Probing nanomechanical properties from biomolecules to living cells

Atomic force microscopy is being increasingly used to explore the physical properties of biological structures. This technique involves the application of a force to the sample and a monitoring of the ensuing deformation process. The available experimental setups can be broadly divided into two categories, one of which involves a stretching and the other an indentation of the organic materials. In this review, we will focus on the indentation technique and will illustrate its application to biological materials with examples that range from single molecules to living cell

Gel Electrophoresis of DNA Knots in Weak and Strong Electric Fields

Gel electrophoresis allows to separate knotted DNA (nicked circular) of equal length according to the knot type. At low electric fields, complex knots being more compact, drift faster than simpler knots. Recent experiments have shown that the drift velocity dependence on the knot type is inverted when changing from low to high electric fields. We present a computer simulation on a lattice of a closed, knotted, charged DNA chain drifting in an external electric field in a topologically restricted medium. Using a simple Monte Carlo algorithm, the dependence of the electrophoretic migration of the DNA molecules on the type of knot and on the electric field intensity was investigated. The results are in qualitative agreement with electrophoretic experiments done under conditions of low and high electric fields: especially the inversion of the behavior from low to high electric field could be reproduced. The knot topology imposes on the problem the constrain of self-avoidance, which is the final cause of the observed behavior in strong electric field.Comment: 17 pages, 5 figure

The Swiss Tropical and Public Health Institute: past, present and future

Compared internationally, the history of the Swiss Tropical and Public Health Institute (Swiss TPH) is unusual. Founded in 1944, at a time of utmost isolation, it was a response to specific needs of the government of Switzerland during the Second World War. In 1943, the Swiss Federal Council approached universities in Switzerland and asked them to submit project proposal that had the potential to mitigate possible post-war unemployment and threatening economic isolation. Members of the University of Basel proposed to establish a Swiss Tropical Institute (today: Swiss TPH). With its harbour at the River Rhine, Basel was an important international transport hub. The city was and still is the headquarters of important pharmaceutical companies, such as Novartis Pharma AG and F. Hoffmann-La Roche AG, which were looking for new markets overseas. Last but not least, scientific expeditions to Africa were rather common in the 19(th) and the beginning of the 20(th) century for members of Basel's bourgeoisie. Initially, Swiss TPH focused primarily on basic research into diseases of poverty, but over the years it has developed into an important player in public, international and global health. This article sees the development of the institute as a reflection of the visions of its directors from the founder Professor Rudolf Geigy to Professor Jurg Utzinger, who is the current Swiss TPH director. It includes interviews with the four latest of them, discussing their experiences and attempts to adapt the institute to an ever changing global environment. From these lessons learnt we hope to gain insights that could be relevant for today's leaders of scientific institutes; foster public-private partnerships and contribute to solve some of the most pressing global health challenges

Conformation of Circular DNA in 2 Dimensions

The conformation of circular DNA molecules of various lengths adsorbed in a 2D conformation on a mica surface is studied. The results confirm the conjecture that the critical exponent $\nu$ is topologically invariant and equal to the SAW value (in the present case $\nu=3/4$), and that the topology and dimensionality of the system strongly influences the cross-over between the rigid regime and the self-avoiding regime at a scale $L\approx 8 \ell_p$. Additionally, the bond correlation function scales with the molecular length $L$ as predicted. For molecular lengths $L\leq5 \ell_p$, circular DNA behaves like a stiff molecule with approximately elliptic shape.Comment: 4 pages, 5 figure

Nanomechanical sensor applied to blood culture pellets: a fast approach to determine the antibiotic susceptibility against agents of bloodstream infections.

The management of bloodstream infection, a life-threatening disease, largely relies on early detection of infecting microorganisms and accurate determination of their antibiotic susceptibility to reduce both mortality and morbidity. Recently we developed a new technique based on atomic force microscopy capable of detecting movements of biologic samples at the nanoscale. Such sensor is able to monitor the response of bacteria to antibiotic's pressure, allowing a fast and versatile susceptibility test. Furthermore, rapid preparation of a bacterial pellet from a positive blood culture can improve downstream characterization of the recovered pathogen as a result of the increased bacterial concentration obtained. Using artificially inoculated blood cultures, we combined these two innovative procedures and validated them in double-blind experiments to determine the susceptibility and resistance of Escherichia coli strains (ATCC 25933 as susceptible and a characterized clinical isolate as resistant strain) towards a selection of antibiotics commonly used in clinical settings. On the basis of the variance of the sensor movements, we were able to positively discriminate the resistant from the susceptible E. coli strains in 16 of 17 blindly investigated cases. Furthermore, we defined a variance change threshold of 60% that discriminates susceptible from resistant strains. By combining the nanomotion sensor with the rapid preparation method of blood culture pellets, we obtained an innovative, rapid and relatively accurate method for antibiotic susceptibility test directly from positive blood culture bottles, without the need for bacterial subculture

Erythrocyte's aging in microgravity highlights how environmental stimuli shape metabolism and morphology

The determination of the function of cells in zero-gravity conditions is a subject of interest in many different research fields. Due to their metabolic unicity, the characterization of the behaviour of erythrocytes maintained in prolonged microgravity conditions is of particular importance. Here, we used a 3D-clinostat to assess the microgravity-induced modifications of the structure and function of these cells, by investigating how they translate these peculiar mechanical stimuli into modifications, with potential clinical interest, of the biochemical pathways and the aging processes. We compared the erythrocyte's structural parameters and selected metabolic indicators that are characteristic of the aging in microgravity and standard static incubation conditions. The results suggest that, at first, human erythrocytes react to external stimuli by adapting their metabolic patterns and the rate of consumption of the cell resources. On longer timeframes, the cells translate even small differences in the environment mechanical solicitations into structural and morphologic features, leading to distinctive morphological patterns of agin

Impact of mining projects on water and sanitation infrastructures and associated child health outcomes: a multi-country analysis of Demographic and Health Surveys (DHS) in sub-Saharan Africa

BACKGROUND: Access to improved water and sanitation infrastructures are key determinants of health. The sub-Saharan African region in particular is lagging behind the ambitious goal of the 2030 Agenda for Sustainable Development to ensure universal access to improved and reliable water and sanitation for all (Sustainable Development Goal (SDG) 6). Large mining projects can promote economic growth and hence investments in water and sanitation infrastructures, but at the same time lead to rapid population growth and environmental degradation. In turn, these changes can pose risks and opportunities for child health (SDG 3). In this study we aim to quantify the impacts of mining projects on access to water and sanitation infrastructure as well as diarrhea and malnutrition among children using data from 131 Demographic and Health Surveys from sub-Saharan Africa. RESULTS: From a sample of around 1.2 million households, data within the proximity of 52 mine-panels were selected for longitudinal analyses, resulting in 41,896 households and 32,112 children. Improvements in access to modern water and sanitation infrastructures after mine opening were much larger in households near mining sites than in comparison areas located further away (adjusted relative risk ratio (aRRR) water: 18.60, 95 % confidence interval (CI): 13.08-26.46 and aRRR sanitation: 2.56, 95 % CI: 1.32-4.99). However, these associations were weaker among poorer households. In areas close to the mining sites, stunting and underweight prevalence decreased more strongly upon mine opening (adjusted odds ratio (aOR) stunting: 0.62, 95 % CI: 0.43-0.90; aOR underweight: 0.55, 95 % CI: 0.36-0.84). No differential changes were seen for wasting and diarrhea. Large impact heterogeneity was observed both within and across countries. CONCLUSIONS: Our results suggest that the opening of mines is associated with improvements in access to modern water and sanitation infrastructures (SDG 6) as well as in some health outcomes (SDG 3). However, the large impact heterogeneity suggests that the assessment and management of mining-related impacts on communities should have an increased equity-focus, in order to "leave no one behind" in the work towards the 2030 Agenda for Sustainable Development. Overall, the findings of this study underscore that the resource extraction sector has the potential to make positive and substantial contributions towards achieving the SDGs

Probing nanomechanical properties from biomolecules to living cells.

Atomic force microscopy is being increasingly used to explore the physical properties of biological structures. This technique involves the application of a force to the sample and a monitoring of the ensuing deformation process. The available experimental setups can be broadly divided into two categories, one of which involves a stretching and the other an indentation of the organic materials. In this review, we will focus on the indentation technique and will illustrate its application to biological materials with examples that range from single molecules to living cells

Probing nanomechanical properties from biomolecules to living cells

Atomic force microscopy is being increasingly used to explore the physical properties of biological structures. This technique involves the application of a force to the sample and a monitoring of the ensuing deformation process. The available experimental setups can be broadly divided into two categories, one of which involves a stretching and the other an indentation of the organic materials. In this review, we will focus on the indentation technique and will illustrate its application to biological materials with examples that range from single molecules to living cells

Industrial mining and HIV risk: evidence from 39 mine openings across 16 countries in sub-Saharan Africa

OBJECTIVES: The aim of this study was to assess the impact of natural resource extraction projects on HIV transmission risks in local communities in sub-Saharan Africa. DESIGN: Difference-in-differences design using repeated cross-sectional data from around newly opened mines. METHODS: We combined data on mine openings with HIV data from the Demographic and Health Surveys (DHS). Using logistic regression models, we compared HIV related indicators between mining (i.e. up to 10 km distance from the mine) and comparison (i.e. 10-50 km) areas before and after mine opening to identify their impact on HIV prevalence, sexual behavior and HIV knowledge. RESULTS: A total of 33,086 individuals across 39 mine openings were analyzed. Adjusting for baseline differences and temporal trends in the study regions, mine opening increased the odds of HIV infection almost two-fold (odds ratio (OR): 1.93, 95% confidence interval (CI): 1.19-3.14). Strongest effects were seen in high-prevalence countries and in the 20-29 years age group. In mining communities around operational mines there was a tendency towards lower HIV knowledge (OR: 0.81, 95% CI: 0.63-1.04). New mine openings increased the odds of risky sexual behaviors, such as having multiple sex partners (OR: 1.61, 95% CI: 1.02-2.55), high-risk sexual partners (OR: 1.45, 95% CI: 1.03-2.05) and unprotected sex with high-risk partners (OR: 1.77, 95% CI: 1.18-2.67). CONCLUSION: The findings suggest that in our sample of households surrounding industrial mines, HIV infection risks substantially increase upon mine opening. Existing strategies for addressing mining-related risks for HIV transmission seem to be insufficient. Further efforts for mitigating and monitoring impacts of mines are needed. Video Abstract: http://links.lww.com/QAD/C557