Initial Glimpse Research Articles

Social Media and Couples: What Are the Important Factors for Understanding Relationship Satisfaction?

The current study sought to examine specific Facebook behaviors, related to one's relationship and their association with relationship satisfaction. Data were collected from 115 undergraduates who were in a relationship and had an active Facebook account. Participants completed a number of measures focused on their relationship and gave the researcher access to their Facebook profiles to record the frequency of all posts (comments and status updates), pictures, tags, and likes from the previous two weeks. Each of these behaviors was then coded as relationship-specific (involving one's partner) or not. Descriptive statistics were calculated for each relationship-specific Facebook behavior. A number of participants did not include relationship information on their Facebook page. Only relationship status and having one's partner in a profile picture were significantly associated with relationship satisfaction. The current study is the first of its kind to examine the association between relationship-specific Facebook behaviors and relationship satisfaction, beyond that of one's relationship status or profile photo alone. The results of this study provide an initial glimpse into the specific relationship-oriented behaviors that individuals engage in on social media. Furthermore, the results provide guidance on macro- versus micro-analysis of online behavior for other researchers who are examining social media and couples' relationships.

Integrating Embryonic Development and Evolutionary History to Characterize Tentacle-Specific Cell Types in a Ctenophore.

The origin of novel traits can promote expansion into new niches and drive speciation. Ctenophores (comb jellies) are unified by their possession of a novel cell type: the colloblast, an adhesive cell found only in the tentacles. Although colloblast-laden tentacles are fundamental for prey capture among ctenophores, some species have tentacles lacking colloblasts and others have lost their tentacles completely. We used transcriptomes from 36 ctenophore species to identify gene losses that occurred specifically in lineages lacking colloblasts and tentacles. We cross-referenced these colloblast- and tentacle-specific candidate genes with temporal RNA-Seq during embryogenesis in Mnemiopsis leidyi and found that both sets of candidates are preferentially expressed during tentacle morphogenesis. We also demonstrate significant upregulation of candidates from both data sets in the tentacle bulb of adults. Both sets of candidates were enriched for an N-terminal signal peptide and protein domains associated with secretion; among tentacle candidates we also identified orthologs of cnidarian toxin proteins, presenting tantalizing evidence that ctenophore tentacles may secrete toxins along with their adhesive. Finally, using cell lineage tracing, we demonstrate that colloblasts and neurons share a common progenitor, suggesting the evolution of colloblasts involved co-option of a neurosecretory gene regulatory network. Together these data offer an initial glimpse into the genetic architecture underlying ctenophore cell-type diversity.

Journal Digest

Journal Digest

Neuron-specific regulation of superoxide dismutase amid pathogen-induced gut dysbiosis

Superoxide dismutase, an enzyme that converts superoxide into less-toxic hydrogen peroxide and oxygen, has been shown to mediate behavioral response to pathogens. However, it remains largely unknown how superoxide dismutase is regulated in the nervous system amid pathogen-induced gut dysbiosis. Although there are five superoxide dismutases in C. elegans, our genetic analyses suggest that SOD-1 is the primary superoxide dismutase to mediate the pathogen avoidance response. When C. elegans are fed a P. aeruginosa diet, the lack of SOD-1 contributes to enhanced lethality. We found that guanylyl cyclases GCY-5 and GCY-22 and neuropeptide receptor NPR-1 act antagonistically to regulate SOD-1 expression in the gustatory neuron ASER. After C. elegans ingests a diet that contributes to high levels of oxidative stress, the temporal regulation of SOD-1 and the SOD-1–dependent response in the gustatory system demonstrates a sophisticated mechanism to fine-tune behavioral plasticity. Our results may provide the initial glimpse of a strategy by which a multicellular organism copes with oxidative stress amid gut dysbiosis.

Variations in Zn and S isotope chemistry of sedimentary sphalerite, Wusihe Zn-Pb deposit, Sichuan Province, China

The Sichuan–Yunnan–Guizhou (SYG) metallogenic province, southwestern China, is one of the largest Zn-Pb producers in the world. The Zn-Pb deposits in this area have been studied over many years and are commonly classified as Mississippi Valley Type (MVT) deposits. We investigated geological and mineralogical features of the Wusihe deposit and found that ores formed at the sedimentary metallogenic stage exhibit banded and normal grading textures and have different mineral assemblages from other deposits in this area. These features have not been reported previously, suggesting special formation mechanisms for these sedimentary ores. In this study, we firstly investigate the isotope geochemistry of Zn and S in syngenetic sphalerite from the Wusihe deposit. We elucidate spatial and temporal variations of Zn and S isotopes to provide a better understanding for Zn and S isotope fractionation during the hydrothermal processes. The δ34SCDT values of microdrilled sphalerite range from 9.4‰ to 20.9‰ (mean = 14.3‰), which are ca.15‰ lower than that of sulfate from the Dengying Formation, suggesting that reduced sulfur in sphalerite formed through thermochemical sulfate reduction (TSR) but not microbial sulfate reduction (MSR). At the hand specimen scale, no significant Zn isotopic fractionation was observed from bottom to top of the banded sphalerite ore and we propose a model that Zn isotopes are homogeneous in Zn-bearing hydrothermal fluid, and Zn2+ was rapidly and completely precipitated to form sphalerite. This process results in minor Zn isotopic variations in sphalerite (Δ66Zn = 0.08‰) and initial hydrothermal fluid composition was calculated to be δ66Zn values = 0.37 ± 0.03‰. By contrast, positive linear relationships were observed in the sphalerite ore with normal grading between δ66Zn and δ34SCDT values and between δ34SCDT values and Zn/Cd ratios, which are not reported previously. Combined with previous studies, it is proposed that the variations in fluid temperatures may be the key factor that results in such positive correlations.In addition, this study gives some new insights into geochemical and isotopic behavior of Zn and S in hydrothermal systems, and provides an initial glimpse into the utilization of Zn isotopes as an environmental tracer for reconstruction of Zn isotope compositions in the Ediacaran Ocean.

Engineering models for softening and relaxation of Gr. 91 steel in creep-fatigue conditions

Purpose There are a number of different approaches for calculating creep-fatigue (CF) damage for design, such as the French nuclear code RCC-MRx, the American ASME III NH and the British R5 assessment code. To acquire estimates for the CF damage, that are not overly conservative, both the cyclic material softening/hardening and the potential changes in relaxation behavior have to be considered. The data presented here and models are an initial glimpse of the ongoing European FP7 project MATISSE effort to model the softening and relaxation behavior of Grade 91 steel under CF loading. The resulting models are used for calculating the relaxed stress at arbitrary location in the material cyclic softening curve. The initial test results show that softening of the material is not always detrimental. The initial model development and the pre-assessment of the MATISSE data show that the relaxed stress can be robustly predicted with hold time, strain range and the cyclic life fraction as the main input parameters. The paper aims to discuss these issues. Design/methodology/approach Engineering models have been developed for predicting cyclic softening and relaxation for Gr. 91 steel at 550 and 600°C. Findings A simple engineering model can adequately predict the low cycle fatigue (LCF) and CF softening rates of Gr. 91 steel. Also a simple relaxation model was successfully defined for predicting relaxed stress of both virgin and cyclically softened material. Research limitations/implications The data are not yet complete and the models will be updated when the complete set of data in the MATISSE project is available. Practical implications The models described can be used for predicting P91 material softening in an arbitrary location (n/Nf0) of the LCF and CF cyclic life. Also the relaxed stress in the softened material can be estimated. Originality/value The models are simple in nature but are able to estimate both material softening and relaxation in arbitrary location of the softening curve. This is the first time the Wilshire methodology has been applied on cyclic relaxation data.

The Holistic Processing Account of Visual Expertise in Medical Image Perception: A Review.

In the field of medical image perception, the holistic processing perspective contends that experts can rapidly extract global information about the image, which can be used to guide their subsequent search of the image (Swensson, 1980; Nodine and Kundel, 1987; Kundel et al., 2007). In this review, we discuss the empirical evidence supporting three different predictions that can be derived from the holistic processing perspective: Expertise in medical image perception is domain-specific, experts use parafoveal and/or peripheral vision to process large regions of the image in parallel, and experts benefit from a rapid initial glimpse of an image. In addition, we discuss a pivotal recent study (Litchfield and Donovan, 2016) that seems to contradict the assumption that experts benefit from a rapid initial glimpse of the image. To reconcile this finding with the existing literature, we suggest that global processing may serve multiple functions that extend beyond the initial glimpse of the image. Finally, we discuss future research directions, and we highlight the connections between the holistic processing account and similar theoretical perspectives and findings from other domains of visual expertise.

Systematic Analysis of Human Protein Phosphatase Interactions and Dynamics

Coordinated activities of protein kinases and phosphatases ensure phosphorylation homeostasis, which, when perturbed, can instigate diseases, including cancer. Yet, in contrast to kinases, much less is known about protein phosphatase functions and their interactions and complexes. Here, we used quantitative affinity proteomics to assay protein-protein interactions for 54 phosphatases distributed across the three major protein phosphatase families, with additional analysis of their 12 co-factors. We identified 838 high-confidence interactions, of which 631, to our knowledge, have not been reported before. We show that inhibiting the activity of phosphatases PP1 and PP2A by okadaic acid disrupts their specific interactions, supporting the potential of therapeutics that target these proteins. Additional analyses revealed candidate physical and functional interaction links to phosphatase-based regulation of several signaling pathways and to human cancer. Our study provides an initial glimpse of the protein interaction landscape of phosphatases and their functions in cellular regulation.

Worth a quick look? Initial scene previews can guide eye movements as a function of domain-specific expertise but can also have unforeseen costs.

Rapid scene recognition is a global visual process we can all exploit to guide search. This ability is thought to underpin expertise in medical image perception yet there is no direct evidence that isolates the expertise-specific contribution of processing scene previews on subsequent eye movement performance. We used the flash-preview moving window paradigm (Castelhano & Henderson, 2007) to investigate this issue. Expert radiologists and novice observers underwent 2 experiments whereby participants viewed a 250-ms scene preview or a mask before searching for a target. Observers looked for everyday objects from real-world scenes (Experiment 1), and searched for lung nodules from medical images (Experiment 2). Both expertise groups exploited the brief preview of the upcoming scene to more efficiently guide windowed search in Experiment 1, but there was only a weak effect of domain-specific expertise in Experiment 2, with experts showing small improvements in search metrics with scene previews. Expert diagnostic performance was better than novices in all conditions but was not contingent on seeing the scene preview, and scene preview actually impaired novice diagnostic performance. Experiment 3 required novice and experienced observers to search for a variety of abnormalities from different medical images. Rather than maximizing the expertise-specific advantage of processing scene previews, both novices and experienced radiographers were worse at detecting abnormalities with scene previews. We discuss how restricting access to the initial glimpse can be compensated for by subsequent search and discovery processing, but there can still be costs in integrating a fleeting glimpse of a medical scene. (PsycINFO Database Record

Abstract PL08-04: High-throughput drug screens in cancer cell models to enable precision cancer medicine

Abstract Alterations in cancer genomes strongly influence clinical responses to therapy and can be used as molecular biomarkers of response to targeted agents. However, the identification of biomarkers for effective patient stratification remains a considerable challenge for the development of effective therapies. We are performing large-scale drug sensitivity screens using genetically characterised in vitro cellular models of human cancer. Cancer cells are profiled for differential sensitivity to clinical, pre-clinical and experimental anti-cancer compounds and drug response is linked with genomic features. We aim to identify the molecular features of cancer cells which impact on drug sensitivity and resistance, and investigate the molecular rationale for the observed sensitivity. This provides insights into mechanism of drug action, identifies opportunities for re-purposing existing drugs for new indications, and enables the identification of biomarkers to facilitate the development of targeted cancer therapies. I will describe results from our recent analysis of how cancer-driving alterations identified from the analysis of 11,000 patient tumours correlate with response to 265 compounds profiled in a panel of 1,000 human cancer cell-lines. This comprehensive analysis provides an initial glimpse of the landscape of pharmacogenomic interactions operative in human cancer, and is a resource to identify novel therapeutic possibilities for selected cancer sub-populations. Citation Format: Mathew Garnett. High-throughput drug screens in cancer cell models to enable precision cancer medicine. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr PL08-04.

“I’m thankful for being Native and my body is part of that”: The body pride experiences of young Aboriginal women in Canada

Body pride may be a predictor of health and well-being among Aboriginal youth. Body pride could potentially be addressed in health interventions, but it is critical to understand how body pride is conceptualized among Aboriginal youth. The purpose of this qualitative description study was to better understand the experiences of body pride among young Aboriginal women living in urban centers in Alberta, Canada. Eight young Aboriginal women (15–18 years old) participated in one-on-one interviews. A qualitative content analysis highlighted five themes that represent the participants’ meanings of body pride. Participants described how body pride is: (a) accepting everything about your body, (b) who you are and how you show it, (c) connected to culture, (d) being healthy, and (e) being thankful to be Native. This research makes a contribution to the growing body pride literature by providing an initial glimpse into the complexities of young Aboriginal women's body pride experiences.

Reconstitution of the 26S proteasome reveals functional asymmetries in its AAA+ unfoldase (936.1)

The 26S proteasome is the major protease in eukaryotic cells responsible for selective protein degradation to mediate protein quality control and regulation, yet the detailed mechanisms by which the proteasomal heterohexameric AAA+ unfoldase drives ATP‐dependent protein degradation remain poorly understood. Delineating the roles of the six distinct ATPase subunits in substrate processing has been hindered by limitations in working with endogenous proteasomes due to misassembly or lethal degradation defects. We therefore developed a heterologous expression system to produce the unfoldase subcomplex from Saccharomyces cerevisiae in Escherichia coli and reconstituted the proteasome in vitro to perform systematic mutational analyses of the individual ATPase subunits. Our studies demonstrate that the six ATPases have distinct functions in degradation, corresponding to their positions in the spiral staircases adopted by their large AAA+ domains in the absence or presence of substrate. ATP hydrolysis in subunits at the top of the staircases is critical for substrate engagement and translocation. Whereas the unfoldase relies on this vertical asymmetry for substrate processing, interaction with the peptidase exhibits a pronounced three‐fold symmetry. Only three ATPase subunits, arranged in alternate positions within the unfoldase ring, contain a conserved C‐terminal hydrophobic/aromatic/unspecified (HbYX) motif that is critical for both peptidase binding and gate‐opening, whereas the C‐terminal tails of the interjacent ATPase subunits are dispensable. Our study provides an initial glimpse into the potential importance of the spiral staircase configurations of proteasomal ATPase subunits in substrate processing and highlights how the 26S proteasome may deviate from simpler, homomeric AAA+ proteases.Grant Funding Source: Supported by US National Institutes of Health grant R01‐GM094497‐01A1

IDO2 is critical for IDO1-mediated T-cell regulation and exerts a non-redundant function in inflammation

IDO2 is implicated in tryptophan catabolism and immunity but its physiological functions are not well established. Here we report the characterization of mice genetically deficient in IDO2, which develop normally but exhibit defects in IDO-mediated T-cell regulation and inflammatory responses. Construction of this strain was prompted in part by our discovery that IDO2 function is attenuated in macrophages from Ido1 (-/-) mice due to altered message splicing, generating a functional mosaic with implications for interpreting findings in Ido1 (-/-) mice. No apparent defects were observed in Ido2 (-/-) mice in embryonic development or hematopoietic differentiation, with wild-type profiles documented for kynurenine in blood serum and for immune cells in spleen, lymph nodes, peritoneum, thymus and bone marrow of naive mice. In contrast, upon immune stimulation we determined that IDO1-dependent T regulatory cell generation was defective in Ido2 (-/-) mice, supporting Ido1-Ido2 genetic interaction and establishing a functional role for Ido2 in immune modulation. Pathophysiologically, both Ido1 (-/-) and Ido2 (-/-) mice displayed reduced skin contact hypersensitivity responses, but mechanistic distinctions were apparent, with only Ido2 deficiency associated with a suppression of immune regulatory cytokines that included GM-CSF, G-CSF, IFN-γ, TNF-α, IL-6 and MCP-1/CCL2. Different contributions to inflammation were likewise indicated by the finding that Ido2 (-/-) mice did not phenocopy Ido1 (-/-) mice in the reduced susceptibility of the latter to inflammatory skin cancer. Taken together, our results offer an initial glimpse into immune modulation by IDO2, revealing its genetic interaction with IDO1 and distinguishing its non-redundant contributions to inflammation.

Reconstitution of the 26S Proteasome Reveals Functional Asymmetries in its Heterohexameric AAA+ Unfoldase

The 26S proteasome is the major protease in eukaryotic cells responsible for selective protein degradation to mediate protein quality control and regulation. However, the detailed mechanisms by which the proteasomal heterohexameric AAA+ unfoldase drives ATP-dependent protein degradation remain poorly understood. Delineating the roles of the six distinct ATPase subunits in substrate processing has been hindered by limitations in working with endogenous proteasomes due to misassembly or lethal degradation defects. We therefore developed a heterologous expression system to produce the unfoldase subcomplex from Saccharomyces cerevisiae in Escherichia coli and reconstituted the proteasome in vitro to perform systematic mutational analyses of the individual ATPase subunits. Our studies demonstrate that the six ATPases have distinct functions in degradation, corresponding to their positions in the spiral staircases adopted by their large AAA+ domains in the absence or presence of substrate. ATP hydrolysis in subunits at the top of the staircases is critical for substrate engagement and translocation. Whereas the unfoldase relies on this vertical asymmetry for substrate processing, interaction with the peptidase exhibits a pronounced three-fold symmetry. Only three ATPase subunits, arranged in alternate positions within the unfoldase ring, contain a conserved C-terminal hydrophobic/aromatic/unspecified (HbYX) motif that is critical for both peptidase binding and gate-opening, whereas the C-terminal tails of the interjacent ATPase subunits are dispensable. Our study provides an initial glimpse into the potential importance of the spiral staircase configurations of proteasomal ATPase subunits in substrate processing and highlights how the 26S proteasome may deviate from simpler, homomeric AAA+ proteases.

Importance of having agreeable friends in adolescence (especially when you are not)

Using the actor–partner interdependence model, we examined whether adolescent's agreeableness, best friend's agreeableness, and the interaction between adolescent-friend agreeableness are important for interpersonal functioning. Adolescents (N = 158) in fifth to eighth grades who were part of best friend pairs completed personality and friendship measures. Adolescents' adjustment and victimization experiences were assessed by peer nominations. For boys, best friend's agreeableness moderated the relationship between the target boy's agreeableness and overt victimization, relational victimization, and externalizing problems. For girls, best friend's agreeableness moderated the relationship between the target girl's agreeableness and internalizing problems and prosocial skills. This study provides an initial glimpse into how traits of friends can influence outcomes beyond what would be expected from adolescents' personality alone.

Evidence for Extensive Genetic Diversity and Substructuring of theBabesia bovisMetapopulation

Babesia bovis is a tick-transmitted haemoprotozoan and a causative agent of bovine babesiosis, a cattle disease that causes significant economic loss in tropical and subtropical regions. A panel of nineteen micro- and minisatellite markers was used to estimate population genetic parameters of eighteen parasite isolates originating from different continents, countries and geographic regions including North America (Mexico, USA), South America (Argentina, Brazil), the Middle East (Israel) and Australia. For eleven of the eighteen isolates, a unique haplotype was inferred suggesting selection of a single genotype by either in vitro cultivation or amplification in splenectomized calves. Furthermore, a high genetic diversity (H = 0.780) over all marker loci was estimated. Linkage disequilibrium was observed in the total study group but also in sample subgroups from the Americas, Brazil, and Israel and Australia. In contrast, corresponding to their more confined geographic origin, samples from Israel and Argentina were each found to be in equilibrium suggestive of random mating and frequent genetic exchange. The genetic differentiation (F(ST)) of the total study group over all nineteen loci was estimated by analysis of variance (Θ) and Nei's estimation of heterozygosity (G(ST')) as 0.296 and 0.312, respectively. Thus, about 30% of the genetic diversity of the parasite population is associated with genetic differences between parasite isolates sampled from the different geographic regions. The pairwise similarity of multilocus genotypes (MLGs) was assessed and a neighbour-joining dendrogram generated. MLGs were found to cluster according to the country/continent of origin of isolates, but did not distinguish the attenuated from the pathogenic parasite state. The distant geographic origin of the isolates studied allows an initial glimpse into the large extent of genetic diversity and differentiation of the B. bovis population on a global scale.

Stained-glass politics and descriptive representation: does associational leadership by women engender political engagement among women?

The vast literature on the political effects of descriptive representation focuses solely on representatives in government. However, since non-governmental associations are essential to citizens' political engagement, we extend the reach of the descriptive representation literature to include associational leadership. We offer an initial glimpse at what this form of investigation may entail, asking what effect descriptive representation of women within religious associations (i.e. in the pulpit) might have on the political engagement of members of their congregations. Using a set of matched data gathered from clergy and members of their congregations, our findings suggest that women's associational leadership could be an important force boosting women's political engagement, although this is conditional on the content of elite political communication and, at times, comes at the expense of men's involvement in politics.

Functional anatomy of distant-acting mammalian enhancers

Transcriptional enhancers are a major class of functional element embedded in the vast non-coding portion of the human genome. Acting over large genomic distances, enhancers play critical roles in the tissue and cell type-specific regulation of genes, and there is mounting evidence that they contribute to the aetiology of many human diseases. Methods for genome-wide mapping of enhancer regions are now available, but the functional architecture contained within human enhancer elements remains unclear. Here, we review recent approaches aimed at understanding the functional anatomy of individual enhancer elements, using systematic qualitative and quantitative assessments of mammalian enhancer variants in cultured cells and in vivo. These studies provide direct insight into common architectural characteristics of enhancers including the presence of multiple transcription factor-binding sites and the mixture of both transcriptionally activating and repressing domains within the same enhancer. Despite such progress in understanding the functional composition of enhancers, the inherent complexities of enhancer anatomy continue to limit our ability to predict the impact of sequence changes on in vivo enhancer function. While providing an initial glimpse into the mutability of mammalian enhancers, these observations highlight the continued need for experimental enhancer assessment as genome sequencing becomes routine in the clinic.

Meaning in life: An important factor for the psychological well-being of chronically ill patients?

This study aimed to investigate 2 dimensions of meaning in life--Presence of Meaning (i.e., the perception of your life as significant, purposeful, and valuable) and Search for Meaning (i.e., the strength, intensity, and activity of people's efforts to establish or increase their understanding of the meaning in their lives)--and their role for the well-being of chronically ill patients. A sample of 481 chronically ill patients (M = 50 years, SD = 7.26) completed measures on meaning in life, life satisfaction, optimism, and acceptance. We hypothesized that Presence of Meaning and Search for Meaning will have specific relations with all 3 aspects of well-being. Cluster analysis was used to examine meaning in life profiles. RESULTS supported 4 distinguishable profiles (High Presence High Search, Low Presence High Search, High Presence Low Search, and Low Presence Low Search) with specific patterns in relation to well-being and acceptance. Specifically, the 2 profiles in which meaning is present showed higher levels of well-being and acceptance, whereas the profiles in which meaning is absent are characterized by lower levels. Furthermore, the results provided some clarification on the nature of the Search for Meaning process by distinguishing between adaptive (the High Presence High Search cluster) and maladaptive (the Low Presence High Search cluster) searching for meaning in life. The present study provides an initial glimpse in how meaning in life may be related to the well-being of chronically ill patients and the acceptance of their condition. Clinical implications are discussed.

Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems

Contact-dependent growth inhibition (CDI) systems encode polymorphic toxin/immunity proteins that mediate competition between neighboring bacterial cells. We present crystal structures of CDI toxin/immunity complexes from Escherichia coli EC869 and Burkholderia pseudomallei 1026b. Despite sharing little sequence identity, the toxin domains are structurally similar and have homology to endonucleases. The EC869 toxin is a Zn(2+)-dependent DNase capable of completely degrading the genomes of target cells, whereas the Bp1026b toxin cleaves the aminoacyl acceptor stems of tRNA molecules. Each immunity protein binds and inactivates its cognate toxin in a unique manner. The EC869 toxin/immunity complex is stabilized through an unusual β-augmentation interaction. In contrast, the Bp1026b immunity protein exploits shape and charge complementarity to occlude the toxin active site. These structures represent the initial glimpse into the CDI toxin/immunity network, illustrating how sequence-diverse toxins adopt convergent folds yet retain distinct binding interactions with cognate immunity proteins. Moreover, we present visual demonstration of CDI toxin delivery into a target cell.