The helix is a common secondary structural motif found in proteins, and the mechanism of helix-coil interconversion is key to understanding the protein-folding problem. We report the observation of the fast kinetics (nanosecond to millisecond) of helix melting in a small 21-residue alanine-based peptide. The unfolding reaction is initiated using a laser-induced temperature jump and probed using time-resolved infrared spectroscopy. The model peptide exhibits fast unfolding kinetics with a time constant of 160 +/- 60 ns at 28 degrees C in response to a laser-induced temperature jump of 18 degrees C which is completed within 20 ns. Using the unfolding time and the measured helix-coil equilibrium constant of the model peptide, a folding rate constant of approximately 6 x 10(7) s-1 (t1/2 = 16 ns) can be inferred for the helix formation reaction at 28 degrees C. These results demonstrate that secondary structure formation is fast enough to be a key event at early times in the protein-folding process and that helices are capable of forming before long range tertiary contacts are made.

Population ageing is rapidly becoming a global issue and will have a major impact on health policies and programmes. The World Health Organization's Study on global AGEing and adult health (SAGE) aims to address the gap in reliable data and scientific knowledge on ageing and health in low- and middle-income countries. SAGE is a longitudinal study with nationally representative samples of persons aged 50+ years in China, Ghana, India, Mexico, Russia and South Africa, with a smaller sample of adults aged 18-49 years in each country for comparisons. Instruments are compatible with other large high-income country longitudinal ageing studies. Wave 1 was conducted during 2007-2010 and included a total of 34 124 respondents aged 50+ and 8340 aged 18-49. In four countries, a subsample consisting of 8160 respondents participated in Wave 1 and the 2002/04 World Health Survey (referred to as SAGE Wave 0). Wave 2 data collection will start in 2012/13, following up all Wave 1 respondents. Wave 3 is planned for 2014/15. SAGE is committed to the public release of study instruments, protocols and meta- and micro-data: access is provided upon completion of a Users Agreement available through WHO's SAGE website (www.who.int/healthinfo/systems/sage) and WHO's archive using the National Data Archive application (http://apps.who.int/healthinfo/systems/surveydata).

We report the fast relaxation dynamics of ''native'' apomyoglobin (pH 5.3) following a 10-ns, laserinduced temperature jump. The structural dynamics are probed using time-resolved infrared spectroscopy. The infrared kinetics monitored within the amide I absorbance of the polypeptide backbone exhibit two distinct relaxation phases which have different spectral signatures and occur on very different time scales ( ‫؍‬ 1633 cm ؊1 , ‫؍‬ 48 ns; ‫؍‬ 1650 cm ؊1 , ‫؍‬ 132 s). We assign these two spectral components to discrete substructures in the protein: helical structure that is solvated (1633 cm ؊1 ) and native helix that is protected from solvation by interhelix tertiary interactions (1650 cm ؊1 ). Folding rate coefficients inferred from the observed relaxations at 60؇C are k f(solvated) ‫؍‬ (7 to 20) ؋ 10 6 s ؊1 and k f(native) ‫؍‬ 3.6 ؋ 10 3 s ؊1 , respectively. The faster rate is interpreted as the intrinsic rate of solvated helix formation, whereas the slower rate is interpreted as the rate of formation of tertiary contacts that determine a native helix. Thus, at 60؇C helix formation precedes the formation of tertiary structure by over three orders of magnitude in this protein. Furthermore, the distinct thermodynamics and kinetics observed for the apomyoglobin substructures suggest that they fold independently, or quasi-independently. The observation of inhomogeneous folding for apomyoglobin is remarkable, given the relatively small size and structural simplicity of this protein.The mechanisms by which a protein searches vast conformational space to attain its native fold in reasonable times and by which the three-dimensional structure is encoded in the primary sequence have not been resolved experimentally. In particular, the critical early-time structural dynamics which carry a protein along the pathway(s) from extended, disordered conformations to a compact fold are poorly characterized. A major impediment has been the conventional solutionmixing approach to initiation of a folding reaction, which imposes a short-time observation limit of greater than 1 ms.

Objectives Limited evidence is available on HIV, aging and comorbidities in sub-Saharan Africa. This article describes the prevalence of HIV and chronic comorbidities among those aged 50 years and older in South Africa using nationally representative data. Design The WHO’s Study of global AGEing and adult health (SAGE) was conducted in South Africa in 2007–2008. SAGE includes nationally representative cohorts of persons aged 50 years and older, with comparison samples of those aged 18–49 years, which aims to study health and its determinants. Methods Logistic and linear regression models were applied to data from respondents aged 50 years and older to determine associations between age, sex and HIV status and various outcome variables including prevalence of seven chronic conditions. Results HIV prevalence among adults aged 50 and older in South Africa was 6.4% and was particularly elevated among Africans, women aged 50–59 and those living in rural areas. Rates of chronic disease were higher among all older adults compared with those aged 18–49. Of those aged 50 years and older, 29.6% had two or more of the seven chronic conditions compared with 8.8% of those aged 18–49 years (P < 0.0001). When controlling for age and sex among those aged 50 and older, BMI was lower among HIV-infected older adults aged 50 and older (27.5 kg/m2) than in HIV-uninfected individuals of the same age (30.6) (P < 0.0001). Grip strength among HIV-infected older adults was significantly (P=0.004) weaker than among similarly-aged HIV-uninfected individuals. Conclusion HIV-infected older adults in South Africa have high rates of chronic disease and weakness. Studies are required to examine HIV diagnostics and treatment instigation rates among older adults to ensure equity of access to quality care, as the number and percentage of older adults living with HIV is likely to increase.

Diagrammatic perturbation theory combined with a spherical tensor treatment allows the degenerate four-wave mixing (DFWM) signal resulting from an isotropic molecular sample to be decomposed into a sum of three multipole moments in the weak-field (no saturation) limit. The zeroth moment gives the relative internal-state population contribution, the first moment the orientation contribution, and the second moment the alignment contribution to the DFWM spectra. This treatment makes explicit how the magnitude of the DFWM signal depends on the polarizations of the other three beams and the collisional relaxation caused by the environment. A general expression is derived for the DFWM signal for an arbitrary geometric configuration of the beams (arbitrary phase matching geometry). Under the assumption that the rates of collisional relaxation of the population, the orientation, and the alignment are the same, simple analytic expressions are found for the most commonly used experimental configurations, which should facilitate the practical analysis of DFWM spectra.

The high cooperation rate and quality of the spots collected suggest that the collection of DBSs in population-based research is a feasible and viable alternative to venous blood draws. The relative ease of sample collection, transport, and storage are significant benefits. Care should be taken, however, when comparing results from analysis of DBS samples with those obtained from serum or plasma samples.

Sensory function is important in studies of aging and health both because it is an important health outcome and also because a decline in functioning can be symptomatic of or predict other health conditions. Although the objective measures provide considerably more precision than the self-report items, the latter can be valuable for imputation of missing data and for understanding differences in how older adults perceive their own sensory ability.

The fast relaxation dynamics of the acid destabilized I form of apomyoglobin (pH* 3, 0.15 M NaCl; apoMb-I) following a laser-induced temperature-jump have been probed using time-resolved infrared spectroscopy. Only a fast, single exponential phase is observed (bleach centered at v = 1633 cm-1 and transient absorbance at 1666 cm-1) with relaxation times of 38 ns at 30 degrees C and 36 ns at 57 degrees C; no additional slow (microsecond) phase is observed as previously found in the native form of apomyoglobin. Folding times of approximately 66 ns are derived from the observed rates based on a simple two-state model. The equilibrium melting of the 1633 cm-1 component shows noncooperative linear behavior over the temperature range studied (10-60 degrees C). The low amide I' frequency, the fast relaxation dynamics, and the noncooperative melting behavior are characteristic of isolated solvated helix. The analysis of the amide-I' band reveals another major component at 1650 cm-1 assigned to native-like structure stabilized by tertiary contacts involving the AGH core, which does not show dynamic or static melting under our conditions. ApoMb-I has generally been taken to be a "molten globule" species. The present results indicate a heterogeneous structure consisting of separate regions of native-like unit(s), solvated helices, and disordered coil, excluding a homogeneous molten globule as a model for apoMb-I. From the current studies and other results, a detailed model of the folding of apomyoglobin is presented.