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Indoor tanning is a risky behavior that dramatically increases skin cancer risk. Researchers from multiple disciplines aim to better understand this behavior to develop interventions and messages to curtail it. As such, we investigated the role of social norms and outcome expectations as predictors of tanning behavior as part of a larger test of constructs included in the Theory of Normative Social Behavior. In addition to offering additional empirical results to support theoretical claims for the importance of social norms and outcome expectations in predicting health behaviors, we offer indoor tanning-specific operationalizations in a conditional process model with the aim of assessing how content-specific measurements predict indoor tanning intentions. Results of a survey of adult indoor tanners from across the U.S. ( N  = 262) highlight when and how descriptive norms influence tanning intentions through the mediating roles of anticipatory socialization, injunctive norms, and health threat, and through the moderating role of mood-based tanning motivations. Implications for theory building as well as for intervention and message design are discussed.

Site-specific 2'- O -ribose methylation is an abundant post-transcriptional modification mediated by small non-coding nuclear RNAs known as box C/D modification guide RNAs. The minimal structural requirements for these guide RNAs to function in higher eukaryotes are still unclear. To address this question, we generated a series of mutant variants of Drosophila box C/D scaRNA:MeU2-C28 and tested their modification guide activities in the Xenopus oocyte system. Our data suggest that box C/D guide RNA function requires either a terminal or an internal consensus kink-turn structure. We identified the minimal functional box C/D guide RNA. It consists of a single-domain molecule with (i) a terminal stem with a consensus kink-turn domain, (ii) one box C and box D connected by a 14-nucleotide antisense element and (iii) a one-nucleotide spacer between the box C and the antisense element. In this single domain RNA, the sequence of the spacer is more important than its length. We suggest that the secondary structure of box C/D RNAs, essential for guide RNA function, is more complex than generally supposed. At the same time, the expression of functional extremely short single-domain box C/D RNAs is possible in higher eukaryotes.

This study combined conceptual frameworks from health information seeking, appraisal theory of emotions, and social determinants of health literatures to examine how emotional states and education predict online health information seeking. Nationally representative data from the Health Information National Trends Survey (HINTS 4, Cycle 3) were used to test the roles of education, anxiety, anger, sadness, hope, happiness, and an education by anxiety interaction in predicting online health information seeking. Results suggest that women, tablet owners, smartphone owners, the college educated, those who are sad some or all of the time, and those who are anxious most of the time were significantly more likely to seek online health information. Conversely, being angry all of the time decreased the likelihood of seeking. Furthermore, two significant interactions emerged between anxiety and education levels. Discrete psychological states and demographic factors (gender and education) individually and jointly impact information seeking tendencies.

Technologies that define the atomic-level structure of neutralization-sensitive epitopes on viral surface proteins are transforming vaccinology and guiding new vaccine development approaches. Previously, iterative rounds of protein engineering were performed to preserve the prefusion conformation of the respiratory syncytial virus (RSV) fusion (F) glycoprotein, resulting in a stabilized subunit vaccine candidate (DS-Cav1), which showed promising results in mice and macaques. Here, phase I human immunogenicity data reveal a more than 10-fold boost in neutralizing activity in serum from antibodies targeting prefusion-specific surfaces of RSV F. These findings represent a clinical proof of concept for structure-based vaccine design, suggest that development of a successful RSV vaccine will be feasible, and portend an era of precision vaccinology., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Much research has investigated what happens when celebrities disclose an illness (via media) to the public. While audience involvement (i.e., identification and parasocial relationships) is often the proposed mechanism linking illness disclosures with audience behavior change, survey designs have prevented researchers from understanding if audience involvement prior to the illness disclosure actually predicts post-disclosure emotions, cognitions, and behaviors. Rooted in previous work on audience involvement as well as the Extended Parallel Process Model, the present study uses a national online experiment ( N  = 1,068) to test how pre-disclosure audience involvement may initiate post-disclosure effects for the message context of skin cancer. The data demonstrate that pre-disclosure audience involvement as well as the celebrity's framing of the disclosure can shape emotional responses (i.e., fear and hope), and that cognitive perceptions of the illness itself also influence behavioral intentions.

Fear appeal research has focused, understandably, on fear as the primary emotion motivating attitude and behavior change. However, while the threat component of fear appeals associates with fear responses, a fear appeals' efficacy component likely associates with a different emotional experience: hope. Drawing from appraisal theories of emotion in particular, this article theorizes about the role of hope in fear appeals, testing hypotheses with two existing data sets collected within the context of sun safety messages. In both studies, significant interactions between hope and self-efficacy emerged to predict behavioral intentions. Notable main effects for hope also emerged, though with less consistency. Further, these effects persisted despite controlling for the four cognitions typically considered central to fear appeal effectiveness. These results, consistent across two samples, support the claim that feelings of hope in response to fear appeals contribute to their persuasive success. Implications for developing a recursive model of fear appeal processing are discussed.

When a celebrity dies and news coverage repeatedly pays homages to the celebrity's life, it is possible that audiences experience nostalgia as they fondly recall past memories of that celebrity. Nostalgia has yet to be examined as a mechanism of audience behavior related to the health condition associated with that celebrity. As such, we proposed a conceptual model of the interplay of predictors of feeling nostalgic after a celebrity death (i.e., identification, audience age, audience gender, consumption of media about the celebrity death, and previous viewing of celebrity-related media) and two outcomes: prosocial behaviors (e.g., donating to or volunteering for a health-related organization associated with the celebrity) and social sharing of information with others. We conducted a nationwide survey ( N = 466) within weeks following the death of television star Mary Tyler Moore to test our model. The results demonstrate that nostalgia is evoked by a number of factors after a celebrity death, and that together with these previously studied predictors it can influence outcomes of interest.

Most intronic RNAs are degraded within seconds or minutes after their excision from newly formed transcripts. However, stable intronic sequence RNAs (sisRNAs) have been described from oocytes of the frog Xenopus , from Drosophila embryos, and from human cell lines. In Xenopus oocytes, sisRNAs are abundant in both the nucleus and cytoplasm, they occur in the form of lariats, and they are stable for days. In this study we demonstrate that cytoplasmic sisRNAs are also found in human, mouse, chicken, and zebrafish cells. They exist as circular (lariat) molecules, mostly 100-500 nucleotides in length, and are derived from many housekeeping genes. They tend to have an unusual cytosine branchpoint (with the exception of those from the frog). Stable lariats are exported from the nucleus to the cytoplasm by the NXF1/NXT1 system, demonstrating that their presence in the cytoplasm is not due to passive diffusion. Lariats in the cytoplasm are not associated with transcripts of the genes from which they are derived. The biological significance of cytoplasmic sisRNAs remains obscure., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

We report that 7SL, the RNA component of the signal recognition particle (SRP), is an abundant noncoding RNA (ncRNA) in mature red blood cells (RBCs) of human, mouse, and the frog Xenopus. 7SL RNA in RBCs is not associated with the canonical proteins of the SRP. Instead, it coimmunoprecipitates from a lysate of RBCs with a number of membrane-binding proteins. Human and mouse RBCs also contain a previously undescribed 68 nt RNA, sRN7SL, derived from the "S domain" of 7SL RNA. We discuss the possibility that 7SL RNA is selectively protected from nucleases by association with the RBC membrane. Because 7SL is not associated with the canonical proteins of the SRP, it could represent a nonfunctional remnant of the protein synthetic machinery. Alternatively, it could play a new, as yet undefined role in RBC metabolism., (© 2018 Talhouarne and Gall; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

The branch point recognition region of spliceosomal snRNA U2 is heavily modified post-transcriptionally in most eukaryotic species. We focused on this region to learn how nearby positions may interfere with each other when targeted for modification. Using an in vivo yeast Saccharomyces cerevisiae cell system, we tested the modification activity of several guide RNAs from human, mouse, the frog Xenopus tropicalis , the fruit fly Drosophila melanogaster , and the worm Caenorhabditis elegans We experimentally verified predictions for vertebrate U2 modification guide RNAs SCARNA4 and SCARNA15, and identified a C. elegans ortholog of SCARNA15. We observed crosstalk between sites in the heavily modified regions, such that modification at one site may inhibit modification at nearby sites. This is true for the branch point recognition region of U2 snRNA, the 5' loop of U5 snRNA, and certain regions of rRNAs, when tested either in yeast or in HeLa cells. The position preceding a uridine targeted for isomerization by a box H/ACA guide RNA is the most sensitive for noncanonical base-pairing and modification (either pseudouridylation or 2'- O -methylation). Based on these findings, we propose that modification must occur stepwise starting with the most vulnerable positions and ending with the most inhibiting modifications. We discuss possible strategies that cells use to reach complete modification in heavily modified regions., (© 2018 Deryusheva and Gall; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Celebrity cancer deaths can focus public attention on the disease like few events can. However, not all celebrities or their families are open about the exact cause of death. Anecdotal reports suggest that some do not reveal the exact cause of death due to fears of stigma associated with the specific type of cancer. However, empirical evidence regarding whether or how the cause of death actually impacts public perceptions and behaviors is lacking. A three (cause of death: nonspecified cancer, liver cancer, or lung cancer) by two (celebrity obituary: David Bowie or Alan Rickman) fully factorial between-subjects online experiment (N = 390) tested a proposed model of effects on identification, discrete emotional reactions, stigma-related perceptions, and behavioral intentions. Results suggest that specific causes of death do not have a direct impact on stigma but they can alter identification and emotional reactions, such as compassion and anxiety, which subsequently shape stigma-related perceptions and behavioral intentions.

Researchers have documented the ways in which media stigmatize mental illness. However, media also portray mental illness trivially when diseases are mocked, oversimplified, shown to be less severe than in actuality, or represented as beneficial to an individual. Trivialization of mental illnesses could potentially lead audiences to be less likely to seek help or less likely to support related policy efforts. Therefore, it is important to understand how audiences recall and react to stigmatizing and trivializing mental illness portrayals. An experiment (N = 175) asked participants to recall either a media portrayal where mental illness was stigmatized or a portrayal where it was trivialized. Results suggest that audiences recall certain components of stigmatization and trivialization better than others. And, recollections of trivialization were associated with different patterns of word use than stigmatization. A second experiment (N = 141) found similar patterns when showing participants specific examples of different mental illness portrayals and asking them to immediately recall the content. Overall, these results suggest that theory and conceptual models about the nature and effects of mental illness portrayals could be updated to include both stigmatization and trivialization.

The pseudouridine at position 43 in vertebrate U2 snRNA is one of the most conserved post-transcriptional modifications of spliceosomal snRNAs; the equivalent position is pseudouridylated in U2 snRNAs in different phyla including fungi, insects, and worms. Pseudouridine synthase Pus1p acts alone on U2 snRNA to form this pseudouridine in yeast Saccharomyces cerevisiae and mouse. Furthermore, in S. cerevisiae , Pus1p is the only pseudouridine synthase for this position. Using an in vivo yeast cell system, we tested enzymatic activity of Pus1p from the fission yeast Schizosaccharomyces pombe , the worm Caenorhabditis elegans , the fruit fly Drosophila melanogaster , and the frog Xenopus tropicalis We demonstrated that Pus1p from C. elegans has no enzymatic activity on U2 snRNA when expressed in yeast cells, whereas in similar experiments, position 44 in yeast U2 snRNA (equivalent to position 43 in vertebrates) is a genuine substrate for Pus1p from S. cerevisiae , S. pombe , Drosophila , Xenopus , and mouse. However, when we analyzed U2 snRNAs from Pus1 knockout mice and the pus1Δ S. pombe strain, we could not detect any changes in their modification patterns when compared to wild-type U2 snRNAs. In S. pombe , we found a novel box H/ACA RNA encoded downstream from the RPC10 gene and experimentally verified its guide RNA activity for positioning Ψ43 and Ψ44 in U2 snRNA. In vertebrates, we showed that SCARNA8 (also known as U92 scaRNA) is a guide for U2-Ψ43 in addition to its previously established targets U2-Ψ34/Ψ44., (© 2017 Deryusheva and Gall; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Background: Unlike other types of cancer, skin cancer incidence rates are on the rise and adolescent females are particularly likely to tan indoors, a major risk factor. However, little research has examined the role of media use in encouraging or discouraging this dangerous behavior in this population., Aims: To empirically assess the links between media use, indoor tanning-related outcome expectations, and behavioral intentions., Method: A survey of adolescent females ( N = 510) ages 15 to 18 in the Southeastern United States assessed demographics, types of media use, and indoor tanning intentions., Results: Significant correlations between media use and indoor tanning outcome expectations were found. Use of interpersonal and social media (i.e., talking on the phone, texting, and online social media) were positively associated with positive outcome expectations about indoor tanning and negatively associated with negative outcome expectations. A path analysis revealed that interpersonal/social media use had indirect associations with indoor tanning intentions via tanning outcome expectations. Mass media use (e.g., news media, entertainment media, and magazines) was not significantly associated with most indoor tanning outcome expectations but did have a direct negative association with behavioral intentions., Discussion: There are important relationships between media use, indoor tanning outcome expectations, and behavioral intentions. Interpersonal and social media use may help cultivate outcome expectations that encourage indoor tanning, which in turn may increase intentions to tan, while news media consumption in particular may reduce intentions to tan., Conclusion: These findings highlight the social nature of adolescent females and point to specific intervention channels for reducing indoor tanning among this population.

Based on the previous work investigating public reactions to celebrity cancer deaths as well as on the appraisal theory of emotions, an online survey (N = 641) was conducted after the cancer death of popular sportscaster Stuart Scott. The aim was to better understand how the public shared news and reactions with others and if this social sharing impacted prosocial cancer-related behaviors (e.g., donating, volunteering, talking to others about cancer research). Two hierarchical logistic regression models were run. In the first, identification with Scott and emotional reactions to hearing about his death were significant predictors of sharing, even after controlling for demographics. In the second, feeling hopeful and having shared information with others predicted prosocial cancer-related behaviors. These results suggest promising strategies for designing more effective cancer awareness messages and fundraising campaigns after celebrity cancer announcements.

The toxic proline:arginine (PR n ) poly-dipeptide encoded by the (GGGGCC) n repeat expansion in the C9orf72 form of heritable amyotrophic lateral sclerosis (ALS) binds to the central channel of the nuclear pore and inhibits the movement of macromolecules into and out of the nucleus. The PR n poly-dipeptide binds to polymeric forms of the phenylalanine:glycine (FG) repeat domain, which is shared by several proteins of the nuclear pore complex, including those in the central channel. A method of chemical footprinting was used to characterize labile, cross-β polymers formed from the FG domain of the Nup54 protein. Mutations within the footprinted region of Nup54 polymers blocked both polymerization and binding by the PR n poly-dipeptide. The aliphatic alcohol 1,6-hexanediol melted FG domain polymers in vitro and reversed PR n -mediated enhancement of the nuclear pore permeability barrier. These data suggest that toxicity of the PR n poly-dipeptide results in part from its ability to lock the FG repeats of nuclear pore proteins in the polymerized state. Our study offers a mechanistic interpretation of PR n poly-dipeptide toxicity in the context of a prominent form of ALS.

In order to better understand drivers of dangerous indoor tanning behaviors, researchers developed the Comprehensive Indoor Tanning Expectations scale. To examine the longitudinal effectiveness of Comprehensive Indoor Tanning Expectations, we surveyed young women in the Southeastern United States at two time points ( N = 553). The scale demonstrated strong test-retest reliability. Participants who believed indoor tanning would improve their mood and afford social approval were significantly more likely to tan 6 months later, while participants who believed indoor tanning leads to psychological/physical discomfort were significantly less likely to tan 6 months later. Knowing the psychological bases for indoor tanning can inform intervention and message design.

We describe methods for studying the giant transcriptionally active lampbrush chromosomes (LBCs) found in the oocyte, or unlaid egg, of frogs and salamanders. Individual LBCs can be up to 1 mm in length and they reside in a gigantic nucleus, itself up to 0.5 mm in diameter. The large size of the chromosomes permits unparalleled observations of active genes by light optical microscopy, but at the same time special techniques are required for isolating the nucleus, removing the nuclear envelope, and spreading the chromosomes on a microscope slide. The oocyte nucleus, also called the germinal vesicle (GV), is isolated in a medium that allows partial gelling of the nuclear actin and preserves the delicate structure of the LBCs. This step is carried out manually under a dissecting microscope using jeweler's forceps. Next, the nuclear envelope is removed, again manually with jeweler's forceps. The nuclear contents are quickly transferred to a medium that disperses the actin gel and allows the undamaged LBCs to settle onto a microscope slide. At this point the LBCs and other nuclear organelles can be viewed by phase contrast or differential interference contrast microscopy, although finer details are obscured by Brownian motion. For high resolution microscopical observation or molecular analysis, the whole preparation is centrifuged to attach the delicate LBCs firmly to the slide. A brief fixation in paraformaldehyde is then followed by immunofluorescent staining or in situ hybridization. LBCs are in a transcriptionally active state and their enormous size permits molecular analysis at the individual gene level using confocal or super-resolution microscopy.

Foot-in-the-door (FITD) involves obtaining compliance with a small request to boost compliance with a larger request. Only a few studies to date have tested the technique in health and fundraising contexts, and even fewer have examined the psychological processes involved. To address these gaps, we conducted an experiment as an actual fundraiser for a cancer-awareness organization. The technique activated a self-concept as a supporter of cancer awareness among those in the FITD condition. Donation amount was also higher among those in FITD, but only among those with higher levels of worry and low to moderate levels of preference for consistency.

Research indicates that when people seek health information, they typically look for information about a specific symptom, preventive measure, disease, or treatment. It is unclear, however, whether general or disease-specific theoretical models best predict how people search for health information. We surveyed undergraduates (N = 963) at a large public southeastern university to examine health information seeking in two incongruent health contexts (sexual health and cancer) to test whether a general model would hold for specific topics that differed in their immediate personal relevance for the target population. We found that the planned risk information seeking model was statistically a good fit for the data. Yet multiple predicted paths were not supported in either data set. Certain variables, such as attitudes, norms, and affect, appear to be strong predictors of intentions to seek information across health contexts. Implications for theory building, research methodology, and applied work in health-related risk information seeking are discussed.

Tanning bed use before age 35 has been strongly associated with several types of skin cancer. The current study sought to advance an understanding of audience segmentation for indoor tanning among young women. Panhellenic sorority systems at two universities in the Southeastern United States participated in this study. A total of 1,481 young women took the survey; 421 (28%) had tanned indoors in the previous 12 months and were the focus of the analyses reported in this article. Results suggested two distinct tanner types: regular (n = 60) and irregular (n = 353) tanners. Regular tanners tanned more frequently (M = 36.2 vs. 8.6 times per year) and reported significantly higher positive outcome expectations (p < .001) and lower negative outcome expectations (p < .01) than irregular tanners, among other significant differences. Hierarchical logistic regression analysis revealed several significant (p < .001) predictors of regular tanning type, with tanning dependence emerging as the strongest predictor of this classification (OR = 2.25). Implications for developing anti-tanning messages directed at regular and irregular tanners are discussed.

In situ hybridization is the technique by which specific RNA or DNA molecules are detected in cytological preparations. Basically it involves formation of a hybrid molecule between an endogenous single-stranded RNA or DNA in the cell and a complementary single-stranded RNA or DNA probe. In its original form the probe was labeled with (3)H and the hybrid was detected by autoradiography. The first successful experiments in 1968 involved detection of the highly amplified ribosomal DNA in oocytes of the frog Xenopus, followed soon after by the reiterated "satellite DNA" in mouse and Drosophila chromosomes. Fluorescent probes were developed about ten years later., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This paper reports genome sizes of one Hawaiian Scaptomyza and 16 endemic Hawaiian Drosophila species that include five members of the antopocerus species group, one member of the modified mouthpart group, and ten members of the picture wing clade. Genome size expansions have occurred independently multiple times among Hawaiian Drosophila lineages, and have resulted in an over 2.3-fold range of genome sizes among species, with the largest observed in Drosophila cyrtoloma (1C = 0.41 pg). We find evidence that these repeated genome size expansions were likely driven by the addition of significant amounts of heterochromatin and satellite DNA. For example, our data reveal that the addition of seven heterochromatic chromosome arms to the ancestral haploid karyotype, and a remarkable proportion of ~70 % satellite DNA, account for the greatly expanded size of the D. cyrtoloma genome. Moreover, the genomes of 13/17 Hawaiian picture wing species are composed of substantial proportions (22-70 %) of detectable satellites (all but one of which are AT-rich). Our results suggest that in this tightly knit group of recently evolved species, genomes have expanded, in large part, via evolutionary amplifications of satellite DNA sequences in centric and pericentric domains (especially of the X and dot chromosomes), which have resulted in longer acrocentric chromosomes or metacentrics with an added heterochromatic chromosome arm. We discuss possible evolutionary mechanisms that may have shaped these patterns, including rapid fixation of novel expanded genomes during founder-effect speciation.

Social network sites (SNSs) like Twitter continue to attract users, many of whom turn to these spaces for social support for serious illnesses like cancer. Building on literature that explored the functionality of online spaces for health-related social support, we propose a typology that situates this type of support in an SNS-based open cancer community based on the type (informational or emotional) and the direction (expression or reception) of support. A content analysis applied the typology to a 2-year span of Twitter messages using the popular hashtag "#stupidcancer." Given that emotions form the basis for much of human communication and behavior, including aspects of social support, this content analysis also examined the relationship between emotional expression and online social support in tweets about cancer. Furthermore, this study looked at the various ways in which Twitter allows for message sharing across a user's entire network (not just among the cancer community). This work thus begins to lay the conceptual and empirical groundwork for future research testing the effects of various types of social support in open, interactive online cancer communities.

Importance: Paraneoplastic pemphigus (PNP) is routinely diagnosed by the presence of autoantibodies for desmoplakin by indirect immunofluorescence (IIF) on rat bladder epithelium (RBE). IIF on RBE has recently been found to be positive in select cases of other blistering disorders. A new ELISA that detects envoplakin autoantibodies has recently been developed for the diagnosis of PNP. In this study, we measure the specificity of IIF on RBE and compare it to the new ELISA., Observations: We measured the specificity of IIF on RBE to be 86% which is on the lower end of the previously reported specificity of 83% to 98.9%. The ELISA for envoplakin autoantibodies has a technical sensitivity of 100%, diagnostic sensitivity of 83%, and specificity of 91%., Conclusions and Relevance: This ELISA for envoplakin autoantibodies is now commercially available and technically easier to perform then the immunoblot. We recommend that this new ELISA serves as a confirmatory test in cases of a positive IIF on RBE given its higher specificity.

Recombinant adenoviral vectors (rAds) are lead vaccine candidates for protection against a variety of pathogens, including Ebola, HIV, tuberculosis, and malaria, due to their ability to potently induce T cell immunity in humans. However, the ability to induce protective cellular immunity varies among rAds. Here, we assessed the mechanisms that control the potency of CD8 T cell responses in murine models following vaccination with human-, chimpanzee-, and simian-derived rAds encoding SIV-Gag antigen (Ag). After rAd vaccination, we quantified Ag expression and performed expression profiling of innate immune response genes in the draining lymph node. Human-derived rAd5 and chimpanzee-derived chAd3 were the most potent rAds and induced high and persistent Ag expression with low innate gene activation, while less potent rAds induced less Ag expression and robustly induced innate immunity genes that were primarily associated with IFN signaling. Abrogation of type I IFN or stimulator of IFN genes (STING) signaling increased Ag expression and accelerated CD8 T cell response kinetics but did not alter memory responses or protection. These findings reveal that the magnitude of rAd-induced memory CD8 T cell immune responses correlates with Ag expression but is independent of IFN and STING and provide criteria for optimizing protective CD8 T cell immunity with rAd vaccines.

The lack of a theory-based understanding of indoor tanning is a major impediment to the development of effective messages to prevent or reduce this behavior. This study applied the Comprehensive Indoor Tanning Expectations (CITE) scale in an analysis of indoor tanning behavior among sorority women (total N = 775). Confirmatory factor analyses indicated that CITE positive and negative expectations were robust, multidimensional factors and that a hierarchical structure fit the data well. Social cognitive theory-based structural equation models demonstrated that appearance-oriented variables were significantly associated with outcome expectations. Outcome expectations were, in turn, significantly associated with temptations to tan, intention to tan indoors, and indoor tanning behavior. The implications of these findings for the development of messages to prevent and reduce indoor tanning behavior are discussed in two domains: (a) messages that attempt to change broader societal perceptions about tan skin, and (b) messages that focus more narrowly on indoor tanning-challenging positive expectations, enhancing negative expectations, and encouraging substitution of sunless tanning products.

Fluorescent in situ hybridization (FISH) is a technique for determining the cytological localization of RNA or DNA molecules. There are many approaches available for generating in situ hybridization probes and conducting the subsequent hybridization steps. Here, we describe a simple and reliable FISH method to label small RNAs (200-500 nucleotides in length) that are enriched in nuclear bodies in Drosophila melanogaster ovaries, such as Cajal bodies (CBs) and histone locus bodies (HLBs). This technique can also be applied to other Drosophila tissues, and to abundant mRNAs such as histone transcripts.

Emotionally evocative public service announcements are one way that public health advocates hope to persuade people to take action against skin cancer, the most common type of cancer in the United States. This article describes an experiment (N = 193) to test the ways mixed emotional appeals influence communication and health outcomes. The data indicate that mixed emotional appeals foster feelings of compassion, which in turn motivate individual and social behaviors. The findings also provide insight into how audience reactions of fear impact postmessage behaviors. Implications for future research and health message design are discussed.

We previously demonstrated that the oocyte nucleus (germinal vesicle or GV) of Xenopus tropicalis contains a population of stable RNA molecules derived from the introns of most expressed genes. Here we show that similar stable intronic sequence (sis) RNAs occur in the oocyte cytoplasm. About 9000 cytoplasmic sisRNAs have been identified, all of which are resistant to the exonuclease RNase R. About half have been confirmed as lariat molecules and the rest are presumed to be lariats, whereas nuclear sisRNAs are a mixture of lariat and linear molecules. Cytoplasmic sisRNAs are more abundant on a molar basis than nuclear sisRNAs and are derived from short introns, mostly under 1 kb in length. Both nuclear and cytoplasmic sisRNAs are transmitted intact to the egg at GV breakdown and persist until at least the blastula stage of embryogenesis, when zygotic transcription begins. We compared cytoplasmic sisRNAs derived from orthologous genes of X. tropicalis and X. laevis, and found that the specific introns from which sisRNAs are derived are not conserved. The existence of sisRNAs in the cytoplasm of the oocyte, their transmission to the fertilized egg, and their persistence during early embryogenesis suggest that they might play a regulatory role in mRNA translation., (© 2014 Talhouarne and Gall; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Importance: Strong links between indoor tanning behavior and skin cancer have been demonstrated across several studies. Understanding the complex belief systems that underlie indoor tanning in young women is a crucial first step in developing interventions to deter this behavior., Objectives: To develop and validate a comprehensive, multidimensional, theory-based outcome expectations measure to advance an understanding of the sets of beliefs that underlie indoor tanning behavior among young women., Design, Setting, and Participants: Cross-sectional study comprising a web-based survey of 11 sororities at a large university in the southeastern United States. Study participants (n = 706) were aged 18 to 25 years; 45.3% had tanned indoors in their lifetime and 30.3% in the past year., Main Outcomes and Measures: Intention to tan indoors, frequency of indoor tanning behavior in the past year, and indoor tanner type (nontanner, former tanner, or current tanner)., Results: A comprehensive scale assessing indoor tanning outcome expectations was developed. In total, 6 positive outcome expectations factors and 5 negative outcome expectations factors were identified. These subscales were reliable (coefficient α range, 0.86-0.95) and were significantly (mostly at P < .001) correlated with a set of established measures, including appearance motivation, indoor tanning attitudes and norms, and intention to tan indoors. Examination of subscales across the 3 indoor tanning groups also revealed significant (P < .001) differences on all 11 subscales. Current tanners had the most positive and least negative perceptions about indoor tanning, while nontanners had the most negative and least positive perceptions. Former tanners tended to fall in between these 2 groups. The 2 subscales with the largest differences across the groups were mood enhancement (positive outcome expectation) and psychological/physical discomfort (negative outcome expectation). Multiple linear regression analyses demonstrated several outcome expectations subscales to be significantly associated with intention to tan indoors and frequency of indoor tanning behavior., Conclusions and Relevance: Results suggest that the Comprehensive Indoor Tanning Expectations (CITE) Scale provides a reliable and valid assessment of the complex sets of beliefs that underlie indoor tanning, including positive (motivational) and negative (deterrent) beliefs. This new scale may further advance research on indoor tanning beliefs and can guide health communications to prevent and deter indoor tanning behavior.

Vaccines constructed from rare-serotype recombinant adenovirus vectors (rAd) such as rAd serotype 28 (rAd28) and rAd35 are currently being explored as alternatives to rAd5-based vaccines because they circumvent the problems with pre-existing immunity that complicate the effectiveness of rAd5 vaccines. However, previous work has demonstrated that the immunogenicity of rAd28 and rAd35 is substantially lower than rAd5. Here we show that rAd28 and rAd35 increase apoptosis of antigen presenting cells (APCs), such as monocytes, relative to rAd5 and mock infected controls. APCs undergoing apoptosis showed an increased loss of vector-insert expression. Loss of vector-insert expression correlated with activation of NK cells, which resulted in apoptosis of co-cultured monocytes. Finally, we show that activation of NK cells is dependent on IFNα which is produced by exposure to rAd28 or rAd35, but not to rAd5. Taken together, these data demonstrate that IFNα-induced activation of NK cells leads to increased monocyte apoptosis and subsequent vector-insert loss. This may be a possible mechanism that results in reduced immunogenicity of rAd28 and rAd35-based vectors., (Published by Elsevier Ltd.)

Respiratory syncytial virus (RSV) is a major cause of infectious lower respiratory disease in infants and the elderly. As there is no vaccine for RSV, we developed a genetic vaccine approach that induced protection of the entire respiratory tract from a single parenteral administration. The approach was based on adenovirus vectors derived from newly isolated nonhuman primate viruses with low seroprevalence. We show for the first time that a single intramuscular (IM) injection of the replication-deficient adenovirus vectors expressing the RSV fusion (F0) glycoprotein induced immune responses that protected both the lungs and noses of cotton rats and mice even at low doses and for several months postimmunization. The immune response included high titers of neutralizing antibody that were maintained ≥ 24 weeks and RSV-specific CD8+ and CD4+ T cells. The vectors were as potently immunogenic as a human adenovirus 5 vector in these two key respiratory pathogen animal models. Importantly, there was minimal alveolitis and granulocytic infiltrates in the lung, and type 2 cytokines were not produced after RSV challenge even under conditions of partial protection. Overall, this genetic vaccine is highly effective without potentiating immunopathology, and the results support development of the vaccine candidate for human testing.

Announcements by public figures and celebrities about cancer diagnosis or death represent significant events in public life. But what are the substantive effects of such events, if any? The purpose of this article is to systematically review studies that examined the impact of public figure cancer announcements on cancer-oriented outcomes. Using comprehensive search procedures, we identified k = 19 studies that examined 11 distinct public figures. The most commonly studied public figures were Jade Goody, Kylie Minogue, Nancy Reagan, and Steve Jobs, with the most common cancers studied being breast (53%), cervical (21%), and pancreatic (21%) cancer. Most studies assessed multiple outcome variables, including behavioral outcomes (k = 15), media coverage (k = 10), information seeking (k = 8), cancer incidence (k = 3), and interpersonal communication (k = 2). Results fairly consistently indicated that cancer announcements from public figures had meaningful effects on many, if not most, of these outcome variables. While such events essentially act as naturally occurring interventions, the effects tend to be relatively short term. Gaps in this literature include few contemporary studies of high-profile public figures in the United States and a general lack of theory-based research. Directions for future research as well as implications for cancer communication and prevention are discussed.

The present study aimed to examine the public reaction to the death of Steve Jobs, focusing on general and cancer-specific information seeking and interpersonal communication. Shortly after Jobs's death, employees from a large university in the Southeastern United States (N = 1,398) completed a web-based survey. Every employee had heard about Steve Jobs's death, and 97% correctly identified pancreatic cancer as the cause of his death. General (50%) and pancreatic cancer-specific (7%) information seeking, as well as general (74%) and pancreatic cancer-specific (17%) interpersonal communication, took place in response to Steve Jobs's death. In multivariate logistic regression analyses controlling for demographics and several cancer-oriented variables, both identification with Steve Jobs and cancer worry in response to Steve Jobs's death significantly (p < .05) predicted pancreatic cancer information seeking as well as interpersonal communication about pancreatic cancer. Additional analyses revealed that cancer worry partially mediated the effects of identification on these outcome variables. Implications of these results for future research as well as cancer prevention and communication efforts are discussed.

The spliceosomal small nuclear RNAs (snRNAs) are modified post-transcriptionally by introduction of pseudouridines and 2'-O-methyl modifications, which are mediated by box H/ACA and box C/D guide RNAs, respectively. Because of their concentration in the nuclear Cajal body (CB), these guide RNAs are known as small CB-specific (sca) RNAs. In the cell, scaRNAs are associated with the WD-repeat protein WDR79. We used coimmunoprecipitation with WDR79 to recover seven new scaRNAs from Drosophila cell lysates. We demonstrated concentration of these new scaRNAs in the CB by in situ hybridization, and we verified experimentally that they can modify their putative target RNAs. Surprisingly, one of the new scaRNAs targets U6 snRNA, whose modification is generally assumed to occur in the nucleolus, not in the CB. Two other scaRNAs have dual guide functions, one for an snRNA and one for 28S rRNA. Again, the modification of 28S rRNA is assumed to take place in the nucleolus. These findings suggest that canonical scaRNAs may have functions in addition to their established role in modifying U1, U2, U4, and U5 snRNAs. We discuss the likelihood that processing by scaRNAs is not limited to the CB.

We have generated hexon-modified adenovirus serotype 5 (Ad5) vectors that are not neutralized by Ad5-specific neutralizing antibodies in mice. These vectors are attractive for the advancement of vaccine products because of their potential for inducing robust antigen-specific immune responses in people with prior exposure to Ad5. However, hexon-modified Ad5 vectors displayed an approximate 10-fold growth defect in complementing cells, making potential vaccine costs unacceptably high. Replacing hypervariable regions (HVRs) 1, 2, 4, and 5 with the equivalent HVRs from Ad43 was sufficient to avoid Ad5 preexisting immunity and retain full vaccine potential. However, the resulting vector displayed the same growth defect as the hexon-modified vector carrying all 9 HVRs from Ad43. The growth defect is likely due to a defect in capsid assembly, since DNA replication and late protein accumulation were normal in these vectors. We determined that the hexon-modified vectors have a 32°C cold-sensitive phenotype and selected revertants that restored vector productivity. Genome sequencing identified a single base change resulting in a threonine-to-methionine amino acid substitution at the position equivalent to residue 342 of the wild-type protein. This mutation has a suppressor phenotype (SP), since cloning it into our Ad5 vector containing all nine hypervariable regions from Ad43, Ad5.H(43m-43), increased yields over the version without the SP mutation. This growth improvement was also shown for an Ad5-based hexon-modified vector that carried the hexon hypervariable regions of Ad48, indicating that the SP mutation may have broad applicability for improving the productivity of different hexon-modified vectors.

We have isolated and cultured three distinct adenoviruses from wild gorillas. Phylogenetic analysis grouped the viruses with human adenovirus species C based on DNA polymerase, hexon, and E4ORF6 genes. The three wild gorilla adenoviruses clustered with the other species C captive gorilla adenoviruses, forming a branch separate from human and chimpanzee/bonobo adenoviruses. Animal sera to the three newly isolated viruses did not cross-neutralize, demonstrating serological distinctiveness. The human adenovirus 5 fiber knob blocked infection, suggesting use of the Coxsackie and Adenovirus Receptor. These viruses may provide viral vectors with properties distinct from chimpanzee adenovirus and human adenovirus vectors., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Recombinant adenoviral vectors (rAds) are the most potent recombinant vaccines for eliciting CD8(+) T cell-mediated immunity in humans; however, prior exposure from natural adenoviral infection can decrease such responses. In this study we show low seroreactivity in humans against simian- (sAd11, sAd16) or chimpanzee-derived (chAd3, chAd63) compared with human-derived (rAd5, rAd28, rAd35) vectors across multiple geographic regions. We then compared the magnitude, quality, phenotype, and protective capacity of CD8(+) T cell responses in mice vaccinated with rAds encoding SIV Gag. Using a dose range (1 × 10(7)-10(9) particle units), we defined a hierarchy among rAd vectors based on the magnitude and protective capacity of CD8(+) T cell responses, from most to least, as: rAd5 and chAd3, rAd28 and sAd11, chAd63, sAd16, and rAd35. Selection of rAd vector or dose could modulate the proportion and/or frequency of IFN-γ(+)TNF-α(+)IL-2(+) and KLRG1(+)CD127(-)CD8(+) T cells, but strikingly ∼30-80% of memory CD8(+) T cells coexpressed CD127 and KLRG1. To further optimize CD8(+) T cell responses, we assessed rAds as part of prime-boost regimens. Mice primed with rAds and boosted with NYVAC generated Gag-specific responses that approached ∼60% of total CD8(+) T cells at peak. Alternatively, priming with DNA or rAd28 and boosting with rAd5 or chAd3 induced robust and equivalent CD8(+) T cell responses compared with prime or boost alone. Collectively, these data provide the immunologic basis for using specific rAd vectors alone or as part of prime-boost regimens to induce CD8(+) T cells for rapid effector function or robust long-term memory, respectively.

Lampbrush chromosomes (LBCs) are transcriptionally active chromosomes found in the germinal vesicle (GV) of large oocytes of many vertebrate and invertebrate animals and also in the giant single-celled alga Acetabularia. These cells are all in prophase of the first meiotic division. Nevertheless, many meiotic cells do not develop LBCs, arguing that LBCs are not an essential feature of meiosis. LBCs probably represent the most active transcriptional state that can be attained by cells that must give rise to diploid progeny. Polyploidy permits cells to reach higher rates of transcription per nucleus but precludes a return to diploidy. In this sense, LBCs represent a relatively inefficient transcriptional compromise employed by large meiotic cells. These considerations help to explain why transcriptionally active GVs develop LBCs, but they do not explain why LBCs have never been seen in somatic cells, diploid or otherwise. If LBCs are truly limited to germ cells, then some of their unusual features may reflect reprogramming of the genome. If this is the case, LBCs provide unique opportunities to study reprogramming at the level of the individual transcription unit.

We have examined transcription loops on lampbrush chromosomes of the newt Notophthalmus by superresolution microscopy. Because of the favorable, essentially two-dimensional morphology of these loops, an average optical resolution in the x-y plane of about 50 nm was achieved. We analyzed the distribution of the multifunctional RNA-binding protein CELF1 on specific loops. CELF1 distribution is consistent with a model in which individual transcripts are tightly folded and hence closely packed against the loop axis.

We have identified novel nuclear bodies, which we call pearls, in the giant oocyte nuclei of Xenopus laevis and Xenopus tropicalis. Pearls are attached to the lampbrush chromosomes at specific loci that are transcribed by RNA polymerase III, and they disappear after inhibition of polymerase III activity. Pearls are enriched for small Cajal body-specific RNAs (scaRNAs), which are guide RNAs that modify specific nucleotides on splicing snRNAs. Surprisingly, snRNAs themselves are not present in pearls, suggesting that pearls are not functionally equivalent to Cajal bodies in other systems, which contain both snRNAs and scaRNAs. We suggest that pearls may function in the processing of RNA polymerase III transcripts, such as tRNA, 5S rRNA, and other short non-coding RNAs.

We previously demonstrated that sperm heads from amphibians (Xenopus and Rana) and zebrafish (Danio) could form giant lampbrush chromosomes when injected into the nucleus of amphibian oocytes. However, similar experiments with mammalian sperm heads were unsuccessful. Here, we describe a slightly modified procedure and demonstrate that human sperm heads can form giant lampbrush chromosomes when injected into the oocyte nucleus of the frog Xenopus laevis or the newt Notophthalmus viridescens. Human and other mammalian chromosomes do not form recognizable lampbrush chromosomes in their own oocytes or in any somatic cells. These experiments thus demonstrate that the lampbrush condition is an inducible state and that the amphibian oocyte nucleus contains all factors required to remodel the inactive chromatin of a mammalian sperm into a transcriptionally active state. They also demonstrate that absence of lampbrush chromosomes from human oocytes must relate to specific features of mammalian oogenesis, not to permanent genetic or epigenetic changes in the chromatin.

To compare nuclear and cytoplasmic RNA from a single cell type, free of cross-contamination, we studied the oocyte of the frog Xenopus tropicalis, a giant cell with an equally giant nucleus. We isolated RNA from manually dissected nuclei and cytoplasm of mature oocytes and subjected it to deep sequencing. Cytoplasmic mRNA consisted primarily of spliced exons derived from ∼6700 annotated genes. Nearly all of these genes were represented in the nucleus by intronic sequences. However, unspliced nascent transcripts were not detected. Inhibition of transcription or splicing for 1-2 d had little or no effect on the abundance of nuclear intronic sequences, demonstrating that they are unusually stable. RT-PCR analysis showed that these stable intronic sequences are transcribed from the coding strand and that a given intron can be processed into more than one molecule. Stable intronic sequence RNA (sisRNA) from the oocyte nucleus constitutes a new class of noncoding RNA. sisRNA is detectable by RT-PCR in samples of total RNA from embryos up to the mid-blastula stage, when zygotic transcription begins. Storage of sisRNA in the oocyte nucleus and its transmission to the developing embryo suggest that it may play important regulatory roles during oogenesis and/or early embryogenesis.

The immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (HA), which regularly changes its antigenic structure. Antibodies that target the highly conserved stem region of HA neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. Efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous influenza immunity may abrogate the induction of such broadly protective antibodies. We show here that prime-boost immunization can induce broadly neutralizing antibody responses in influenza-immune mice and ferrets that were previously infected or vaccinated. HA stem-directed antibodies were elicited in mice primed with a DNA vaccine and boosted with inactivated vaccine from H1N1 A/New Caledonia/20/1999 (1999 NC) HA regardless of preexposure. Similarly, gene-based vaccination with replication-defective adenovirus 28 (rAd28) and 5 (rAd5) vectors encoding 1999 NC HA elicited stem-directed neutralizing antibodies and conferred protection against unmatched 1934 and 2007 H1N1 virus challenge in influenza-immune ferrets. Indeed, previous exposure to certain strains could enhance immunogenicity: The strongest HA stem-directed immune response was observed in ferrets previously infected with a divergent 1934 H1N1 virus. These findings suggest that broadly neutralizing antibodies against the conserved stem region of HA can be elicited through vaccination despite previous influenza exposure, which supports the feasibility of developing stem-directed universal influenza vaccines for humans.

The RV144 trial demonstrated that an experimental AIDS vaccine can prevent human immunodeficiency virus type 1 (HIV-1) infection in humans. Because of its limited efficacy, further understanding of the mechanisms of preventive AIDS vaccines remains a priority, and nonhuman primate (NHP) models of lentiviral infection provide an opportunity to define immunogens, vectors, and correlates of immunity. In this study, we show that prime-boost vaccination with a mismatched SIV envelope (Env) gene, derived from simian immunodeficiency virus SIVmac239, prevents infection by SIVsmE660 intrarectally. Analysis of different gene-based prime-boost immunization regimens revealed that recombinant adenovirus type 5 (rAd5) prime followed by replication-defective lymphocytic choriomeningitis virus (rLCMV) boost elicited robust CD4 and CD8 T-cell and humoral immune responses. This vaccine protected against infection after repetitive mucosal challenge with efficacies of 82% per exposure and 62% cumulatively. No effect was seen on viremia in infected vaccinated monkeys compared to controls. Protection correlated with the presence of neutralizing antibodies to the challenge viruses tested in peripheral blood mononuclear cells. These data indicate that a vaccine expressing a mismatched Env gene alone can prevent SIV infection in NHPs and identifies an immune correlate that may guide immunogen selection and immune monitoring for clinical efficacy trials.

Recombinant adenovirus (rAd) vectors are being investigated as vaccine delivery vehicles in preclinical and clinical studies. rAds constructed from different serotypes differ in receptor usage, tropism, and ability to activate cells, aspects of which likely contribute to their different immunogenicity profiles. In this study, we compared the infectivity and cell stimulatory capacity of recombinant adenovirus serotype 5 (rAd5), recombinant adenovirus serotype 28 (rAd28), and recombinant adenovirus serotype 35 (rAd35) in association with their respective immunogenicity profiles. We found that rAd28 and rAd35 infected and led to the in vitro maturation and activation of both human and mouse dendritic cells more efficiently compared with rAd5. In stark contrast to rAd5, rAd28 and rAd35 induced production of IFN-α and stimulated IFN-related intracellular pathways. However, the in vivo immunogenicity of rAd28 and rAd35 was significantly lower than that of rAd5. Deletion of IFN-α signaling during vaccination with rAd28 and rAd35 vectors increased the magnitude of the insert-specific T cell response to levels induced by vaccination with rAd5 vector. The negative impact of IFN-α signaling on the magnitude of the T cell response could be overcome by increasing the vaccine dose, which was also associated with greater polyfunctionality and a more favorable long-term memory phenotype of the CD8 T cell response in the presence of IFN-α signaling. Taken together, our results demonstrate that rAd-induced IFN-α production has multiple effects on T cell immunogenicity, the understanding of which should be considered in the design of rAd vaccine vectors.