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

Superdiffusion in a Model for Diffusion in a Molecularly Crowded Environment

We present a model for diffusion in a molecularly crowded environment. The model consists of random barriers in percolation network. Random walks in the presence of slowly moving barriers show normal diffusion for long times, but anomalous diffusion at intermediate times. The effective exponents for square distance versus time usually are below one at these intermediate times, but can be also larger than one for high barrier concentrations. Thus we observe sub- as well as super-diffusion in a crowded environment.Comment: 8 pages including 4 figure

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

Salerno's model of DNA reanalysed: could solitons have biological significance?

We investigate the sequence-dependent behaviour of localised excitations in a toy, nonlinear model of DNA base-pair opening originally proposed by Salerno. Specifically we ask whether ``breather'' solitons could play a role in the facilitated location of promoters by RNA polymerase. In an effective potential formalism, we find excellent correlation between potential minima and {\em Escherichia coli} promoter recognition sites in the T7 bacteriophage genome. Evidence for a similar relationship between phage promoters and downstream coding regions is found and alternative reasons for links between AT richness and transcriptionally-significant sites are discussed. Consideration of the soliton energy of translocation provides a novel dynamical picture of sliding: steep potential gradients correspond to deterministic motion, while ``flat'' regions, corresponding to homogeneous AT or GC content, are governed by random, thermal motion. Finally we demonstrate an interesting equivalence between planar, breather solitons and the helical motion of a sliding protein ``particle'' about a bent DNA axis.Comment: Latex file 20 pages, 5 figures. Manuscript of paper to appear in J. Biol. Phys., accepted 02/09/0

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

Determining the mechanical properties of electrospun poly-ε-caprolactone (PCL) nanofibers using AFM and a novel fiber anchoring technique

Due to its low cost, biocompatibility and slow bioresorption, poly-ε-caprolactone (PCL) continues to be a suitable material for select biomedical engineering applications. We used a combined atomic force microscopy (AFM)/optical microscopy technique to determine key mechanical properties of individual electrospun PCL nanofibers with diameters between 440–1040 nm. Compared to protein nanofibers, PCL nanofibers showed much lower adhesion, as they slipped on the substrate when mechanically manipulated. We, therefore, first developed a novel technique to anchor individual PCL nanofibers to micrometer-sized ridges on a substrate, and then mechanically tested anchored nanofibers. When held at constant strain, tensile stress relaxed with fast and slow relaxation times of 1.0 ± 0.3 s and 8.8 ± 3.1 s, respectively. The total tensile modulus was 62 ± 26 MPa, the elastic (non-relaxing) component of the tensile modulus was 53 ± 36 MPa. Individual PCL fibers could be stretched elastically (without permanent deformation) to strains of 19–23%. PCL nanofibers are rather extensible; they could be stretched to a strain of at least 98%, and a tensile strength of at least 12 MPa, before they slipped off the AFM tip. PCL nanofibers that had aged for over a month at ambient conditions became stiffer and less elastic. Our technique provides accurate nanofiber mechanical data, which are needed to guide construction of scaffolds for cells and other biomedical devices

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

National, regional, and global trends in insufficient physical activity among adults from 2000 to 2022:A pooled analysis of 507 population-based surveys with 5·7 million participants

Background Insufficient physical activity increases the risk of non-communicable diseases, poor physical and cognitivefunction, weight gain, and mental ill-health. Global prevalence of adult insufficient physical activity was last publishedfor 2016, with limited trend data. We aimed to estimate the prevalence of insufficient physical activity for 197 countriesand territories, from 2000 to 2022.Methods We collated physical activity reported by adults (aged ≥18 years) in population-based surveys. Insufficientphysical activity was defined as not doing 150 minutes of moderate-intensity activity, 75 minutes of vigorous-intensityactivity, or an equivalent combination per week. We used a Bayesian hierarchical model to compute estimates ofinsufficient physical activity by country or territory, year, age, and sex. We assessed whether countries or territories,regions, and the world would meet the global target of a 15% relative reduction of the prevalence of insufficientphysical activity by 2030 if 2010–22 trends continue.Findings We included 507 surveys across 163 countries and territories. The global age-standardised prevalence ofinsufficient physical activity was 31·3% (95% uncertainty interval 28·6–34·0) in 2022, an increase from 23·4%(21·1–26·0) in 2000 and 26·4% (24·8–27·9) in 2010. Prevalence was increasing in 103 (52%) of 197 countries andterritories and six (67%) of nine regions, and was declining in the remainder. Prevalence was 5 percentage pointshigher among female (33·8% [29·9–37·7]) than male (28·7% [25·0–32·6]) individuals. Insufficient physical activityincreased in people aged 60 years and older in all regions and both sexes, but age patterns differed for those youngerthan 60 years. If 2010–22 trends continue, the global target of a 15% relative reduction between 2010 and 2030 will notbe met (posterior probability &lt;0·01); however, two regions, Oceania and sub-Saharan Africa, were on track withconsiderable uncertainty (posterior probabilities 0·70–0·74).Interpretation Concerted multi-sectoral efforts to reduce insufficient physical activity levels are needed to meet the2030 target. Physical activity promotion should not exacerbate sex, age, or geographical inequalities