Reliability of the sliding scale for collecting affective responses to words.

Warriner, Shore, Schmidt, Imbault, and Kuperman, Canadian Journal of Experimental Psychology, 71; 71-88 (2017) have recently proposed a slider task in which participants move a manikin on a computer screen toward or further away from a word, and the distance (in pixels) is a measure of the word's valence. Warriner, Shore, Schmidt, Imbault, and Kuperman, Canadian Journal of Experimental Psychology, 71; 71-88 (2017) showed this task to be more valid than the widely used rating task, but they did not examine the reliability of the new methodology. In this study we investigated multiple aspects of this task's reliability. In Experiment 1 (Exps. 1.1-1.6), we showed that the sliding scale has high split-half reliability (r = .868 to .931). In Experiment 2, we also showed that the slider task elicits consistent repeated responses both within a single session (Exp. 2: r = .804) and across two sessions separated by one week (Exp. 3: r = .754). Overall, the slider task, in addition to having high validity, is highly reliable.

A single baseline ultrasound assessment of fibroid presence and size is strongly predictive of future uterine procedure: 8-year follow-up of randomly sampled premenopausal women aged 35-49 years.

STUDY QUESTION: How well can a single baseline ultrasound assessment of fibroid burden (presence or absence of fibroids and size of largest, if present) predict future probability of having a major uterine procedure? SUMMARY ANSWER: During an 8-year follow-up period, the risk of having a major uterine procedure was 2% for those without fibroids and increased with fibroid size for those with fibroids, reaching 47% for those with fibroids ≥ 4 cm in diameter at baseline. WHAT IS KNOWN ALREADY: Uterine fibroids are a leading indication for hysterectomy. However, when fibroids are found, there are few available data to help clinicians advise patients about disease progression. STUDY DESIGN, SIZE, DURATION: Women who were 35-49 years old were randomly selected from the membership of a large urban health plan; 80% of those determined to be eligible were enrolled and screened with ultrasound for fibroids ≥ 0.5 cm in diameter. African-American and white premenopausal participants who responded to at least one follow-up interview (N = 964, 85% of those eligible) constituted the study cohort. During follow-up (5822 person-years), participants self-reported any major uterine procedure (67% hysterectomies). Life-table analyses and Cox regression (with censoring for menopause) were used to estimate the risk of having a uterine procedure for women with no fibroids, small (<2 cm in diameter), medium (2-3.9 cm), and large fibroids (≥ 4 cm). Differences between African-American and white women, importance of a clinical diagnosis of fibroids prior to study enrollment, and the impact of submucosal fibroids on risk were investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS: There was a greater loss to follow-up for African-Americans than whites (19 versus 11%). For those with follow-up data, 64% had fibroids at baseline, 33% of whom had had a prior diagnosis. Of those with fibroids, 27% had small fibroids (<2 cm in diameter), 46% had medium (largest fibroid 2-3.9 cm in diameter), and 27% had large fibroids (largest ≥ 4 cm in diameter). Twenty-one percent had at least one submucosal fibroid. MAIN RESULTS AND THE ROLE OF CHANCE: Major uterine procedures were reported by 115 women during follow-up. The estimated risk of having a procedure in any given year of follow-up for those with fibroids compared with those without fibroids increased markedly with fibroid-size category (from 4-fold, confidence interval (CI) (1.4-11.1) for the small fibroids to 10-fold, CI (4.4-24.8) for the medium fibroids, to 27-fold, CI (11.5-65.2) for the large fibroids). This influence of fibroid size on risk did not differ between African-Americans and whites (P-value for interaction = 0.88). Once fibroid size at enrollment was accounted for, having a prior diagnosis at the time of ultrasound screening was not predictive of having a procedure. Exclusion of women with a submucosal fibroid had little influence on the results. The 8-year risk of a procedure based on lifetable analyses was 2% for women with no fibroids, 8, 23, and 47%, respectively, for women who had small, medium or large fibroids at enrollment. Given the strong association of fibroid size with subsequent risk of a procedure, these findings are unlikely to be due to chance. LIMITATIONS, REASONS FOR CAUTION: Despite a large sample size, the number of women having procedures during follow-up was relatively small. Thus, covariates such as BMI, which were not important in our analyses, may have associations that were too small to detect with our sample size. Another limitation is that the medical procedures were self-reported. However, we attempted to retrieve medical records when participants agreed, and 77% of the total procedures reported were verified. Our findings are likely to be generalizable to other African-American and white premenopausal women in their late 30s and 40s, but other ethnic groups have not been studied. WIDER IMPLICATIONS OF THE FINDINGS: Though further studies are needed to confirm and extend the results, our findings provide an initial estimate of disease progression that will be helpful to clinicians and their patients.

Practices and perspectives on advanced diagnostic and interventional bronchoscopy among pediatric pulmonologists in the United States.

INTRODUCTION: Advanced diagnostic bronchoscopy includes endobronchial ultrasound (EBUS) guided transbronchial lung and lymph node biopsies, CT navigation and robotic bronchoscopy. Interventional bronchoscopy refers to procedures performed for therapeutic purposes such as balloon dilation of the airway, tissue debulking, cryotherapy, removal of foreign bodies and insertion of endobronchial valves [1]. For adult patients, these procedures are standard of care [2, 3]. Despite a lack of formalized training, there are numerous case reports and case series describing the use of advanced diagnostic and interventional bronchoscopy techniques in children. The safety and feasibility of EBUS-TBNA, cryotherapy techniques, endobronchial valves among other techniques have been demonstrated in these publications [1, 4-9]. METHODS: We sought to better understand the current practices and perspectives on interventional and advanced bronchoscopy among pediatric pulmonologists through surveys sent to pediatric teaching hospitals across the United States. RESULTS: We received 43 responses representing 28 programs from 25 states. The highest bronchoscopy procedure volume occurred in the 0-5 years age group. Among our respondents, 31% self-identified as a pediatric interventional/advanced bronchoscopist. 79% believe that advanced and interventional training is feasible in pediatric pulmonology and 77% believe it should be offered to pediatric pulmonary fellows. DISCUSSION: This is the first study to characterize current practices and perspectives regarding advanced diagnostic and interventional bronchoscopy procedures among pediatric pulmonologists in the United States. Pediatric interventional pulmonology (IP) is in its infancy and its beginnings echo those of the adult IP where only certain centers were performing these procedures.

Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study.

OBJECTIVES: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Príbram region, Czech Republic. METHODS: A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. RESULTS: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. CONCLUSIONS: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out.

Cingulin contains globular and coiled-coil domains and interacts with ZO-1, ZO-2, ZO-3, and myosin.

We characterized the sequence and protein interactions of cingulin, an M(r) 140-160-kD phosphoprotein localized on the cytoplasmic surface of epithelial tight junctions (TJ). The derived amino acid sequence of a full-length Xenopus laevis cingulin cDNA shows globular head (residues 1-439) and tail (1,326-1,368) domains and a central alpha-helical rod domain (440-1,325). Sequence analysis, electron microscopy, and pull-down assays indicate that the cingulin rod is responsible for the formation of coiled-coil parallel dimers, which can further aggregate through intermolecular interactions. Pull-down assays from epithelial, insect cell, and reticulocyte lysates show that an NH(2)-terminal fragment of cingulin (1-378) interacts in vitro with ZO-1 (K(d) approximately 5 nM), ZO-2, ZO-3, myosin, and AF-6, but not with symplekin, and a COOH-terminal fragment (377-1,368) interacts with myosin and ZO-3. ZO-1 and ZO-2 immunoprecipitates contain cingulin, suggesting in vivo interactions. Full-length cingulin, but not NH(2)-terminal and COOH-terminal fragments, colocalizes with endogenous cingulin in transfected MDCK cells, indicating that sequences within both head and rod domains are required for TJ localization. We propose that cingulin is a functionally important component of TJ, linking the submembrane plaque domain of TJ to the actomyosin cytoskeleton.

Transcriptional regulation in the yeast life cycle.

The transition from haploid to diploid in homothallic yeast involves a defined sequence of events which are regulated at the level of transcription. Transcription factors encoded by SWI genes activate the HO endonuclease gene at a precise stage in the cell cycle of mother cells. The HO endonuclease initiates a transposition event which activates genes of the opposite mating type by causing them to move away from a silencer element. The activated mating type genes then regulate genes involved in cell signaling such as the mating type-specific pheromones and their receptors. Since HO is only activated in one of the sister cells after division (the mother), adjacent cells of opposite mating type are generated which respond to each others' secreted pheromones by inducing genes involved in conjugation. This leads to the formation of a diploid in which many of the genes involved in mating and mating-type switching become repressed due to the heterozygosity of the mating-type locus. This article summarizes what is known about these transcriptional controls and discusses possible parallels in higher eukaryotes.

Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length.

The yeast protein RAP1, initially described as a transcriptional regulator, binds in vitro to sequences found in a number of seemingly unrelated genomic loci. These include the silencers at the transcriptionally repressed mating-type genes, the promoters of many genes important for cell growth, and the poly[(cytosine)1-3 adenine] [poly(C1-3A)] repeats of telomeres. Because RAP1 binds in vitro to the poly(C1-3A) repeats of telomeres, it has been suggested that RAP1 may be involved in telomere function in vivo. In order to test this hypothesis, the telomere tract lengths of yeast strains that contained conditionally lethal (ts) rap1 mutations were analyzed. Several rap1ts alleles reduced telomere length in a temperature-dependent manner. In addition, plasmids that contain small, synthetic telomeres with intact or mutant RAP1 binding sites were tested for their ability to function as substrates for poly(C1-3A) addition in vivo. Mutations in the RAP1 binding sites reduced the efficiency of the addition reaction.

A protein-counting mechanism for telomere length regulation in yeast.

In the yeast Saccharomyces cerevisiae, telomere elongation is negatively regulated by the telomere repeat-binding protein Rap1p, such that a narrow length distribution of telomere repeat tracts is observed. This length regulation was shown to function independently of the orientation of the telomere repeats. The number of repeats at an individual telomere was reduced when hybrid proteins containing the Rap1p carboxyl terminus were targeted there by a heterologous DNA-binding domain. The extent of this telomere tract shortening was proportional to the number of targeted molecules, consistent with a feedback mechanism of telomere length regulation that can discriminate the precise number of Rap1p molecules bound to the chromosome end.

Urinary lithiasis in childhood in the Bristol clinical area.

A series of 59 consecutive cases of urinary calculi in childhood is presented, being acquired from one local area (Bristol). These children were treated from 1950 to 1973. The peak presentation was in the 2nd and 3rd year of life, with a secondary peak in the 10th year. Anatomical (39%), metabolic (8.5%) or primary infective abnormalities (29%) were demonstrable, but 22% had to be left in an unsatisfactory "idiopathic classification''. The overall recurrence rate of 7% was reduced to 3.5% when those patients with cystinuria were excluded. The local water supply areas have been studied and a tentative association is suggested between patients and their environment when they live in an area where the water is not only hard but also alkaline (pHgreater than 8).

Eye Tracking Effort Expenditure and Autonomic Arousal to Social and Circumscribed Interest Stimuli in Autism Spectrum Disorder.

The social communicative deficits and repetitive behaviours seen in Autism Spectrum Disorder (ASD) may be affected by altered stimulus salience and reward attribution. The present study used eye tracking and a behavioural measure to index effort expenditure, arousal, and attention, during viewing of images depicting social scenes and subject-specific circumscribed interests in a group of 10 adults with ASD (mean age 25.4 years) and 19 typically-developing controls (mean age 20.7 years) Split-plot and one-way repeated measures ANOVAs were used to explore results. A significant difference between the ASD and control group was found in the amount of effort expended to view social and circumscribed images. The ASD group also displayed significant differences in pupillary response to social and circumscribed images, indicative of changes in autonomic arousal. Overall, the results support the social motivation hypothesis in ASD (Chevallier et al., Trends Cogn Sci 16(4):231-239, 2012) and suggest a role for autonomic arousal in the ASD symptom dyad.

Telomeric chromatin: replicating and wrapping up chromosome ends.

Recent advances in our understanding of the specialized chromatin structure at telomeres, the ends of eukaryotic chromosomes, have focused on three separate areas: replication of telomeres through the coordinated action of conventional DNA polymerases and the telomerase enzyme, protection of the chromosome end from DNA damage checkpoint sensors and DNA-repair processes, and the discovery of a novel deacetylase enzyme (Sir2p) required for the establishment and maintenance of telomeric heterochromatin. Although the number of proteins and the complexity of their interactions at telomeres continues to grow, a picture of at least some of the major players and mechanisms underlying telomere replication, end 'capping' and chromatin assembly is beginning to emerge.

Anomalous left coronary artery from the pulmonary artery (ALCAPA) diagnosed in adulthood: Varied clinical presentation, therapeutic approach and outcome.

INTRODUCTION: The diagnosis of ALCAPA syndrome is sporadic in adulthood, of the limited cases in the literature most are incidental or without symptoms. There is a broad spectrum of clinical manifestations of ALCAPA syndrome however, including sudden cardiac death. CASES: We present herewith a series of 12 consecutive patients with ALCAPA, all diagnosed in adulthood (between 18 and 73 years of age). Five patients developed symptoms (breathlessness) after the fourth decade of life, 3 were undiagnosed despite a history of previous mitral valve repair, one presented with heart failure, one with resuscitated cardiac arrest, whereas two patients were asymptomatic. We review in this paper, the clinical history, diagnostic approach and therapeutic choices of ALCAPA syndrome. CONCLUSION: ALCAPA syndrome is not confined to childhood, late diagnosis in adulthood has a varied clinical presentation. ALCAPA syndrome should be particularly considered as a potential, albeit uncommon cause of mitral regurgitation and/or dilated cardiomyopathy.

Genetic recombination: sex-change operations in yeast.

The 'directionality' of mating-type switching in building yeast is determined by mechanisms that regulate genetic recombination along the whole left arm of chromosome III. In MATa cells, a cis-acting 'recombinational enhancer' activates this entire region, while in MATalpha cells the enhancer is turned off by the alpha2 repressor.

Transcriptional silencing: replication redux.

Recent studies indicate that, contrary to long-held belief, DNA replication does not have a direct role in transcriptional silencing, but progression through S phase of the cell cycle is nevertheless required for the establishment of silent chromatin.

Aging. Silence is golden.

A pioneering genetic analysis of aging in yeast has revealed that a protein complex known to play an essential role in transcriptional silencing at mating-type loci and telomeres also controls aging and stress resistance.

Cellular senescence: lessons from yeast for human aging?

Recent results point to an important role for the nucleolus in the senescence of yeast cells. A further report suggests that the formation and preferential accumulation in mother cells of extrachromosomal rDNA circles is a cause of aging in yeast; this may be an ancient and conserved mechanism of senescence.

Yeast Ku protein plays a direct role in telomeric silencing and counteracts inhibition by rif proteins.

Yku70p/Yku80p, the yeast Ku protein homologue, is a DNA end-binding heterodimer involved in non-homologous end joining. It also binds to telomeres, where it plays an important role in the maintenance of telomeric DNA structure [1] [2] [3] [4] [5]. Ku protein, together with Rap1p, a telomeric DNA (TG(1-3) repeat)-binding protein, is also required to initiate transcriptional silencing, or telomere-position effect (TPE). Here, we provide evidence for a direct role of Ku in TPE, which is most likely to be in either the recruitment or activation of Sir4 protein at the telomere. Surprisingly, however, the essential role of Ku in TPE is to overcome the inhibitory effect of two Rap1p-interacting proteins, Rif1p and Rif2p, both of which also play an important role in telomere length regulation [6] [7]. Previous studies showed that Rif and Sir proteins compete for binding to the carboxyl terminus of Rap1p [7] [8] [9]. In the absence of this competition, for example, when RIF genes are mutated, Ku is no longer necessary for TPE, whereas the Rap1p carboxyl terminus is still absolutely required. We show that Rif1p is localized to telomeres, indicating that its inhibitory effect on TPE is direct. Our data implicate a role for Ku in the competition between Sir and Rif proteins for access to the telomeric array of Rap1p molecules, which results in a balance between telomeric silencing and telomere length control.

RAP1: a protean regulator in yeast.

The yeast protein RAP1 is a sequence-specific DNA-binding protein that binds to many promoters, to two elements that silence mating-type genes, and to [(C)1-3A]n tracts at telomeres. RAP1 is essential for cell viability and can function as either an activator or a repressor of transcription, depending upon the context of its binding site. Recent experiments suggest that its function may be determined by different sets of protein-protein interactions at promoters and silencers. At the ends of chromosomes, RAP1 plays an important role in both silencing (telomere position effect) and telomere structure.

Crystal structure of the TCR co-receptor CD8alphaalpha in complex with monoclonal antibody YTS 105.18 Fab fragment at 2.88 A resolution.

The CD8 glycoprotein functions as an essential element in the control of T-cell selection, maturation and the TCR-mediated response to peptide antigen. CD8 is expressed as both heterodimeric CD8alphabeta and homodimeric CD8alphaalpha isoforms, which have distinct physiological roles and exhibit tissue-specific expression patterns. CD8alphaalpha has previously been crystallized in complex with class I pMHC and, more recently, with the mouse class Ib thymic leukemia antigen (TL). Here, we present the crystal structure of a soluble form of mouse CD8alphaalpha in complex with rat monoclonal antibody YTS 105.18 Fab fragment at 2.88 A resolution. YTS 105.18, which is commonly used in the blockade of CD8+ T-cell activation in response to peptide antigen, is specific for mouse CD8alpha. The YTS 105.18 Fab is one of only five rat IgG Fab structures to have been reported to date. Analysis of the YTS 105.18 Fab epitope on CD8alpha reveals that this antibody blocks CD8 activity by hydrogen bonding to residues that are critical for interaction with both class I pMHC and TL. Structural comparison of the liganded and unliganded forms of soluble CD8alphaalpha indicates that the mouse CD8alphaalpha immunoglobulin-domain dimer does not undergo significant structural alteration upon interaction either with class I pMHC or TL.

Multiple interactions in Sir protein recruitment by Rap1p at silencers and telomeres in yeast.

Initiation of transcriptional silencing at mating type loci and telomeres in Saccharomyces cerevisiae requires the recruitment of a Sir2/3/4 (silent information regulator) protein complex to the chromosome, which occurs at least in part through its association with the silencer- and telomere-binding protein Rap1p. Sir3p and Sir4p are structural components of silent chromatin that can self-associate, interact with each other, and bind to the amino-terminal tails of histones H3 and H4. We have identified a small region of Sir3p between amino acids 455 and 481 that is necessary and sufficient for association with the carboxyl terminus of Rap1p but not required for Sir complex formation or histone binding. SIR3 mutations that delete this region cause a silencing defect at HMR and telomeres. However, this impairment of repression is considerably less than that displayed by Rap1p carboxy-terminal truncations that are defective in Sir3p binding. This difference may be explained by the ability of the Rap1p carboxyl terminus to interact independently with Sir4p, which we demonstrate by in vitro binding and two-hybrid assays. Significantly, the Rap1p-Sir4p two-hybrid interaction does not require Sir3p and is abolished by mutation of the carboxyl terminus of Rap1p. We propose that both Sir3p and Sir4p can directly and independently bind to Rap1p at mating type silencers and telomeres and suggest that Rap1p-mediated recruitment of Sir proteins operates through multiple cooperative interactions, at least some of which are redundant. The physical separation of the Rap1p interaction region of Sir3p from parts of the protein required for Sir complex formation and histone binding raises the possibility that Rap1p can participate directly in the maintenance of silent chromatin through the stabilization of Sir complex-nucleosome interactions.