Characterization of the transverse relaxation rates in lipid bilayers

The 2H NMR transverse relaxation rates of a deuterated phospholipid bilayer reflect slow motions in the bilayer membrane. A study of dimyristoyl lecithin specifically deuterated at several positions of the hydrocarbon chains indicates that these motions are cooperative and are confined to the hydrocarbon chains of the lipid bilayer. However, lipid head group interactions do play an important role in modulating the properties of the cooperative fluctuations of the hydrocarbon chains (director fluctuations), as evidenced by the effects of various lipid additives on the 2H NMR transverse relaxation rates of the dimyristoyl lecithin bilayer

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

The nature of the intramolecular hydrogen bond in the enol tautomer of 2,4-pentanedione

NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document. The nature of the intramolecular hydrogen bond in the enol tautomer of 2,4-pentanedione has been studied in detail using high resolution proton, deuteron and [...] magnetic resonance spectroscopy. An unusually large deuterium isotope effect on the chemical shift of the bridge hydrogen has been observed. This unexpected result, together with the observation of a pronounced temperature dependence for both the bridge proton and deuteron resonances, as well as a temperature dependence of the carbonyl resonances, suggest that two states with different chemical shifts for the bridge hydrogen are involved in rapid equilibrium and that the anomalous deuterium isotope effect has its origin in the effect of deuterium substitution on the energy separation between these states. The results of a least-squares analysis of the OH and the OD temperature data in terms of a two-state model indicate that the energy separation for the proton and deuterated systems in the two states are [...] and [...]; but essentially identical chemical shifts were obtained for the OH proton as for the OD deuteron in each state (-14.15 and -10.10 ppm from the enol methyl group respectively). It is proposed that these states correspond to the symmetric and asymmetric structures of the intramoleculax hydrogen bond. Results of our CNDO/2 calculations on the enol tautomer have indicated that these two structures have quite similar energies. In particular, it is suggested that the potential function associated with the vibrational motion of the bridge hydrogen is symmetric double minimum in nature when the donor-acceptor vibration (symmetric stretch) is in its zeroth vibrational state and the potential function becomes asymmetric when the symmetric stretch is excited by one or more vibrational quanta. By exciting the symmetric [...] stretch, we expect a charge shift in the [...] system which can alter the effective potential function for the bridge hydrogen. The [...] transition of the symmetric stretch is observed at [...] in the Raman spectrum of the normal compound and [...] in the deuterated molecule. This difference of [...] in the energy separation of the ground and first excited vibrational states of the symmetric stretch would be expected to give rise to the large deuterium isotope effect observed in our magnetic resonance experiments

High-Resolution Proton Magnetic Resonance Spectra of a Rabbit Sciatic Nerve

Proton magnetic resonance spectra (220-megahertz field) of an isolated rabbit sciatic nerve in its native state have been observed and assigned to the extracellular water, intracellular water, and phospholipids of the nerve. This study indicates that the nerve fibers contain fluid-like hydrophobic regions, in agreement with the results of recent electron spin resonance spin-labeled studies of excitable membranes of nerve and muscle

Hydrophobic mismatch in gramicidin A'/Lecithin systems

Gramicidin A’ (GA’) has been added to three lipid systems of varying hydrophobic thicknesses: dimyristoyllecithin (DML), dipalmitoyllecithin (DPL), and distearoyllecithin (DSL). The similarity in length between the hydrophobic portion of GA’ and the hydrocarbon chains of the lipid bilayers has been studied by using ^(31)P and ^2H NMR. Hydrophobic mismatch has been found to be most severe in the DML bilayer system and minimal in the case of DSL. In addition, the effects of hydrophobic mismatch on the cooperative properties of the bilayer have been obtained from ^2H NMR relaxation measurements. The results indicate that incorporation of the peptide into the bilayer disrupts the cooperative director fluctuations characteristic of pure multilamellar lipid dispersions. Finally, the GA’llecithin ratio at which the well-known transformation from bilayer to reverse hexagonal (H_(II)) phase occurs (Van Echteld et al., 1982; Chupin et al., 1987) is shown to depend on the acyl chain length of the phospholipid. A rationale is proposed for this chain length dependence

The Anomalous Deuterium Isotope Effect on the Chemical Shift of the Bridge Hydrogen in the Enol Tautomer of 2,4-Pentanedione

The nature of the intramolecular hydrogen bond in the enol tautomer of 2,4-pentanedione has been investigated by high resolution proton and deuteron magnetic resonance spectroscopy. An unusually large deuterium isotope effect on the chemical shift of the bridge hydrogen has been observed. This unexpected result, together with the observation of a pronounced temperature dependence for both the proton and deuteron resonances, suggests that two states with different chemical shifts for the bridge hydrogen are involved in rapid equilibrium and that the anomalous deuterium isotope effect has its origin in the effect of deuterium substitution on the energy separation between these states. It is proposed that these states correspond to the symmetrical and asymmetrical structures of the intramolecular hydrogen bond