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Coenzyme Q (ubiquinone or Q) plays a well known electron transport function in the respiratory chain, and recent evidence suggests that the reduced form of ubiquinone (QH2) may play a second role as a potent lipid-soluble antioxidant. To probe the function of QH2 as an antioxidant in vivo, we have made use of a Q-deficient strain of Saccharomyces cerevisiae harboring a deletion in the COQ3 gene [Clarke, C. F., Williams, W. and Teruya, J. H. (1991) J. Biol. Chem. 266, 16636-16644]. Q-deficient yeast and the wild-type parental strain were subjected to treatment with polyunsaturated fatty acids, which are prone to autoxidation and breakdown into toxic products. In this study we find that Q-deficient yeast are hypersensitive to the autoxidation products of linolenic acid and other polyunsaturated fatty acids. In contrast, the monounsaturated oleic acid, which is resistant to autoxidative breakdown, has no effect. The hypersensitivity of the coq3delta strains can be prevented by the presence of the COQ3 gene on a single copy plasmid, indicating that the sensitive phenotype results solely from the inability to produce Q. As a result of polyunsaturated fatty acid treatment, there is a marked elevation of lipid hydroperoxides in the coq3 mutant as compared with either wild-type or respiratory-deficient control strains. The hypersensitivity of the Q-deficient mutant can be rescued by the addition of butylated hydroxytoluene, alpha-tocopherol, or trolox, an aqueous soluble vitamin E analog. The results indicate that autoxidation products of polyunsaturated fatty acids mediate the cell killing and that QH2 plays an important role in vivo in protecting eukaryotic cells from these products

HR professionals can't create the perfect business plan without first knowing their customers' needs. By conducting a Customer Needs Assessment, evaluating its current situation and planning on how to get from here to there, HR can align itself for success.

We present and discuss a new dataset of gridded emissions covering the historical period (1850-2000) in decadal increments at a horizontal resolution of 0.5° in latitude and longitude. The primary purpose of this inventory is to provide consistent gridded emissions of reactive gases and aerosols for use in chemistry model simulations needed by climate models for the Climate Model Intercomparison Program #5 (CMIP5) in support of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment report (AR5). Our best estimate for the year 2000 inventory represents a combination of existing regional and global inventories to capture the best information available at this point; 40 regions and 12 sectors are used to combine the various sources. The historical reconstruction of each emitted compound, for each region and sector, is then forced to agree with our 2000 estimate, ensuring continuity between past and 2000 emissions. Simulations from two chemistry-climate models are used to test the ability of the emission dataset described here to capture long-term changes in atmospheric ozone, carbon monoxide and aerosol distributions. The simulated long-term change in the Northern mid-latitudes surface and mid-troposphere ozone is not quite as rapid as observed. However, stations outside this latitude band show much better agreement in both present-day and long-term trend. The model simulations indicate that the concentration of carbon monoxide is underestimated at the Mace Head station; however, the long-term trend over the limited observational period seems to be reasonably well captured. The simulated sulfate and black carbon deposition over Greenland is in very good agreement with the ice-core observations spanning the simulation period. Finally, aerosol optical depth and additional aerosol diagnostics are shown to be in good agreement with previously published estimates and observations.

In higher plants, the circadian clock orchestrates fundamental processes such as light signaling and the transition to flowering. We isolated mutants of the circadian clock from an Arabidopsis thaliana mutagenized reporter line by screening for seedlings with long hypocotyl phenotypes and subsequently assaying for abnormal clock-regulated CAB2::LUC expression. This screen identified five mutant alleles of a clock gene, LUX ARRHYTHMO (LUX), that significantly affect amplitude and robustness of rhythms in both constant white light and dark conditions. In addition, the transition from vegetative to floral development is accelerated and hypocotyl elongation is accentuated in these mutants under light:dark cycles. We genetically mapped the mutations by bulk segregant analysis with high-density oligonucleotide array genotyping to a small putative Myb transcription factor related to other clock components and response regulators in Arabidopsis. The negative arm of the Arabidopsis circadian clock, CIRCADIAN CLOCK ASSOCIATED (CCA1) and LATE ELONGATED HYPOCOTYL (LHY), is repressed in the lux mutants, whereas TIMING OF CAB2 EXPRESSION (TOC1) is activated. We demonstrate that CCA1 and LHY bind to the evening element motif in the LUX promoter, which strongly suggests that these proteins repress LUX expression, as they do TOC1. The data are also consistent with LUX being necessary for activation of CCA1 and LHY expression.

High-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments have focused on specific biological processes and perturbations. Here, we have generated and analyzed gene expression from a set of samples spanning a broad range of biological conditions. Specifically, we profiled gene expression from 91 human and mouse samples across a diverse array of tissues, organs, and cell lines. Because these samples predominantly come from the normal physiological state in the human and mouse, this dataset represents a preliminary, but substantial, description of the normal mammalian transcriptome. We have used this dataset to illustrate methods of mining these data, and to reveal insights into molecular and physiological gene function, mechanisms of transcriptional regulation, disease etiology, and comparative genomics. Finally, to allow the scientific community to use this resource, we have built a free and publicly accessible website (http://expression.gnf.org) that integrates data visualization and curation of current gene annotations.

Aims This study was performed to determine if the contribution of biological N 2 fixation (BNF) associated with Brazilian sugarcane cultivars could be increased by the inoculation with N 2 -fixing bacteria. Methods The field experiment was planted with two sugarcane cultivars, inoculated or not, with five N 2 -fixing bacteria. All plant tissues, including belowground, were harvested for determination of dry matter, N accumulation and 15 N abundance at five occasions until 450 days after planting. Results Inoculation significantly increased total N accumulation in the aerial tissue of cultivar RB867515 from 147 to 199 kg N ha −1 and cultivar RB92579 from 126 to 192 N kg ha −1 . At final harvest 15 N abundances of entire sugarcane plants compared to that of plant-available N indicated that BNF inputs were over 64%. Total N derived from BNF and the soil was increased by inoculation, by 50 and 17 kg N ha −1 and 36 and 67 kg N ha −1 , for the two cultivars respectively. Conclusions Without inoculation, the two sugarcane cultivars obtained over 65% of N from BNF. Inoculation with the five component inoculant increased N accumulation from soil and BNF but with little impact on the proportion of N derived from BNF.

Background INTELLiVENT–Adaptive Support Ventilation (ASV) is a fully automated closed-loop mode of ventilation for use in critically ill patients. Evidence for benefit of INTELLiVENT–ASV in comparison to ventilation that is not fully automated with regard to duration of ventilation and quality of breathing is largely lacking. We test the hypothesis that INTELLiVENT–ASV shortens time spent on a ventilator and improves the quality of breathing. Methods The “Effects of Automated Closed–loop VenTilation versus Conventional Ventilation on Duration and Quality of Ventilation” (ACTiVE) study is an international, multicenter, two-group randomized clinical superiority trial. In total, 1200 intensive care unit (ICU) patients with an anticipated duration of ventilation of > 24 h will be randomly assigned to one of the two ventilation strategies. Investigators screen patients aged 18 years or older at start of invasive ventilation in the ICU. Patients either receive automated ventilation by means of INTELLiVENT–ASV, or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is the number of days free from ventilation and alive at day 28; secondary endpoints are quality of breathing using granular breath-by-breath analysis of ventilation parameters and variables in a time frame of 24 h early after the start of invasive ventilation, duration of ventilation in survivors, ICU and hospital length of stay (LOS), and mortality rates in the ICU and hospital, and at 28 and 90 days. Discussion ACTiVE is one of the first randomized clinical trials that is adequately powered to compare the effects of automated closed-loop ventilation versus conventional ventilation on duration of ventilation and quality of breathing in invasively ventilated critically ill patients. The results of ACTiVE will support intensivist in their choices regarding the use of automated ventilation. Trial registration ACTiVE is registered in clinicaltrials.gov (study identifier: NCT04593810 ) on 20 October 2020.

Data from the first phase of the Human Tumor Atlas Network (HTAN) are now available, comprising 8,425 biospecimens from 2,042 research participants profiled with more than 20 molecular assays. The data were generated to study the evolution from precancerous to advanced disease. The HTAN Data Coordinating Center (DCC) has enabled their dissemination and effective reuse. We describe the diverse datasets, how to access them, data standards, underlying infrastructure and governance approaches, and our methods to sustain community engagement. HTAN data can be accessed through the HTAN Portal, explored in visualization tools—including CellxGene, Minerva and cBioPortal—and analyzed in the cloud through the NCI Cancer Research Data Commons. Infrastructure was developed to enable data ingestion and dissemination through the Synapse platform. The HTAN DCC’s flexible and modular approach to sharing complex cancer research data offers valuable insights to other data-coordination efforts and researchers looking to leverage HTAN data. This Perspective outlines the datasets, access methods, data standards, infrastructure, governance and community-engagement strategies of the Human Tumor Atlas Network.

To compare the number of alarms, interventions and nurses’ acceptance of automated ventilation with INTELLiVENT-ASV versus conventional ventilation strategy in patients receiving postoperative ventilation after cardiac surgery. This preplanned secondary analysis of the ‘POSITiVE’ randomized clinical trial compared INTELLiVENT-ASV (automated ventilation) with conventional ventilation in postoperative cardiac surgery patients. The number of critical alarms and manual ventilator interventions were compared during the first three hours of ventilation or until extubation. Nurses’ acceptance was assessed using a Technology Acceptance Model 2-based questionnaire and a user acceptance score from 1 to 10. POSITiVE randomized 220 patients (109 to automated and 111 to conventional ventilation). The average number of critical alarms per monitoring hour was similar between the automated and conventional group (5.6 vs 5.7; p = 0.823). The automated group required fewer manual interventions per monitoring hour for both ventilation control (0.7 vs 1.9; p < 0.001) and alarm management (2.0 vs 2.8; p < 0.001). The automated ventilation mode scored higher for perceived usefulness (2.6 vs 2.1; p < 0.001) and user acceptance (8.0 vs 7.0; p < 0.001), but similar for perceived ease of use. Automated ventilation for postoperative cardiac surgery patients had similar alarm frequencies as conventional ventilation, but reduced the number of interventions and showed higher nurses’ acceptance, indicating its potential to optimize patient care and reduce nurses’ workload. Our findings suggest that automated ventilation modes like INTELLiVENT-ASV can reduce the frequency of manual interventions and improve nurses’ acceptance, which may help alleviate nurses’ workload for postoperative cardiac surgery patients.

Background fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD. Methods fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N  = 23) and ASD-negative (HLN, N  = 91), and low-likelihood ASD-negative (LLN, N  = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses. Results OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices ( p  = 0.012), but none for HLP versus HLN ( p  = 0.047) nor HLN versus LLN ( p  = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)– temporal default mode network (tDMN) pair ( p  = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN ( p  = 0.0461 and 0.0004). HLP did not differ from HLN ( p  = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN ( p  = 0.0036). Conclusions 24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis.