Source-sink plasmid transfer dynamics maintain gene mobility in soil bacterial communities

Horizontal gene transfer is a fundamental process in bacterial evolution that can accelerate adaptation via the sharing of genes between lineages. Conjugative plasmids are the principal genetic elements mediating the horizontal transfer of genes, both within and between bacterial species. In some species, plasmids are unstable and likely to be lost through purifying selection, but when alternative hosts are available, interspecific plasmid transfer could counteract this and maintain access to plasmid-borne genes. To investigate the evolutionary importance of alternative hosts to plasmid population dynamics in an ecologically relevant environment, we established simple soil microcosm communities comprising two species of common soil bacteria, Pseudomonas fluorescens and Pseudomonas putida, and a mercury resistance (Hg R) plasmid, pQBR57, both with and without positive selection [i.e., addition of Hg(II)]. In single-species populations, plasmid stability varied between species: although pQBR57 survived both with and without positive selection in P. fluorescens, it was lost or replaced by nontransferable Hg R captured to the chromosome in P. putida. A simple mathematical model suggests these differences were likely due to pQBR57's lower intraspecific conjugation rate in P. putida. By contrast, in two-species communities, both models and experiments show that interspecific conjugation from P. fluorescens allowed pQBR57 to persist in P. putida via source-sink transfer dynamics. Moreover, the replacement of pQBR57 by nontransferable chromosomal Hg R in P. putida was slowed in coculture. Interspecific transfer allows plasmid survival in host species unable to sustain the plasmid in monoculture, promoting community-wide access to the plasmid-borne accessory gene pool and thus potentiating future evolvability

Acoustic, psychophysical, and neuroimaging measurements of the effectiveness of active cancellation during auditory functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) is one of the principal neuroimaging techniques for studying human audition, but it generates an intense background sound which hinders listening performance and confounds measures of the auditory response. This paper reports the perceptual effects of an active noise control (ANC) system that operates in the electromagnetically hostile and physically compact neuroimaging environment to provide significant noise reduction, without interfering with image quality. Cancellation was first evaluated at 600 Hz, corresponding to the dominant peak in the power spectrum of the background sound and at which cancellation is maximally effective. Microphone measurements at the ear demonstrated 35 dB of acoustic attenuation [from 93 to 58 dB sound pressure level (SPL)], while masked detection thresholds improved by 20 dB (from 74 to 54 dB SPL). Considerable perceptual benefits were also obtained across other frequencies, including those corresponding to dips in the spectrum of the background sound. Cancellation also improved the statistical detection of sound-related cortical activation, especially for sounds presented at low intensities. These results confirm that ANC offers substantial benefits for fMRI research

The Undiscovered Truths of Collaborative Value Creation in UK Grocery Retail Category Management Relationships

Extended Abstract Category management is a collaborative approach to product selection and management between manufacturers and retailers, to enable the effective management of product categories rather than individual brands (Gooner et al., 2011; Hubner, 2011, Neilsen et al., 2006). This paper reports the emerging findings from qualitative research that explores the undiscovered truths of collaborative value creation in UK grocery retail category management relationships. Previous research in this field is mainly quantitative and does not always reflect the true nature of UK grocery retail practice. These past studies focus on the consumer alone being the creator of value. However, category management literature highlights the ‘triple win’ (value for retailers, manufacturers and consumers) in the collaborative ideal. The UK grocery market has gone through unprecedented change over recent years due to economic recession, environmental impacts and a shift in consumer habits and demands (IGD, 2019; Kantar, 2019; Shopper Intelligence, 2019). The research seeks to explore ways to assist the UK food industry practitioners to address these issues. After reviewing the literature gaps emerged, including the reality of value creation within category management relationships from an industry perspective. To gain a deeper understanding of the practitioner’s perspective a qualitative research study was undertaken in the form of semi-structured interviews. This method was chosen to bridge the gap between academia and practice and facilitate a basis for future category management strategies. Senior managers from UK food manufacturers and retailers were interviewed in response to the recommendations made by Lindbolm and Olkkonen (2008) to provide privileged data. The interviews generated written transcripts which were analysed and coded using a thematic analysis, to determine common themes. The themes that emerged were firstly, the changing role of the category captain to create more value in a disruptive UK grocery market. Secondly, the reality of value creation is that despite the notion it being a harmonious relationship it does not always result in value co-creation. Indeed, it emerged that there is value no-creation, and even value co-destruction within the category management relationship. Finally, it became apparent that due to the nature of the market and the rise in private label penetration within the UK grocery retail market that smaller niche and private label only suppliers can acquire the category partner/leader role within the category management relationship. The findings from the supplier and retailer interviews included a variety of questions surrounding their roles related to category management, but also commercial and marketing. The common view from the food industry practitioners was that the future of the category captain function is uncertain. Suppliers claim that it is moving away from a category management perspective to category leadership, whereas the retailers believe that it is still an effective management model due to the exponential growth of the food discounters. This demonstrates that the true beliefs of the supplier and the retailer are in fact different, and co-destruction as well as co-creation exists. Retailer strategies are predominantly focused on driving private label whereas the bigger branded suppliers want to expand their own ranges. Co-destruction occurs due to the mis-alignment of the strategies between the supplier and retailer. Private label creates an open and trusted relationship between the supplier and the retailer. This allows an opportunity for overall category growth and inclusion of all category suppliers regardless of size and resource contribution, and in line with competition legislation. This study has contributed to category management literature and practice which has implications for both academia and food industry practice. From an academic standpoint the key contribution was the fact that the category captain role is either currently non-existent or being phased out by the practitioners. The literature however still believes it exists in the traditional function. Practitioners however agree the role has changed and it should now be a leadership function rather than a traditional management task. It is therefore important that the gap between knowledge and practice is reduced to ensure the literature reflects what really happens. In conclusion, the study has aimed to bridge the gap between academia and practice by focusing on the three themes. The research has found that category management literature and practice are quite different, and this study is the first of its type to link the two together. Further research within category management should include more practitioner insight through qualitative studies to focus on the often-unclear belief of the suppliers and retailers. This establishes the benchmark for wider quantitative research and attract a broader range of suppliers including private label and smaller niche brands. This should also include a wider range of categories than those of this study and include categories such as chilled convenience

Cdc42 and Par6–PKCζ regulate the spatially localized association of Dlg1 and APC to control cell polarization

Cell polarization is essential in a wide range of biological processes such as morphogenesis, asymmetric division, and directed migration. In this study, we show that two tumor suppressor proteins, adenomatous polyposis coli (APC) and Dlg1-SAP97, are required for the polarization of migrating astrocytes. Activation of the Par6–PKCζ complex by Cdc42 at the leading edge of migrating cells promotes both the localized association of APC with microtubule plus ends and the assembly of Dlg-containing puncta in the plasma membrane. Biochemical analysis and total internal reflection fluorescence microscopy reveal that the subsequent physical interaction between APC and Dlg1 is required for polarization of the microtubule cytoskeleton

Relaxed Bell Inequalities with Arbitrary Measurement Dependence for Each Observer

Bell's inequality was originally derived under the assumption that experimenters are free to select detector settings independently of any local "hidden variables" that might affect the outcomes of measurements on entangled particles. This assumption has come to be known as "measurement independence" (also referred to as "freedom of choice" or "settings independence"). For a two-setting, two-outcome Bell test, we derive modified Bell inequalities that relax measurement independence, for either or both observers, while remaining locally causal. We describe the loss of measurement independence for each observer using the parameters $M_1$ and $M_2$, as defined by Hall in 2010, and also by a more complete description that adds two new parameters, which we call $\hat{M}_1$ and $\hat{M}_2$, deriving a modified Bell inequality for each description. These "relaxed" inequalities subsume those considered in previous work as special cases, and quantify how much the assumption of measurement independence needs to be relaxed in order for a locally causal model to produce a given violation of the standard Bell-Clauser-Horne-Shimony-Holt (Bell-CHSH) inequality. We show that both relaxed Bell inequalities are tight bounds on the CHSH parameter by constructing locally causal models that saturate them. For any given Bell inequality violation, the new two-parameter and four-parameter models each require significantly less mutual information between the hidden variables and measurement settings than previous models. We conjecture that the new models, with optimal parameters, require the minimum possible mutual information for a given Bell violation. We further argue that, contrary to various claims in the literature, relaxing freedom of choice need not imply superdeterminism.Comment: 26pp, 7 figures. Minor edits to match published versio

Multidrug resistance plasmids commonly reprogram the expression of metabolic genes in <i>Escherichia coli</i>

Multidrug-resistant Escherichia coli is a leading cause of global mortality. Transfer of plasmids carrying genes encoding beta-lactamases, carbapenamases, and colistin resistance between lineages is driving the rising rates of hard-to-treat nosocomial and community infections. Multidrug resistance (MDR) plasmid acquisition commonly causes transcriptional disruption, and while a number of studies have shown strain-specific fitness and transcriptional effects of an MDR plasmid across diverse bacterial lineages, fewer studies have compared the impacts of different MDR plasmids in a common bacterial host. As such, our ability to predict which MDR plasmids are the most likely to be maintained and spread in bacterial populations is limited. Here, we introduced eight diverse MDR plasmids encoding resistances against a range of clinically important antibiotics into E. coli K-12 MG1655 and measured their fitness costs and transcriptional impacts. The scale of the transcriptional responses varied substantially between plasmids, ranging from &gt;650 to &lt;20 chromosomal genes being differentially expressed. However, the scale of regulatory disruption did not correlate significantly with the magnitude of the plasmid fitness cost, which also varied between plasmids. The identities of differentially expressed genes differed between transconjugants, although the expression of certain metabolic genes and functions were convergently affected by multiple plasmids, including the downregulation of genes involved in L-methionine transport and metabolism. Our data show the complexity of the interaction between host genetic background and plasmid genetic background in determining the impact of MDR plasmid acquisition on E. coli.IMPORTANCE: The increase in infections that are resistant to multiple classes of antibiotics, including those isolates that carry carbapenamases, beta-lactamases, and colistin resistance genes, is of global concern. Many of these resistances are spread by conjugative plasmids. Understanding more about how an isolate responds to an incoming plasmid that encodes antibiotic resistance will provide information that could be used to predict the emergence of MDR lineages. Here, the identification of metabolic networks as being particularly sensitive to incoming plasmids suggests the possible targets for reducing plasmid transfer. </p

Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial

BACKGROUND: The study hypothesis is that administration of inhaled nitric oxide (NO) plus oxygen to subjects with submassive pulmonary embolism (PE) will improve right ventricular (RV) systolic function and reduce RV strain and necrosis, while improving patient dyspnea, more than treatment with oxygen alone. METHODS: This article describes the rationale and protocol for a registered (NCT01939301), nearly completed phase II, 3-center, randomized, double-blind, controlled trial. Eligible patients have pulmonary imaging-proven acute PE. Subjects must be normotensive, and have RV dysfunction on echocardiography or elevated troponin or brain natriuretic peptide and no fibrinolytics. Subjects receive NO plus oxygen or placebo for 24 hours (±3 hours) with blood sampling before and after treatment, and mandatory echocardiography and high-sensitivity troponin posttreatment to assess the composite primary end point. The sample size of N=78 was predicated on 30% more NO-treated patients having a normal high-sensitivity troponin (<14 pg/mL) and a normal RV on echocardiography at 24 hours with α=.05 and β=.20. Safety was ensured by continuous spectrophotometric monitoring of percentage of methemoglobinemia and a predefined protocol to respond to emergent changes in condition. Blinding was ensured by identical tanks, software, and physical shielding of the device display and query of the clinical care team to assess blinding efficacy. RESULTS: We have enrolled 78 patients over a 31-month period. No patient has been withdrawn as a result of a safety concern, and no patient has had a serious adverse event related to NO. CONCLUSIONS: We present methods and a protocol for the first double-blinded, randomized trial of inhaled NO to treat PE

A Search for Exozodiacal Clouds with Kepler

Planets embedded within dust disks may drive the formation of large scale clumpy dust structures by trapping dust into resonant orbits. Detection and subsequent modeling of the dust structures would help constrain the mass and orbit of the planet and the disk architecture, give clues to the history of the planetary system, and provide a statistical estimate of disk asymmetry for future exoEarth-imaging missions. Here we present the first search for these resonant structures in the inner regions of planetary systems by analyzing the light curves of hot Jupiter planetary candidates identified by the Kepler mission. We detect only one candidate disk structure associated with KOI 838.01 at the 3-sigma confidence level, but subsequent radial velocity measurements reveal that KOI 838.01 is a grazing eclipsing binary and the candidate disk structure is a false positive. Using our null result, we place an upper limit on the frequency of dense exozodi structures created by hot Jupiters. We find that at the 90% confidence level, less than 21% of Kepler hot Jupiters create resonant dust clumps that lead and trail the planet by ~90 degrees with optical depths >~5*10^-6, which corresponds to the resonant structure expected for a lone hot Jupiter perturbing a dynamically cold dust disk 50 times as dense as the zodiacal cloud.Comment: 22 pages, 6 figures, Accepted for publication in Ap

Star Formation in QSO Host Galaxies

Many of the conditions that are necessary for starbursts appear to be important in the triggering of QSOs. However, it is still debatable whether starbursts are ubiquitously present in galaxies harboring QSOs. In this paper we review our current knowledge from observations of the role of starbursts in different types of QSOs. Post-starburst stellar populations are potentially present in the majority of QSO hosts. QSOs with far-infrared colors similar to those of ultraluminous infrared galaxies invariably reside in merging galaxies that have interaction-induced starbursts of a few hundred Myr or less. Similar, but dramatically more luminous post-starburst populations are found in the recently discovered class of QSOs known as post-starburst QSOs, or Q+A's. Both of these classes, however, comprise only a small fraction (10-15%) of the total QSO population. The so-called "red" QSOs generally suffer from strong extinction at optical wavelengths, making them ideal candidates for the study of hosts. Their stellar populations typically show a post-starburst component as well, though with a larger range of ages. Finally, optical "classical" QSO hosts show traces of major star formation episodes (typically involving >10% of the mass of the stellar component) in the more distant past (1-2 Gyr). These starbursts appear to be linked to past merger events. It remains to be determined whether these mergers were also responsible for triggering the QSO activity that we observe today.Comment: 8 pages, 5 figures, invited review for "QSO Host Galaxies: Evolution and Environment", held at the Lorentz Center, Universiteit Leiden, August, 200