1,030 research outputs found

    Function of cofactor Akirin2 in the regulation of gene expression in model human Caucasian neutrophil-like HL60 cells

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    The Akirin family of transcription cofactors are involved throughout the metazoan in the regulation of different biological processes (BPs) such as immunity, interdigital regression, muscle and neural development. Akirin do not have catalytic or DNA-binding capability and exert its regulatory function primarily through interacting proteins such as transcription factors, chromatin remodelers, and RNA-associated proteins. In the present study, we focused on the human Akirin2 regulome and interactome in neutrophil-like model human Caucasian promyelocytic leukemia HL60 cells. Our hypothesis is that metazoan evolved to have Akirin2 functional complements and different Akirin2-mediated mechanisms for the regulation of gene expression. To address this hypothesis, experiments were conducted using transcriptomics, proteomics and systems biology approaches in akirin2 knockdown and wildtype (WT) HL60 cells to characterize Akirin2 gene/protein targets, functional complements and to provide evidence of different mechanisms that may be involved in Akirin2-mediated regulation of gene expression. The results revealed Akirin2 gene/protein targets in multiple BPs with higher representation of immunity and identified immune response genes as candidate Akirin2 functional complements. In addition to linking chromatin remodelers with transcriptional activation, Akirin2 also interacts with histone H3.1 for regulation of gene expression. © 2021 The Author(s)

    Role of quantum coherence in chromophoric energy transport

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    The role of quantum coherence and the environment in the dynamics of excitation energy transfer is not fully understood. In this work, we introduce the concept of dynamical contributions of various physical processes to the energy transfer efficiency. We develop two complementary approaches, based on a Green's function method and energy transfer susceptibilities, and quantify the importance of the Hamiltonian evolution, phonon-induced decoherence, and spatial relaxation pathways. We investigate the Fenna-Matthews-Olson protein complex, where we find a contribution of coherent dynamics of about 10% and of relaxation of 80%.Comment: 5 pages, 3 figures, included static disorder, correlated environmen

    The DISCOVER codec: Architecture, Techniques and Evaluation

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    Distributed Video Coding is becoming more and more popular among the research community, because of its interesting theoretical contributions and because there are still many open problems waiting to be solved. This paper introduces the codec architecture and the associated tools adopted by DISCOVER (DIStributed COding for Video sERvices), a European project which has been devoted to the advancement of Distributed Video Coding for two years. Along with the general description and pointers to references with more detailed information, this paper also presents some of the results obtained with the DISCOVER codec. An extended performance analysis and the codec’s executable file are both publicly available on the project’s web site www.discoverdvc.org

    Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

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    Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P \u3c0.002), none of which achieved an AUC \u3e0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169

    Quantum entanglement in photosynthetic light harvesting complexes

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    Light harvesting components of photosynthetic organisms are complex, coupled, many-body quantum systems, in which electronic coherence has recently been shown to survive for relatively long time scales despite the decohering effects of their environments. Within this context, we analyze entanglement in multi-chromophoric light harvesting complexes, and establish methods for quantification of entanglement by presenting necessary and sufficient conditions for entanglement and by deriving a measure of global entanglement. These methods are then applied to the Fenna-Matthews-Olson (FMO) protein to extract the initial state and temperature dependencies of entanglement. We show that while FMO in natural conditions largely contains bipartite entanglement between dimerized chromophores, a small amount of long-range and multipartite entanglement exists even at physiological temperatures. This constitutes the first rigorous quantification of entanglement in a biological system. Finally, we discuss the practical utilization of entanglement in densely packed molecular aggregates such as light harvesting complexes.Comment: 14 pages, 7 figures. Improved presentation, published versio

    Major consequences of an intense dense shelf water cascading event on deep-sea benthic trophic conditions and meiofaunal biodiversity

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    Numerous submarine canyons around the world are preferential conduits for episodic dense shelf water cascading (DSWC), which quickly modifies physical and chemical ambient conditions while transporting large amounts of material towards the base of slope and basin. Observations conducted during the last 20 yr in the Lacaze-Duthiers and Cap de Creus canyons (Gulf of Lion, NW Mediterranean Sea) report several intense DSWC events. The effects of DSWC on deep-sea ecosystems are almost unknown. To investigate the effects of these episodic events, we analysed changes in the meiofaunal biodiversity inside and outside the canyon. Sediment samples were collected at depths varying from ca. 1000 to > 2100 m in May 2004 (before a major event), April 2005 (during a major cascading event) and in October 2005, August 2006, April 2008 and April 2009 (after a major event). We report here that the late winter-early spring 2005 cascading led to a reduction of the organic matter contents in canyon floor sediments down to 1800 m depth, whereas surface sediments at about 2200 m depth showed an increase. Our findings suggest that the nutritional material removed from the shallower continental shelf, canyon floor and flanks, and also the adjacent open slope was rapidly transported to the deep margin. During the cascading event the meiofaunal abundance and biodiversity in the studied deep-sea sediments were significantly lower than after the event. Benthic assemblages during the cascading were significantly different from those in all other sampling periods in both the canyon and deep margin. After only six months from the cessation of the cascading, benthic assemblages in the impacted sediments were again similar to those observed in other sampling periods, thus illustrating a quick recovery. Since the present climate change is expected to increase the intensity and frequency of these episodic events, we anticipate that they will increasingly affect benthic bathyal ecosystems, which may eventually challenge their resilience

    The Dynamics of the Pulmonary Microbiome During Mechanical Ventilation in the Intensive Care Unit and the Association with Occurrence of Pneumonia

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    RATIONALE: Ventilator-associated pneumonia (VAP) is the most common nosocomial infections in patients admitted to the ICU. The adapted island model predicts several changes in the respiratory microbiome during intubation and mechanical ventilation. OBJECTIVES: We hypothesised that mechanical ventilation and antibiotic administration decrease the diversity of the respiratory microbiome and that these changes are more profound in patients who develop VAP. METHODS: Intubated and mechanically ventilated ICU-patients were included. Tracheal aspirates were obtained three times a week. 16S rRNA gene sequencing with the Roche 454 platform was used to measure the composition of the respiratory microbiome. Associations were tested with linear mixed model analysis and principal coordinate analysis. MEASUREMENTS AND MAIN RESULTS: 111 tracheal aspirates were obtained from 35 patients; 11 had VAP, 18 did not have VAP. Six additional patients developed pneumonia within the first 48 hours after intubation. Duration of mechanical ventilation was associated with a decrease in α diversity (Shannon index; fixed-effect regression coefficient (β): -0.03 (95% CI -0.05 to -0.005)), but the administration of antibiotic therapy was not (fixed-effect β: 0.06; 95% CI -0.17 to 0.30). There was a significant difference in change of β diversity between patients who developed VAP and control patients for Bray-Curtis distances (p=0.03) and for Manhattan distances (p=0.04). Burkholderia, Bacillales and, to a lesser extent, Pseudomonadales positively correlated with the change in β diversity. CONCLUSION: Mechanical ventilation, but not antibiotic administration, was associated with changes in the respiratory microbiome. Dysbiosis of microbial communities in the respiratory tract was most profound in patients who developed VAP.info:eu-repo/semantics/publishedVersio
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