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Based on these observations, we suggest that TET3 is involved in molecular alterations that govern hippocampal-dependent functions. These results reveal a critical role for epigenetic modifications in modulating brain functions, opening new insights into the molecular basis of neurological disorders.Plant-inhabiting microorganisms interact directly with each other affecting disease progression. However, the role of host plant and plant habitat in shaping pathobiome composition and their implication for host susceptibility/resistance to a particular disease are currently unknown. For the elucidation of these questions, both epiphytic and endophytic bacterial communities, present in asymptomatic and symptomatic twigs from olive cultivars displaying different susceptibilities to olive knot (OK) disease, were investigated using culturing methods. OK disease was the main driver of the bacterial community, causing changes on their diversity, abundance and composition. OK disease effect was most notorious on OK-susceptible cultivar and when considering the endophytic communities. Plant habitat (epiphytes vs. endophytes) also contributed to the bacterial community assembling, in particular on symptomatic twigs (knots) of OK-susceptible cultivar. In contrast, host cultivar had little effect on the bacterial community composition, but OK-symptomatic twigs (knots) revealed to be more affected by this driver. Overall, the pathobiome seems to result from an intricate interaction between the pathogen, the resident bacteria, and the plant host. Specific bacterial genera were associated to the presence or absence of OK disease in each cultivar. Their ability to trigger and/or suppress disease should be studied in the future.BACKGROUND Epigenetic therapy through demethylation of 5-methylcytosine has been largely ineffective in treating lung cancer, most likely due to poor tissue distribution with oral or subcutaneous delivery of drugs such as 5-azacytidine (5AZA). An inhalable, stable dry powder formulation of 5AZA was developed. METHODS Pharmacokinetics of inhaled dry powder and aqueous formulations of 5AZA were compared to an injected formulation. Efficacy studies and effect of therapy on the epigenome were conducted in an orthotopic rat lung cancer model for inhaled formulations. RESULTS Inhaled dry powder 5AZA showed superior pharmacokinetic properties in lung, liver, brain and blood compared to the injected formulation and for all tissues except lung compared to an inhaled aqueous formulation. Only dry powder 5AZA was detected in brain (~4-h half-life). Inhaled dry powder was superior to inhaled aqueous 5AZA in reducing tumour burden 70-95%. Superiority of inhaled 5AZA dry powder was linked to effectively reprogramming the cancer genome through demethylation and gene expression changes in cancer signalling and immune pathways. CONCLUSIONS These findings could lead to widespread use of this drug as the first inhaled dry powder therapeutic for treating local and metastatic lung cancer, for adjuvant therapy, and in combination with immunotherapy to improve patient survival.Acute kidney injury (AKI) increases early mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients and may accelerate chronic kidney disease (CKD) development. We analyzed prospective variables related to AKI and CKD in 422 allo-HCT recipients to establish risk factors of severe acute renal failure and CKD. Renal function and creatinine were periodically assessed from baseline till the last follow-up. Sixty-three patients (14%) developed severe AKI (AKI-3) at 100 days post transplant and 15% at 12 months. Variables associated with AKI-3 were age above 55 years [hazard ratio (HR) 2.4; p = 0.019], total body irradiation (TBI) (HR 1.8; p = 0.044), high-risk cytomegalovirus reactivation (HR 1.8; p = 0.041), and methotrexate as GVHD prophylaxis (HR 2.1; p = 0.024). AKI-3 increased the mortality risk (HR 2.5, 95% confidence interval 1.9-3.4). The CKD prevalence in 161 living patients was 10.2% at the last follow-up and in most, CKD developed 1 year post HCT, independent of AKI. The CKD at 1 year post HCT was associated with increased mortality (HR 3.54; p less then 0.001). Interestingly, pretransplant CKD was associated with early mortality (HR 5.6; p less then 0.001). In fact, pre- and posttransplant CKD had independent unfavorable long-term outcomes. These pretransplant factors can potentially be targeted to improve allo-HCT outcomes.An amendment to this paper has been published and can be accessed via a link at the top of the paper.MBW protein complexes containing MYB, bHLH and WD40 repeat factors are known transcriptional regulators of secondary metabolites production such as proanthocyanidins and anthocyanins, and developmental processes such as trichome formation in many plant species. DkMYB2 and DkMYB4 (MYB-type), DkMYC1 (bHLH-type) and DkWDR1 (WD40-type) factors have been proposed by different authors to take part of persimmon MBW complexes for proanthocyanidin accumulation in immature fruit, leading to its characteristic astringent flavour with important agronomical and ecological effects. We have confirmed the nuclear localization of these proteins and their mutual physical interaction by bimolecular fluorescence complementation analysis. In addition, transient expression of DkMYB2, DkMYB4 and DkMYC1 cooperatively increase the expression of a persimmon anthocyanidin reductase gene (ANR), involved in the biosynthesis of cis-flavan-3-ols, the structural units of proanthocyanidin compounds. Collectively, these data support the presence of MBW complexes in persimmon fruit and suggest their coordinated participation in ANR regulation for proanthocyanidin production.Maize, a major food source for the world, is a high-yield commodity crop, and one of five major crops in Thailand. Occupying about 33% of the Thai upland farmlands, maize farming has been growing tremendously especially in northern Thailand. However, after harvesting, open burning is widely used in order to get rid of maize cobs and husks in land preparation for the next period. The current maize farming practices have caused several problems to local communities as well as urban dwellers. The objectives of this research were (i) to analyze the life cycle inventory of maize cultivation, maize cob pellet production and heavy fuel oil production in northern Thailand using IDEA v2.0 and ecoinvent v3.0 databases; (ii) to evaluate environmental impacts of maize cultivation, maize cob pellet production and heavy fuel oil production using A Global Scale Environmental Life Cycle Impact Assessment (LIME-3) with the results of weighting (Country-specific) based on monetary valuation of end-points. This study evaluated e found to be more substantial. The results of present study are particularly relevant to policy choices for improving or using the good practices for maize cultivation, which would reduce the environmental performance of maize production systems in the area. To address the air pollution issue from biomass open burning of agricultural residues in the study area, the government agencies in Thailand should be responsible for promoting better biomass management for the future.Anadromous salmon and sea trout smolts face challenging migrations from freshwater to the marine environment characterised by high mortality. Therefore, the timing of smolt migration is likely to be critical for survival. Time-series comparing migration of Atlantic salmon and sea trout smolts in the same river, and their response to the same environmental cues, are scarce. Here, we analysed migration timing of ~41 000 Atlantic salmon and sea trout smolts over a 19-year period from the river Guddalselva, western Norway. this website Trout displayed a longer migration window in earlier years, which decreased over time to become more similar to the salmon migration window. On average, salmon migrated out of the river earlier than trout. Migration of both species was significantly influenced by river water temperature and water discharge, but their relative influence varied across the years. On average, body-length of smolts of both species overlapped, however, size differences were observed within the migration period and among the years. We conclude that salmon and trout smolts in this river are highly synchronised and migrate in response to the same range of linked environmental cues.Identification of AD (Alzheimer's disease)-related genes obtained from blood samples is crucial for early AD diagnosis. We used three public datasets, ADNI, AddNeuroMed1 (ANM1), and ANM2, for this study. Five feature selection methods and five classifiers were used to curate AD-related genes and discriminate AD patients, respectively. In the internal validation (five-fold cross-validation within each dataset), the best average values of the area under the curve (AUC) were 0.657, 0.874, and 0.804 for ADNI, ANMI, and ANM2, respectively. In the external validation (training and test sets from different datasets), the best AUCs were 0.697 (training ADNI to testing ANM1), 0.764 (ADNI to ANM2), 0.619 (ANM1 to ADNI), 0.79 (ANM1 to ANM2), 0.655 (ANM2 to ADNI), and 0.859 (ANM2 to ANM1), respectively. These results suggest that although the classification performance of ADNI is relatively lower than that of ANM1 and ANM2, classifiers trained using blood gene expression can be used to classify AD for other data sets. In addition, pathway analysis showed that AD-related genes were enriched with inflammation, mitochondria, and Wnt signaling pathways. Our study suggests that blood gene expression data are useful in predicting the AD classification.The brain combines sounds from the two ears, but what is the algorithm used to achieve this summation of signals? Here we combine psychophysical amplitude modulation discrimination and steady-state electroencephalography (EEG) data to investigate the architecture of binaural combination for amplitude-modulated tones. Discrimination thresholds followed a 'dipper' shaped function of pedestal modulation depth, and were consistently lower for binaural than monaural presentation of modulated tones. The EEG responses were greater for binaural than monaural presentation of modulated tones, and when a masker was presented to one ear, it produced only weak suppression of the response to a signal presented to the other ear. Both data sets were well-fit by a computational model originally derived for visual signal combination, but with suppression between the two channels (ears) being much weaker than in binocular vision. We suggest that the distinct ecological constraints on vision and hearing can explain this difference, if it is assumed that the brain avoids over-representing sensory signals originating from a single object. These findings position our understanding of binaural summation in a broader context of work on sensory signal combination in the brain, and delineate the similarities and differences between vision and hearing.We conducted a systematic review and meta-analysis to assess the clinical efficacy of high-flow nasal cannula (HFNC) therapy as apneic oxygenation in critically ill patients who require endotracheal intubation in the intensive care unit (ICU). This systematic review and meta-analysis included six randomized controlled trials and a prospective study identified in PubMed, Embase, Cochrane Library, and the Web of Science until August 18, 2019. In this meta-analysis including 956 participants, HFNC was noninferior to standard of care during endotracheal intubation regarding incidence of severe hypoxemia, mean lowest oxygen saturation, and in-hospital mortality. HFNC significantly shortened the ICU stay by a mean of 1.8 days. In linear meta-regression interaction analysis, the risk ratio of severe hypoxemia decreased with increasing baseline partial oxygen pressure (PaO2) to fraction of inspired oxygen (FiO2) ratio. In subgroup analysis, HFNC significantly reduced the incidence of severe hypoxemia during endotracheal intubation in patients with mild hypoxemia (PaO2/FiO2> 200 mmHg; risk difference, -0.
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