DNA Supercoiling-Induced Shapes Alter Minicircle Hydrodynamic Properties

DNA in cells is organized in negatively supercoiled loops. The resulting torsional and bending strain allows DNA to adopt a surprisingly wide variety of 3-D shapes. This interplay between negative supercoiling, looping, and shape influences how DNA is stored, replicated, transcribed, repaired, and likely every other aspect of DNA activity. To understand the consequences of negative supercoiling and curvature on the hydrodynamic properties of DNA, we submitted 336 bp and 672 bp DNA minicircles to analytical ultracentrifugation (AUC). We found that the diffusion coefficient, sedimentation coefficient, and the DNA hydrodynamic radius strongly depended on circularity, loop length, and degree of negative supercoiling. Because AUC cannot ascertain shape beyond degree of non-globularity, we applied linear elasticity theory to predict DNA shapes, and combined these with hydrodynamic calculations to interpret the AUC data, with reasonable agreement between theory and experiment. These complementary approaches, together with earlier electron cryotomography data, provide a framework for understanding and predicting the effects of supercoiling on the shape and hydrodynamic properties of DNA

Understanding older patients' willingness to have medications deprescribed in primary care: a protocol for a cross-sectional survey study in nine European countries.

INTRODUCTION To reduce inappropriate polypharmacy, deprescribing should be part of patients' regular care. Yet deprescribing is difficult to implement, as shown in several studies. Understanding patients' attitudes towards deprescribing at the individual and country level may reveal effective ways to involve older adults in decisions about medications and help to implement deprescribing in primary care settings. In this study we aim to investigate older adults' perceptions and views on deprescribing in different European countries. Specific objectives are to investigate the patients' willingness to have medications deprescribed by medication type and to have herbal or dietary supplements reduced or stopped, the role of the Patient Typology (on medication perspectives), and the impact of the patient-GP relationship in these decisions. METHODS AND ANALYSIS This cross-sectional survey study has two parts: Part A and Part B. Data collection for Part A will take place in nine countries, in which per country 10 GPs will recruit 10 older patients (≥65 years old) each (n = 900). Part B will be conducted in Switzerland only, in which an additional 35 GPs will recruit five patients each and respond to a questionnaire themselves, with questions about the patients' medications, their willingness to deprescribe those, and their patient-provider relationship. For both Part A and part B, a questionnaire will be used to assess the willingness of older patients with polypharmacy to have medications deprescribed and other relevant information. For Part B, this same questionnaire will have additional questions on the use of herbal and dietary supplements. DISCUSSION The international study design will allow comparisons of patient perspectives on deprescribing from different countries. We will collect information about willingness to have medications deprescribed by medication type and regarding herbal and dietary supplements, which adds important information to the literature on patients' preferences. In addition, GPs in Switzerland will also be surveyed, allowing us to compare GPs' and patients' views and preferences on stopping or reducing specific medications. Our findings will help to understand patients' attitudes towards deprescribing, contributing to improvements in the design and implementation of deprescribing interventions that are better tailored to patients' preferences

Building primary care capacity to treat tobacco dependence: Lessons from evaluating a Teach the Teacher programme in low- and middle-income countries

Smoking and other forms of tobacco use are prevalent in many middle and low-income countries and are a leading preventable cause of non-communicable diseases (NCDs). Primary care is uniquely positioned to deliver support and services for tobacco cessation. However, despite being a cost-effective intervention and globally recognised and mandated by the World Health Organization, tobacco cessation services, such as Very Brief Advice (VBA) are currently underprovided. Scalable capacity building programmes are needed to strengthen the knowledge, confidence and competence of practising clinicians. The International Primary Care Respiratory Group designed and implemented a three-tiered “Teach the Teacher” (TtT) programme to build teaching capacity in treating tobacco dependence in Romania, Bulgaria. North Macedonia, and the Kyrgyz Republic. The TtT model engaged national educators in adapting a core VBA+ curriculum—designed to reflect limited access to pharmacotherapy and specialist services—and cascaded teaching through local networks of primary care professionals. Evaluation of the TtT model showed that while co-developing context-specific curricula for treating tobacco dependence is feasible and effective, sustained success requires structural reforms—such as improving access to cessation support, incentivising providers, and embedding tobacco dependence treatment into national education and policy frameworks. The TtT approach offers a replicable model for rapid capacity-building, but its full potential depends on alignment with broader health system priorities

Labour Supply during Lockdown and a "New Normal": The Case of the Netherlands

We document the evolution of hours of work using monthly data from February to June 2020. During this period, the Netherlands experienced a quick spread of the SARS-CoV-2 virus, enacted a lockdown for a period of six weeks and gradually opened thereafter. We show that during lock-down, substitutability between work from home and at the workplace or essential worker status are key to maintain a large fraction of pre-crisis hours of work. These pandemic-specific mechanisms become much less important as social distancing restrictions are eased in May and June. Labor supply recovers quickly in sectors affected heavily during lockdown, but goes down in other areas of the economy. The latter is unlikely caused by pandemic-induced supply changes; diminished demand is a more plausible explanation. Analyzing take-up of economic support programs, we find suggestive evidence that wage subsidies and other programs helped limit the early-stage impact of the crisis along the extensive margin

Drivers of Working Hours and Household Income Dynamics during the COVID-19 Pandemic: The Case of the Netherlands

Using customized panel data spanning the entire year of 2020, we analyze the dynamics of working hours and household income across different stages of the CoVid-19 pandemic. Similar to many other countries, during this period the Netherlands experienced a quick spread of the SARS-CoV-2 virus, adopted a set of fairly strict social distancing measures, gradually reopened, and imposed another lockdown to contain the second wave. We show that socio-economic status is strongly related to changes in working hours, especially when strict economic restrictions are in place. In contrast, household income is equally unaffected for all socio-economic groups. Examining the drivers of these observations, we find that pandemic-specific job characteristics (the ability to work from home and essential worker status) explain most of the socio-economic gradient in total working hours. Furthermore, household income is largely decoupled from shocks to working hours for employees. We provide suggestive evidence that large-scale labor hoarding schemes have helped insure employees against demand shocks to their employees

Labour Supply in the Early Stages of the COVID-19 Pandemic: Empirical Evidence on Hours, Home Office, and Expectations

Using a survey module administered in late March 2020, we analyze how working hours change under the social distancing regulations enacted to fight the CoViD-19 pandemic. We study the Netherlands, which are a prototypical Western European country, both in terms of its welfare system and its response to the pandemic. We show that total hours decline and more so for the self-employed and those with lower educational degrees. The education gradient appears because workers with a tertiary degree work a much higher number of hours from home. The strength of this effect is dampened by the government defining some workers to be essential for the working of the economy. Across sectors, we show that there are two clusters: One dominated by office-type occupations with high shares of academics, home-office hours, and low fractions of essential workers; and one where manual tasks and social interactions are prevalent with low shares of academics, home office hours, and often high shares of essential workers. Short-term expectations show that workers expect current patterns to prevail and that they expect a lot from government support schemes. In particular, many workers expect to keep their jobs in early June due to government support and the expected unemployment response is far lower than in the U.S. or the U.K.

An empirical assessment of the MODIS land cover dynamics and TIMESAT land surface phenology algorithms

Observations of vegetation phenology at regional-to-global scales provide important information regarding seasonal variation in the fluxes of energy, carbon, and water between the biosphere and the atmosphere. Numerous algorithms have been developed to estimate phenological transition dates using time series of remotely sensed spectral vegetation indices. A key challenge, however, is that different algorithms provide inconsistent results. This study provides a comprehensive comparison of start of season (SOS) and end of season (EOS) phenological transition dates estimated from 500 m MODIS data based on two widely used sources of such data: the TIMESAT program and the MODIS Global Land Cover Dynamics (MLCD) product. Specifically, we evaluate the impact of land cover class, criteria used to identify SOS and EOS, and fitting algorithm (local versus global) on the transition dates estimated from time series of MODIS enhanced vegetation index (EVI). Satellite-derived transition dates from each source are compared against each other and against SOS and EOS dates estimated from PhenoCams distributed across the Northeastern United States and Canada. Our results show that TIMESAT and MLCD SOS transition dates are generally highly correlated (r = 0.51-0.97), except in Central Canada where correlation coefficients are as low as 0.25. Relative to SOS, EOS comparison shows lower agreement and higher magnitude of deviations. SOS and EOS dates are impacted by noise arising from snow and cloud contamination, and there is low agreement among results from TIMESAT, the MLCD product, and PhenoCams in vegetation types with low seasonal EVI amplitude or with irregular EVI time series. In deciduous forests, SOS dates from the MLCD product and TIMESAT agree closely with SOS dates from PhenoCams, with correlations as high as 0.76. Overall, our results suggest that TIMESAT is well-suited for local-to-regional scale studies because of its ability to tune algorithm parameters, which makes it more flexible than the MLCD product. At large spatial scales, where local tuning is not feasible, the MLCD product provides a readily available data set based on a globally consistent approach that provides SOS and EOS dates that are comparable to results from TIMESAT

DNA supercoiling-induced shapes alter minicircle hydrodynamic properties

ABSTRACTDNA in cells is organized in negatively supercoiled loops. The resulting torsional and bending strain allows DNA to adopt a surprisingly wide variety of 3-D shapes. This interplay between negative supercoiling, looping, and shape influences how DNA is stored, replicated, transcribed, repaired, and likely every other aspect of DNA activity. To understand the consequences of negative supercoiling and curvature on the hydrodynamic properties of DNA, we submitted 336 bp and 672 bp DNA minicircles to analytical ultracentrifugation (AUC). We found that the diffusion coefficient, sedimentation coefficient, and the DNA hydrodynamic radius strongly depended on circularity, loop length, and degree of negative supercoiling. Because AUC cannot ascertain shape beyond degree of non-globularity, we applied linear elasticity theory to predict DNA shapes, and combined these with hydrodynamic calculations to interpret the AUC data, with reasonable agreement between theory and experiment. These complementary approaches, together with earlier electron cryotomography data, provide a framework for understanding and predicting the effects of supercoiling on the shape and hydrodynamic properties of DNA.</jats:p