Pmp27 Promotes Peroxisomal Proliferation

Peroxisomes perform many essential functions in eukaryotic cells. The weight of evidence indicates that these organelles divide by budding from preexisting peroxisomes. This process is not understood at the molecular level. Peroxisomal proliferation can be induced in Saccharomyces cerevisiae by oleate. This growth substrate is metabolized by peroxisomal enzymes. We have identified a protein, Pmp27, that promotes peroxisomal proliferation. This protein, previously termed Pmp24, was purified from peroxisomal membranes, and the corresponding gene, PMP27, was isolated and sequenced. Prop27 shares sequence similarity with the Pmp30 family in Candida boidinii. Pmp27 is a hydrophobic peroxisomal membrane protein but it can be extracted by high pH, suggesting that it does not fully span the bilayer. Its expression is regulated by oleate. The function of Pmp27 was probed by observing the phenotype of strains in which the protein was eliminated by gene disruption or overproduced by expression from a multicopy plasmid. The strain containing the disruption (3B) was able to grow on all carbon sources tested, including oleate, although growth on oleate, glycerol, and acetate was slower than wild type. Strain 3B contained peroxisomes with all of the enzymes of β-oxidation. However, in addition to the presence of a few modestly sized peroxisomes seen in a typical thin section of a cell growing on oleate-containing medium, cells of strain 3B also contained one or two very large peroxisomes. In contrast, cells in a strain in which Pmp27 was overexpressed contained an increased number of normal-sized peroxisomes. We suggest that Pmp27 promotes peroxisomal proliferation by participating in peroxisomal elongation or fission.

Coherent Backscattering of Ultracold Atoms

We report on the direct observation of coherent backscattering (CBS) of ultracold atoms, in a quasi-two-dimensional configuration. Launching atoms with a well-defined momentum in a laser speckle disordered potential, we follow the progressive build up of the momentum scattering pattern, consisting of a ring associated with multiple elastic scattering, and the CBS peak in the backward direction. Monitoring the depletion of the initial momentum component and the formation of the angular ring profile allows us to determine microscopic transport quantities. The time resolved evolution of the CBS peak is studied and is found a fair agreement with predictions, at long times as well as at short times. The observation of CBS can be considered a direct signature of coherence in quantum transport of particles in disordered media. It is responsible for the so called weak localization phenomenon, which is the precursor of Anderson localization.Comment: 5 pages, 4 figure

Effect of lisdexamfetamine dimesylate on sleep in adults with attention-deficit/hyperactivity disorder

<p>Abstract</p> <p>Background</p> <p>Sleep problems are common in adults with attention-deficit/hyperactivity disorder (ADHD). This analysis aimed to evaluate the impact of lisdexamfetamine dimesylate (LDX) on sleep quality in adults with ADHD.</p> <p>Methods</p> <p>This 4-week, phase 3, double-blind, forced-dose escalation study of adults aged 18 to 55 years with ADHD randomized participants to receive placebo (n = 62), or 30 (n = 119), 50 (n = 117), or 70 (n = 122) mg/d LDX, taken once a day in the morning. The self-rated Pittsburgh Sleep Quality Index (PSQI) was administered at baseline and at week 4 to assess sleep quality. The PSQI global score assesses 7 sleep components (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction) each scored from 0 (no difficulty) to 3 (severe difficulty).</p> <p>Results</p> <p>The mean baseline PSQI global score was 5.8 for LDX and 6.3 for placebo (<it>P </it>= .19) indicating poor overall sleep quality. At endpoint, least squares (LS) mean change from baseline was -0.8 for LDX vs -0.5 for placebo (<it>P </it>= .33). The daytime functioning component showed significant improvement in LS mean change at endpoint for LDX compared with placebo (LDX -0.4 vs placebo 0.0, <it>P </it>= .0001). LS mean changes for the other 6 PSQI components did not significantly differ from placebo. Sleep-related treatment-emergent adverse events with an incidence ≥2% in the active treatment and placebo groups, respectively, were insomnia (19.3% and 4.8%), initial insomnia (5.0% and 3.2%), middle insomnia (3.6% and 0%), sleep disorder (0.6% and 3.2%), somnolence (0.3% and 3.2%), and fatigue (4.7% and 4.8%), and were generally mild or moderate in severity.</p> <p>Conclusion</p> <p>For most subjects, LDX was not associated with an overall worsening of sleep quality and significantly improved daytime functioning in adults with ADHD.</p> <p>Trial Registration</p> <p>clinicaltrials.gov Identifier: NCT00334880</p

Intragenic alternative splicing coordination is essential for Caenorhabditis elegans slo-1 gene function

Alternative splicing is critical for diversifying eukaryotic proteomes, but the rules governing and coordinating splicing events among multiple alternate splice sites within individual genes are not well understood. We developed a quantitative PCR-based strategy to quantify the expression of the 12 transcripts encoded by the Caenorhabditis elegans slo-1 gene, containing three alternate splice sites. Using conditional probability-based models, we show that splicing events are coordinated across these sites. Further, we identify a point mutation in an intron adjacent to one alternate splice site that disrupts alternative splicing at all three sites. This mutation leads to aberrant synaptic transmission at the neuromuscular junction. In a genomic survey, we found that a UAAAUC element disrupted by this mutation is enriched in introns flanking alternate exons in genes with multiple alternate splice sites. These results establish that proper coordination of intragenic alternative splicing is essential for normal physiology of slo-1 in vivo and identify putative specialized cis-regulatory elements that regulate the coordination of intragenic alternative splicing

Is Low Health Literacy Associated with Increased Emergency Department Utilization and Recidivism?

OBJECTIVES: The objective was to determine whether patients with low health literacy have higher emergency department (ED) utilization and higher ED recidivism than patients with adequate health literacy. METHODS: The study was conducted at an urban academic ED with more than 95,000 annual visits that is part of a 13-hospital health system, using electronic records that are captured in a central data repository. As part of a larger, cross-sectional, convenience sample study, health literacy testing was performed using the short test of functional health literacy in adults (S-TOFHLA) and standard test thresholds identifying those with inadequate, marginal, and adequate health literacy. The authors collected patients' demographic and clinical data, including items known to affect recidivism. This was a structured electronic record review directed at determining 1) the median number of total ED visits in this health system within a 2-year period and 2) the proportion of patients with each level of health literacy who had return visits within 3, 7, and 14 days of index visits. Descriptive data for demographics and ED returns are reported, stratified by health literacy level. The Mantel-Haenszel chi-square was used to test whether there is an association between health literacy and ED recidivism. A negative binomial multivariable model was performed to examine whether health literacy affects ED use, including variables significant at the 0.1 alpha level on bivariate analysis and retaining those significant at an alpha of 0.05 in the final model. RESULTS: Among 431 patients evaluated, 13.2% had inadequate, 10% had marginal, and 76.3% had adequate health literacy as identified by S-TOFHLA. Patients with inadequate health literacy had higher ED utilization compared to those with adequate health literacy (p = 0.03). Variables retained in the final model included S-TOFHLA score, number of medications, having a personal doctor, being a property owner, race, insurance, age, and simple comorbidity score. During the study period, 118 unique patients each made at least one return ED visit within a 14-day period. The proportion of patients with inadequate health literacy making at least one return visit was higher than that of patients with adequate health literacy at 14 days, but was not significantly higher within 3 or 7 days. CONCLUSIONS: In this single-center study, higher utilization of the ED by patients with inadequate health literacy when compared to those with adequate health literacy was observed. Patients with inadequate health literacy made a higher number of return visits at 14 days but not at 3 or 7 days

Wild Buckwheat Is Unlikely to Pose a Risk to Buckwheat-Allergic Individuals

Buckwheat (Fagopyrum esculentum) is a commonly allergenic food especially in Asia where buckwheat is more commonly consumed. Wild buckwheat (Polygonum convolvulus, recently changed to Fallopia convolvulus) is an annual weed prevalent in grain-growing areas of the United States. Wild buckwheat is not closely related to edible buckwheat although the seeds do have some physical resemblance. A large shipment of wheat into Japan was halted by the discovery of the adventitious presence of wild buckwheat seeds over possible concerns for buckwheat-allergic consumers. However, IgE-binding was not observed to an extract of wild buckwheat using sera from 3 buckwheat-allergic individuals either by radio-allergosorbent test inhibition or by immunoblotting after protein separation by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Furthermore, the extract of wild buckwheat was not detected in a buckwheat enzyme-linked immunosorbent assay developed with antisera against common buckwheat. Thus, wild buckwheat is highly unlikely to pose any risk to buckwheat-allergic individuals. The common names of plants should not be a factor in the risk assessment for possible cross-allergenicity

Do subjective measures improve the ability to identify limited health literacy in a clinical setting?

BACKGROUND: Existing health literacy assessments developed for research purposes have constraints that limit their utility for clinical practice, including time requirements and administration protocols. The Brief Health Literacy Screen (BHLS) consists of 3 self-administered Single-Item Literacy Screener (SILS) questions and obviates these clinical barriers. We assessed whether the addition of SILS items or the BHLS to patient demographics readily available in ambulatory clinical settings reaching underserved patients improves the ability to identify limited health literacy. METHODS: We analyzed data from 2 cross-sectional convenience samples of patients from an urban academic emergency department (n = 425) and a primary care clinic (n = 486) in St. Louis, Missouri. Across samples, health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine-Revised (REALM-R), Newest Vital Sign (NVS), and the BHLS. Our analytic sample consisted of 911 adult patients, who were primarily female (62%), black (66%), and had at least a high school education (82%); 456 were randomly assigned to the estimation sample and 455 to the validation sample. RESULTS: The analysis showed that the best REALM-R estimation model contained age, sex, education, race, and 1 SILS item (difficulty understanding written information). In validation analysis this model had a sensitivity of 62%, specificity of 81%, a positive likelihood ratio (LR(+)) of 3.26, and a negative likelihood ratio (LR(−)) of 0.47; there was a 28% misclassification rate. The best NVS estimation model contained the BHLS, age, sex, education and race; this model had a sensitivity of 77%, specificity of 72%, LR(+) of 2.75, LR(−) of 0.32, and a misclassification rate of 25%. CONCLUSIONS: Findings suggest that the BHLS and SILS items improve the ability to identify patients with limited health literacy compared with demographic predictors alone. However, despite being easier to administer in clinical settings, subjective estimates of health literacy have misclassification rates >20% and do not replace objective measures; universal precautions should be used with all patients