Contact-free scanning and imaging with the scanning ion conductance microscope

Scanning ion conductance microscopy (SICM) offers the ability to obtain very high resolution topographical images of living cells. In addition, the probe can be used to measure cell responses such as muscle contraction or to map ion channel activity to specific subcellular locations. For biological imaging one of the great advantages of SICM lies in its ability to perform contact-free scanning; imaging cells or tissues without touching the cell surface. However, it is not yet clear when the requirements of this scan mode are met. We have used finite element modelling (FEM) to examine the conditions for contact free scanning and we have validated our modelling using both experimental data and by comparing our results to predictions in analytically tractable situations. Our findings provide a framework for understanding the conditions for contact-free scanning and also extend previous findings with regard to SICM resolution. Finally, we demonstrate the importance of our findings by imaging cells under a variety of conditions

Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families

Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4×10−6 (serial isolates) to 4.5×10−6 (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5–17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude

OH maser emission in the THOR survey of the northern Milky Way*

Context. OH masers trace diverse physical processes, from the expanding envelopes around evolved stars to star-forming regions or supernovae remnants. Providing a survey of the ground-state OH maser transitions in the northern hemisphere inner Milky Way facilitates the study of a broad range of scientific topics. Aims. We want to identify the ground-state OH masers at ∼18 cm wavelength in the area covered by The HI/OH/Recombination line survey of the Milky Way (THOR). We will present a catalogue of all OH maser features and their possible associated environments. Methods. The THOR survey covers longitude and latitude ranges of 14. ◦3 < l < 66. ◦8 and b < ± 1.◦25. All OH ground state lines 2Π3/2 (J = 3/2) at 1612 (F = 1−2), 1665 (F = 1−1), 1667 (F = 2−2) and 1720 MHz (F = 2−1) have been observed, employing the Very Large Array (VLA) in its C configuration. The spatial resolution of the data varies between 12.5" and 19", the spectral resolution is 1.5 km s−1, and the rms sensitivity of the data is ∼10 mJy beam−1 per channel. Results. We identify 1585 individual maser spots (corresponding to single spectral features) distributed over 807 maser sites (regions of size ∼103−104 AU). Based on different criteria from spectral profiles to literature comparison, we try to associate the maser sites with astrophysical source types. Approximately 51% of the sites exhibit the double-horned 1612 MHz spectra typically emitted from the expanding shells of evolved stars. The separations of the two main velocity features of the expanding shells typically vary between 22 and 38 km s−1. In addition to this, at least 20% of the maser sites are associated with star-forming regions. While the largest fraction of 1720 MHz maser spots (21 out of 53) is associated with supernova remnants, a significant fraction of the 1720 MHz maser spots (17) are also associated with star-forming regions. We present comparisons to the thermal 13CO(1–0) emission as well as to other surveys of class II CH3OH and H2O maser emission. The catalogue attempts to present associations to astrophysical sources where available, and the full catalogue is available in electronic form. Conclusions. This OH maser catalogue presents a unique resource of stellar and interstellar masers in the northern hemisphere. It provides the basis for a diverse range of follow-up studies from envelopes around evolved stars to star-forming regions and Supernova remnants

Computational and mathematical approaches to societal transitions

After an introduction of the theoretical framework and concepts of transition studies, this article gives an overview of how structural change in social systems has been studied from various disciplinary perspectives. This overview first leads to the conclusion that computational and mathematical approaches and their practical form, modeling, up till now, have been almost absent in the research and theorizing of structural change or transitions in social systems. Second, this review of the social science literature suggests numerous theoretical constructs relevant for transition modeling. Relevant concepts include the conceptualization of the micro-to-macro link, the importance of explaining both stability and change, quantitative and qualitative definitions of structural change, the use of dichotomies, synchronic and diachronic reasoning in explaining structural change, definitions of basic patterns of social change, the conceptualization of resistance to change and intentional and normative aspects of social change. This article employs these theoretical concepts to describe and discuss the models presented in this special issue in order to develop an understanding of what exactly entails a computational or mathematical approach to societal transitions

Excess maternal salt intake produces sex-specific hypertension in offspring: putative roles for kidney and gastrointestinal sodium handling.

Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth - a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L). Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L), with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3-14.8] vs. 2.8 [2.0-8.3] nmol/L median [IQR]). Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9-21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger), member 3 (SLC9A3) together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young

Population Structure of Staphylococcus aureus from Remote African Babongo Pygmies

Staphylococcus aureus is a bacterium that colonizes humans worldwide. The anterior nares are its main ecological niche. Carriers of S. aureus are at a higher risk of developing invasive infections. Few reports indicated a different clonal structure and profile of virulence factors in S. aureus isolates from Sub-Saharan Africa. As there are no data about isolates from remote indigenous African populations, we conducted a cross-sectional survey of S. aureus nasal carriage in Gabonese Babongo Pygmies. The isolates were characterized regarding their susceptibility to antibiotic agents, possession of virulence factors and clonal lineage. While similar carriage rates were found in populations of industrialized countries, isolates that encode the genes for the Panton-Valentine leukocidin (PVL) were clearly more prevalent than in European countries. Of interest, many methicillin-susceptible S. aureus isolates from Babongo Pygmies showed the same genetic background as pandemic methicillin-resistant S. aureus (MRSA) clones. We advocate a surveillance of S. aureus in neglected African populations to control the development of resistance to antibiotic drugs with particular respect to MRSA and to assess the impact of the high prevalence of PVL-positive isolates

The Role for HNF-1β-Targeted Collectrin in Maintenance of Primary Cilia and Cell Polarity in Collecting Duct Cells

Collectrin, a homologue of angiotensin converting enzyme 2 (ACE2), is a type I transmembrane protein, and we originally reported its localization to the cytoplasm and apical membrane of collecting duct cells. Recently, two independent studies of targeted disruption of collectrin in mice resulted in severe and general defects in renal amino acid uptake. Collectrin has been reported to be under the transcriptional regulation by HNF-1α, which is exclusively expressed in proximal tubules and localized at the luminal side of brush border membranes. The deficiency of collectrin was associated with reduction of multiple amino acid transporters on luminal membranes. In the current study, we describe that collectrin is a target of HNF-1β and heavily expressed in the primary cilium of renal collecting duct cells. Collectrin is also localized in the vesicles near the peri-basal body region and binds to γ-actin-myosin II-A, SNARE, and polycystin-2-polaris complexes, and all of these are involved in intracellular and ciliary movement of vesicles and membrane proteins. Treatment of mIMCD3 cells with collectrin siRNA resulted in defective cilium formation, increased cell proliferation and apoptosis, and disappearance of polycystin-2 in the primary cilium. Suppression of collectrin mRNA in metanephric culture resulted in the formation of multiple longitudinal cysts in ureteric bud branches. Taken together, the cystic change and formation of defective cilium with the interference in the collectrin functions would suggest that it is necessary for recycling of the primary cilia-specific membrane proteins, the maintenance of the primary cilia and cell polarity of collecting duct cells. The transcriptional hierarchy between HNF-1β and PKD (polycystic kidney disease) genes expressed in the primary cilia of collecting duct cells has been suggested, and collectrin is one of such HNF-1β regulated genes

A barrier to homologous recombination between sympatric strains of the cooperative soil bacterium Myxococcus xanthus

The bacterium Myxococcus xanthus glides through soil in search of prey microbes, but when food sources run out, cells cooperatively construct and sporulate within multicellular fruiting bodies. M. xanthus strains isolated from a 16 × 16-cm-scale patch of soil were previously shown to have diversified into many distinct compatibility types that are distinguished by the failure of swarming colonies to merge upon encounter. We sequenced the genomes of 22 isolates from this population belonging to the two most frequently occurring multilocus sequence type (MLST) clades to trace patterns of incipient genomic divergence, specifically related to social divergence. Although homologous recombination occurs frequently within the two MLST clades, we find an almost complete absence of recombination events between them. As the two clades are very closely related and live in sympatry, either ecological or genetic barriers must reduce genetic exchange between them. We find that the rate of change in the accessory genome is greater than the rate of amino-acid substitution in the core genome. We identify a large genomic tract that consistently differs between isolates that do not freely merge and therefore is a candidate region for harbouring gene(s) responsible for self/non-self discrimination

Environmental risk assessments for transgenic crops producing output trait enzymes

The environmental risks from cultivating crops producing output trait enzymes can be rigorously assessed by testing conservative risk hypotheses of no harm to endpoints such as the abundance of wildlife, crop yield and the rate of degradation of crop residues in soil. These hypotheses can be tested with data from many sources, including evaluations of the agronomic performance and nutritional quality of the crop made during product development, and information from the scientific literature on the mode-of-action, taxonomic distribution and environmental fate of the enzyme. Few, if any, specific ecotoxicology or environmental fate studies are needed. The effective use of existing data means that regulatory decision-making, to which an environmental risk assessment provides essential information, is not unnecessarily complicated by evaluation of large amounts of new data that provide negligible improvement in the characterization of risk, and that may delay environmental benefits offered by transgenic crops containing output trait enzymes

Weber, Marx, and work values: Evidence from transition economies

Are work values a cause (Weber) or consequence (Marx) of the economic environment? The collapse of the Soviet Union at the end of 1991 provides a unique opportunity to investigate this link. Using data collected from an employee survey conducted in over 340 workplaces in Armenia, Azerbaijan and Russia, we investigate generational differences in adherence to the Protestant work ethic (PWE). Our results indicate that Marx was 'right' about the link between work values and economic environment. That is, despite economic and cultural differences emerging during the transformation process, in all three countries, participating workers born after 1981 adhere more strongly to PWE than workers born before 1977. Moreover, the estimate magnitudes are very similar across these economically and culturally diverse countries. More generally, PWE adherence is stronger among participating workers with an internal locus of control and among supervisors. PWE adherence also tends to be stronger among participants with high relative earnings, as well as among those working in organizations that reward hard work with the chance to develop new skills or learn new things. © 2013 Elsevier B.V