Tobacco Use in Adolescents With Disabilities: A Literature Review.

The use of tobacco products by adolescents has greatly increased in recent years. Adolescents with disabilities have demonstrated higher instances of e-cigarette and tobacco use in relation to their peers without disabilities. Repercussions for e-cigarette and tobacco use increase negative physical and health implications and financial which ultimately will further the gap for individuals with disabilities over time. It is argued that adolescents with disabilities are more susceptible to begin using tobacco and remain using tobacco which can lead to further use of addictive substances. In this paper, the researcher explained the use of tobacco within the adolescent population, specifically for individuals with disabilities, the impact of tobacco use for individuals with disabilities, reviewed previous studies on tobacco use for adolescents with disabilities, points to the need for educational policy reform, and stated certain recommendations for mitigating tobacco use in adolescents with disabilities, which may result in positive future outcomes. The literature review indicated that the targeted interventions in schools or peer groups reduces tobacco use in adolescents with disabilities.

A post-transcriptional regulon controlled by TtpA, the single tristetraprolin family member expressed in Dictyostelium discoideum.

Post-transcriptional processes mediated by mRNA binding proteins represent important control points in gene expression. In eukaryotes, mRNAs containing specific AU-rich motifs are regulated by binding of tristetraprolin (TTP) family tandem zinc finger proteins, which promote mRNA deadenylation and decay, partly through interaction of a conserved C-terminal CNOT1 binding (CNB) domain with CCR4-NOT protein complexes. The social ameba Dictyostelium discoideum shared a common ancestor with humans more than a billion years ago, and expresses only one TTP family protein, TtpA, in contrast to three members expressed in humans. Evaluation of ttpA null-mutants identified six transcripts that were consistently upregulated compared to WT during growth and early development. The 3'-untranslated regions (3'-UTRs) of all six 'TtpA-target' mRNAs contained multiple TTP binding motifs (UUAUUUAUU), and one 3'-UTR conferred TtpA post-transcriptional stability regulation to a heterologous mRNA that was abrogated by mutations in the core TTP-binding motifs. All six target transcripts were upregulated to similar extents in a C-terminal truncation mutant, in contrast to less severe effects of analogous mutants in mice. All six target transcripts encoded probable membrane proteins. In Dictyostelium, TtpA may control an 'RNA regulon', where a single RNA binding protein, TtpA, post-transcriptionally co-regulates expression of several functionally related proteins.

Identification of Alternative Polyadenylation in Cyanidioschyzon merolae Through Long-Read Sequencing of mRNA.

Alternative polyadenylation (APA) is widespread among metazoans and has been shown to have important impacts on mRNA stability and protein expression. Beyond a handful of well-studied organisms, however, its existence and consequences have not been well investigated. We therefore turned to the deep-branching red alga, Cyanidioschyzon merolae, to study the biology of polyadenylation in an organism highly diverged from humans and yeast. C. merolae is an acidothermophilic alga that lives in volcanic hot springs. It has a highly reduced genome (16.5 Mbp) and has lost all but 27 of its introns and much of its splicing machinery, suggesting that it has been under substantial pressure to simplify its RNA processing pathways. We used long-read sequencing to assess the key features of C. merolae mRNAs, including splicing status and polyadenylation cleavage site (PAS) usage. Splicing appears to be less efficient in C. merolae compared with yeast, flies, and mammalian cells. A high proportion of transcripts (63%) have at least two distinct PAS's, and 34% appear to utilize three or more sites. The apparent polyadenylation signal UAAA is used in more than 90% of cases, in cells grown in both rich media or limiting nitrogen. Our documentation of APA for the first time in this non-model organism highlights its conservation and likely biological importance of this regulatory step in gene expression.

It takes two (Las1 HEPN endoribonuclease domains) to cut RNA correctly.

The ribosome biogenesis factor Las1 is an essential endoribonuclease that is well-conserved across eukaryotes and a newly established member of the higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain-containing nuclease family. HEPN nucleases participate in diverse RNA cleavage pathways and share a short HEPN nuclease motif (RφXXXH) important for RNA cleavage. Most HEPN nucleases participate in stress-activated RNA cleavage pathways; Las1 plays a fundamental role in processing pre-rRNA. Underscoring the significance of Las1 function in the cell, mutations in the human LAS1L (LAS1-like) gene have been associated with neurological dysfunction. Two juxtaposed HEPN nuclease motifs create Las1's composite nuclease active site, but the roles of the individual HEPN motif residues are poorly defined. Here using a combination of in vivo experiments in Saccharomyces cerevisiae and in vitro assays, we show that both HEPN nuclease motifs are required for Las1 nuclease activity and fidelity. Through in-depth sequence analysis and systematic mutagenesis, we determined the consensus HEPN motif in the Las1 subfamily and uncovered its canonical and specialized elements. Using reconstituted Las1 HEPN-HEPN' chimeras, we defined the molecular requirements for RNA cleavage. Intriguingly, both copies of the Las1 HEPN motif were important for nuclease function, revealing that both HEPN motifs participate in coordinating the RNA within the Las1 active site. We also established that conformational flexibility of the two HEPN domains is important for proper nuclease function. The results of our work reveal critical information about how dual HEPN domains come together to drive Las1-mediated RNA cleavage.

Building the perfect curse word: A psycholinguistic investigation of the form and meaning of taboo words.

Taboo words represent a potent subset of natural language. It has been hypothesized that "tabooness" reflects an emergent property of negative valence and high physiological arousal of word referents. Many taboo words (e.g., dick, shit) are indeed consistent with this claim. Nevertheless, American English is also rife with negatively valenced, highly arousing words the usage of which is not socially condemned (e.g., cancer, abortion, welfare). We evaluated prediction of tabooness of single words and novel taboo compound words from a combination of phonological, lexical, and semantic variables (e.g., semantic category, word length). For single words, physiological arousal and emotional valence strongly predicted tabooness with additional moderating contributions from form (phonology) and meaning (semantic category). In Experiment 2, raters judged plausibility for combinations of common nouns with taboo words to form novel taboo compounds (e.g., shitgibbon). A mixture of formal (e.g., ratio of stop consonants, length) and semantic variables (e.g., ± receptacle, ± profession) predicted the quality of novel taboo compounding. Together, these studies provide complementary evidence for interactions between word form and meaning and an algorithmic prediction of tabooness in American English. We discuss applications for models of taboo word representation.

Importance of the Conserved Carboxyl-Terminal CNOT1 Binding Domain to Tristetraprolin Activity In Vivo.

Tristetraprolin (TTP) is an anti-inflammatory protein that modulates the stability of certain cytokine/chemokine mRNAs. After initial high-affinity binding to AU-rich elements in 3' untranslated regions of target mRNAs, mediated through its tandem zinc finger (TZF) domain, TTP promotes the deadenylation and ultimate decay of target transcripts. These transcripts and their encoded proteins accumulate abnormally in TTP knockout (KO) mice, leading to a severe inflammatory syndrome. To assess the importance of the highly conserved C-terminal CNOT1 binding domain (CNBD) of TTP to the TTP deficiency phenotype in mice, we created a mouse model in which TTP lacked its CNBD. CNBD deletion mice exhibited a less severe phenotype than the complete TTP KO mice. In macrophages, the stabilization of target transcripts seen in KO mice was partially normalized in the CNBD deletion mice. In cell-free experiments, recombinant TTP lacking its CNBD could still activate target mRNA deadenylation by purified recombinant Schizosaccharomyces pombe CCR4/NOT complexes, although to a lesser extent than full-length TTP. Thus, TTP lacking its CNBD can still act to promote target mRNA instability in vitro and in vivo These data have implications for TTP family members throughout the eukarya, since species from all four kingdoms contain proteins with linked TZF and CNOT1 binding domains.

The tandem zinc finger RNA binding domain of members of the tristetraprolin protein family.

Tristetraprolin (TTP), the prototype member of the protein family of the same name, was originally discovered as the product of a rapidly inducible gene in mouse cells. Development of a knockout (KO) mouse established that absence of the protein led to a severe inflammatory syndrome, due in part to elevated levels of tumor necrosis factor (TNF). TTP was found to bind directly and with high affinity to specific AU-rich sequences in the 3'-untranslated region of the TNF mRNA. This initial binding led to promotion of TNF mRNA decay and inhibition of its translation. Many additional TTP target mRNAs have since been identified, some of which are cytokines and chemokines involved in the inflammatory response. There are three other proteins in the mouse with similar activities and domain structures, but whose KO phenotypes are remarkably different. Moreover, proteins with similar domain structures and activities have been found throughout eukaryotes, demonstrating that this protein family arose from an ancient ancestor. The defining characteristic of this protein family is the tandem zinc finger (TZF) domain, a 64 amino acid sequence with many conserved residues that is responsible for the direct RNA binding. We discuss here many aspects of this protein domain that have been elucidated since the original discovery of TTP, including its sequence conservation throughout eukarya; its apparent continued evolution in some lineages; its functional dependence on many key conserved residues; its "interchangeability" among evolutionarily distant species; and the evidence that RNA binding is required for the physiological functions of the proteins. This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein-RNA Recognition RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

Increasing contraception use among women receiving teratogenic medications in a rheumatology clinic.

Teratogenic medications are often prescribed to women of childbearing age with autoimmune diseases. Literature suggests that appropriate use of contraception among these women is low, potentially resulting in high-risk unintended pregnancies. Preliminary review in our clinic showed suboptimal documentation of women's contraceptive use. We therefore designed a quality improvement initiative to target three process measures: documentation of contraception usage and type, contraception counselling and provider action after counselling. We reviewed charts of rheumatology clinic female patients aged 18-45 over the course of 10 months; for those who were on teratogenic medications (methotrexate, leflunomide, mycophenolate and cyclophosphamide), we looked for evidence of documentation of contraception use. We executed multiple plan-do-study-act (PDSA) cycles to develop and evaluate interventions, which centred on interprofessional provider education, modification of electronic medical record (EMR) templates, periodic provider reminders, patient screening questionnaires and frequent feedback to providers on performance. Among eligible patients (n=181), the baseline rate of documentation of contraception type was 46%, the rate of counselling was 30% and interventions after counselling occurred in 33% of cases. Averaged intervention data demonstrated increased provider performance in all three domains: documentation of contraception type increased to 64%, counselling to 45% and provider action to 46%. Of the patients with documented contraceptives, 50% used highly effective, 27% used effective and 23% used ineffective contraception methods. During this project, one unintentional pregnancy occurred in a patient on methotrexate not on contraception. Our interventions improved three measures related to contraception counselling and documentation, but there remains a need for ongoing quality improvement efforts in our clinic. This high-risk population requires increased provider engagement to improve contraception compliance, coupled with system-wide EMR changes to increase sustainability.

An Ancient Family of RNA-Binding Proteins: Still Important!

RNA-binding proteins are important modulators of mRNA stability, a crucial process that determines the ultimate cellular levels of mRNAs and their encoded proteins. The tristetraprolin (TTP) family of RNA-binding proteins appeared early in the evolution of eukaryotes, and has persisted in modern eukaryotes. The domain structures and biochemical functions of family members from widely divergent lineages are remarkably similar, but their mRNA 'targets' can be very different, even in closely related species. Recent gene knockout studies in species as distantly related as plants, flies, yeasts, and mice have demonstrated crucial roles for these proteins in a wide variety of physiological processes. Inflammatory and hematopoietic phenotypes in mice have suggested potential therapeutic approaches for analogous human disorders.

Functional equivalence of an evolutionarily conserved RNA binding module.

Members of the tristetraprolin (TTP) family of proteins participate in the regulation of mRNA turnover after initially binding to AU-rich elements in target mRNAs. Related proteins from most groups of eukaryotes contain a conserved tandem zinc finger (TZF) domain consisting of two closely spaced, similar CCCH zinc fingers that form the primary RNA binding domain. There is considerable sequence variation within the TZF domains from different family members within a single organism and from different organisms, raising questions about sequence-specific effects on RNA binding and decay promotion. We hypothesized that TZF domains from evolutionarily distant species are functionally interchangeable. The single family member expressed in the fission yeast Schizosaccharomyces pombe, Zfs1, promotes the turnover of several dozen transcripts, some of which are involved in cell-cell interactions. Using knockin techniques, we replaced the TZF domain of S. pombe Zfs1 with the equivalent domains from human TTP and the single family member proteins expressed in the silkworm Bombyx mori, the pathogenic yeast Candida guilliermondii, and the plant Chromolaena odorata. We found that the TZF domains from these widely disparate species could completely substitute for the native S. pombe TZF domain, as determined by measurement of target transcript levels and the flocculation phenotype characteristic of Zfs1 deletion. Recombinant TZF domain peptides from several of these species bound to an AU-rich RNA oligonucleotide with comparably high affinity. We conclude that the TZF domains from TTP family members in these evolutionarily widely divergent species are functionally interchangeable in mRNA binding and decay.

Post-transcriptional regulation of transcript abundance by a conserved member of the tristetraprolin family in Candida albicans.

Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins bind to AU-rich regions in target mRNAs, leading to their deadenylation and decay. Family members in Saccharomyces cerevisiae influence iron metabolism, whereas the single protein expressed in Schizosaccharomyces pombe, Zfs1, regulates cell-cell interactions. In the human pathogen Candida albicans, deep sequencing of mutants lacking the orthologous protein, Zfs1, revealed significant increases (> 1.5-fold) in 156 transcripts. Of these, 113 (72%) contained at least one predicted TTP family member binding site in their 3'UTR, compared with only 3 of 56 (5%) down-regulated transcripts. The zfs1Δ/Δ mutant was resistant to 3-amino-1,2,4-triazole, perhaps because of increased expression of the potential target transcript encoded by HIS3. Sequences of the proteins encoded by the putative Zfs1 targets were highly conserved among other species within the fungal CTG clade, while the predicted Zfs1 binding sites in these mRNAs often 'disappeared' with increasing evolutionary distance from the parental species. C. albicans Zfs1 bound to the ideal mammalian TTP binding site with high affinity, and Zfs1 was associated with target transcripts after co-immunoprecipitation. Thus, the biochemical activities of these proteins in fungi are highly conserved, but Zfs1-like proteins may target different transcripts in each species.

Competencies for addressing gender and power in couple therapy: a socio emotional approach.

Power imbalances between partners are intrinsic to relationship distress and intricately connected to emotional experience, couple communication processes, and socio cultural contexts such as gender. The ability to work with the power dynamics between partners is thus critical to the practice of couple therapy. However, few practical guidelines for dealing with this issue are available. The authors present seven clinical competencies regarding gender and power issues that they identified by examining their own work: (a) identify enactments of cultural discourse, (b) attune to underlying socio cultural emotion, (c) name underlying power processes, (d) facilitate relational safety, (e) foster mutual attunement, (f) create a model of equality, and (g) facilitate shared relationship responsibility. Each competency is illustrated through a case example. The competencies represent an over-arching guide to practice that may be integrated with other clinical approaches and is particularly useful for training and supervision.

Exposure to websites that encourage self-harm and suicide: prevalence rates and association with actual thoughts of self-harm and thoughts of suicide in the United States.

This article provides 12-month prevalence rates of youth exposure to websites which encourage self-harm or suicide and examines whether such exposure is related to thoughts of self-harm and thoughts of suicide in the past 30 days. Data were collected via telephone from a nationally representative survey of 1560 Internet-using youth, ages 10-17 residing in the United States. One percent (95% CI: 0.5%, 1.5%) of youth reported visiting a website that encouraged self-harm or suicide. Youth who visited such websites were seven times more likely to say they had thought about killing themselves; and 11 times more likely to think about hurting themselves, even after adjusting for several known risk factors for thoughts of self-harm and thoughts of suicide. Given that youth thinking about self-harm and suicide are more likely to visit these sites, they may represent an opportunity for identification of youth in need of crisis intervention.

Testing the Index of Problematic Online Experiences (I-POE) with a national sample of adolescents.

This article assesses the utility of the Index of Problematic Online Experiences (I-POE) in a national sample of adolescents in the United States. The study was based on a cross-sectional national telephone survey of 1560 Internet users, ages 10 through 17. Data were collected between August, 2010 and January, 2011. The I-POE is an 18-item binary response index which can be used to assess problematic internet use across multiple behaviors and activities. Exploratory and confirmatory factor analysis supported a revised index with two factors: a 9-item "excessive use" scale and a 9-item "online social and communication problems" scale among this population. The I-POE showed favorable psychometric properties including adequate internal consistency for the overall scale and for the two subscales. Scores correlate with offline emotional and behavioral difficulties and the I-POE could have value for use as a part of broad mental health assessment procedures in clinical or school settings.

Posttranscriptional regulation of cell-cell interaction protein-encoding transcripts by Zfs1p in Schizosaccharomyces pombe.

Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins can bind directly to AU-rich elements in mRNAs and promote transcript deadenylation and decay. The yeast Schizosaccharomyces pombe expresses a single TTP family member, Zfs1p. In this study, we identified probable Zfs1p target mRNAs by comparing transcript levels in wild-type yeast and zfs1Δ mutants, using deep sequencing and microarray approaches. We also used direct RNA sequencing to determine polyadenylation site locations and to confirm the presence of potential Zfs1p target sequences within the target mRNA. These studies identified a set of transcripts containing potential Zfs1p binding sites that accumulated significantly in the zfs1Δ mutants; a subset of these transcripts decayed more slowly in the zfs1Δ mutants and bound directly to Zfs1p in coimmunoprecipitation assays. One apparent direct target encodes the transcription factor Cbf12p, which is known to increase cell-cell adhesion and flocculation when overexpressed. Studies of zfs1Δ cbf12Δ double mutants demonstrated that the increased flocculation seen in zfs1Δ mutants is due, at least in part, to a direct effect on the turnover of cbf12 mRNA. These data suggest that Zfs1p can both directly and indirectly regulate the levels of transcripts involved in cell-cell adhesion in this species.

Exploring the role of the internet in juvenile prostitution cases coming to the attention of law enforcement.

This exploratory analysis examines the role of the Internet in juvenile prostitution cases coming to the attention of law enforcement. The National Juvenile Prostitution Study (N-JPS) collected information from a national sample of law enforcement agencies about the characteristics of juvenile prostitution cases. In comparison to non-Internet juvenile prostitution cases, Internet juvenile prostitution cases involved younger juveniles and police were more likely to treat juveniles as victims rather than offenders. In addition, these cases were significantly more likely to involve a family or acquaintance exploiter. This analysis suggests that the role of the Internet may impact legal and social service response to juveniles involved in prostitution. In addition, it highlights the need for interventions that acknowledge the vulnerabilities of youth involved in this type of commercial sexual exploitation.

CCR7/CCL19 controls expression of EDG-1 in T cells.

T lymphocytes circulate between the blood, tissues, and lymph. These T cells carry out immune functions, using the C-C chemokine receptor 7 (CCR7) and its cognate ligands, CCL19 and CCL21, to enter and travel through the lymph nodes. Distinct roles for each ligand in regulating T lymphocyte trafficking have remained elusive. We report that in the human T cell line HuT78 and in primary murine T lymphocytes, signaling from CCR7/CCL19 leads to increased expression and phosphorylation of extracellular signal-regulated kinase 5 (ERK5) within eight hours of stimulation. Within 48-72 h we observed peak levels of endothelial differentiation gene 1 (EDG-1), which mediates the egress of T lymphocytes from lymph nodes. The increased expression of EDG-1 was preceded by up-regulation of its transcription factor, Krüppel-like factor 2 (KLF-2). To determine the cellular effect of disrupting ERK5 signaling from CCR7, we examined the migration of ERK5(flox/flox)/Lck-Cre murine T cells to EDG-1 ligands. While CCL19-stimulated ERK5(flox/flox) naïve T cells showed increased migration to EDG-1 ligands at 48 h, the migration of ERK5(flox/flox)/Lck-Cre T cells remained at a basal level. Accordingly, we define a novel signaling pathway that controls EDG-1 up-regulation following stimulation of T cells by CCR7/CCL19. This is the first report to link the two signaling events that control migration through the lymph nodes: CCR7 mediates entry into the lymph nodes and EDG-1 signaling controls their subsequent exit.

Identification of robust hypoxia biomarker candidates from fin of medaka (Oryzias latipes).

Aquatic hypoxia caused by organic pollution and eutrophication is a pressing worldwide water pollution problem. Better methods for monitoring oxygen levels are needed to assist efforts to maintain and protect the health of natural aquatic environments. In this project, we used a Japanese ricefish (medaka, Oryzias latipes) 8K oligonucleotide array as a platform to identify potential hypoxic biomarkers in different organs (fin, gill, liver and brain) upon exposure to hypoxia. The microarray results were validated by qRT-PCR employing a subset of candidate biomarkers. Interestingly, the largest number and most significant of hypoxia responding array features were detected in hypoxia exposed fin tissues. We identified 173 array features that exhibited a significant response (over 2 fold change in expression) upon exposure to hypoxic conditions and validated a subset of these by quantitative RT-PCR. These gene targets were subjected to annotation and gene ontology mining. Positively identifiable gene targets that may be useful for development of a rapid and accurate biomarker test using fin clips are discussed in relation to previous reports on hypoxia responsive genes.

Anti-synthetase syndrome presenting as cryptogenic organizing pneumonia.

Interstitial lung disease (ILD) is a unique group of lung diseases that can be associated with inflammatory conditions, such as polymyositis-dermatomyositis (PM-DM). Presentation of PM-DM with ILD is not uncommon but clinical and radiological features can be similar to other conditions (e.g. atypical pneumonia) and can be challenging to diagnose. Delayed diagnosis of PM-DM can be associated with progression of pulmonary involvement and potentially increase morbidity. We report a patient presenting with pulmonary symptoms who had positive anti-Jo-1 antibodies and cryptogenic organizing pneumonia features on biopsy, which is a rare reported finding.