Prothrombin fragment 1-membrane interactions: a calcium-43 NMR study

The 43Ca NMR spectra are reported for solutions of prothrombin fragment 1 in the presence and absence of phospholipid. The calcium NMR spectrum permits distinction between three thermodynamic classes of calcium-binding interactions. The calcium ion in the lipid-free solutions was labile, with maximum residence times estimated for the average protein site in the range of 0.5-1 ms. The calcium spectrum was sensitive to the protein association and the addition of phospholipid, which appears to sharpen the calcium specificity for the protein sites. The calcium NMR spectra in the presence of phospholipid are similar to those in lipid-free solutions, which suggests that the calcium ion remains labile in the lipid-protein complex.     

Direct Measurements of Smartphone Screen-Time: Relationships with Demographics and Sleep

BackgroundSmartphones are increasingly integrated into everyday life, but frequency of use has not yet been objectively measured and compared to demographics, health information, and in particular, sleep quality.AimsThe aim of this study was to characterize smartphone use by measuring screen-time directly, determine factors that are associated with increased screen-time, and to test the hypothesis that increased screen-time is associated with poor sleep.MethodsWe performed a cross-sectional analysis in a subset of 653 participants enrolled in the Health eHeart Study, an internet-based longitudinal cohort study open to any interested adult (≥ 18 years). Smartphone screen-time (the number of minutes in each hour the screen was on) was measured continuously via smartphone application. For each participant, total and average screen-time were computed over 30-day windows. Average screen-time specifically during self-reported bedtime hours and sleeping period was also computed. Demographics, medical information, and sleep habits (Pittsburgh Sleep Quality Index–PSQI) were obtained by survey. Linear regression was used to obtain effect estimates.ResultsTotal screen-time over 30 days was a median 38.4 hours (IQR 21.4 to 61.3) and average screen-time over 30 days was a median 3.7 minutes per hour (IQR 2.2 to 5.5). Younger age, self-reported race/ethnicity of Black and "Other" were associated with longer average screen-time after adjustment for potential confounders. Longer average screen-time was associated with shorter sleep duration and worse sleep-efficiency. Longer average screen-times during bedtime and the sleeping period were associated with poor sleep quality, decreased sleep efficiency, and longer sleep onset latency.ConclusionsThese findings on actual smartphone screen-time build upon prior work based on self-report and confirm that adults spend a substantial amount of time using their smartphones. Screen-time differs across age and race, but is similar across socio-economic strata suggesting that cultural factors may drive smartphone use. Screen-time is associated with poor sleep. These findings cannot support conclusions on causation. Effect-cause remains a possibility: poor sleep may lead to increased screen-time. However, exposure to smartphone screens, particularly around bedtime, may negatively impact sleep.     

Targeting and processing of nuclear-encoded apicoplast proteins in plastid segregation mutants of Toxoplasma gondii

The apicoplast is a distinctive organelle associated with apicomplexan parasites, including Plasmodium sp. (which cause malaria) and Toxoplasma gondii (the causative agent of toxoplasmosis). This unusual structure (acquired by the engulfment of an ancestral alga and retention of the algal plastid) is essential for long-term parasite survival. Similar to other endosymbiotic organelles (mitochondria, chloroplasts), the apicoplast contains proteins that are encoded in the nucleus and post-translationally imported. Translocation across the four membranes surrounding the apicoplast is mediated by an N-terminal bipartite targeting sequence. Previous studies have described a recombinant "poison" that blocks plastid segregation during mitosis, producing parasites that lack an apicoplast and siblings containing a gigantic, nonsegregating plastid. To learn more about this remarkable phenomenon, we examined the localization and processing of the protein produced by this construct. Taking advantage of the ability to isolate apicoplast segregation mutants, we also demonstrated that processing of the transit peptide of nuclear-encoded apicoplast proteins requires plastid-associated activity.     

The genetic analysis of age-dependent traits: modeling the character process

The extension of classical quantitative genetics to deal with function-valued characters (also called infinite-dimensional characters) such as growth curves, mortality curves, and reaction norms, was begun by Kirkpatrick and co-workers. In this theory, the analogs of variance components for single traits are covariance functions for function-valued traits. In the approach presented here, we employ a variety of parametric models for covariance functions that have a number of desirable properties: the functions (1) are positive definite, (2) can be estimated using procedures like those currently used for single traits, (3) have a small number of parameters, and (4) allow simple hypotheses to be easily tested. The methods are illustrated using data from a large experiment that examined the effects of spontaneous mutations on age-specific mortality rates in Drosophila melanogaster. Our methods are shown to work better than a standard multivariate analysis, which assumes the character value at each age is a distinct character. Advantages over existing methods that model covariance functions as a series of orthogonal polynomials are discussed.     

Generalized character process models: estimating the genetic basis of traits that cannot be observed and that change with age or environmental conditions

The genetic analysis of characters that change as a function of some independent and continuous variable has received increasing attention in the biological and statistical literature. Previous work in this area has focused on the analysis of normally distributed characters that are directly observed. We propose a framework for the development and specification of models for a quantitative genetic analysis of function-valued characters that are not directly observed, such as genetic variation in age-specific mortality rates or complex threshold characters. We employ a hybrid Markov chain Monte Carlo algorithm involving a Monte Carlo EM algorithm coupled with a Markov chain approximation to the likelihood, which is quite robust and provides accurate estimates of the parameters in our models. The methods are investigated using simulated data and are applied to a large data set measuring mortality rates in the fruit fly, Drosophila melanogaster.     

Genome-wide gene expression in response to parasitoid attack in <Emphasis Type="Italic">Drosophila</Emphasis>

Background  

Parasitoids are insect parasites whose larvae develop in the bodies of other insects. The main immune defense against parasitoids is encapsulation of the foreign body by blood cells, which subsequently often melanize. The capsule sequesters and kills the parasite. The molecular processes involved are still poorly understood, especially compared with insect humoral immunity.     

Comparative analysis of haplotype association mapping algorithms

Background  

Finding the genetic causes of quantitative traits is a complex and difficult task. Classical methods for mapping quantitative trail loci (QTL) in miceuse an F2 cross between two strains with substantially different phenotype and an interval mapping method to compute confidence intervals at each position in the genome. This process requires significant resources for breeding and genotyping, and the data generated are usually only applicable to one phenotype of interest. Recently, we reported the application of a haplotype association mapping method which utilizes dense genotyping data across a diverse panel of inbred mouse strains and a marker association algorithm that is independent of any specific phenotype. As the availability of genotyping data grows in size and density, analysis of these haplotype association mapping methods should be of increasing value to the statistical genetics community.     

Congenital bifid sternum: repair in early infancy and literature review

Sternal clefting is an unusual congenital anomaly that should be repaired in early infancy. Early surgery is facilitated by a highly compliant bony thorax. The surgical technique is described, including the (1) removal of a wedge at the confluence of the two lateral sternal bands to allow their apposition, (2) intraoperative assessment of pulmonary compliance and central venous pressure, (3) use of bilateral pectoral flaps, and (4) resulting avoidance of major costochondral stair-step osteotomies. The suggested age of repair is 1 to 4 weeks of age.