Environmental complexity is more important than mutation in driving the evolution of latent novel traits in E. coli.

Recent experiments show that adaptive Darwinian evolution in one environment can lead to the emergence of multiple new traits that provide no immediate benefit in this environment. Such latent non-adaptive traits, however, can become adaptive in future environments. We do not know whether mutation or environment-driven selection is more important for the emergence of such traits. To find out, we evolve multiple wild-type and mutator E. coli populations under two mutation rates in simple (single antibiotic) environments and in complex (multi-antibiotic) environments. We then assay the viability of evolved populations in dozens of new environments and show that all populations become viable in multiple new environments different from those they had evolved in. The number of these new environments increases with environmental complexity but not with the mutation rate. Genome sequencing demonstrates the reason: Different environments affect pleiotropic mutations differently. Our experiments show that the selection pressure provided by an environment can be more important for the evolution of novel traits than the mutational supply experienced by a wild-type and a mutator strain of E. coli

Subnatural linewidth using electromagnetically induced transparency in Doppler-broadened vapor

We obtain subnatural linewidth (i.e. $<\Gamma$) for probe absorption in room-temperature Rb vapor using electromagnetically induced transparency (EIT) in a $\Lambda$ system. For stationary atoms, the EIT dip for a resonant control laser is as wide as the control Rabi frequency $\Omega_c$. But in thermal vapor, the moving atoms fill the transparency band so that the final EIT dip remains subnatural even when $\Omega_c > \Gamma$. We observe linewidths as small as $\Gamma/7$ in the $D_2$ line of Rb.Comment: 6 pages, 7 figure

Intestinal organoids model human responses to infection by commensal and Shiga toxin producing Escherichia coli

Infection with Shiga toxin (Stx) producing Escherichia coli O157:H7 can cause the potentially fatal complication hemolytic uremic syndrome, and currently only supportive therapy is available. Lack of suitable animal models has hindered study of this disease. Induced human intestinal organoids (iHIOs), generated by in vitro differentiation of pluripotent stem cells, represent differentiated human intestinal tissue. We show that iHIOs with addition of human neutrophils can model E. coli intestinal infection and innate cellular responses. Commensal and O157:H7 introduced into the iHIO lumen replicated rapidly achieving high numbers. Commensal E. coli did not cause damage, and were completely contained within the lumen, suggesting defenses, such as mucus production, can constrain non-pathogenic strains. Some O157:H7 initially co-localized with cellular actin. Loss of actin and epithelial integrity was observed after 4 hours. O157:H7 grew as filaments, consistent with activation of the bacterial SOS stress response. SOS is induced by reactive oxygen species (ROS), and O157:H7 infection increased ROS production. Transcriptional profiling (RNAseq) demonstrated that both commensal and O157:H7 upregulated genes associated with gastrointestinal maturation, while infection with O157:H7 upregulated inflammatory responses, including interleukin 8 (IL-8). IL-8 is associated with neutrophil recruitment, and infection with O157:H7 resulted in recruitment of human neutrophils into the iHIO tissue

Prospective Validation of Eight Different Adherence Measures for Use with Administrative Claims Data among Patients with Schizophrenia

ABSTRACTObjectiveThe aim of this study was to compare the predictive validity of eight different adherence measures by studying the variability explained between each measure and hospitalization episodes among Medicaid-eligible persons diagnosed with schizophrenia on antipsychotic monotherapy.MethodsThis study was a retrospective analysis of the Arkansas Medicaid administrative claims data. Continuously eligible adult schizophrenia (ICD-9-CM = 295.**) patients on antipsychotic monotherapy were identified in the recruitment period from July 2000 through April 2004. Adherence rates to antipsychotic therapy in year 1 were calculated using eight different measures identified from the literature. Univariate and multivariable logistic regression models were used to prospectively predict all-cause and mental health-related hospitalizations in the follow-up year.ResultsAdherence rates were computed for 3395 schizophrenic patients with a mean age of 42.9 years, of which 52.5% (n = 1782) were females, and 52.8% (n = 1793) were white. The proportion of days covered (PDC) and continuous measure of medication gaps measures of adherence had equal C-statistics of 0.571 in predicting both all-cause and mental health-related hospitalizations. The medication possession ratio (MPR) continuous multiple interval measure of oversupply were the second best measures with equal C-statistics of 0.568 and 0.567 for any-cause and mental health-related hospitalizations. The multivariate adjusted models had higher C-statistics but provided the same rank order results.ConclusionsMPR and PDC were among the best predictors of any-cause and mental health-related hospitalization, and are recommended as the preferred adherence measures when a single measure is sought for use with administrative claims data for patients not on polypharmacy

Molecular Defects of Vitamin B6 Metabolism Associated with Neonatal Epileptic Encephalopathy

Neonatal epileptic encephalopathy (NEE) is a seizure disorder that occurs within hours from birth and arises from central nervous system (CNS) dysfunctions of various origins, including metabolic or inflammatory conditions, abnormalities of brain structure and cerebrovascular diseases. In some rare circumstances, NEE is refractory to conventional antiepileptic drugs (AEDs) but responds very well to treatment with vitamin B6 in the form of either pyridoxine (PN) or pyridoxal 5’-phosphate (PLP). Vitamin B6-dependent NEE derives either from a deficiency of PLP, from inborn errors in enzymes, such as pyridoxine 5’-phosphate oxidase (PNPOx) and pyridoxal kinase (PL kinase) involved in the PLP salvage pathway or from inherited mutations of enzymes, such as -aminoadipic semialdehyde dehydrogenase (also known as antiquitin) involved in other metabolic pathways, which lead to the accumulation of intermediates that react with PLP, reducing its availability. Clinical phenotypes observed in vitamin B6-dependent NEE patients may include fetal distress, hypoglycemia, acidosis, anemia, and asphyxia. The health state of untreated patients may undergo progressive deterioration, which can lead to death within weeks. Surviving children are usually mentally retarded and are dependent on vitamin B6 to control the disease. Several known cases of B-dependent NEE, however do not or only mildly manifest some of the above clinical features, and are characterized by mild to moderate developmental delay. This chapter will review the molecular mechanism of how in-born errors in PNPOx or antiquitin affect PLP levels in the cell and lead to NEE. We will also review important clinical and general features associated with PLP dependent NEE, and provide some directions for clinicians to diagnose and treat or manage the diseas

Enabling Automated, Rich, and Versatile Data Management for Android Apps with BlueMountain

Abstract Today&apos;s mobile apps often leverage cloud services to manage their own data as well as user data, enabling many desired features such as backup and sharing. However, this comes at a cost; developers have to manually craft their logic and potentially repeat a similar process for different cloud providers. In addition, users are restricted to the design choices made by developers; for example, once a developer releases an app that uses a particular cloud service, it is impossible for a user to later customize the app and choose a different service. In this paper, we explore the design space of an app instrumentation tool that automatically integrates cloud storage services for Android apps. Our goal is to allow developers to treat all storage operations as local operations, and automatically enable cloud features customized for individual needs of users and developers. We discuss various scenarios that can benefit from such an automated tool, challenges associated with the development of it, and our ideas to address these challenges

Temporal Patterns of Medications Dispensed to Children and Adolescents in a National Insured Population

This study aimed to comprehensively describe prevalence and temporal dispensing patterns for medications prescribed to children and adolescents in the United States. Participants were 1.6 million children (49% female) under 18 years old enrolled in a nation-wide, employer-provided insurance plan. All medication claims from 1999–2006 were reviewed retrospectively. Drugs were assigned to 16 broad therapeutic categories. Effects of trend over time, seasonality, age and gender on overall and within category prevalence were examined. Results: Mean monthly prevalence for dispensed medications was 23.5% (range 19.4–27.5), with highest rates in winter and lowest in July. The age group with the highest prevalence was one-year-old children. On average each month, 17.1% of all children were dispensed a single drug and 6.4% were dispensed two or more. Over time, prevalence for two or more drugs did not change, but the proportion of children dispensed a single drug decreased (slope -.02%, p = .001). Overall, boys had higher monthly rates than girls (average difference 0.9%, p = .002). However, differences by gender were greatest during middle childhood, especially for respiratory and central nervous system agents. Contraceptives accounted for a large proportion of dispensed medication to older teenage girls. Rates for the drugs with the highest prevalence in this study were moderately correlated (average Pearson r.66) with those from a previously published national survey. Conclusion: On average, nearly one quarter of a population of insured children in the United States was dispensed medication each month. This rate decreased somewhat over time, primarily because proportionally fewer children were dispensed a single medication. The rate for two or more drugs dispensed simultaneously remained steady

Expression Patterns of Genes Involved in Sugar Metabolism and Accumulation during Apple Fruit Development

Both sorbitol and sucrose are imported into apple fruit from leaves. The metabolism of sorbitol and sucrose fuels fruit growth and development, and accumulation of sugars in fruit is central to the edible quality of apple. However, our understanding of the mechanisms controlling sugar metabolism and accumulation in apple remains quite limited. We identified members of various gene families encoding key enzymes or transporters involved in sugar metabolism and accumulation in apple fruit using homology searches and comparison of their expression patterns in different tissues, and analyzed the relationship of their transcripts with enzyme activities and sugar accumulation during fruit development. At the early stage of fruit development, the transcript levels of sorbitol dehydrogenase, cell wall invertase, neutral invertase, sucrose synthase, fructokinase and hexokinase are high, and the resulting high enzyme activities are responsible for the rapid utilization of the imported sorbitol and sucrose for fruit growth, with low levels of sugar accumulation. As the fruit continues to grow due to cell expansion, the transcript levels and activities of these enzymes are down-regulated, with concomitant accumulation of fructose and elevated transcript levels of tonoplast monosaccharide transporters (TMTs), MdTMT1 and MdTMT2; the excess carbon is converted into starch. At the late stage of fruit development, sucrose accumulation is enhanced, consistent with the elevated expression of sucrose-phosphate synthase (SPS), MdSPS5 and MdSPS6, and an increase in its total activity. Our data indicate that sugar metabolism and accumulation in apple fruit is developmentally regulated. This represents a comprehensive analysis of the genes involved in sugar metabolism and accumulation in apple, which will serve as a platform for further studies on the functions of these genes and subsequent manipulation of sugar metabolism and fruit quality traits related to carbohydrates

Genetic diversity and the emergence of ethnic groups in Central Asia

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