative arrival of offspring, for example a shift in hatching time, can affect competition at the intraspecific level through size‐mediated priority effects, where the larger individuals gain more resources. These priority effects are likely to be affected by climate warming and the rate of intraspecific predation, that is cannibalism.

In a laboratory experiment, we examined size‐mediated priority effects in larvae of the univoltine damselfly, Lestes sponsa, at two different temperatures (21 and 23°C). We created three size groups of larvae by manipulating hatching time: early hatched with a large size (extra‐advanced), intermediate hatched with an intermediate size (advanced) and late hatched with a small size (non‐advanced). Thereafter, we reared the larvae from these groups in non‐mixed and mixed groups of 12 larvae.

We found strong priority and temperature effects. First, extra‐advanced larvae most often had higher survival, growth and development rates than non‐advanced larvae in mixed groups, compared to groups that consisted of only extra‐advanced larvae. Second, temperature increased growth and development rates and cannibalism.

However, the strength of priority effects did not differ between the two experimental temperatures, because there was no statistical interaction between temperature and treatments. That is, the mixed and non‐mixed groups of non‐advanced, advanced and extra‐advanced larvae showed the same relative change in life‐history traits across the two temperatures.

Non‐advanced and advanced larvae had similar or higher growth rate and mass in mixed groups compared to non‐mixed groups, suggesting that predation from advanced larvae in the mixed group released resources for the non‐advanced and advanced larvae that survived despite cannibalism risk. Thus, a thinning effect occurred due to cannibalism caused by priority effects.

The results suggest that a shift in the relative arrival of offspring can cause temperature‐dependent priority effects, mediated through cannibalism, growth and development, which may change the size distribution and abundance of emerging aquatic insects.
Seasonal differences in baseline innate immune function are better explained by environment than annual cycle stage in a year‐round breeding tropical songbird
Authors: Nwaogu Chima J. , Cresswell Will , Versteegh Maaike A. , Tieleman B. Irene
Published: January 2019

Seasonal variation in innate immunity is often attributed to either temporal environmental variation or to life‐history trade‐offs that arise from specific annual cycle stages but decoupling them is difficult in natural populations.

Here, we effectively decouple seasonal environmental variation from annual cycle stage effects by exploiting cross‐seasonal breeding and moult in the tropical Common Bulbul Pycnonotus barbatus. We test how annual cycle stage interacts with a key seasonal environmental variable, rainfall, to determine immunity at population and individual level. If immune challenge varies with precipitation, we might expect immune function to be higher in the wet season due to increased environmental productivity. If breeding or moult imposes resource constraints on birds, depending on or independent of precipitation, we might expect lower immune indices during breeding or moult.

We sampled blood from 818 birds in four annual cycle stage categories: breeding, moult, simultaneous breeding and moulting, or neither. We quantified indices of innate immunity (haptoglobin, nitric oxide (NOx) and ovotransferrin concentrations, and haemagglutination and haemolysis titres) over two annual cycles of wet and dry seasons.

Environment (but not annual cycle stage or interactions between both) explained variation in all immune indices, except NOx. NOx concentration differed between annual cycle stages but not between seasons. However, within the wet season, haptoglobin, NOx, ovotransferrin and haemolysis differed significantly between breeding and non‐breeding females. Aside from some recorded inconsistencies, population level results were largely similar to results within individuals that were measured repeatedly. Unexpectedly, most immune indices were higher in the dry season and during breeding.

Higher immune indices may be explained if fewer or poorer quality resources force birds to increase social contact, thereby exposing individuals to novel antigens and increased infection risk, independently of environmental productivity. Breeding birds may also show higher immunity if less immune‐competent and/or infected females omit breeding. We conclude that seasonal environmental variation impacts immunity more directly in natural animal populations than via resource trade‐offs. In addition, immune indices were more often variable within than among individuals, but some indices are characteristic of individuals, and so may offer selective advantages if heritable.
Compensatory mechanisms to climate change in the widely distributed species Silene vulgaris
Authors: Kahl Sandra M. , Lenhard Michael , Joshi Jasmin
Published: January 2019

The adaptation of plants to future climatic conditions is crucial for their survival. Not surprisingly, phenotypic responses to climate change have already been observed in many plant populations. These responses may be due to evolutionary adaptive changes or phenotypic plasticity. Especially plant species with a wide geographic range are either expected to show genetic differentiation in response to differing climate conditions or to have a high phenotypic plasticity.

We investigated phenotypic responses and plasticity as an estimate of the adaptive potential in the widespread species Silene vulgaris. In a greenhouse experiment, 25 European populations covering a geographic range from the Canary Islands to Sweden were exposed to three experimental precipitation and two temperature regimes mimicking a possible climate‐change scenario for central Europe. We hypothesized that southern populations have a better performance under high temperature and drought conditions, as they are already adapted to a comparable environment.

We found that our treatments significantly influenced the plants, but did not reveal a latitudinal difference in response to climate treatments for most plant traits. Only flower number showed a stronger plasticity in northern European populations (e.g. Swedish populations) where numbers decreased more drastically with increased temperature and decreased precipitation treatment.

Synthesis. The significant treatment response in Silene vulgaris, independent of population origin – except for the number of flowers produced – suggests a high degree of universal phenotypic plasticity in this widely distributed species. This reflects the likely adaptation strategy of the species and forms the basis for a successful survival strategy during upcoming climatic changes. However, as flower number, a strongly fitness‐related trait, decreased more strongly in northern populations under a climate‐change scenario, there might be limits to adaptation even in this widespread, plastic species.
Children with SEND and the emotional impact on parents
Authors: Holland John , Pell Gabrielle ,   KIDS
Published: January 2019

Children bring joy, new experiences and challenges into the lives of their families, and the focus of this article is on the often unrecognised emotional challenges and stigma experienced by parents of children with special educational needs and/or disabilities (SEND). This study involved a random sample group of 240 parents using a service in the Hull and East Riding areas of the UK. These parents filled in a questionnaire, the results of which showed that there were points of particular stress for some families, often involving their initial concerns when their children’s difficulties were unrecognised, the diagnosis itself, and then obtaining support. In addition, for some families, this stress led to the breakdown of parental relationships. Significant areas of additional stress included parents having feelings of guilt and emotional strain, with experiences of isolation for the family and negative impacts on parental mental health. Furthermore, some parents revealed incidences of stigma and a refusal to accept diagnoses and concerns, even from within the wider family. Likewise, some parents found that family and friends were not sympathetic or supportive. Finally, a number of parents also described detrimental impacts on siblings and expressed concerns about the education of and future outcomes for their child.
The Perfect uberPOOL: A Case Study on Trade‐Offs
Authors: LO JENNY , MORSEMAN STEVE
Published: January 2019

One of Uber's company missions is to make carpooling more affordable and reliable for riders, and effortless for drivers. In 2014 the company launched uberPOOL to make it easy for riders to share their trip with others heading in the same direction. Fundamental to the mechanics of uberPOOL is the intelligence that matches riders for a trip, which can introduce various uncertainties into the user experience. Core to the business objective is understanding how to deliver a ‘Perfect POOL'—an ideal situation where 3 people in the vehicle are able to get in and out at the same time and location allowing for a more predictable and affordable experience. This case study argues that, for a reduced fare and a more direct route, riders are willing to forego the convenience of getting picked up at their door in exchange for waiting and walking a set amount to meet their driver.

This case study explores the integration of qualitative and quantitative research to understand user tradeoffs. Methods utilized were in‐person interviews and two large‐scale surveys: a maxdiff and a conjoint, each with a different purpose. The study started with a multi‐city qualitative research study designed to understand how users make trade‐offs among their transportation options, suggesting key characteristics of a ‘Perfect POOL.’ The team followed up with a maxdiff survey to validate these characteristics and identify the factors most important for riders’ decisions. A customized conjoint survey was then built to study what values each product feature contributes to maximize rider opt‐in to the ‘Perfect POOL’ product. The team subsequently explored ways to translate the trade‐offs revealed by the conjoint survey back into the product experience. This case study will discuss the conjoint survey's outcomes and implications that directly confirmed the hypothesis that riders are willing to make experiential trade‐offs. Learnings from this multi‐phase research led to the initial Beta‐launch of Express POOL in November 2017.
Gaming Evidence: Power, Storytelling and the “Colonial Moment” in a Chicago Systems Change Project
Authors: HEINTZ NATHAN
Published: January 2019

In 2016 The Chicago Community Trust (“The Trust”), a local Chicago foundation, partnered with Roller Strategies (“Roller”), an international professional services firm, to deploy an innovative mixed‐methods approach to community‐driven social change on the South Side of Chicago. This partnership convened a diverse group of stakeholders representing a microcosm of the social system, and launched a project with the aim of developing resilient livelihoods for youth aged 18–26 in three specific South Side neighborhoods. Roller designed and facilitated a process through which the stakeholder group scoped, launched, piloted and prototyped community‐driven initiatives. While innovative and successful by some metrics, the project had its challenges. The convening institutions and their staff were often perceived as “outsiders” and “experts” without intimate local knowledge of the social challenges they were attempting to address. This dynamic played out in complex power maneuvers across groups in the system. The cultural narratives and interests already at play in the system were employed by individuals and groups at all levels to shape the landscape of agency and power in the system, while attempting to retain the methodological and narrative legitimacy of the publicly‐facing project. This case study will explore the narratives and power dynamics at play within the system, look into the causes of these dynamics, and explore the impact they had on the effectiveness of the project as a whole.
Confessions across Digital Distances
Authors: SHUTT JESS
Published: January 2019

Digital environments can expand the distances between people. While this is often challenging, it can also be leveraged to do great things. This Pecha Kucha explores how we can take this negative divide between people and flip it on its head to discover more powerful insights. By looking at a range of studies focused on sensitive subjects, we explore how technology has the power to create a safer environment for vulnerable participants. While technology is an often underutilized research tool, these technology enabled environments can lead to richer data and insights. As a result, we, as researchers, can create the space needed to share some of our most intimate stories.
Tracey's Struggle
Authors: O'NEIL SHELLEY , COCHRANE CHARLIE
Published: January 2019

Despite the ‘foodie’ reputation perpetuated by reality TV, cooking shows, and food blogs, many Australians struggle with eating healthy food. MasterFoods brand has been a household name in Australian supermarket groceries for 70 years and have a 2020 brand ambition to help all Australians enjoy the rewards that good food can bring. So they asked Jump the Fence to conduct an ethnographic study to understand people with challenges around physical access, time, money, and skill with food. Tracey from Southwest Sydney is one of five people the study focused on. Tracey's welcoming generosity and honesty are profound and reveal the complex layers of psychological, cultural and situational barriers she has to eating well.
Importance of Mean Platelet Volume in Predicting Cardiac Mechanics Parameters and Carotid‐Intima Media Thickness in Children With End‐Stage Renal Disease and Comparison With Healthy Children
Authors: Gheissari Alaleh , Dehghan Bahar , Ghaed Sharafi Bijan , Abedini Amin , Merrikhi Alireza , Madihi Yahya , Mehrkash Mehryar
Published: January 2019

Cardiovascular disease (CVD) is the major cause of death in children with ESRD. Echocardiography and Doppler ultrasound are useful devices for diagnosing cardiovascular abnormalities in such patients. However, they are expensive, difficult to perform as a routine, and not available in many centers. Therefore, finding a more accessible and inexpensive method for CVD evaluation biomarkers is needed. The aim of this study was to evaluate the relationship between mean platelet volume (MPV) as a routine hematological parameter with cardiac mechanics characteristics in children with ESRD. Forty‐two children under dialysis and 60 age‐ and sex‐matched healthy subjects as control group were enrolled in the study. Carotid‐intima media thickness (CIMT) and echocardiographic parameters were measured in both groups. In addition, hematological and biochemical variables were evaluated in blood samples of participants. MPV was significantly higher in patients than in controls. CIMT, left ventricular mass index (LVMI), end diastolic diameter, strain rate, and global longitudinal strain were significantly different between the two groups. MPV was positively correlated with LVMI and inversely with ejection fraction. In receiver operating characteristic (ROC) curve analysis, the area under the ROC curve (AUC) values for MPV in predicting left ventricular hypertrophy (LVH) and abnormal CIMT were 0.65 (P = 0.07) and 0.53 (P = 0.74), respectively. MPV was correlated with some cardiac abnormalities in children with ESRD. However, it could not show appropriate predictive values in diagnosing LVH and subclinical atherosclerosis. Further studies with prospective design could shed more light in this topic.
Pseudomonas bacteriocin syringacin M released upon desiccation suppresses the growth of sensitive bacteria in plant necrotic lesions
Authors: Li Jun‐Zhou , Zhou Li‐Ying , Peng You‐Liang , Fan Jun
Published: January 2019

Bacteriocins are regarded as important factors mediating microbial interactions, but their exact role in community ecology largely remains to be elucidated. Here, we report the characterization of a mutant strain, derived from Pseudomonas syringae pv. tomato DC3000 (Pst), that was incapable of growing in plant extracts and causing disease. Results showed that deficiency in a previously unannotated gene saxE led to the sensitivity of the mutant to Ca2+ in leaf extracts. Transposon insertions in the bacteriocin gene syrM, adjacent to saxE, fully rescued the bacterial virulence and growth of the ΔsaxE mutant in plant extracts, indicating that syrM‐saxE encode a pair of bacteriocin immunity proteins in Pst. To investigate whether the syrM‐saxE system conferred any advantage to Pst in competition with other SyrM‐sensitive pathovars, we compared the growth of a SyrM‐sensitive strain co‐inoculated with Pst strains with or without the syrM gene and observed a significant syrM‐dependent growth reduction of the sensitive bacteria on plate and in lesion tissues upon desiccation–rehydration treatment. These findings reveal an important biological role of SyrM‐like bacteriocins and help to understand the complex strategies used by P. syringae in adaptation to the phyllosphere niche in the context of plant disease.
Minor allele frequency thresholds strongly affect population structure inference with genomic data sets
Authors: Linck Ethan , Battey C. J.
Published: January 2019

A common method of minimizing errors in large DNA sequence data sets is to drop variable sites with a minor allele frequency (MAF) below some specified threshold. Although widespread, this procedure has the potential to alter downstream population genetic inferences and has received relatively little rigorous analysis. Here we use simulations and an empirical single nucleotide polymorphism data set to demonstrate the impacts of MAF thresholds on inference of population structure—often the first step in analysis of population genomic data. We find that model‐based inference of population structure is confounded when singletons are included in the alignment, and that both model‐based and multivariate analyses infer less distinct clusters when more stringent MAF cutoffs are applied. We propose that this behaviour is caused by the combination of a drop in the total size of the data matrix and by correlations between allele frequencies and mutational age. We recommend a set of best practices for applying MAF filters in studies seeking to describe population structure with genomic data.
Non‐monotonic NPV Function Leads to Spurious NPVs and Multiple IRR Problems: A New Method that Resolves these Problems
Authors: Arjunan Kannapiran C.
Published: January 2019

The causes and effects of non‐monotonic NPV functions are evaluated and the results presented in this paper. Reinvestment of intermediate income causes non‐monotonic NPV function. Non‐monotonic NPV function not only leads to multiple IRRs but also to spurious NPVs. The capital amortisation (CAS) method used in this analysis transparently reveals if there is any reinvestment. A modified CAS method, discussed in this paper, eliminates the reinvestment and resolves the problems of non‐monotonic NPV function, reinvestment, spurious NPVs and multiple IRR. The current practice of using NPV as the preferred criterion, when there are multiple IRRs, is not appropriate.