Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

A vector-valued ground motion intensity measure incorporating normalized spectral area

A vector-valued intensity measure is presented, which incorporates a relative measure represented by the normalized spectral area. The proposed intensity measure is intended to have high correlation with specific relative engineering demand parameters, which collectively can provide information regarding the damage state and collapse potential of the structure. Extensive dynamic analyses are carried out on a single-degree-of-freedom system with a modified Clough–Johnston hysteresis model, using a dataset of 40 ground motions, in order to investigate the proposed intensity measure characteristics. Response is expressed using the displacement ductility, and the normalized hysteretic energy, both of which are relative engineering demand parameters. Through regression analysis the correlation between the proposed intensity measure and the engineering demand parameters is evaluated. Its domain of applicability is investigated through parametric analysis, by varying the period and the strain-hardening stiffness. Desirable characteristics such as efficiency, sufficiency, and statistical independence are examined. The proposed intensity measure is contrasted to another one, with respect to its correlation to the engineering demand parameters. An approximate procedure for estimating the optimum normalized spectral area is also presented. It is demonstrated that the proposed intensity measure can be used in intensity-based assessments, and, with proper selection of ground motions, in scenario-based assessments

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

Boost Camp’, a universal school-based transdiagnostic prevention program targeting adolescent emotion regulation; evaluating the effectiveness by a clustered RCT : a protocol paper

Abstract Background The transition from childhood into adolescence can be considered as a critical developmental period. Moreover, adolescence is associated with a decreased use of adaptive emotion regulation strategies and an increased use of maladaptive emotion regulation strategies increasing the risk of emotional problems. Targeting emotion regulation is therefore seen as an innovative prevention approach. The present study aims to evaluate the effectiveness of Boost camp, an innovative school-based prevention program targeting ER, on adolescents’ emotion regulation skills and emotional wellbeing. Also secondary outcomes and possible moderators will be included. Methods The aim is to reach 300 adolescents (16 class groups, 6 schools) in their first year of high school. A clustered Randomized Controlled Trial (RCT) with two conditions, intervention (n = 150) and control (n = 150), will be set up. Adolescents in the intervention condition will receive 14 lessons over the course of 2 days, followed by Booster sessions, and will be compared with adolescents in a non-intervention control group. The outcomes will be measured by self-report questionnaires at baseline, immediately after Boost camp, and at three and 6 months follow-up. Discussion Data-collection is planned to be completed in May 2018. Data-analyses will be finished the end of 2018. The presented paper describes the Boost camp program and the clustered RCT design to evaluate its effectiveness. It is expected that Boost camp will have beneficial effects. If found effective, Boost camp will have the potential to increase adolescent’s ER and well-being, and reduce the risk to become adults in need. The trials is registered on the 13th of June 2017 in ISRCTN registry [ISRCTN68235634]

Correlated electron metal properties of the honeycomb ruthenate Na₂RuO₃

We report the synthesis and characterization of polycrystalline Na_{2}RuO_{3}, a layered material in which the Ru^{4+} (4d^{4} configuration) form a honeycomb lattice. The optimal synthesis condition was found to produce a nearly ordered Na_{2}RuO_{3} (C2/c phase), as assessed from the refinement of the time-of-flight neutron powder diffraction. Magnetic susceptibility measurements reveal a large temperature-independent Pauli paramagnetism [x_{0} ~ 1.42(2) x 10^{-3} emu/mol Oe] with no evidence of magnetic ordering down to 1.5 K, and with an absence of dynamic magnetic correlations, as evidenced by neutron scattering spectroscopy. The intrinsic susceptibility (x_{0}) together with the Sommerfeld coefficient of gamma = 11.7(2) mJ/Ru mol K^{2} estimated from heat capacity measurements gives an enhanced Wilson ratio of R_{w} ≈ 8.9(1), suggesting that magnetic correlations may be present in this material. While transport measurements on pressed pellets show nonmetallic behavior, photoemission spectroscopy indicates a small but finite density of states at the Fermi energy, suggesting that the bulk material is metallic. Except for resistivity measurements, which may have been compromised by near-surface and interface effects, all other probes indicate that Na_{2}RuO_{3} is a moderately correlated electron metal. Our results thus stand in contrast to earlier reports that Na_{2}RuO_{3} is an antiferromagnetic insulator at low temperatures

Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis.

Molecular, genetic and pathological evidence suggests that deficits in GABAergic parvalbumin-positive interneurons contribute to schizophrenia pathophysiology through alterations in the brain's excitation-inhibition balance that result in impaired behaviour and cognition. Although the factors that trigger these deficits are diverse, there is increasing evidence that they converge on a common pathological hub that involves NMDA receptor hypofunction and oxidative stress. These factors have been separately linked to schizophrenia pathogenesis, but evidence now suggests that they are mechanistically interdependent and contribute to a common schizophrenia-associated pathology

Improving the quality of publications in and advancing the entire paradigms of clinical and social pharmacy practice research: the Granada statements; [Améliorer la qualité des publications et faire progresser l'ensemble des paradigmes de la recherche sur la pratique clinique et sociale de la pharmacie: les déclarations de Grenade]

Pharmacy and pharmaceutical sciences embrace a series of different disciplines. Pharmacy practice has been defined as the scientific discipline that studies the different aspects of the practice of pharmacy and its impact on health care systems, medicine use, and patient care. Thus, pharmacy practice studies embrace both clinical pharmacy and social pharmacy elements. Like any other scientific discipline, clinical and social pharmacy practice disseminates research findings using scientific journals. Clinical pharmacy and social pharmacy journal editors have a role in promoting the discipline by enhancing the quality of the articles published. As has occurred in other health care areas (i.e., medicine and nursing), a group of clinical and social pharmacy practice journal editors gathered in Granada, Spain to discuss how journals could contribute to strengthening pharmacy practice as a discipline. The result of that meeting was compiled in these Granada Statements, which comprise 18 recommendations gathered into six topics: the appropriate use of terminology, impactful abstracts, the required peer reviews, journal scattering, more effective and wiser use of journal and article performance metrics, and authors selection of the most appropriate pharmacy practice journal to submit their work. Copyright (c) 2023 John Libbey Eurotext

Improving the quality of publications in and advancing the paradigms of clinical and social pharmacy practice research: The Granada statements

Pharmacy and pharmaceutical sciences embrace a series of different disciplines. Pharmacy practice has been defined as the scientific discipline that studies the different aspects of the practice of pharmacy and its impact on health care systems, medicine use, and patient care. Thus, pharmacy practice studies embrace both clinical pharmacy and social pharmacy elements. Like any other scientific discipline, clinical and social pharmacy practice disseminates research findings using scientific journals. Clinical pharmacy and social pharmacy journal editors have a role in promoting the discipline by enhancing the quality of the articles published. As has occurred in other health care areas (i.e., medicine and nursing), a group of clinical and social pharmacy practice journal editors gathered in Granada, Spain to discuss how journals could contribute to strengthening pharmacy practice as a discipline. The result of that meeting was compiled in these Granada Statements, which comprise 18 recommendations gathered into six topics: the appropriate use of terminology, impactful abstracts, the required peer reviews, journal scattering, more effective and wiser use of journal and article performance metrics, and authors selection of the most appropriate pharmacy practice journal to submit their work. (c) 2023 FIP

Improving the Quality of Publications in and Advancing the Paradigms of Clinical and Social Pharmacy Practice Research: The Granada Statements

Pharmacy and pharmaceutical sciences embrace a series of different disciplines. Pharmacy practice has been defined as the scientific discipline that studies the different aspects of the practice of pharmacy and its impact on health care systems, medicine use, and patient care. Thus, pharmacy practice studies embrace both clinical pharmacy and social pharmacy elements. Like any other scientific discipline, clinical and social pharmacy practice disseminates research findings using scientific journals. Clinical pharmacy and social pharmacy journal editors have a role in promoting the discipline by enhancing the quality of the articles published. As has occurred in other health care areas (i.e., medicine and nursing), a group of clinical and social pharmacy practice journal editors gathered in Granada, Spain to discuss how journals could contribute to strengthening pharmacy practice as a discipline. The result of that meeting was compiled in these Granada Statements, which comprise 18 recommendations gathered into six topics: the appropriate use of terminology, impactful abstracts, the required peer reviews, journal scattering, more effective and wiser use of journal and article performance metrics, and authors selection of the most appropriate pharmacy practice journal to submit their work.</jats:p