Rapid Evolution of an Invasive Plant

Exotic plants often face different conditions from those experienced where they are native. The general issue of how exotics respond to unfamiliar environments within their new range is not well understood. Phenotypic plasticity has historically been seen as the primary mechanism enabling exotics to colonize large, environmentally diverse areas. However, new work indicates that exotics can evolve quickly, suggesting that contemporary evolution may be more important in invasion ecology than previously appreciated. To determine the influence of contemporary evolution, phenotypic plasticity, and founder effects in affecting phenotypic variation among introduced plants, we compared the size, fecundity, and leaf area of St. John\u27s wort (Hypericum perforatum) collected from native European and introduced western and central North American populations in common gardens in Washington, California, Spain, and Sweden. We also determined genetic relationships among these plants by examining variation in amplified fragment length polymorphism (AFLP) markers. There was substantial genetic variation among introduced populations and evidence for multiple introductions of H. perforatum into North America. Across common gardens introduced plants were neither universally larger nor more fecund than natives. However, within common gardens, both introduced and native populations exhibited significant latitudinally based clines in size and fecundity. Clines among introduced populations broadly converged with those among native populations. Introduced and native plants originating from northern latitudes generally outperformed those originating from southern latitudes when grown in northern latitude gardens of Washington and Sweden. Conversely, plants from southern latitudes performed best in southern gardens in Spain and California. Clinal patterns in leaf area, however, did not change between gardens; European and central North American plants from northern latitudes had larger leaves than plants from southern latitudes within these regions in both Washington and California, the two gardens where this trait was measured. Introduced plants did not always occur at similar latitudes as their most closely related native progenitor, indicating that pre-adaptation (i.e., climate matching) is unlikely to be the sole explanation for clinal patterns among introduced populations. Instead, results suggest that introduced plants are evolving adaptations to broad-scale environmental conditions in their introduced range

Pesquisa dos Modelos de Valor Adicionado (MVA) para as políticas de educação: Delimitação da discussão

In this manuscript, the guest editors of the EPAA Special Issue on “Value-Added Model (VAM) Research for Educational Policy” (1) introduce the background and policy context surrounding the increased use of VAMs for teacher evaluation and accountability purposes across the United States; (2) summarize the five research papers and one research-based commentary that were peer-reviewed and selected for inclusion in this special issue; and (3) discuss the relevance of the papers both individually and collectively. Their importance is discussed in terms of each paper’s contribution to the general research on this topic and each paper’s potential to inform educational policy. In addition, the papers reflect our shared thinking about VAMs, VAM output, and the inference-based decisions for which VAMs are increasingly being used.En este artículo, los editores invitados de este número especial de EPAA/AAPE sobre la investigación  de los Modelos de Valor Agregado (MVA) para las políticas educativas: (1) presentan los antecedentes y el contexto político que rodean la utilización de MVA en la evaluación de los docentes y rendición de cuentas en los Estados Unidos, (2) un resumen de los cinco trabajos de investigación y el  comentarios que fueron seleccionados para su inclusión en este número especial, y (3) analizamos la pertinencia de los documentos, tanto individual como colectivamente. Su importancia se discuten en términos de la contribución de cada documento para la investigación general sobre este tema y el potencial de cada artículo para informar la política educativa. Además, los documentos reflejan nuestro pensamiento sobre la producción de MVA y las decisiones basadas en MVA son cada vez más utilizados.Neste artigo, os editores convidados desta edição especial da EPAA/AAPE sobre a Pesquisa dos Modelos de Valor Adicionado (MVA) para as políticas de educação: (1) Apresentam  o contexto político em torno do uso dos MVA na avaliação de professores e de responsabilização nos Estados Unidos, (2) um resumo dos cinco trabalhos de pesquisa e o comentário que foram selecionados para inclusão nesta edição especial, e (3) analisar a relevância dos trabalhos selecionados tanto individualmente como coletivamente. Sua importância é discutida em termos da contribuição de cada artigo para a pesquisa geral sobre este tema e as potencialidades de cada artigo para informar a política educacional. Além disso, os artigos refletem o nosso pensamento sobre a produção de decisões e MVA, e como são cada vez mais utilizados

Protein Complexes and Proteolytic Activation of the Cell Wall Hydrolase RipA Regulate Septal Resolution in Mycobacteria

Peptidoglycan hydrolases are a double-edged sword. They are required for normal cell division, but when dysregulated can become autolysins lethal to bacteria. How bacteria ensure that peptidoglycan hydrolases function only in the correct spatial and temporal context remains largely unknown. Here, we demonstrate that dysregulation converts the essential mycobacterial peptidoglycan hydrolase RipA to an autolysin that compromises cellular structural integrity. We find that mycobacteria control RipA activity through two interconnected levels of regulation in vivo—protein interactions coordinate PG hydrolysis, while proteolysis is necessary for RipA enzymatic activity. Dysregulation of RipA protein complexes by treatment with a peptidoglycan synthase inhibitor leads to excessive RipA activity and impairment of correct morphology. Furthermore, expression of a RipA dominant negative mutant or of differentially processed RipA homologues reveals that RipA is produced as a zymogen, requiring proteolytic processing for activity. The amount of RipA processing differs between fast-growing and slow-growing mycobacteria and correlates with the requirement for peptidoglycan hydrolase activity in these species. Together, the complex picture of RipA regulation is a part of a growing paradigm for careful control of cell wall hydrolysis by bacteria during growth, and may represent a novel target for chemotherapy development

Effectiveness of the Swachh Bharat Mission and barriers to ending open defecation in India: a systematic review

In 2016, nearly 60% of the population of India practiced open defecation (OD), which was 4 times the global rate, and reducing OD in India will be essential in meeting Sustainable Development Goal (SDG) 6.2 and improving global public health. The government of India launched the Swachh Bharat Mission (SBM) in 2014 with one key goal for all Indian states to achieve OD-free (ODF) status by 2019. Despite reports from the Government of India on the success of SBM, the true ODF status of Indian states is still unknown. A systematic review of peer-reviewed literature was conducted to assess the impact of SBM on OD in India, evaluate the barriers to reducing OD, and provide recommendations for future interventions to reduce or eliminate OD in India. A total of 237 publications were screened, and 22 were selected for inclusion. While the Prime Minister declared India ODF in 2019, studies suggest that the government monitoring system overestimates numbers of ODF villages and toilet coverage. Reasons for households’ continued OD practice include financial constraints, lack of water supply, governmental mistrust, cultural beliefs, and personal preference. Community incentives and penalties have been used to encourage proper sanitation practices with varying success. Overarching strategies and approaches that have worked well across study districts to reduce OD include high involvement of district leadership and innovative behavior-change and local community mobilization campaigns

The role of salt bridges, charge density, and subunit flexibility in determining disassembly routes of protein complexes

Mass spectrometry can be used to characterize multiprotein complexes, defining their subunit stoichiometry and composition following solution disruption and collision-induced dissociation (CID). While CID of protein complexes in the gas phase typically results in the dissociation of unfolded subunits, a second atypical route is possible wherein compact subunits or subcomplexes are ejected without unfolding. Because tertiary structure and subunit interactions may be retained, this is the preferred route for structural investigations. How can we influence which pathway is adopted? By studying properties of a series of homomeric and heteromeric protein complexes and varying their overall charge in solution, we found that low subunit flexibility, higher charge densities, fewer salt bridges, and smaller interfaces are likely to be involved in promoting dissociation routes without unfolding. Manipulating the charge on a protein complex therefore enables us to direct dissociation through structurally informative pathways that mimic those followed in solution

Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration

Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.02) and protein biosynthesis (p = 0.03). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetylaspartylglutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects

Heterodyne mixing of millimetre electromagnetic waves and sub-THz sound in a semiconductor device

We demonstrate heterodyne mixing of a 94 GHz millimetre wave photonic signal, supplied by a Gunn diode oscillator, with coherent acoustic waves of frequency ~ 100 GHz, generated by pulsed laser excitation of a semiconductor surface. The mixing takes place in a millimetre wave Schottky diode, and the intermediate frequency electrical signal is in the 1 – 12 GHz range. The mixing process preserves all the spectral content in the acoustic signal that falls within the intermediate frequency bandwidth. Therefore this technique may find application in high-frequency acoustic spectroscopy measurements, exploiting the nanometre wavelength of sub-THz sound. The result also points the way to exploiting acoustoelectric effects in photonic devices working at sub-THz and THz frequencies, which could provide functionalities at these frequencies, e.g. acoustic wave filtering, that are currently in widespread use at lower (GHz) frequencies

Population Pharmacokinetic Model and Meta-analysis of Outcomes of Amphotericin B Deoxycholate Use in Adults with Cryptococcal Meningitis

There is a limited understanding of the population pharmacokinetics (PK) and pharmacodynamics (PD) of amphotericin B deoxycholate (DAmB) for cryptococcal meningitis (CM). A PK study was conducted in n=42 patients receiving DAmB 1 mg/kg q24h. A 2-compartment PK model was developed. Patient weight influenced clearance and volume in the final structural model. Monte Carlo simulations estimated drug exposure associated with various DAmB dosages. A search was conducted for trials reporting outcomes of CM patients treated with DAmB monotherapy and a meta-analysis was performed.The PK parameter means (standard deviation) were: clearance, 0.03 (0.01) x weight + 0.95 (0.02) litres/hour; volume, 0.89 (0.90) x weight + 1.54 (1.13) litres; first-order rate constant from central to peripheral compartment, 7.12 (6.50) hours-1; from peripheral to central compartment, 12.13 (12.50) hours-1 The meta-analysis suggested that DAmB dosage explained most of the heterogeneity in cerebrospinal fluid (CSF) sterility, but not in mortality outcomes. Simulations of area under concentration-time curve (AUC144-168) resulted in median (interquartile range) values 5.83 mg.h/litre (4.66-8.55), 10.16 (8.07-14.55) and 14.51 (11.48-20.42), with dosages of 0.4, 0.7 and 1.0 mg/kg q24h respectively.DAmB PK is described adequately by a linear model that incorporates weight on clearance and volume. Inter-patient PK variability is modest and unlikely to be responsible for variability in clinical outcome. There is a discord between the impact that drug exposure has on CSF sterility and on mortality outcomes, which may be due to cerebral pathology not reflected in CSF fungal burden, in addition to clinical variables

Standardised patient study to assess tuberculosis case detection within the private pharmacy sector in Vietnam.

BACKGROUND: Of the estimated 10 million people affected by (TB) each year, one-third are never diagnosed. Delayed case detection within the private healthcare sector has been identified as a particular problem in some settings, leading to considerable morbidity, mortality and community transmission. Using unannounced standardised patient (SP) visits to the pharmacies, we aimed to evaluate the performance of private pharmacies in the detection and treatment of TB. METHODS: A cross-sectional study was undertaken at randomly selected private pharmacies within 40 districts of Vietnam. Trained actors implemented two standardised clinical scenarios of presumptive TB and presumptive multidrug-resistant TB (MDR-TB). Outcomes were the proportion of SPs referred for medical assessment and the proportion inappropriately receiving broad-spectrum antibiotics. Logistic regression evaluated predictors of SPs' referral. RESULTS: In total, 638 SP encounters were conducted, of which only 155 (24.3%) were referred for medical assessment; 511 (80·1%) were inappropriately offered antibiotics. A higher proportion of SPs were referred without having been given antibiotics if they had presumptive MDR-TB (68/320, 21.3%) versus presumptive TB (17/318, 5.3%; adjusted OR=4.8, 95% CI 2.9 to 7.8). Pharmacies offered antibiotics without a prescription to 89.9% of SPs with presumptive TB and 70.3% with presumptive MDR-TB, with no clear follow-up plan. CONCLUSIONS: Few SPs with presumptive TB were appropriately referred for medical assessment by private pharmacies. Interventions to improve appropriate TB referral within the private pharmacy sector are urgently required to reduce the number of undiagnosed TB cases in Vietnam and similar high-prevalence settings

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016