Produced water (PW) represents the largest volume waste stream in oil and gas production operations from most offshore platforms. PW is difficult to monitor as releases are rapidly diluted and concentrations can reach trace levels. The use of passive samplers can over come this. Here polyethylene (PE) was calibrated for a diverse range of PW pollutants. Zebrafish were exposed to dilutions of PW and passive sampler extracts in order to investigate the relationship between freely dissolved chemical concentrations and acute toxic effects. The raw PW had an LC50 of 13% (percentage of PW in the standardized zebrafish medium). Observed non-viable deformations to embryos (at 5 hpf) included heart and yolk edema, head, spine and tail deformations. The dose-response relationship of lethal effects showed that if 0.0041 g of PE is exposed to this PW, then extracted, 50% of exposed D. rerio will suffer lethal effects. The sum of tested freely dissolved concentrations that led to 50% lethal effects (mortality and non-viable deformations) was 2.32 × 10-4 mg/L for PW and 7.92 × 10-2 mg/L for PE. This implies that exposure to raw PW was more toxic than exposure to PE extracts. This toxicity was attributed both to the presence of contaminants as well as PW salinity. Passive samplers are able to detect very low freely dissolved pollutant concentrations which is important for assessing the spatial dilution of PW releases. Bioassays provide complimentary information as they account for all toxic compounds including those that are not taken up by passive samplers.

• MeSH
• biotest MeSH
• chemické látky znečišťující vodu analýza   chemie   MeSH
• monitorování životního prostředí metody   MeSH
• odpadní voda chemie   MeSH
• průmysl ropy a zemního plynu normy   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The importance of cellular metabolic adaptation in inducing robust T cell responses is well established. However, the mechanism by which T cells link information regarding nutrient supply to clonal expansion and effector function is still enigmatic. Herein, we report that the metabolic sensor adenosine monophosphate-activated protein kinase (AMPK) is a critical link between cellular energy demand and translational activity and, thus, orchestrates optimal expansion of T cells in vivo. AMPK deficiency did not affect T cell fate decision, activation, or T effector cell generation; however, the magnitude of T cell responses in murine in vivo models of T cell activation was markedly reduced. This impairment was global, as all T helper cell subsets were similarly sensitive to loss of AMPK which resulted in reduced T cell accumulation in peripheral organs and reduced disease severity in pathophysiologically as diverse models as T cell transfer colitis and allergic airway inflammation. T cell receptor repertoire analysis confirmed similar clonotype frequencies in different lymphoid organs, thereby supporting the concept of a quantitative impairment in clonal expansion rather than a skewed qualitative immune response. In line with these findings, in-depth metabolic analysis revealed a decrease in T cell oxidative metabolism, and gene set enrichment analysis indicated a major reduction in ribosomal biogenesis and mRNA translation in AMPK-deficient T cells. We, thus, provide evidence that through its interference with these delicate processes, AMPK orchestrates the quantitative, but not the qualitative, manifestation of primary T cell responses in vivo.

• MeSH
• adenylátkinasa genetika   metabolismus   MeSH
• aktivace lymfocytů MeSH
• buňky Th17 fyziologie   MeSH
• CD4-pozitivní T-lymfocyty MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• fyziologická adaptace MeSH
• kolitida imunologie   MeSH
• messenger RNA genetika   metabolismus   MeSH
• myši knockoutované MeSH
• myši MeSH
• převzatá imunita MeSH
• regulace genové exprese enzymů MeSH
• regulační T-lymfocyty fyziologie   MeSH
• T-lymfocyty pomocné-indukující fyziologie   MeSH
• Th1 buňky fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• léčivé rostliny MeSH
• nutriční vědy MeSH
• potraviny MeSH
• potravní doplňky MeSH
• prebiotika MeSH
• probiotika MeSH
• střevní mikroflóra MeSH
• Publikační typ
• kongresy MeSH
• sborníky MeSH
• zprávy MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• gastroenterologie
• nutriční terapie, dietoterapie a výživa

Exposure to aristolochic acid (AA) is associated with human nephropathy and urothelial cancer. The tumour suppressor TP53 is a critical gene in carcinogenesis and frequently mutated in AA-induced urothelial tumours. We investigated the impact of p53 on AAI-induced nephrotoxicity and DNA damage in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with 3.5 mg/kg body weight (bw) AAI daily for 2 or 6 days. Renal histopathology showed a gradient of intensity in proximal tubular injury from Trp53(+/+) to Trp53(-/-) mice, especially after 6 days. The observed renal injury was supported by nuclear magnetic resonance (NMR)-based metabonomic measurements, where a consistent Trp53 genotype-dependent trend was observed for urinary metabolites that indicate aminoaciduria (i.e. alanine), lactic aciduria (i.e. lactate) and glycosuria (i.e. glucose). However, Trp53 genotype had no impact on AAI-DNA adduct levels, as measured by 32P-postlabelling, in either target (kidney and bladder) or non-target (liver) tissues, indicating that the underlying mechanisms of p53-related AAI-induced nephrotoxicity cannot be explained by differences in AAI genotoxicity. Performing gas chromatography-mass spectrometry (GC-MS) on kidney tissues showed metabolic pathways affected by AAI treatment, but again Trp53 status did not clearly impact on such metabolic profiles. We also cultured primary mouse embryonic fibroblasts (MEFs) derived from Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice and exposed them to AAI in vitro (50 µM for up to 48 h). We found that Trp53 genotype impacted on the expression of NAD(P)H:quinone oxidoreductase (Nqo1), a key enzyme involved in AAI bioactivation. Nqo1 induction was highest in Trp53(+/+) MEFs and lowest in Trp53(-/-) MEFs; and it correlated with AAI-DNA adduct formation, with lowest adduct levels being observed in AAI-exposed Trp53(-/-) MEFs. Overall, our results clearly demonstrate that p53 status impacts on AAI-induced renal injury, but the underlying mechanism(s) involved remain to be further explored. Despite the impact of p53 on AAI bioactivation and DNA damage in vitro, such effects were not observed in vivo.

• MeSH
• cytochrom P-450 CYP1A1 genetika   MeSH
• exprese genu účinky léků   MeSH
• fibroblasty účinky léků   metabolismus   patologie   MeSH
• kultivované buňky MeSH
• kyseliny aristolochové metabolismus   toxicita   MeSH
• mutageny metabolismus   toxicita   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• NAD(P)H dehydrogenasa (chinon) genetika   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• poškození DNA * MeSH
• proximální tubuly ledvin účinky léků   metabolismus   patologie   MeSH
• vyšetření funkce ledvin MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Magnesium homeostasis is essential for life and depends on magnesium transporters, whose activity and ion selectivity need to be tightly controlled. Rhomboid intramembrane proteases pervade the prokaryotic kingdom, but their functions are largely elusive. Using proteomics, we find that Bacillus subtilis rhomboid protease YqgP interacts with the membrane-bound ATP-dependent processive metalloprotease FtsH and cleaves MgtE, the major high-affinity magnesium transporter in B. subtilis. MgtE cleavage by YqgP is potentiated in conditions of low magnesium and high manganese or zinc, thereby protecting B. subtilis from Mn2+ /Zn2+ toxicity. The N-terminal cytosolic domain of YqgP binds Mn2+ and Zn2+ ions and facilitates MgtE cleavage. Independently of its intrinsic protease activity, YqgP acts as a substrate adaptor for FtsH, a function that is necessary for degradation of MgtE. YqgP thus unites protease and pseudoprotease function, hinting at the evolutionary origin of rhomboid pseudoproteases such as Derlins that are intimately involved in eukaryotic ER-associated degradation (ERAD). Conceptually, the YqgP-FtsH system we describe here is analogous to a primordial form of "ERAD" in bacteria and exemplifies an ancestral function of rhomboid-superfamily proteins.

• MeSH
• ATPázy spojené s různými buněčnými aktivitami metabolismus   MeSH
• Bacillus subtilis růst a vývoj   metabolismus   MeSH
• bakteriální proteiny metabolismus   MeSH
• endopeptidasy metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• proteomika metody   MeSH
• regulace genové exprese u bakterií MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• farmakoterapie MeSH
• poruchy nálady farmakoterapie   MeSH
• psychotropní léky MeSH
• Publikační typ
• kongresy MeSH
• sborníky MeSH

• Konspekt
• Psychiatrie
• NLK Obory
• psychofarmakologie
• psychiatrie

• MeSH
• fyziologické jevy MeSH
• fyziologie MeSH
• Publikační typ
• obrazové publikace MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• fyziologie
• NLK Publikační typ
• učebnice vysokých škol

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

• MeSH
• depresivní porucha unipolární * genetika   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   MeSH
• neurozobrazování MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 12 May 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.c.4878591.v1.

• MeSH
• COVID-19 psychologie   MeSH
• dospělí MeSH
• emoce * MeSH
• emoční regulace * MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

• MeSH
• chirurgie MeSH
• lékařství MeSH
• traumatologie MeSH
• Publikační typ
• přehledy MeSH

• Konspekt
• Ortopedie. Chirurgie. Oftalmologie
• NLK Obory
• lékařství
• chirurgie
• traumatologie