Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. The most common ...CF-associated mutation is ΔF508, which deletes a phenylalanine in position 508. In vitro studies indicate that the resultant protein, CFTR-ΔF508, is misprocessed, although the in vivo consequences of this mutation remain uncertain. To better understand the effects of the ΔF508 mutation in vivo, we produced CFTR(ΔF508/ΔF508) pigs. Our biochemical, immunocytochemical, and electrophysiological data on CFTR-ΔF508 in newborn pigs paralleled in vitro predictions. They also indicated that CFTR(ΔF508/ΔF508) airway epithelia retain a small residual CFTR conductance, with maximal stimulation producing ~6% of wild-type function. Cyclic adenosine 3',5'-monophosphate (cAMP) agonists were less potent at stimulating current in CFTR(Δ)(F508/)(Δ)(F508) epithelia, suggesting that quantitative tests of maximal anion current may overestimate transport under physiological conditions. Despite residual CFTR function, four older CFTR(ΔF508/ΔF508) pigs developed lung disease similar to human CF. These results suggest that this limited CFTR activity is insufficient to prevent lung or gastrointestinal disease in CF pigs. These data also suggest that studies of recombinant CFTR-ΔF508 misprocessing predict in vivo behavior, which validates its use in biochemical and drug discovery experiments. These findings help elucidate the molecular pathogenesis of the common CF mutation and will guide strategies for developing new therapeutics.
The County Health Rankings (CHR) system provides health rankings for U.S. counties. These factors may have utility for evaluating and predicting health outcomes. This study examined the association ...between CHR factors and the prevalence of child overweight/obesity (OWOB) in the state of Pennsylvania over 3 years.
The prevalence of childhood OWOB was obtained for all Pennsylvania school districts for the 2009-10 through 2011-12 school years. Correlational and inferential statistical analyses were used to examine the associations between the prevalence of OWOB in grades K-6 (OWOB1) and 7-12 (OWOB2) and z-score for the overall CHR Health Factors rank, as well as for individual predictive factors (Health Behaviors, Clinical Care, Social and Economic Factors and Physical Environment).
Low to moderate correlations (0.29-0.43) were found between OWOB1 and CHR factors. Weaker and less consistent correlations were found for adolescents. There was a significantly higher prevalence of OWOB in counties with poorer CHR scores.
County-level adult indicators of health are significantly associated with levels of child obesity. Future studies should examine the relationship between CHR and other health outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The impact of preserved museum specimens is transforming and increasing by three-dimensional (3D) imaging that creates high-fidelity online digital specimens. Through examples from the openVertebrate ...(oVert) Thematic Collections Network, we describe how we created a digitization community dedicated to the shared vision of making 3D data of specimens available and the impact of these data on a broad audience of scientists, students, teachers, artists, and more. High-fidelity digital 3D models allow people from multiple communities to simultaneously access and use scientific specimens. Based on our multiyear, multi-institution project, we identify significant technological and social hurdles that remain for fully realizing the potential impact of digital 3D specimens.
Evidence suggests that subliminal stimuli can influence ostensibly volitional, executive processes but it is unclear whether this is highly task-specific. To address this we used a set-switching ...task. Volunteers saw a word pair and reported either if both words had the same number of syllables or if both were concrete. Task selection was random and instructed by a hexagon/triangle preceding the words. A subliminally-presented square or diamond reliably preceded each of these consciously perceived instruction-shapes. Significant congruency effects were observed in a subsequent Test Phase in which primes no longer reliably predicted the task (and in which high/low tones now served as conscious instructions). The Generalization Phase required novel phonological (rhyme) or semantic (category) judgments. Remarkably, unconscious priming congruency effects carried over in those participants who had shown priming in the Test Phase, the degree correlating across the two conditions. In a final phase of the study, participants were asked to discriminate between the two originally presented prime shapes. Those participants whose discriminations were more accurate showed reduced priming relative to participants with less accurate discriminations. The results suggest that, rather than being highly task specific, priming can operate at the level of a generalizable process and that greater awareness of primes may lessen their impact on behavior.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Increasing scalp hair fullness is a global unmet consumer need. An approach to decrease hair shedding by reducing scalp stratum corneum oxidation via a combination of antioxidant and ...barrier‐enhancing technologies has been previously demonstrated. The purpose of this study was to test the effectiveness of the individual antioxidant piroctone olamine in two different product forms (shampoo or leave‐on product) for activity to improve hair retention.
Methods
Female subjects with self‐perceived hair thinning participated in an 8‐week, double‐blind, placebo‐controlled, randomized clinical study to evaluate either a piroctone olamine (PO) containing shampoo or a PO containing leave on treatment, each relative to their corresponding placebo formulation Too many periods. Results for phototrichograms, TEWL, and biomarker analysis of scalp condition for the shampoo treatments are discussed. Phototrichogram results are shared for the assessment of the leave on treatment.
Results
Statistically significant increases in hair amount were observed by phototrichogram after use of both PO‐containing products versus placebo formulations. The PO shampoo treatment also significantly decreased oxidative stress on the hair and scalp, and improved scalp condition as assessed by TEWL and scalp biomarker values.
Conclusion
These results illustrate the effectiveness of a cosmetic antioxidant to improve scalp condition thereby improving hair retention. The observed improvements in scalp condition are consistent with previous reports with other antioxidant technologies and suggest that the hair retention effect was achieved by preventing oxidative damage to the scalp.
When searching for a known target, mental representations of target features, or templates, guide attention towards matching objects and facilitate recognition. When only distractor features are ...known, distractor templates allow irrelevant objects to be recognised and attention to be shifted away. This is particularly true in X-ray baggage search, a challenging real-world visual search task with implications for public safety, where targets may be unknown, difficult to predict and concealed by an adversary, but distractors are typically benign and easier to identify. In the present study, we draw on basic principles of distractor suppression and rejection to investigate a counterintuitive ‘targetless’ approach to training baggage search. In a simulated X-ray baggage search task, we observed significant benefits to target detection sensitivity (
d′
) for targetless relative to target-based training, but no effects of performance-contingent rewards or the inclusion of superordinate semantic categories during training. The benefits of targetless search training were most apparent for stimuli involving less spatial overlap (occlusion), which likely represents the difficulty and greater individual variation involved in searching more visually complex images. Together, these results demonstrate the effectiveness of a counterintuitive targetless approach to training target detection in X-ray baggage search, based on basic principles of distractor suppression and rejection, with potential for use as a real-world training tool.
One of the essential processing events during pre-mRNA maturation is the post-transcriptional addition of a polyadenine poly(A) tail. The 3'-end poly(A) track protects mRNA from unregulated ...degradation, and indicates the integrity of mRNA through recognition by mRNA export and translation machinery. The position of a poly(A) site is predetermined by signals in the pre-mRNA sequence that are recognized by a complex of polyadenylation factors. These signals are generally tri-part sequence patterns around the cleavage site that serves as the future poly(A) site. In plants, there is little sequence conservation among these signal elements, which makes it difficult to develop an accurate algorithm to predict the poly(A) site of a given gene. We attempted to solve this problem.
Based on our current working model and the profile of nucleotide sequence distribution of the poly(A) signals and around poly(A) sites in Arabidopsis, we have devised a Generalized Hidden Markov Model based algorithm to predict potential poly(A) sites. The high specificity and sensitivity of the algorithm were demonstrated by testing several datasets, and at the best combinations, both reach 97%. The accuracy of the program, called poly(A) site sleuth or PASS, has been demonstrated by the prediction of many validated poly(A) sites. PASS also predicted the changes of poly(A) site efficiency in poly(A) signal mutants that were constructed and characterized by traditional genetic experiments. The efficacy of PASS was demonstrated by predicting poly(A) sites within long genomic sequences.
Based on the features of plant poly(A) signals, a computational model was built to effectively predict the poly(A) sites in Arabidopsis genes. The algorithm will be useful in gene annotation because a poly(A) site signifies the end of the transcript. This algorithm can also be used to predict alternative poly(A) sites in known genes, and will be useful in the design of transgenes for crop genetic engineering by predicting and eliminating undesirable poly(A) sites.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract only
e13136
Background: Next Generation Sequencing (NGS) is increasingly used to identify actionable mutations for oncology treatment. We examined the results of NGS at our institution. ...Methods: We retrospectively reviewed the medical charts of 305 consecutive patients who had genomic testing performed on tumor samples from March 2014 to April 2017. Next Generation Sequencing was performed by Foundation One testing. Results: Of the 305 tissue samples sent to Foundation One, 189 reports were potentially usable. Reports were unusable due to an insufficient quantity of tissue (43), inadequate follow-up (32), cessation of oncologic care due to transferring to hospice or expiring (32), or a report not being generated due to the order being cancelled (4) or undocumented reasons (5). Of the 189 usable reports, 76 (40.21%) demonstrated an aberration targetable by on-label therapies, 126 (66.67%) via off-label therapies (66 of these had no available on-label treatment), and 170 (89.94%) revealed actionable aberrations via all potential avenues, including clinical trials. 19 (6.2%) yielded a change in management, 6 of these changes were utilizing on-label therapies, 6 were via off-label therapies, 3 were via enrollment in a clinical trial, and 4 involved discontinuing a medication with a predicted poor response. For the 6 patients with off-label use, median duration of treatment was 46 days and discontinued secondary to death (3 patients) or progression (3 patients). Conclusions: Only a minority of NGS assay results (6.2% percent of all tests ordered and 10% of useable tests) resulted in a management change. A small minority (6 patients, 1.9%) were started on off-label therapy based on NSG results and overall had poor responses to off-label treatment. While in theory NGS may improve oncology outcome, the results of our initial 305 patients who had NGS was poor.
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