A Quantitative Study of the Deocyribonucleic Acid and Ribonucleic Acid in the Livers of Albino Mice During the Estrus Cycle

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A Quantitative Study of the DNA and RNA in the Livers of Albino Mice During the Estrus Cycle

Several investigators have suggested that the nucleic acid content of mouse liver varied with the estrus cycle. Nucleic acids were extracted with trichloroacetic acid and ethanol. The quantity of DNA and RNA was determined with a spectrophotometer. No significant differences were observed in the quantity of DNA or RNA throughout the estrus cycle. Diversity in the amount of nucleic acids present among the livers of non-litter mates was one-third greater that that among litter mates. In studies of the nucleio acid content of mouse liver, little is gained by controlling the estrus cycle, but using litter mates is suggested to demonstrate small fluctuations

The relationship between EQ-5D, HAQ and pain in patients with rheumatoid arthritis: further validation and development of the limited dependent variable, mixture model approach

Objective: To provide robust estimates of EQ-5D as a function of the Health Assessment Questionnaire (HAQ) and pain in patients with rheumatoid arthritis. Method: Repeated observations of patients diagnosed with RA in a US observational cohort (n=100,398 observations) who provided data on HAQ, pain on a visual analogue scale and the EQ-5D questionnaire. We use a bespoke mixture modelling approach to appropriately reflect the characteristics of the EQ-5D instrument and compare this to results from linear regression. Results: The addition of pain alongside HAQ as an explanatory variable substantially improves explanatory power. The preferred model is a four component mixture. Unlike the linear regression it exhibits very good fit to the data, does not suffer from problems of bias or predict values outside the feasible range. Conclusions: It is appropriate to model the relationship between HAQ and EQ-5D but only if suitable statistical methods are applied. Linear models underestimate the QALY benefits, and therefore the cost effectiveness, of therapies. The bespoke mixture model approach outlined here overcomes this problem. The addition of pain as an explanatory variable greatly improves the estimates

Session 2: The U.S. Perspective

This panel provides an overview of the current state of protection of moral rights in the United States, including discussion of the “patchwork” approach of federal and state laws, as well as judicial opinions

ULF waves in the low‐latitude boundary layer and their relationship to magnetospheric pulsations: A multisatellite observation

On April 30 (day 120), 1985, the magnetosphere was compressed at 0923 UT and the subsolar magnetopause remained near 7 REgeocentric for ∼2 hours, during which the four spacecraft Spacecraft Charging At High Altitude (SCATHA), GOES 5, GOES 6, and Active Magnetospheric Particle Tracer Explorers (AMPTE) CCE were all in the magnetosphere on the morning side. SCATHA was in the low-latitude boundary layer (LLBL) in the second half of this period. The interplanetary magnetic field was inferred to be northward from the characteristics of precipitating particle fluxes as observed by the low-altitude satellite Defense Meteorological Satellite Program (DMSP) F7 and also from absence of substorms. We used magnetic field and particle data from this unique interval to study ULF waves in the LLBL and their relationship to magnetic pulsations in the magnetosphere. The LLBL was identified from the properties of particles, including bidirectional field-aligned electron beams at ∼200 eV. In the boundary layer the magnetic field exhibited both a 5–10 min irregular compressional oscillation and a broadband (Δƒ/ƒ ∼ 1) primarily transverse oscillations with a mean period of ∼50 s and a left-hand sense of polarization about the mean field. The former can be observed by other satellites and is likely due to pressure variations in the solar wind, while the latter is likely due to a Kelvin-Helmholtz (K.-H.) instability occurring in the LLBL or on the magnetopause. Also, a strongly transverse ∼3-s oscillation was observed in the LLBL. The magnetospheric pulsations, which exhibited position dependent frequencies, may be explained in terms of field line resonance with a broadband source wave, that is, either the pressure-induced compressional wave or the K.-H. wave generated in or near the boundary layer

An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba dictyostelium discoideum

Mutations in either of two presenilin genes can cause familial Alzheimer's disease. Presenilins have both proteolysis-dependent functions, as components of the γ-secretase complex, and proteolysis-independent functions in signalling. In this study, we investigate a conserved function of human presenilins in the development of the simple model organism Dictyostelium discoideum. We show that the block in Dictyostelium development caused by the ablation of both Dictyostelium presenilins is rescued by the expression of human presenilin 1, restoring the terminal differentiation of multiple cell types. This developmental role is independent of proteolytic activity, because the mutation of both catalytic aspartates does not affect presenilin ability to rescue development, and the ablation of nicastrin, a γ-secretase component that is crucial for proteolytic activity, does not block development. The role of presenilins during Dictyostelium development is therefore independent of their proteolytic activity. However, presenilin loss in Dictyostelium results in elevated cyclic AMP (cAMP) levels and enhanced stimulation-induced calcium release, suggesting that presenilins regulate these intracellular signalling pathways. Our data suggest that presenilin proteins perform an ancient non-proteolytic role in regulating intracellular signalling and development, and that Dictyostelium is a useful model for analysing human presenilin function

2-Year Change in Revised Hammersmith Scale Scores in a Large Cohort of Untreated Paediatric Type 2 and 3 SMA Participants

The Revised Hammersmith Scale (RHS) is a 36-item ordinal scale developed using clinical expertise and sound psychometrics to investigate motor function in participants with Spinal Muscular Atrophy (SMA). In this study, we investigate median change in the RHS score up to two years in paediatric SMA 2 and 3 participants and contextualise it to the Hammersmith Functional Motor Scale-Expanded (HFMSE). These change scores were considered by SMA type, motor function, and baseline RHS score. We consider a new transitional group, spanning crawlers, standers, and walkers-with-assistance, and analyse that alongside non-sitters, sitters, and walkers. The transitional group exhibit the most definitive change score trend, with an average 1-year decline of 3 points. In the weakest patients, we are most able to detect positive change in the RHS in the under-5 age group, whereas in the stronger patients, we are most able to detect decline in the RHS in the 8-13 age group. The RHS has a reduced floor effect compared to the HFMSE, although we show that the RHS should be used in conjunction with the RULM for participants scoring less than 20 points on the RHS. The timed items in the RHS have high between-participant variability, so participants with the same RHS total can be differentiated by their timed test items

The Relevance of Marine Chemical Ecology to Plankton and Ecosystem Function: An Emerging Field

Marine chemical ecology comprises the study of the production and interaction of bioactive molecules affecting organism behavior and function. Here we focus on bioactive compounds and interactions associated with phytoplankton, particularly bloom-forming diatoms, prymnesiophytes and dinoflagellates. Planktonic bioactive metabolites are structurally and functionally diverse and some may have multiple simultaneous functions including roles in chemical defense (antipredator, allelopathic and antibacterial compounds), and/or cell-to-cell signaling (e.g., polyunsaturated aldehydes (PUAs) of diatoms). Among inducible chemical defenses in response to grazing, there is high species-specific variability in the effects on grazers, ranging from severe physical incapacitation and/or death to no apparent physiological response, depending on predator susceptibility and detoxification capability. Most bioactive compounds are present in very low concentrations, in both the producing organism and the surrounding aqueous medium. Furthermore, bioactivity may be subject to synergistic interactions with other natural and anthropogenic environmental toxicants. Most, if not all phycotoxins are classic secondary metabolites, but many other bioactive metabolites are simple molecules derived from primary metabolism (e.g., PUAs in diatoms, dimethylsulfoniopropionate (DMSP) in prymnesiophytes). Producing cells do not seem to suffer physiological impact due to their synthesis. Functional genome sequence data and gene expression analysis will provide insights into regulatory and metabolic pathways in producer organisms, as well as identification of mechanisms of action in target organisms. Understanding chemical ecological responses to environmental triggers and chemically-mediated species interactions will help define crucial chemical and molecular processes that help maintain biodiversity and ecosystem functionality