Escherichia coli genome-wide promoter analysis: Identification of additional AtoC binding target elements

<p>Abstract</p> <p>Background</p> <p>Studies on bacterial signal transduction systems have revealed complex networks of functional interactions, where the response regulators play a pivotal role. The AtoSC system of <it>E. coli </it>activates the expression of <it>atoDAEB </it>operon genes, and the subsequent catabolism of short-chain fatty acids, upon acetoacetate induction. Transcriptome and phenotypic analyses suggested that <it>atoSC </it>is also involved in several other cellular activities, although we have recently reported a palindromic repeat within the <it>atoDAEB </it>promoter as the single, <it>cis</it>-regulatory binding site of the AtoC response regulator. In this work, we used a computational approach to explore the presence of yet unidentified AtoC binding sites within other parts of the <it>E. coli </it>genome.</p> <p>Results</p> <p>Through the implementation of a computational <it>de novo </it>motif detection workflow, a set of candidate motifs was generated, representing putative AtoC binding targets within the <it>E. coli </it>genome. In order to assess the biological relevance of the motifs and to select for experimental validation of those sequences related robustly with distinct cellular functions, we implemented a novel approach that applies Gene Ontology Term Analysis to the motif hits and selected those that were qualified through this procedure. The computational results were validated using Chromatin Immunoprecipitation assays to assess the <it>in vivo </it>binding of AtoC to the predicted sites. This process verified twenty-two additional AtoC binding sites, located not only within intergenic regions, but also within gene-encoding sequences.</p> <p>Conclusions</p> <p>This study, by tracing a number of putative AtoC binding sites, has indicated an AtoC-related cross-regulatory function. This highlights the significance of computational genome-wide approaches in elucidating complex patterns of bacterial cell regulation.</p

Erratum: Clinical Significance of Bronchodilator Responsiveness Evaluated by Forced Vital Capacity in COPD: SPIROMICS Cohort Analysis [Corrigendum].

[This corrects the article DOI: 10.2147/COPD.S220164.]

Three-Month Variability of Commonly Evaluated Biomarkers in Clinically Stable COPD

Seon Cheol Park,1,2 Narongkorn Saiphoklang,1,3 Jonathan Phillips,4 May-Lin Wilgus,1 Russell G Buhr,1 Donald P Tashkin,1 Christopher B Cooper,1,5 Igor Barjaktarevic1 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 2Division of Pulmonology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Thammasat University, Pathum Thani, Thailand; 4Inflammation Discovery Research, Amgen, Thousand Oaks, CA, USA; 5Exercise Physiology Research Laboratory, Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USACorrespondence: Igor Barjaktarevic, Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA, Email [email protected]: Clinical decisions in chronic obstructive pulmonary disease (COPD) treatment often utilize serially assessed physiologic parameters and biomarkers. To better understand the reliability of these tests, we evaluated changes in commonly assessed biomarkers over 3 months in patients with clinically stable COPD.Methods: We performed an observational prospective cohort study of 89 individuals with clinically stable COPD, defined as no exacerbation history within 3 months of enrollment. Biomarkers included lung function and functional performance status, patient-reported outcomes of symptoms and health status, and blood markers of inflammation. The correlation between testing at baseline and at 3-month follow-up was reported as the intraclass correlation coefficient (ICC). “Outliers” had significant variability between tests, defined as > 1.645 standard deviations between the two measurements. Differences in clinical features between outliers and others were compared.Results: Participants with COPD (n = 89) were 70.5 ± 6.7 years old, 54 (61%) male, had a 40 pack-year smoking history with 24.7% being current smokers, and postbronchodilator forced expiratory volume in one second (FEV1) 62.3 ± 22.7% predicted. The biomarkers with excellent agreement between the initial and the follow-up measurements were FEV1 (ICC = 0.96), Saint George’s Respiratory Questionnaire (SGRQ) (ICC = 0.98), COPD Assessment Test (CAT) (ICC = 0.93) and C-reactive protein (CRP) (ICC = 0.90). By contrast, parameters showing less robust agreement were 6-minute walking distance (ICC = 0.75), eosinophil count (ICC = 0.77), erythrocyte sedimentation rate (ICC = 0.75) and white blood cell count (ICC = 0.48). Individuals with greater variability in biomarkers reported chronic bronchitis more often and had higher baseline SGRQ and CAT scores.Conclusion: Our study evaluated the stability of commonly assessed biomarkers in clinically stable COPD and showed excellent agreement between baseline and three-month follow-up values for FEV1, SGRQ, CAT and CRP. Individuals with chronic bronchitis and more symptomatic disease at baseline demonstrated greater variability in 3-month interval biomarkers.Keywords: COPD, biomarkers, stability, repeatability, variabilit

Sentinel Lymph Node Biopsy in Colon Cancer

INTRODUCTION: The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results. METHODS: Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor. The SLN underwent step sections and immunohistochemistry (IHC), if classified free of metastases after routine hematoxylin and eosin examination. RESULTS: At least one SLN (median, n = 2) was identified in 268 of 315 enrolled patients (detection rate, 85%). Center experience, lymphovascular invasion, body mass index (BMI), and learning curve were positively associated with the detection rate. The false-negative rate to identify pN+ patients by SLNB was 46% (38 of 82). BMI showed a significant association to the false-negative rate (P < 0.0001), the number of tumor-involved lymph nodes was inversely associated. If only slim patients (BMI ≤24) were investigated in experienced centers (>22 patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21% (30 of 141) of the patients, classified as pN0 by routine histopathology, revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN. CONCLUSIONS: The contribution of SLNB to conventional nodal staging of colon cancer patients is still unspecified. Technical problems have to be resolved before a definite conclusion can be drawn in this regard. However, SLNB identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes. Further studies must clarify the clinical impact of these findings in terms of prognosis and the indication of adjuvant therapy

Responsible Digital Transformation of Social Welfare Organizations

Digitalization will extensively change what kind of social services social welfare states will provide in the future and how these services are delivered. In addition, organization and financing will alter fundamentally. In Germany, a greater part of social services is organized by social welfare organizations. Digitalization will not only change social services, but also social welfare organizations. Until now, systematic concepts about responsible digital transformation for social welfare organizations are missing and there are no models for social welfare organizations to initiate, design and implement social innovation processes. This chapter gives an overview about organizational development and innovation in the context of social services. Further, ideas for a responsible digital transformation of social welfare organizations are provided and illustrated by an example of the social welfare organization: Workers’ Samaritan Federation North Rhine-Westphalia registered association (ASB NRW e.V.)

The management process underpinning the non-financial reporting: a case-study of a Listed Italian Company

In the current economy, several institutions, organizations, stakeholders, and societies are promoting a new idea of business, based on more ethical, social, and environmental-oriented (Cantino and Cortese 2017; Epstein 2018). Hence, community pressures and stakeholders’ expectations have led to a rise in sustainability reporting and standards and guidelines regarding the disclosure of environmental, social, and governance information mainly provided on a voluntary basis (Salvioni and Bosetti 2014). The preparation of stand-alone corporate non-financial reporting provided by large companies is increased from 70% in 2013 to 73% in 2015, and by the year 2017, about 77% of the companies produced reports regarding environmental, social, and governance (ESG) matters (KPMG 2017). More recently, regulation has begun to be deemed necessary to address matters regarding the firm’s legitimacy, transparency, comparability, and credibility of nonfinancial reporting procedures (Eccles and Serafeim 2015; Vitolla and Ramio 2018). The European Union has introduced the Directive 2014/95/EU to oblige companies in reporting non-financial information. This Directive has aimed to achieve similar levels of transparency across the EU states by allowing high levels of flexibility in taking into account the ESG dimensions and the diversity policies implemented by each company. In Italy, the corresponding Legislative Decree regarding the disclosure of nonfinancial and diversity information has been implemented in 2016, and it operates from 1 January 2017. Despite the growing interest in non-financial information disclosure, studies, examining the reasons for and the activities and managers-related disclosure choices, are still lacking (Bebbington and Larrinaga 2014; Gray 2010; Adams and Larrinaga 2007; Hopwood 2009; Moser and Martin 2012). In fact, to date, most of the studies mainly focus on analyzing the content and structure of the non-financial reports by neglecting research topics such as the process underlying the realization and the development of non-financial disclosure (NFD). Therefore, this study aims to fill that gap by exploring the process steps that lead to the non-financial information disclosure. Due to the explorative nature of this research, a qualitative approach, based on a case study (Eisenhardt and Graebner 2007; Miles et al. 2014), is adopted. The research focus is on a listed Italian company operating in the manufacturing sector. Semi-structured interviews (Qu and Dumay 2011) are used to highlight the activities and the stages characterizing the management processes and valorization practices of non-financial information. Therefore, the research questions are the following: (RQ1) Which actors are involved in the process underpinning the non-financial information disclosure? (RQ2) Which are the phases characterizing the non-financial information disclosure process? And finally, (RQ3) what are the main critical areas meet during the development and the implementation of the non-financial disclosure process? It is the first step of preliminary research of a more extensive project aiming to investigate the implementation practices of non-financial reporting. Therefore, this paper contributes to extending the literature regarding the non-financial reporting by providing a deeper description of the process characterizing the NFD implementation and the critical areas and the opportunities associated with the developing process of this report, after the European regulations, with a focus on the Italian context. The paper is structured as follows. In section two, a brief literature review regarding studies on non-financial information reporting is shown. In section three, an overview of the Italian Legislative Decree n. 254/2016, adopted by the Italian Parliament, regarding the disclosure of non-financial and diversity information, is provided. Finally, the research methodology, findings, and conclusion sections are illustrated