Walks of molecular motors in two and three dimensions

Molecular motors interacting with cytoskeletal filaments undergo peculiar random walks consisting of alternating sequences of directed movements along the filaments and diffusive motion in the surrounding solution. An ensemble of motors is studied which interacts with a single filament in two and three dimensions. The time evolution of the probability distribution for the bound and unbound motors is determined analytically. The diffusion of the motors is strongly enhanced parallel to the filament. The analytical expressions are in excellent agreement with the results of Monte Carlo simulations.Comment: 7 pages, 2 figures, to be published in Europhys. Let

Diffusive hidden Markov model characterization of DNA looping dynamics in tethered particle experiments

In many biochemical processes, proteins bound to DNA at distant sites are brought into close proximity by loops in the underlying DNA. For example, the function of some gene-regulatory proteins depends on such DNA looping interactions. We present a new technique for characterizing the kinetics of loop formation in vitro, as observed using the tethered particle method, and apply it to experimental data on looping induced by lambda repressor. Our method uses a modified (diffusive) hidden Markov analysis that directly incorporates the Brownian motion of the observed tethered bead. We compare looping lifetimes found with our method (which we find are consistent over a range of sampling frequencies) to those obtained via the traditional threshold-crossing analysis (which can vary depending on how the raw data are filtered in the time domain). Our method does not involve any time filtering and can detect sudden changes in looping behavior. For example, we show how our method can identify transitions between long-lived, kinetically distinct states that would otherwise be difficult to discern

The active living gender's gap challenge: 2013-2017 Eurobarometers physical inactivity data show constant higher prevalence in women with no progress towards global reduction goals

BACKGROUND: The World Health Organization (WHO) considers physical inactivity (PIA) as a critical noncommunicable factor for disease and mortality, affecting more women than men. In 2013, the WHO set a 10% reduction of the PIA prevalence, with the goal to be reached by 2025. Changes in the 2013-2017 period of physical inactivity prevalence in the 28 European Union (EU) countries were evaluated to track the progress in achieving WHO 2025 target. METHODS: In 2013 and 2017 EU Special Eurobarometers, the physical activity levels reported by the International Physical Activity Questionnaire of 53,607 adults were analyzed. Data were considered as a whole sample and country-by-country. A χ2 test was used to analyze the physical inactivity prevalence (%) between countries, analyzing women and men together and separately. Additionally, PIA prevalence was analyzed between years (2013-2017) for the overall EU sample and within-country using a Z-Score for two population proportions. RESULTS: The PIA prevalence increased between 2013 and 2017 for the overall EU sample (p <  0.001), and for women (p = 0.04) and men (p < 0.001) separately. Data showed a higher PIA prevalence in women versus men during both years (p <  0.001). When separately considering changes in PIA by gender, only Belgium's women and Luxembourg's men showed a reduction in PIA prevalence. Increases in PIA prevalence over time were observed in women from Austria, Croatia, Germany, Lithuania, Malta, Portugal, Romania, and Slovakia and in men from Bulgaria, Croatia, Czechia, Germany, Italy, Lithuania, Portugal, Romania, Slovakia, and Spain. CONCLUSIONS: PIA prevalence showed an overall increase across the EU and for both women and men between 2013 and 2017, with higher rates of PIA reported for women versus men during both years. PIA prevalence was reduced in only Belgium's women and Luxembourg's men. Our data indicate a limited gender-sensible approach while tacking PIA prevalence with no progress reaching global voluntary reductions of PIA for 2025

Tuning the translational freedom of DNA for high speed AFM

Direct observation is arguably the preferred way to investigate the interactions between two molecular complexes. With the development of high speed atomic force microscopy it is becoming possible to observe directly DNA protein interactions with relevant spatial and temporal resolutions. These interactions are of central importance to biology, bio-nanotechnology but also functional biologically inspired materials. Critically, sample preparation plays a central role in all microscopy studies and minimal perturbation of the sample is desired. Here, we demonstrate the ability to tune the interactions of DNA molecules with the surface such that an association strong enough to enable high resolution AFM imaging while providing sufficient translational freedom to allow the relevant protein DNA interactions to take place, can be maintained. Furthermore, we describe a quantitative method for measuring the DNA mobility, which also allows the dissection of the different contributions to the overall movement of the DNA molecules. We find that for weak surface association, a significant contribution to the movement arises from the interaction of the AFM tip with the DNA. In combination, these methods enable the tuning of the surface translational freedom of DNA molecules to allow the direct study of a wide range of nucleo-protein interactions by high speed atomic force microscopy

Prevalence and socio-demographic correlates of physical activity levels among South African adults in Cape Town and Mount Frere communities in 2008-2009

BACKGROUND: Physical activity has been linked to reduced risk of various cardiometabolic disease, cancer, and premature mortality. We investigated the prevalence and socio-demographic correlates of physical activity among adults in urban and rural communities in South Africa. METHODS: This was a cross-sectional survey comprising 1733 adults aged ?35 years from the Cape Town (urban) and Mount Frere (rural) sites of the Prospective Urban Rural Epidemiology study. Physical activity was assessed using the validated International Physical Activity Questionnaire. Multinomial logistic regressions were used to relate physical activity with socio-demographic characteristics. RESULTS: Overall, 74% of participants engaged in moderate-to-vigorous physical activity. In the adjusted regression models, women were 34% less likely to engage in vigorous physical activity (OR =0.66, 95%-CI = 0.47-0.93). Physical activity decreased with age, varied with marital status, education and occupation, always in differential ways between urban and rural participants (all interactions p ? 0.047). For instance, in urban settings, those with secondary education were more likely to engage in moderate physical activity (OR = 2.06, 95%-CI = 1.08-3.92) than those with tertiary education. Single people were more likely to engage in high physical activity (OR = 2.10, 95%-CI = 1.03-4.28) than divorced. Overall, skilled participants were more likely to engage in vigorous physical activity (OR = 2.07, 95%-CI = 1.41-3.05) driven by significant effect in rural area (OR = 2.70, 95%-CI = 1.51-4.83). Urban participants were more likely to engage in moderate physical activity (OR = 1.67, 95%-CI = 1.31-2.13) than rural participants. CONCLUSIONS: To prevent chronic diseases among South Africans, attention should be paid to specific policies and interventions aimed at promoting PA among young adults in rural and urban setting, and across the social-economic diversity

The Mechanical Properties of Individual, Electrospun Fibrinogen Fibers

We used a combined atomic force microscope (AFM)/fluorescence microscope technique to study the mechanical properties of individual, electrospun fibrinogen fibers in aqueous buffer. Fibers (average diameter 208 nm) were suspended over 12 μm-wide grooves in a striated, transparent substrate. The AFM, situated above the sample, was used to laterally stretch the fibers and to measure the applied force. The fluorescence microscope, situated below the sample, was used to visualize the stretching process. The fibers could be stretched to 2.3 times their original length before breaking; the breaking stress was 22·106 Pa. We collected incremental stress-strain curves to determine the viscoelastic behavior of these fibers. The total stretch modulus was 16·106 Pa and the relaxed, elastic modulus was 6.7·106 Pa. When held at constant strain, electrospun fibrinogen fibers showed a fast and slow stress relaxation time of 3 and 56 seconds. Our fibers were spun from the typically used 90% 1,1,1,3,3,3-hexafluoro-2-propanol (90-HFP) electrospinning solution and resuspended in aqueous buffer. Circular dichroism spectra indicate that alpha-helical content of fibrinogen is ~70% higher in 90-HFP than in aqueous solution. These data are needed to understand the mechanical behavior of electrospun fibrinogen structures. Our technique is also applicable to study other, nanoscopic fibers

Recent advances in understanding hypertension development in sub-Saharan Africa

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the Human Immunodeficiency Virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions, as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies, and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa

Fibrin Fibers Have Extraordinary Extensibility and Elasticity

Blood clots perform an essential mechanical task, yet the mechanical behavior of fibrin fibers, which form the structural framework of a clot, is largely unknown. By using combined atomic force-fluorescence microscopy, we determined the elastic limit and extensibility of individual fibers. Fibrin fibers can be strained 180% (2.8-fold extension) without sustaining permanent lengthening, and they can be strained up to 525% (average 330%) before rupturing. This is the largest extensibility observed for protein fibers. The data imply that fibrin monomers must be able to undergo sizeable, reversible structural changes and that deformations in clots can be accommodated by individual fiber stretching

Changing emotional engagement with running through communal self-tracking: The implications of ‘teleoaffective shaping’ for public health,

Emerging research explores the role of self-tracking in supporting healthy behaviour. Self-tracking comprises a number of interrelated practices; some individual some communal. In this paper we focus on practices that enable interaction between self-trackers through data sharing and communication around personal data. For public health, communal self-tracking has been explored for the additional benefits it provides in addition to self-knowledge. However, under-explored is the emotional entanglement of self-tracking and tracked activities, or the role of practitioners in the dynamic evolution of tracked practices. Qualitative, mixed methods data was collected from leisure-time runners in the SW England who self-track using social fitness app ‘Strava’, and was interpreted through the lens of practice theory. We find that communal self-tracking affords the active shaping of the emotion and purpose of running. This ‘teleoaffective shaping’ allows practitioners to negotiate and reconstitute appealing meanings associated with running to protect their practice loyalty. We identify three mechanisms for teleoaffective shaping afforded by Strava: labelling, reward and materialising effort. Findings advance our understanding of how social fitness apps work to retain practitioners of physically active leisure practices. Future research should further explore the multiple ways that associations with tracked physical activity evolve through entanglement with self-tracking practices

A Comparison of the Mechanical and Structural Properties of Fibrin Fibers with Other Protein Fibers

In the past few years a great deal of progress has been made in studying the mechanical and structural properties of biological protein fibers. Here, we compare and review the stiffness (Young's modulus, E) and breaking strain (also called rupture strain or extensibility, εmax) of numerous biological protein fibers in light of the recently reported mechanical properties of fibrin fibers. Emphasis is also placed on the structural features and molecular mechanisms that endow biological protein fibers with their respective mechanical properties. Generally, stiff biological protein fibers have a Young's modulus on the order of a few Gigapascal and are not very extensible (εmax 100%). These soft, extensible fibers employ a variety of molecular mechanisms, such as extending amorphous regions or unfolding protein domains, to accommodate large strains. We conclude our review by proposing a novel model of how fibrin fibers might achieve their extremely large extensibility, despite the regular arrangement of the monomeric fibrin units within a fiber. We propose that fibrin fibers accommodate large strains by two major mechanisms: (1) an α-helix to β-strand conversion of the coiled coils; (2) a partial unfolding of the globular C-terminal domain of the γ-chain