Conformational Preferences of 3-(Dimethylazinoyl)propanoic Acid as a Function of pH and Solvent; Intermolecular versus Intramolecular Hydrogen Bonding

The conformational equilibrium of 3-(dimethylazinoyl)propanoic acid (DMAPA, azinoyl = N^+(O^−) has a weak pH-dependence in D_2O, with a slight preference for trans in alkaline solutions. The acid ionization constants of the protonated amine oxide and carboxylic functional groups as determined by NMR spectroscopy were 7.9 × 10^(−4) and 6.3 × 10^(−6), respectively. The corresponding value of K_1/K_2 of 1.3 × 10^2 is not deemed large enough to provide experimental NMR evidence for a significant degree of intramolecular hydrogen bonding in D_2O. Conformational preferences of DMAPA are mostly close to statistical (gauche/trans = 2/1) in other protic solvents, e.g., alcohols. However, the un-ionized form of DMAPA appears to be strongly intramolecularly hydrogen-bonded and gauche in aprotic solvents

Distribution of selected healthcare resources for influenza pandemic response in Cambodia.

INTRODUCTION: Human influenza infection poses a serious public health threat in Cambodia, a country at risk for the emergence and spread of novel influenza viruses with pandemic potential. Prior pandemics demonstrated the adverse impact of influenza on poor communities in developing countries. Investigation of healthcare resource distribution can inform decisions regarding resource mobilization and investment for pandemic mitigation. METHODS: A health facility survey performed across Cambodia obtained data on availability of healthcare resources important for pandemic influenza response. Focusing on five key resources considered most necessary for treating severe influenza (inpatient beds, doctors, nurses, oseltamivir, and ventilators), resource distributions were analyzed at the Operational District (OD) and Province levels, refining data analysis from earlier studies. Resources were stratified by respondent type (hospital vs. District Health Office [DHO]). A summary index of distribution inequality was calculated using the Gini coefficient. Indices for local spatial autocorrelation were measured at the OD level using geographical information system (GIS) analysis. Finally, a potential link between socioeconomic status and resource distribution was explored by mapping resource densities against poverty rates. RESULTS: Gini coefficient calculation revealed variable inequality in distribution of the five key resources at the Province and OD levels. A greater percentage of the population resides in areas of relative under-supply (28.5%) than over-supply (21.3%). Areas with more resources per capita showed significant clustering in central Cambodia while areas with fewer resources clustered in the northern and western provinces. Hospital-based inpatient beds, doctors, and nurses were most heavily concentrated in areas of the country with the lowest poverty rates; however, beds and nurses in Non-Hospital Medical Facilities (NHMF) showed increasing concentrations at higher levels of poverty. CONCLUSIONS: There is considerable heterogeneity in healthcare resource distribution across Cambodia. Distribution mapping at the local level can inform policy decisions on where to stockpile resources in advance of and for reallocation in the event of a pandemic. These findings will be useful in determining future health resource investment, both for pandemic preparedness and for general health system strengthening, and provide a foundation for future analyses of equity in health services provision for pandemic mitigation planning in Cambodia

Intraspecific variability drives diversity in food webs

Biodiversity theories neglect individual-level variability in ecological interactions even though empirical work has revealed considerable genetic and phenotypic variation among individuals in natural populations. This impedes assessing the impact of individual-level variability on biodiversity in multi-trophic ecosystems. Here we use a density-dependent and individual-based food web model, tested against the largest individual-based food web to date, to show that non-random intraspecific variation in prey selection alters species diversity in food webs. Predators consuming many prey increase diversity by preferentially selecting common prey; predators consuming few prey inhibit diversity by preferentially selecting rare prey, putting them at risk of extinction. Thus species-level patterns cannot be explained by species-level averages, but instead must consider individual-level variation in prey selection. Individual-level variation occurs in many biological and social contexts, suggesting that analyses of individual-level interaction data will be relevant in a wide range of fields

Low abundances of heavy elements in the solar outer layers: comparisons of solar models with helioseismic inversions

Recent solar photospheric abundance analyses have led to a significant reduction of the metal abundances compared to the previous determinations. The solar models computed with standard opacities and diffusion processes using these new abundances give poor agreement with helioseismic inversions for the sound-speed profile, the surface helium abundance, and the convective zone depth. We attempt to obtain a good agreement between helioseismic inversions and solar models which present the "old" mixture in the interior and new chemical composition in the convective zone. To reach this result, we assume an undermetallic accretion at the beginning of the main sequence. We compute solar models with the Toulouse-Geneva Evolution Code, in which we simulate an undermetallic accretion in the early stages of the main sequence, in order to obtain new mixture in the outer convective zone. We compare the sound-speed profile, the convective zone depth, and the surface helium abundance with those deduced from helioseismology. The model with accretion but without any mixing process inside is in better agreement with helioseismology than the solar model with the new abundances throughout. There is, however, a spike under the convective zone which reaches 3.4%. Furthermore, the convective zone depth and the surface helium abundance are too low. Introducing undershooting below the convective zone allows us to recover the good convective zone radius and the addition of rotation-induced mixing and tachocline allows us to reconcile the surface helium abundance. But in any case the agreement of the sound-speed profile with helioseismic inference is worse than obtained with the old abundances.Comment: 5 pages, 2 figure

Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors.

IntroductionThe interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.MethodsHuman CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-kappaB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice.ResultsIL-17A upregulates the receptor activator for NF-kappaB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts.ConclusionsCollectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases

Solar astronomy

An overview is given of modern solar physics. Topics covered include the solar interior, the solar surface, the solar atmosphere, the Large Earth-based Solar Telescope (LEST), the Orbiting Solar Laboratory, the High Energy Solar Physics mission, the Space Exploration Initiative, solar-terrestrial physics, and adaptive optics. Policy and related programmatic recommendations are given for university research and education, facilitating solar research, and integrated support for solar research

Hemispheric Language Asymmetry in First Episode Psychosis and Schizotypy: The Role of Cannabis Consumption and Cognitive Disorganization

Cannabis use has been related to an elevated psychosis risk and attenuated cognitive functioning. Cannabis-related cognitive impairments are also observed in populations along the psychosis dimension. We here investigated whether a potential behavioral marker of the psychosis dimension (attenuated functional hemispheric asymmetry) is even further attenuated in individuals using cannabis (CU) vs those not using cannabis (nCU). We tested 29 patients with first-episode psychosis (FEP; 11 CU) and 90 healthy controls (38 CU) on lateralized lexical decisions assessing left-hemisphere language dominance. In patients, psychotic symptoms were assessed by Positive & Negative Symptom Scale (PANSS). In controls, self-reported schizotypy was assessed (The Oxford-Liverpool Inventory of Feelings and Experiences: O-LIFE). Results indicated that nCU FEP patients had a relative reduced hemispheric asymmetry, as did controls with increasing cognitive disorganization (CogDis) scores, in particular when belonging to the group of nCU controls. Positive, disorganized and negative PANSS scores in patients and negative and positive schizotypy in controls were unrelated to hemispheric asymmetry. These findings suggest that cannabis use potentially balances rather than exacerbates uncommon hemispheric laterality patterns. Moreover, in healthy populations, the potential stabilization of typical hemispheric asymmetry in CU might be most relevant to individuals with elevated CogDis. We discuss the potential beneficial and harmful effects of cannabis use along the psychosis dimension together with propositions for future studies that should account for the mediating role of additional substances (eg nicotine), cannabis composition (eg cannabidiol content), and individual differences (eg physical health, or absence of significant polysubstance use