Hiding in Plain View: Colloidal Self-Assembly from Polydisperse Populations

We report small-angle x-ray scattering experiments on aqueous dispersions of colloidal silica with a broad monomodal size distribution (polydispersity, 14%; size, 8 nm). Over a range of volume fractions, the silica particles segregate to build first one, then two distinct sets of colloidal crystals. These dispersions thus demonstrate fractional crystallization and multiple-phase (bcc, Laves AB2, liquid) coexistence. Their remarkable ability to build complex crystal structures from a polydisperse population originates from the intermediate-range nature of interparticle forces, and it suggests routes for designing self-assembling colloidal crystals from the bottom up

Protein Pattern Formation

Protein pattern formation is essential for the spatial organization of many intracellular processes like cell division, flagellum positioning, and chemotaxis. A prominent example of intracellular patterns are the oscillatory pole-to-pole oscillations of Min proteins in \textit{E. coli} whose biological function is to ensure precise cell division. Cell polarization, a prerequisite for processes such as stem cell differentiation and cell polarity in yeast, is also mediated by a diffusion-reaction process. More generally, these functional modules of cells serve as model systems for self-organization, one of the core principles of life. Under which conditions spatio-temporal patterns emerge, and how these patterns are regulated by biochemical and geometrical factors are major aspects of current research. Here we review recent theoretical and experimental advances in the field of intracellular pattern formation, focusing on general design principles and fundamental physical mechanisms.Comment: 17 pages, 14 figures, review articl

Use of tobacco and alcohol by Swiss primary care physicians: a cross-sectional survey

BACKGROUND: Health behaviours among doctors has been suggested to be an important marker of how harmful lifestyle behaviours are perceived. In several countries, decrease in smoking among physicians was spectacular, indicating that the hazard was well known. Historical data have shown that because of their higher socio-economical status physicians take up smoking earlier. When the dangers of smoking become better known, physicians began to give up smoking at a higher rate than the general population. For alcohol consumption, the situation is quite different: prevalence is still very high among physicians and the dangers are not so well perceived. To study the situation in Switzerland, data of a national survey were analysed to determine the prevalence of smoking and alcohol drinking among primary care physicians. METHODS: 2'756 randomly selected practitioners were surveyed to assess subjective mental and physical health and their determinants, including smoking and drinking behaviours. Physicians were categorised as never smokers, current smokers and former smokers, as well as non drinkers, drinkers (AUDIT-C < 4 for women and < 5 for men) and at risk drinkers (higher scores). RESULTS: 1'784 physicians (65%) responded (men 84%, mean age 51 years). Twelve percent were current smokers and 22% former smokers. Sixty six percent were drinkers and 30% at risk drinkers. Only 4% were never smokers and non drinkers. Forty eight percent of current smokers were also at risk drinkers and 16% of at risk drinkers were also current smokers. Smoking and at risk drinking were more frequent among men, middle aged physicians and physicians living alone. When compared to a random sample of the Swiss population, primary care physicians were two to three times less likely to be active smokers (12% vs. 30%), but were more likely to be drinkers (96% vs. 78%), and twice more likely to be at risk drinkers (30% vs. 15%). CONCLUSION: The prevalence of current smokers among Swiss primary care physicians was much lower than in the general population in Switzerland, reflecting that the hazards of smoking are well known to doctors. However, the opposite was found for alcohol use, underlining the importance of making efforts in this area to increase awareness among physicians of the dangers of alcohol consumption

The interplay of crack hopping, delamination and interface failure in drying nanoparticle films

Films formed through the drying of nanoparticle suspensions release the build-up of strain through a variety of different mechanisms including shear banding, crack formation and delamination. Here we show that important connections exist between these different phenomena: delamination depends on the dynamics of crack hopping, which in turn is influenced by the presence of shear bands. We also show that delamination does not occur uniformly across the film. As cracks hop they locally initiate the delamination of the film which warps with a timescale much longer than that associated with the hopping of cracks. The motion of a small region of the delamination front, where the shear component of interfacial crack propagation is believed to be enhanced, results in the deposition of a complex zig-zag pattern on the supporting substrate

Spectrum and Inoculum Size Effect of a Rapid Antigen Detection Test for Group A Streptococcus in Children with Pharyngitis

BACKGROUND: The stability of the accuracy of a diagnostic test is critical to whether clinicians can rely on its result. We aimed to assess whether the performance of a rapid antigen detection test (RADT) for group A streptococcus (GAS) is affected by the clinical spectrum and/or bacterial inoculum size. METHODS: Throat swabs were collected from 785 children with pharyngitis in an office-based, prospective, multicenter study (2009-2010). We analysed the effect of clinical spectrum (i.e., the McIsaac score and its components) and inoculum size (light or heavy GAS growth) on the accuracy (sensitivity, specificity, likelihood ratios and predictive values) of a RADT, with laboratory throat culture as the reference test. We also evaluated the accuracy of a McIsaac-score-based decision rule. RESULTS: GAS prevalence was 36% (95CI: 33%-40%). The inoculum was heavy for 85% of cases (81%-89%). We found a significant spectrum effect on sensitivity, specificity, likelihood ratios and positive predictive value (p<0.05) but not negative predictive value, which was stable at about 92%. RADT sensitivity was greater for children with heavy than light inoculum (95% vs. 40%, p<0.001). After stratification by inoculum size, the spectrum effect on RADT sensitivity was significant only in patients with light inoculum, on univariate and multivariate analysis. The McIsaac-score-based decision rule had 99% (97%-100%) sensitivity and 52% (48%-57%) specificity. CONCLUSIONS: Variations in RADT sensitivity only occur in patients with light inocula. Because the spectrum effect does not affect the negative predictive value of the test, clinicians who want to rule out GAS can rely on negative RADT results regardless of clinical features if they accept that about 10% of children with negative RADT results will have a positive throat culture. However, such a policy is more acceptable in populations with very low incidence of complications of GAS infection

Stress from Uncertainty from Graduation to Retirement—A Population-Based Study of Swiss Physicians

BACKGROUND: Uncertainty shapes many decisions made by physicians everyday. Uncertainty and physicians’ inability to handle it may result in substandard care and unexplained variations in patterns of care. OBJECTIVE: To describe socio-demographic and professional characteristics of reactions to uncertainty among physicians from all specialties, including physicians in training. DESIGN: Cross-sectional postal survey. PARTICIPANT: All physicians practicing in Geneva, Switzerland (n = 1,994). MEASUREMENT: Reaction to medical care uncertainty was measured with the Anxiety Due to Uncertainty and Concern About Bad Outcomes scales. The questionnaire also included items about professional characteristics and work-related satisfaction scales. RESULTS: After the first mailing and two reminders, 1,184 physicians responded to the survey. In univariate analysis, women, junior physicians, surgical specialists, generalist physicians, and physicians with lower workloads had higher scores in both scales. In multivariate models, sex, medical specialty, and workload remained significantly associated with both scales, whereas clinical experience remained associated only with concern about bad outcomes. Higher levels of anxiety due to uncertainty were associated with lower scores of work-related satisfaction, while higher levels of concern about bad outcomes were associated with lower satisfaction scores for patient care, personal rewards, professional relations, and general satisfaction, but not for work-related burden or satisfaction with income-prestige. The negative effect of anxiety due to uncertainty on work-related satisfaction was more important for physicians in training. CONCLUSION: Physicians’ reactions to uncertainty in medical care were associated with several dimensions of work-related satisfaction. Physicians in training experienced the greatest impact of anxiety due to uncertainty on their work-related satisfaction. Incorporating strategies to deal with uncertainty into residency training may be useful

Membrane Invaginations Reveal Cortical Sites that Pull on Mitotic Spindles in One-Cell C. elegans Embryos

Asymmetric positioning of the mitotic spindle in C. elegans embryos is mediated by force-generating complexes that are anchored at the plasma membrane and that pull on microtubules growing out from the spindle poles. Although asymmetric distribution of the force generators is thought to underlie asymmetric positioning of the spindle, the number and location of the force generators has not been well defined. In particular, it has not been possible to visualize individual force generating events at the cortex. We discovered that perturbation of the acto-myosin cortex leads to the formation of long membrane invaginations that are pulled from the plasma membrane toward the spindle poles. Several lines of evidence show that the invaginations, which also occur in unperturbed embryos though at lower frequency, are pulled by the same force generators responsible for spindle positioning. Thus, the invaginations serve as a tool to localize the sites of force generation at the cortex and allow us to estimate a lower limit on the number of cortical force generators within the cell

Evolutionary tradeoffs in cellular composition across diverse bacteria

One of the most important classic and contemporary interests in biology is the connection between cellular composition and physiological function. Decades of research have allowed us to understand the detailed relationship between various cellular components and processes for individual species, and have uncovered common functionality across diverse species. However, there still remains the need for frameworks that can mechanistically predict the tradeoffs between cellular functions and elucidate and interpret average trends across species. Here we provide a comprehensive analysis of how cellular composition changes across the diversity of bacteria as connected with physiological function and metabolism, spanning five orders of magnitude in body size. We present an analysis of the trends with cell volume that covers shifts in genomic, protein, cellular envelope, RNA and ribosomal content. We show that trends in protein content are more complex than a simple proportionality with the overall genome size, and that the number of ribosomes is simply explained by cross-species shifts in biosynthesis requirements. Furthermore, we show that the largest and smallest bacteria are limited by physical space requirements. At the lower end of size, cell volume is dominated by DNA and protein content—the requirement for which predicts a lower limit on cell size that is in good agreement with the smallest observed bacteria. At the upper end of bacterial size, we have identified a point at which the number of ribosomes required for biosynthesis exceeds available cell volume. Between these limits we are able to discuss systematic and dramatic shifts in cellular composition. Much of our analysis is connected with the basic energetics of cells where we show that the scaling of metabolic rate is surprisingly superlinear with all cellular components

Roles of Myosin Va and Rab3D in Membrane Remodeling of Immature Secretory Granules

Neuroendocrine secretory granules (SGs) are formed at the trans-Golgi network (TGN) as immature intermediates. In PC12 cells, these immature SGs (ISGs) are transported within seconds to the cell cortex, where they move along actin filaments and complete maturation. This maturation process comprises acidification-dependent processing of cargo proteins, condensation of the SG matrix, and removal of membrane and proteins not destined to mature SGs (MSGs) into ISG-derived vesicles (IDVs). We investigated the roles of myosin Va and Rab3 isoforms in the maturation of ISGs in neuroendocrine PC12 cells. The expression of dominant-negative mutants of myosin Va or Rab3D blocked the removal of the endoprotease furin from ISGs. Furthermore, expression of mutant Rab3D, but not of mutant myosin Va, impaired cargo processing of SGs. In conclusion, our data suggest an implication of myosin Va and Rab3D in the maturation of SGs where they participate in overlapping but not identical tasks