A plant's response to external and internal nitrogen signals/status relies on sensing and signaling mechanisms that operate across spatial and temporal dimensions. From a comprehensive systems ...biology perspective, this involves integrating nitrogen responses in different cell types and over long distances to ensure organ coordination in real time and yield practical applications. In this prospective review, we focus on novel aspects of nitrogen (N) sensing/signaling uncovered using temporal and spatial systems biology approaches, largely in the model Arabidopsis. The temporal aspects span: transcriptional responses to N-dose mediated by Michaelis-Menten kinetics, the role of the master NLP7 transcription factor as a nitrate sensor, its nitrate-dependent TF nuclear retention, its "hit-and-run" mode of target gene regulation, and temporal transcriptional cascade identified by "network walking." Spatial aspects of N-sensing/signaling have been uncovered in cell type-specific studies in roots and in root-to-shoot communication. We explore new approaches using single-cell sequencing data, trajectory inference, and pseudotime analysis as well as machine learning and artificial intelligence approaches. Finally, unveiling the mechanisms underlying the spatial dynamics of nitrogen sensing/signaling networks across species from model to crop could pave the way for translational studies to improve nitrogen-use efficiency in crops. Such outcomes could potentially reduce the detrimental effects of excessive fertilizer usage on groundwater pollution and greenhouse gas emissions.
OBJECTIVES:The “Pneumonia Zero” project is a nationwide multimodal intervention based on the simultaneous implementation of a comprehensive evidence-based bundle measures to prevent ...ventilator-associated pneumonia in critically ill patients admitted to the ICU.
DESIGN:Prospective, interventional, and multicenter study.
SETTING:A total of 181 ICUs throughout Spain.
PATIENTS:All patients admitted for more than 24 hours to the participating ICUs between April 1, 2011, and December 31, 2012.
INTERVENTION:Ten ventilator-associated pneumonia prevention measures were implemented (seven were mandatory and three highly recommended). The database of the National ICU-Acquired Infections Surveillance Study (Estudio Nacional de Vigilancia de Infecciones Nosocomiales ENVIN) was used for data collection. Ventilator-associated pneumonia rate was expressed as incidence density per 1,000 ventilator days. Ventilator-associated pneumonia rates from the incorporation of the ICUs to the project, every 3 months, were compared with data of the ENVIN registry (April–June 2010) as the baseline period. Ventilator-associated pneumonia rates were adjusted by characteristics of the hospital, including size, type (public or private), and teaching (postgraduate) or university-affiliated (undergraduate) status.
MEASUREMENTS AND MAIN RESULTS:The 181 participating ICUs accounted for 75% of all ICUs in Spain. In a total of 171,237 ICU admissions, an artificial airway was present on 505,802 days (50.0% of days of stay in the ICU). A total of 3,474 ventilator-associated pneumonia episodes were diagnosed in 3,186 patients. The adjusted ventilator-associated pneumonia incidence density rate decreased from 9.83 (95% CI, 8.42–11.48) per 1,000 ventilator days in the baseline period to 4.34 (95% CI, 3.22–5.84) after 19–21 months of participation.
CONCLUSIONS:Implementation of the bundle measures included in the “Pneumonia Zero” project resulted in a significant reduction of more than 50% of the incidence of ventilator-associated pneumonia in Spanish ICUs. This reduction was sustained 21 months after implementation.
•A 2-week strawberry intake has a high antioxidant potential.•Plasma antioxidant defenses increase, as well as lag phase prior to lipid oxidation.•Resistance to oxidative hemolysis improves, membrane ...lipid peroxidation does not vary.•Lymphocyte mortality after oxidative challenge reduces and metabolic activity increases.
The health promoting effects of a regular consumption of strawberries deserve attention, and a direct or indirect antioxidant role of strawberry bioactive compounds is among the most probable mechanisms underlying their beneficial properties. In the present study, we evaluated the overall effects of a 2-week daily consumption of strawberries on plasma antioxidant status, membrane lipid susceptibility to ex vivo-induced oxidation, and erythrocyte and mononuclear cell resistance to oxidative damage in apparently healthy volunteers. After strawberry intake, a moderate increase in fasting plasma antioxidant capacity and vitamin C was observed, together with a significant increase in the lag phase preceding plasma lipid oxidation. A significantly enhanced resistance to oxidative hemolysis was confirmed in red blood cells, while no significant changes were found in the extent of their membrane lipid peroxidation. For the first time, increased intake of strawberries for only 2weeks was shown to be sufficient to attenuate mononuclear cell mortality after ex vivo exposure to a single acuteoxidative challenge, but the analysis of DNA oxidative damage gave conflicting results. These findings suggest that a regular consumption of strawberries may enhance body defences against oxidative challenges.
Skin and chronic wound infections are an increasing and urgent health problem worldwide. Their management is difficult and the development of antibiotic resistance by both planktonic and ...biofilm-associated bacteria necessitates the use of alternative treatments. The purpose of this study was to compare the antimicrobial activity of four honeys from different floral and geographical origins:
honey (Cuba) and three
honeys Manuka honey (New Zealand),
honey (Cuba), and African honey (Kenya). The physicochemical parameters were within the ranges reported for these honeys and
honey stood out due to its acidic character. An agar incorporation technique was used to determine the minimum active dilution of each honey against 52 clinical isolates (34 Gram-positive, 17 Gram-negative, and 1
). The antibiofilm activity of honeys was tested by assessing their ability to inhibit biofilm formation and to disrupt preformed biofilms. Overall,
honey had the highest antimicrobial and antibiofilm activity, although a marked disruption in preformed biofilms was shared by all tested honeys. Structural changes induced by
honey on
and
cells were observed by transmission electron microscopy suggesting that this honey has a potent antimicrobial action and may be an excellent candidate for the development of topical preparations for the treatment of infected wounds.
YouTube, Instagram, Facebook, Vimeo, Twitter, etc. have their own logics, dynamics and different audiences. This book analyses how the users of these social networks, especially those of YouTube and ...Instagram, become content prescribers, opinion leaders and, by extension, people of influence. What influence capacity do they have? Why are intimate or personal aspects shared with unknown people? Who are the big beneficiaries? How much is vanity and how much altruism? What business is behind these social networks? What dangers do they contain? What volume of business can we estimate they generate? How are they transforming cultural industries? What legislation is applied? How does the legislation affect these communications when they are sponsored? Is the privacy of users violated with the data obtained? Who is the owner of the content? Are they to blame for ""fake news""? In this changing, challenging and intriguing environment, The Dynamics of Influencer Marketing discusses all of these questions and more. Considering this complexity from different perspectives: technological, economic, sociological, psychological and legal, the book combines the visions of several experts from the academic world and provides a structured framework with a wide approach to understand the new era of influencing, including the dark sides of it. It will be of direct interest to marketing scholars and researchers while also relevant to many other areas affected by the phenomenon of social media influence.
Abstract
Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An ...unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise,
n
= 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX
n
= 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control;
n
= 35, MOD-EX;
n
= 31, and VIG-EX;
n
= 31). We observed no changes in BAT volume (Δ Control: −22.2 ± 52.6 ml; Δ MOD-EX: −15.5 ± 62.1 ml, Δ VIG-EX: −6.8 ± 66.4 ml; P = 0.771) or
18
F-fluorodeoxyglucose uptake (SUVpeak Δ Control: −2.6 ± 3.1 ml; Δ MOD-EX: −1.2 ± 4.8, Δ VIG-EX: −2.2 ± 5.1;
p
= 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.
Deciphering gene regulatory networks (GRNs) is both a promise and challenge of systems biology. The promise lies in identifying key transcription factors (TFs) that enable an organism to react to ...changes in its environment. The challenge lies in validating GRNs that involve hundreds of TFs with hundreds of thousands of interactions with their genome-wide targets experimentally determined by high-throughput sequencing. To address this challenge, we developed ConnecTF, a species-independent, web-based platform that integrates genome-wide studies of TF-target binding, TF-target regulation, and other TF-centric omic datasets and uses these to build and refine validated or inferred GRNs. We demonstrate the functionality of ConnecTF by showing how integration within and across TF-target datasets uncovers biological insights. Case study 1 uses integration of TF-target gene regulation and binding datasets to uncover TF mode-of-action and identify potential TF partners for 14 TFs in abscisic acid signaling. Case study 2 demonstrates how genome-wide TF-target data and automated functions in ConnecTF are used in precision/recall analysis and pruning of an inferred GRN for nitrogen signaling. Case study 3 uses ConnecTF to chart a network path from NLP7, a master TF in nitrogen signaling, to direct secondary TF2s and to its indirect targets in a Network Walking approach. The public version of ConnecTF (https://ConnecTF.org) contains 3,738,278 TF-target interactions for 423 TFs in Arabidopsis, 839,210 TF-target interactions for 139 TFs in maize (Zea mays), and 293,094 TF-target interactions for 26 TFs in rice (Oryza sativa). The database and tools in ConnecTF will advance the exploration of GRNs in plant systems biology applications for model and crop species.
Nitrate is a nutrient and a potent signal that impacts global gene expression in plants. However, the regulatory factors controlling temporal and cell type-specific nitrate responses remain largely ...unknown. We assayed nitrate-responsive transcriptome changes in five major root cell types of the
root as a function of time. We found that gene-expression response to nitrate is dynamic and highly localized and predicted cell type-specific transcription factor (TF)-target interactions. Among cell types, the endodermis stands out as having the largest and most connected nitrate-regulatory gene network. ABF2 and ABF3 are major hubs for transcriptional responses in the endodermis cell layer. We experimentally validated TF-target interactions for ABF2 and ABF3 by chromatin immunoprecipitation followed by sequencing and a cell-based system to detect TF regulation genome-wide. Validated targets of ABF2 and ABF3 account for more than 50% of the nitrate-responsive transcriptome in the endodermis. Moreover, ABF2 and ABF3 are involved in nitrate-induced lateral root growth. Our approach offers an unprecedented spatiotemporal resolution of the root response to nitrate and identifies important components of cell-specific gene regulatory networks.
The purinergic P2X7 receptor (P2X7R) is a sensor of extracellular ATP, a damage-associated molecule that is released from necrotic cells and that induces pro-inflammatory cytokine production and cell ...death. To investigate whether the innate immune response to damage signals could contribute to the development of pulmonary necrotic lesions in severe forms of tuberculosis, disease progression was examined in C57BL/6 and P2X7R-/- mice that were intratracheally infected with highly virulent mycobacterial strains (Mycobacterium tuberculosis strain 1471 of the Beijing genotype family and Mycobacterium bovis strain MP287/03). The low-dose infection of C57BL/6 mice with bacteria of these strains caused the rapid development of extensive granulomatous pneumonia with necrotic areas, intense bacillus dissemination and anticipated animal death. In contrast, in P2X7R-/- mice, the lung pathology presented with moderate infiltrates of mononuclear leukocytes without visible signs of necrosis; the disease attenuation was accompanied by a delay in mortality. In vitro, the hypervirulent mycobacteria grew rapidly inside macrophages and induced death by a P2X7R-dependent mechanism that facilitated the release of bacilli. Furthermore, these bacteria were resistant to the protective mechanisms elicited in macrophages following extracellular ATP stimulation. Based on this study, we propose that the rapid intracellular growth of hypervirulent mycobacteria results in massive macrophage damage. The ATP released by damaged cells engages P2X7R and accelerates the necrotic death of infected macrophages and the release of bacilli. This vicious cycle exacerbates pneumonia and lung necrosis by promoting widespread cell destruction and bacillus dissemination. These findings suggest the use of drugs that have been designed to inhibit the P2X7R as a new therapeutic approach to treat the aggressive forms of tuberculosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose - This paper aims to investigate the link between a sustainable supply chain and companies' financial performance (FP) and provide empirical evidence about the relationship between these two ...constructs. This link is an important, but still unclear, subject. Design/methodology/approach - Multivariate measures of sustainable supply chain performance and companies' FP are used for Granger causality tests on a large, diverse sample of 3,900 companies in a time frame of eight years (2004-2011). Findings - Results indicate general bidirectional causality between sustainable supply chain performance and companies' margins and revenue. However, the link between firms' profitability and sustainable supply chain performance is unidirectional. In addition, the recent financial crisis altered this link between the studied constructs. Finally, a wide diversity in relationship patterns between sustainable supply chain performance and companies' FP emerges when the full sample is divided into different geographical regions and economic sectors as specified by the Global Industry Classification Standard system. Practical implications - This research makes recommendations for improving several processes, such as stakeholder evaluation of the sustainable supply chain performance of companies worldwide and manager testing of environmental policy outcomes. Originality/value - Building on the mostly qualitative literature on sustainable supply chain performance and companies' FP, this research provides quantitative evidence of the gaps between these constructs. This research contributes to the discussions of supply chain management, environmental practices and the drivers of companies' environmental and financial success.
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