Systematic alteration of ATAC-seq for profiling open chromatin in cryopreserved nuclei preparations from livestock tissues.

The use of Assay for Transposase-Accessible Chromatin (ATAC-seq) to profile chromatin accessibility has surged over the past years, but its applicability to tissues has been very limited. With the intent of preserving nuclear architecture during long-term storage, cryopreserved nuclei preparations from chicken lung were used to optimize ATAC-seq. Sequencing data were compared with existing DNase-seq, ChIP-seq, and RNA-seq data to evaluate library quality, ultimately resulting in a modified ATAC-seq method capable of generating high quality chromatin accessibility data from cryopreserved nuclei preparations. Using this method, nucleosome-free regions (NFR) identified in chicken lung overlapped half of DNase-I hypersensitive sites, coincided with active histone modifications, and specifically marked actively expressed genes. Notably, sequencing only the subnucleosomal fraction dramatically improved signal, while separation of subnucleosomal reads post-sequencing did not improve signal or peak calling. The broader applicability of this modified ATAC-seq technique was tested using cryopreserved nuclei preparations from pig tissues, resulting in NFR that were highly consistent among biological replicates. Furthermore, tissue-specific NFR were enriched for binding motifs of transcription factors related to tissue-specific functions, and marked genes functionally enriched for tissue-specific processes. Overall, these results provide insights into the optimization of ATAC-seq and a platform for profiling open chromatin in animal tissues

Seeking the Real Adam Smith and Milton Friedman

In this paper we will analyze the relationship between free market principles and ethics through an exploration of how too many business managers often approach the ideas of Adam Smith and Milton Friedman. In doing so, we aim to provide a thoughtful foundation for future discussions of how we ought to navigate this intersection. We briefly examine questions such as: What is the relationship between the “best” economy in terms of efficiency and the common good for society? Is pursuing one’s individual economic advantage the same as promoting the general interest? As we analyze and discuss these questions, specifically in the context of Smith and Friedman, we also make some alternative normative assertions, grounded in social welfare, about adopting a broader societal perspective for the purpose of business

Preferences and constraints: the value of economic games for studying human behaviour

© 2020 The Authors. As economic games have spread from experimental economics to other social sciences, so too have critiques of their usefulness for drawing inferences about the ‘real world’. What these criticisms often miss is that games can be used to reveal individuals' private preferences in ways that observational and interview data cannot; furthermore, economic games can be designed such that they do provide insights into real-world behaviour. Here, we draw on our collective experience using economic games in field contexts to illustrate how researchers can strategically alter the framing or design of economic games to draw inferences about private-world or real-world preferences. A detailed case study from coastal Colombia provides an example of the subtleties of game design and how games can be combined fruitfully with self-report data. We close with a list of concrete recommendations for how to modify economic games to better match particular research questions and research contexts.Max Planck Institute for Evolutionary Anthropolog

Algorithms for outerplanar graph roots and graph roots of pathwidth at most 2

Deciding whether a given graph has a square root is a classical problem that has been studied extensively both from graph theoretic and from algorithmic perspectives. The problem is NP-complete in general, and consequently substantial effort has been dedicated to deciding whether a given graph has a square root that belongs to a particular graph class. There are both polynomial-time solvable and NP-complete cases, depending on the graph class. We contribute with new results in this direction. Given an arbitrary input graph G, we give polynomial-time algorithms to decide whether G has an outerplanar square root, and whether G has a square root that is of pathwidth at most 2

Measuring Invisible Particle Masses Using a Single Short Decay Chain

We consider the mass measurement at hadron colliders for a decay chain of two steps, which ends with a missing particle. Such a topology appears as a subprocess of signal events of many new physics models which contain a dark matter candidate. From the two visible particles coming from the decay chain, only one invariant mass combination can be formed and hence it is na\"ively expected that the masses of the three invisible particles in the decay chain cannot be determined from a single end point of the invariant mass distribution. We show that the event distribution in the $\log(E_{1T}/E_{2T})$ vs. invariant mass-squared plane, where $E_{1T}$, $E_{2T}$ are the transverse energies of the two visible particles, contains the information of all three invisible particle masses and allows them to be extracted individually. The experimental smearing and combinatorial issues pose challenges to the mass measurements. However, in many cases the three invisible particle masses in the decay chain can be determined with reasonable accuracies.Comment: 45 pages, 32 figure

Rationally designed dendritic silica nanoparticles for oral delivery of exenatide

Type 2 diabetes makes up approximately 85% of all diabetic cases and it is linked to approximately one-third of all hospitalisations. Newer therapies with long-acting biologics such as glucagon-like peptide-1 (GLP-1) analogues have been promising in managing the disease, but they cannot reverse the pathology of the disease. Additionally, their parenteral administration is often associated with high healthcare costs, risk of infections, and poor patient adherence associated with phobia of needles. Oral delivery of these compounds would significantly improve patient compliance; however, poor enzymatic stability and low permeability across the gastrointestinal tract makes this task challenging. In the present work, large pore dendritic silica nanoparticles (DSNPs) with a pore size of ~10 nm were prepared, functionalized, and optimized in order to achieve high peptide loading and improve intestinal permeation of exenatide, a GLP-1 analogue. Compared to the loading capacity of the most popular, Mobil Composition of Matter No. 41 (MCM-41) with small pores, DSNPs showed significantly high loading owing to their large and dendritic pore structure. Among the tested DSNPs, pristine and phosphonate-modified DSNPs (PDSNPs) displayed remarkable loading of 40 and 35% w/w, respectively. Furthermore, particles successfully coated with positively charged chitosan reduced the burst release of exenatide at both pH 1.2 and 6.8. Compared with free exenatide, both chitosan-coated and uncoated PDSNPs enhanced exenatide transport through the Caco-2 monolayer by 1.7 fold. Interestingly, when a triple co-culture model of intestinal permeation was used, chitosan-coated PDSNPs performed better compared to both PDSNPs and free exenatide, which corroborated our hypothesis behind using chitosan to interact with mucus and improve permeation. These results indicate the emerging role of large pore silica nanoparticles as promising platforms for oral delivery of biologics such as exenatide.We thank the National Health and Medical Research Council’s Project Grant GNT1107836 and Early Career Fellowship and Career Development Fellowship to A.P. We also thank NHMRC for EC Fellowship to T.K. We would also like to thank the Centre of Microscopy and Microanalysis at The University of Queensland for providing facilities to conduct TEM. This article was, in part, a result of the project NORTE-01-0145-FEDER-000012, supported by the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds—through the COMPETE 2020–Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274)

Environmental suitability of bare-nosed wombat burrows for Sarcoptes scabiei

Some of the most important pathogens affecting wildlife are transmitted indirectly via the environment. Yet the environmental stages of pathogens are often poorly understood, relative to infection in the host, making this an important research frontier. Sarcoptic mange is a globally widespread disease caused by the parasitic mite Sarcoptes scabiei. The bare-nosed wombat (Vombatus ursinus) is particularly susceptible, and their solitary nature and overlapping use of burrows strongly indicate the importance of environmental transmission. However, due to the challenge of accessing and monitoring within wombat burrows, there has been limited research into their suitability for off-host mite survival and environmental transmission (i.e., to serve as a fomite). We created a model using published laboratory data to predict mite survival times based on temperature and humidity. We then implemented innovative technologies (ground-penetrating radar and a tele-operated robotic vehicle) to map and access wombat burrows to record temperature and relative humidity. We found that the stable conditions within burrows were conducive for off-host survival of S. scabiei, particularly in winter (estimated mite survival of 16.41 ± 0.34 days) and less so in warmer and drier months (summer estimated survival of 5.96 ± 0.37 days). We also compared two areas with higher and lower average mange prevalence in wombats (13.35% and 4.65%, respectively), finding estimated mite survival was slightly higher in the low prevalence area (10.10 and 12.12 days, respectively), contrary to our expectations, suggesting other factors are also important for population prevalence. Our study is the first to demonstrate the suitability of the bare-nosed wombat burrow for off-host mite survival and environmental transmission. Our findings have implications for understanding observed patterns of mange, disease dynamics and disease management for not only bare-nosed wombats, but also other burrow or den-obligate species exposed to S. scabiei via environmental transmission

Cooperative secretions facilitate host range expansion in bacteria

The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses