A universal fluid cell for the imaging of biological specimens in the atomic force microscope.

Recently, atomic force microscope (AFM) manufacturers have begun producing instruments specifically designed to image biological specimens. In most instances, they are integrated with an inverted optical microscope, which permits concurrent optical and AFM imaging. An important component of the set-up is the imaging chamber, whose design determines the nature of the experiments that can be conducted. Many different imaging chamber designs are available, usually designed to optimize a single parameter, such as the dimensions of the substrate or the volume of fluid that can be used throughout the experiment. In this report, we present a universal fluid cell, which simultaneously optimizes all of the parameters that are important for the imaging of biological specimens in the AFM. This novel imaging chamber has been successfully tested using mammalian, plant, and microbial cells.

Impact of thermal proofing of a church on its indoor air-quality - The combustion of candles and incense as a source of pollution

Some years ago, a parish in Geneva decided to reduce heating costs by insulating its church to make it more energy efficient. Three years after the last renovations, it was observed that the internal surfaces of the naves had already become dusty compared with the customary frequency of 10-12 years. Dust even deposited on various surfaces during religious services. Our investigation showed that nearly all the dust found inside the church may in fact be soot from incense and candle combustion. Incense appears to be a significant source of polycyclic aromatic hydrocarbons. With a mechanical ventilation system and petrol lamps resembling candles the problem can be resolved.

Fungal co-culture as a new source of antifungal metabolites

Background: Over the last two decades, mortality from coronary heart disease (CHD) and cerebrovascular disease (CVD) declined by about 30% in the European Union (EU). Design: We analyzed trends in CHD (X ICD codes: I20-I25) and CVD (X ICD codes: I60-I69) mortality in young adults (age 35-44 years) in the EU as a whole and in 12 selected European countries, over the period 1980-2007. Methods: Data were derived from the World Health Organization mortality database. With joinpoint regression analysis, we identified significant changes in trends and estimated average annual percent changes (AAPC). Results: CHD mortality rates at ages 35-44 years have decreased in both sexes since the 1980s for most countries, except for Russia (130/100,000 men and 24/100,000 women, in 2005-7). The lowest rates (around 9/100,000 men, 2/100,000 women) were in France, Italy and Sweden. In men, the steepest declines in mortality were in the Czech Republic (AAPC = -6.1%), the Netherlands (-5.2%), Poland (-4.5%), and England and Wales (-4.5%). Patterns were similar in women, though with appreciably lower rates. The AAPC in the EU was -3.3% for men (rate = 16.6/100,000 in 2005-7) and -2.1% for women (rate = 3.5/100,000). For CVD, Russian rates in 2005-7 were 40/100,000 men and 16/100,000 women, 5 to 10-fold higher than in most western European countries. The steepest declines were in the Czech Republic and Italy for men, in Sweden and the Czech Republic for women. The AAPC in the EU was -2.5% in both sexes, with steeper declines after the mid-late 1990s (rates = 6.4/100,000 men and 4.3/100,000 women in 2005-7). Conclusions: CHD and CVD mortality steadily declined in Europe, except in Russia, whose rates were 10 to 15-fold higher than those of France, Italy or Sweden. Hungary and Poland, and also Scotland, where CHD trends were less favourable than in other western European countries, also emerge as priorities for preventive interventions.

When do we dare to stop biological or immunomodulatory therapy for Crohn's disease? Results of a multidisciplinary European expert panel.

BACKGROUND: Safety and economic issues have increasingly raised concerns about the long term use of immunomodulators or biologics as maintenance therapies for Crohn's disease (CD). Despite emerging evidence suggesting that stopping therapy might be an option for low risk patients, criteria identifying target groups for this strategy are missing, and there is a lack of recommendations regarding this question. METHODS: Multidisciplinary European expert panel (EPACT-II Update) rated the appropriateness of stopping therapy in CD patients in remission. We used the RAND/UCLA Appropriateness Method, and included the following variables: presence of clinical and/or endoscopic remission, CRP level, fecal calprotectin level, prior surgery for CD, and duration of remission (1, 2 or 4 years). RESULTS: Before considering withdrawing therapy, the prerequisites of a C-reactive protein (CRP) and fecal calprotectin measurement were rated as "appropriate" by the panellists, whereas a radiological evaluation was considered as being of "uncertain" appropriateness. Ileo-colonoscopy was considered appropriate 1 year after surgery or after 4 years in the absence of prior surgery. Stopping azathioprine, 6-mercaptopurine or methotrexate mono-therapy was judged appropriate after 4 years of clinical remission. Withdrawing anti-TNF mono-therapy was judged appropriate after 2 years in case of clinical and endoscopic remission, and after 4 years of clinical remission. In case of combined therapy, anti-TNF withdrawal, while continuing the immunomodulator, was considered appropriate after two years of clinical remission. CONCLUSION: A multidisciplinary European expert panel proposed for the first time treatment stopping rules for patients in clinical and/or endoscopic remission, with normal CRP and fecal calprotectin levels.

Mate and fuse: how yeast cells do it.

Many cells are able to orient themselves in a non-uniform environment by responding to localized cues. This leads to a polarized cellular response, where the cell can either grow or move towards the cue source. Fungal haploid cells secrete pheromones to signal mating, and respond by growing a mating projection towards a potential mate. Upon contact of the two partner cells, these fuse to form a diploid zygote. In this review, we present our current knowledge on the processes of mating signalling, pheromone-dependent polarized growth and cell fusion in Saccharomyces cerevisiae and Schizosaccharomyces pombe, two highly divergent ascomycete yeast models. While the global architecture of the mating response is very similar between these two species, they differ significantly both in their mating physiologies and in the molecular connections between pheromone perception and downstream responses. The use of both yeast models helps enlighten both conserved solutions and species-specific adaptations to a general biological problem.

Lifelong dynamics of human CD4+CD25+ regulatory T cells: insights from in vivo data and mathematical modeling.

Despite their limited proliferation capacity, regulatory T cells (T(regs)) constitute a population maintained over the entire lifetime of a human organism. The means by which T(regs) sustain a stable pool in vivo are controversial. Using a mathematical model, we address this issue by evaluating several biological scenarios of the origins and the proliferation capacity of two subsets of T(regs): precursor CD4(+)CD25(+)CD45RO(-) and mature CD4(+)CD25(+)CD45RO(+) cells. The lifelong dynamics of T(regs) are described by a set of ordinary differential equations, driven by a stochastic process representing the major immune reactions involving these cells. The model dynamics are validated using data from human donors of different ages. Analysis of the data led to the identification of two properties of the dynamics: (1) the equilibrium in the CD4(+)CD25(+)FoxP3(+)T(regs) population is maintained over both precursor and mature T(regs) pools together, and (2) the ratio between precursor and mature T(regs) is inverted in the early years of adulthood. Then, using the model, we identified three biologically relevant scenarios that have the above properties: (1) the unique source of mature T(regs) is the antigen-driven differentiation of precursors that acquire the mature profile in the periphery and the proliferation of T(regs) is essential for the development and the maintenance of the pool; there exist other sources of mature T(regs), such as (2) a homeostatic density-dependent regulation or (3) thymus- or effector-derived T(regs), and in both cases, antigen-induced proliferation is not necessary for the development of a stable pool of T(regs). This is the first time that a mathematical model built to describe the in vivo dynamics of regulatory T cells is validated using human data. The application of this model provides an invaluable tool in estimating the amount of regulatory T cells as a function of time in the blood of patients that received a solid organ transplant or are suffering from an autoimmune disease.

The connectome mapper: an open-source processing pipeline to map connectomes with MRI.

Researchers working in the field of global connectivity analysis using diffusion magnetic resonance imaging (MRI) can count on a wide selection of software packages for processing their data, with methods ranging from the reconstruction of the local intra-voxel axonal structure to the estimation of the trajectories of the underlying fibre tracts. However, each package is generally task-specific and uses its own conventions and file formats. In this article we present the Connectome Mapper, a software pipeline aimed at helping researchers through the tedious process of organising, processing and analysing diffusion MRI data to perform global brain connectivity analyses. Our pipeline is written in Python and is freely available as open-source at www.cmtk.org.

What spatial data do we need to develop global mammal conservation strategies?

Spatial data on species distributions are available in two main forms, point locations and distribution maps (polygon ranges and grids). The first are often temporally and spatially biased, and too discontinuous, to be useful (untransformed) in spatial analyses. A variety of modelling approaches are used to transform point locations into maps. We discuss the attributes that point location data and distribution maps must satisfy in order to be useful in conservation planning. We recommend that before point location data are used to produce and/or evaluate distribution models, the dataset should be assessed under a set of criteria, including sample size, age of data, environmental/geographical coverage, independence, accuracy, time relevance and (often forgotten) representation of areas of permanent and natural presence of the species. Distribution maps must satisfy additional attributes if used for conservation analyses and strategies, including minimizing commission and omission errors, credibility of the source/assessors and availability for public screening. We review currently available databases for mammals globally and show that they are highly variable in complying with these attributes. The heterogeneity and weakness of spatial data seriously constrain their utility to global and also sub-global scale conservation analyses.

Coulier, Paul-Jean (1824-1890) : a precursor in the history of fingermark detection and their potential use for identifying their source (1863)

An online copy of a 1863 French book, The Scientific and Industrial Year (English translation of the title), that predates other historically significant writings about fingerprints suggests the use of iodine stains to reproduce papillary lines of the skin and suggests the feasibility of identifying suspects by touch. It also suggests the use of a magnifying glass for comparing those impressions whose origins need to be determined.