Dynamical hierarchy in transition states: Why and how does a system climb over the mountain?

How a reacting system climbs through a transition state during the course of a reaction has been an intriguing subject for decades. Here we present and quantify a technique to identify and characterize local invariances about the transition state of an N-particle Hamiltonian system, using Lie canonical perturbation theory combined with microcanonical molecular dynamics simulation. We show that at least three distinct energy regimes of dynamical behavior occur in the region of the transition state, distinguished by the extent of their local dynamical invariance and regularity. Isomerization of a six-atom Lennard--Jones cluster illustrates this: up to energies high enough to make the system manifestly chaotic, approximate invariants of motion associated with a reaction coordinate in phase space imply a many-body dividing hypersurface in phase space that is free of recrossings even in a sea of chaos. The method makes it possible to visualize the stable and unstable invariant manifolds leading to and from the transition state, i.e., the reaction path in phase space, and how this regularity turns to chaos with increasing total energy of the system. This, in turn, illuminates a new type of phase space bottleneck in the region of a transition state that emerges as the total energy and mode coupling increase, which keeps a reacting system increasingly trapped in that region.     

Physical functioning as a predictor of retirement: Has its importance changed over a thirty-year period in Sweden?

Many countries, including Sweden, are implementing policies aimed at delaying retirement and encouraging older workers to remain on the labour market for longer. During recent decades, there have been several major reforms to the pension and social security systems in Sweden. Moreover, the nature of occupations has shifted towards more non-manual and sedentary activities, older women are today almost as active in the labour market as men in Sweden, and physical functioning has improved over time. In this study, we investigate whether the importance of physical functioning as a predictor for retirement has changed over time, for women and men, respectively. We used four waves of nationally representative data from The Swedish Level of Living Survey from 1981, 1991, 2000, and 2010, together with income register data. We found that greater severity of musculoskeletal pain and mobility limitations increased the likelihood of retirement in all waves. Results from logistic regression models with average marginal effects and predictive margins showed that there is a trend towards physical functioning becoming less important for retirement towards the end of the study period, especially for women, when controlling for occupational-based social class, age, adverse physical working conditions, and job demands. People, especially women, reporting impaired physical functioning did not retire to the same extent as in previous decades. This indicates that people stayed longer in the labour market despite impaired physical functioning, which may have repercussions on well-being and quality of life.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10433-022-00725-y.     

Genetic diversity of PfEMP1-DBL 1-α and its association with severe malaria in a hyperendemic state of India

ObjectiveTo find out the extent of duffy-binding-like (DBL) αgene diversity and the rosetting potential of the parasite population in association with severe malaria.MethodsGenotyping of DBLα domain was done by PCR using three sets of primers (FR, F1R2 and F2R2) and the rosetting frequency was assessed by parasite culture followed by ethidium bromide staining and visualization under a fluorescent microscope.ResultsThe significant association of high parasite density with severe malaria and the positive correlation between rosetting frequency and parasite density in vivo (ρ = 0.613, P< 0.0001) were observed. Moreover, the parasite strains having multiple fragments of F2R2 region and ‘b’ variant of FR region of DBL 1-α showed increased rosetting frequency and supported the strain specific association of disease severity.ConclusionsThe findings suggest that rosetting mediated higher parasitemia might have contributed to the development of severe disease. As the rosetting domain of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), the DBLα binds to multiple host receptors; the significant association of multiple fragments of F2R2 region with severe malaria suggests several receptor-ligand interactions as the possible mechanisms of pathogenesis. Alternatively, the high percentage distribution of smaller fragments with mild malaria suggests the lack of adequate rosetting epitopes that might have contributed to low rosetting frequency in mild malaria.     

Establishment of a nonradioactive assay for 2′-5′ oligoadenylate synthetase and its application in chronic hepatitis C patients receiving interferon-α

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Identification of 7α-hydroxypregnenolone, a novel bioactive amphibian neurosteroid stimulating locomotor activity, and its physiological roles in the regulation of locomotion

We now know that steroids can be synthesized de novo by the brain and the peripheral nervous system. Such steroids are called neurosteroids and de novo neurosteroidogenesis from cholesterol is a conserved property of vertebrate brains. Our studies over the past decade have demonstrated that the brain expresses several kinds of steroidogenic enzymes and produces a variety of neurosteroids in sub-mammalian species. However, neurosteroid biosynthetic pathways in amphibians, as well as other vertebrates may still not be fully mapped. We first found that the newt brain actively produces 7α-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. We then demonstrated that 7α-hydroxypregnenolone acts as a novel bioactive neurosteroid to stimulate locomotor activity of newt by means of the dopaminergic system. Subsequently, we analyzed the physiological roles of 7α-hydroxypregnenolone in the regulation of locomotor activity of newt. This paper summarizes the advances made in our understanding of 7α-hydroxypregnenolone, a newly discovered bioactive amphibian neurosteroid stimulating locomotor activity, and its physiological roles in the regulation of locomotion in newt.