A multi-parametric flow cytometric assay to analyze DNA–protein interactions

Interactions between DNA and transcription factors (TFs) guide cellular function and development, yet the complexities of gene regulation are still far from being understood. Such understanding is limited by a paucity of techniques with which to probe DNA–protein interactions. We have devised magnetic protein immobilization on enhancer DNA (MagPIE), a simple, rapid, multi-parametric assay using flow cytometric immunofluorescence to reveal interactions among TFs, chromatin structure and DNA. In MagPIE, synthesized DNA is bound to magnetic beads, which are then incubated with nuclear lysate, permitting sequence-specific binding by TFs, histones and methylation by native lysate factors that can be optionally inhibited with small molecules. Lysate protein–DNA binding is monitored by flow cytometric immunofluorescence, which allows for accurate comparative measurement of TF-DNA affinity. Combinatorial fluorescent staining allows simultaneous analysis of sequence-specific TF-DNA interaction and chromatin modification. MagPIE provides a simple and robust method to analyze complex epigenetic interactions in vitro

Early Infrared Spectral Development of V1187 Scorpii (Nova Scorpii 2004 No. 2)

We report on an unprecedented infrared time series of spectra of V1187 Sco, a very fast ONeMg nova. The observations covered a 56 day period (2004 August 6-September 30) starting 2 days after the nova's peak brightness. Time evolution of the spectra revealed changing line strengths and profiles on timescales of less than a day to weeks as the nova evolved from early postmaximum to early coronal phases. When our ground-based optical and Spitzer Space Telescope data were combined, the wavelength coverage of 0.38-36 μm allowed an accurate spectral energy distribution to be derived when it was about 6 weeks after outburst. Developing double structure in the He I lines showed them changing from narrow to broad in only a few days. Using the O I lines in combination with the optical spectra, we derived a reddening of E(B - V) = 1.56 ± 0.08 and a distance of 4.9 ± 0.5 kpc. Modeling of the ejected material strongly suggested that it was geometrically thick with ΔR/R = 0.8-0.9 (more of a wind than a shell) and a low filling factor of order a few percent. The line shapes were consistent with a cylindrical jet, bipolar, or spherical Hubble flow expansion with a maximum speed of about -3000 km s-1. The central peak appeared to be more associated with the spherical component, while the two peaks (especially in Hβ) suggested a ring with either a lower velocity component or with its axis inclined to the line of sight

The composition of the protosolar disk and the formation conditions for comets

Conditions in the protosolar nebula have left their mark in the composition of cometary volatiles, thought to be some of the most pristine material in the solar system. Cometary compositions represent the end point of processing that began in the parent molecular cloud core and continued through the collapse of that core to form the protosun and the solar nebula, and finally during the evolution of the solar nebula itself as the cometary bodies were accreting. Disentangling the effects of the various epochs on the final composition of a comet is complicated. But comets are not the only source of information about the solar nebula. Protostellar disks around young stars similar to the protosun provide a way of investigating the evolution of disks similar to the solar nebula while they are in the process of evolving to form their own solar systems. In this way we can learn about the physical and chemical conditions under which comets formed, and about the types of dynamical processing that shaped the solar system we see today. This paper summarizes some recent contributions to our understanding of both cometary volatiles and the composition, structure and evolution of protostellar disks.Comment: To appear in Space Science Reviews. The final publication is available at Springer via http://dx.doi.org/10.1007/s11214-015-0167-

Variety of Methodological Approach in Economics

It has been argued by some that the distinction between orthodox economics and heterodox economics does not fit the growing variety in economic theory, unified by a common methodological approach. On the other hand, it remains a central characteristic of heterodox economics that it does not share this methodological approach, but rather represents a range of alternative methodological approaches. The paper explores the evidence, and arguments, for variety in economics at different levels, and a range of issues which arise. This requires in turn a discussion of the meaning of variety in economics at the different levels of reality, methodology, method and theory. It is concluded that there is scope for more, rather than less, variety in economic methodologies, as well as within methodologies. Further, if variety is not to take the form of “anything goes”, then critical discussion by economists of different approaches to economics, and of variety itself, is required

Regulating and Deregulating the Public Utilities 1830-2010

History can provide invaluable insights into important issues of the economic and social regulation of utilities, and offer lessons towards future debates. But the history of utility regulation – which speaks of changing, diverse and complex experiences around the world – was, unfortunately, sidelined or marginalised when economists and policymakers enthusiastically embraced the question of how to reform the utilities from the 1970s. This paper provides an overview of the three, overarching, `waves' of utility regulation from the nineteenth century to the present, documenting how, when and why the ways in which the roles of the state, the market and firms altered over time. It then contextualises and explains the main contributions of each of the papers included in this special issue of Business History, which cover energy, communications, water, transportation and other urban infrastructure regulation, across Western Europe, the United States and Australia

Effects of interactions between the constituents of chitosan-edible films on their physical properties

The main objective of this work was to evaluate the effect of chitosan and plasticizer concentrations and oil presence on the physical and mechanical properties of edible films. The effect of the film constituents and their in-between interactions were studied through the evaluation of permeability, opacity and mechanical properties. The effects of the studied variables (concentrations of chitosan, plasticizer and oil) were analysed according to a 2 3 factorial design. Pareto charts were used to identify the most significant factors in the studied properties (water vapour, oxygen and carbon dioxide permeability; opacity; tensile strength; elongation at break and Young's modulus). When addressing the influence of the interactions between the films' constituents on the properties above, results show that chitosan and plasticizer concentrations are the most significant factors affecting most of the studied properties, while oil incorporation has shown to be of a great importance in the particular case of transport properties (gas permeability), essentially due to its hydrophobicity. Water vapour permeability values (ranging from 1. 62 × 10 -11 to 4. 24 × 10 -11 g m -1 s -1 Pa -1) were half of those reported for cellophane films. Also the mechanical properties (tensile strength values from 0. 43 to 13. 72 MPa and elongation-at-break values from 58. 62% to 166. 70%) were in the range of those reported for LDPE and HDPE. Based on these results, we recommend the use of 1. 5% (w/w) chitosan concentration to produce films, where the oil and plasticizer proportions will have to be adjusted in a case-by-case basis according to the use intended for the material. This work provides a useful guide to the formulation of chitosan-based film-forming solutions for food packaging applications.The author MA Cerqueira is a recipient of a fellowship from Fundacao para a Ciencia e Tecnologia (FCT, SFRH/BD/23897/2005) and BWS Souza is a recipient of a fellowship from the Coordenacao Aperfeicoamento de Pessoal de Nivel Superior, Brazil (Capes, Brazil)

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

\ua9 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods: People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1\ub773 m2 or more to first eGFR of less than 30 mL/min per 1\ub773 m2 (the therapeutic trial window). Findings: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9\ub76 years (IQR 5\ub79–16\ub77). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2\ub781 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0\ub70001), but better survival rates (standardised mortality ratio 0\ub742 [95% CI 0\ub732–0\ub752]; p<0\ub70001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity