► Paleoenvironmental changes during deposition of oil shales investigated. ► Salinity stratification of the water column reconstructed. ► Anoxic cycles during Late Cretaceous outlined. ► Sources of ...organic matter discussed.
Excellent hydrocarbon source rocks (oil shales), containing Type I organic matter (OM), were deposited in the continental Songliao rift basin during the Late Cretaceous. A major contribution of aquatic organisms (dinoflagellates, green algae, botryococcus) and minor input from macrophytes and land plants to OM accumulation is indicated by n-alkane distribution, steroid composition and δ13C values of individual biomarkers. Microbial communities included heterotrophic bacteria, cyanobacteria and chemoautotrophic bacteria, as well as purple and green sulfur bacteria. The presence of methanotrophic bacteria is indicated by 13C-depleted methyl hopane. The sediments were deposited in a eutrophic, alkaline palaeolake. Highly reducing (saline) bottom water conditions and a stratified water column existed during OM accumulation of the Qingshankou Formation and Member 1 of the Nenjiang Formation. This is indicated by low pristane/phytane, gammacerane index and MTTC ratios, and the presence of β-carotane and aryl isoprenoids. However, an abrupt change in environmental conditions during deposition of Member 2 of the Nenjiang Formation is indicated by significant changes in salinity and redox-sensitive biomarker ratios. A freshwater environment and suboxic conditions in the deep water prevailed during this period. Higher input of terrigenous OM occurred during deposition of the upper Nenjiang Formation.
Good oil-to-source rock correlation was obtained using biomarker fingerprints of oil-stained sandstone from the Quantou Formation and oil shales from the Qingshankou Formation. Based on the extent of isomerisation of C31 hopanes, the oil was most probably derived from oil shales of the Qingshankou Formation in deeper parts of the basin.
Abstract
A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory ...parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively. Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy. Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.
Single-cell atlases often include samples that span locations, laboratories and conditions, leading to complex, nested batch effects in data. Thus, joint analysis of atlas datasets requires reliable ...data integration. To guide integration method choice, we benchmarked 68 method and preprocessing combinations on 85 batches of gene expression, chromatin accessibility and simulation data from 23 publications, altogether representing >1.2 million cells distributed in 13 atlas-level integration tasks. We evaluated methods according to scalability, usability and their ability to remove batch effects while retaining biological variation using 14 evaluation metrics. We show that highly variable gene selection improves the performance of data integration methods, whereas scaling pushes methods to prioritize batch removal over conservation of biological variation. Overall, scANVI, Scanorama, scVI and scGen perform well, particularly on complex integration tasks, while single-cell ATAC-sequencing integration performance is strongly affected by choice of feature space. Our freely available Python module and benchmarking pipeline can identify optimal data integration methods for new data, benchmark new methods and improve method development.
Environmental changes alter the sex fate in about 15% of vertebrate orders, mainly in ectotherms such as fish and reptiles. However, the effects of temperature changes on the endocrine and molecular ...processes controlling gonadal sex determination are not fully understood. Here, we provide evidence that thyroid hormones (THs) act as co-players in heat-induced masculinization through interactions with the stress axis to promote testicular development. We first demonstrated that the thyroid axis (through thyroid-related genes and T3 levels) is highly active in males during the gonadal development in medaka (
Oryzias latipes
). Similarly, T3 treatments promoted female-to-male sex reversal in XX embryos. Subsequently, embryonic exposure to temperature-induced stress up-regulated the genes related to the thyroid and stress axes with a final increase in T3 levels. In this context, we show that blocking the stress axis response by the loss of function of the corticotropin-releasing hormone receptors suppresses thyroid-stimulating hormone expression, therefore, heat-induced activation of the thyroid axis. Thus, our data showed that early activation of the stress axis and, in consequence, the TH axis, too, leaves us with that both being important endocrine players in inducing female-to-male reversal, which can help predict possible upcoming physiological impacts of global warming on fish populations.
The determination of sex is an important hallmark in the life cycle of organisms, in which the fate of gonads and then the individual sex are defined. In gonochoristic teleost fish, this process is ...characterized by a high plasticity, considering that in spite of genotypic sex many environmental factors can cause shifts from one to another molecular pathway, resulting in organisms with mismatching genotypic and phenotypic sexes. Interestingly, in most instances, both female-to-male or male-to-female sex-reversed individuals develop functional gonads with normal gametogenesis and respective progenies with full viability. The study of these mechanisms is being spread to other non-model species or to those inhabiting more extreme environmental conditions. Although water temperature is an important mechanism involved in sex determination, there are other environmental stressors affected by the climate change which are also implicated in stress response-induced masculinization in fish. In this regard, the brain has emerged as the transducer of the environment input that can influence the gonadal fate. Furthermore, the evaluation of other environmental stressors or their synergic effect on sex determination at conditions that simulate the natural environments is growing gradually. Within such scope, the concerns related to climate change impacts rely on the fact that many of biotic and abiotic parameters reported to affect sex ratios are expected to increase concomitantly as a result of increased greenhouse gas emissions and, particularly worrying, many of them are related to male bias in the populations, such as high temperature, hypoxia, and acidity. These environmental changes can also generate epigenetic changes in sex-related genes affecting their expression, with implications on sex differentiation not only of exposed individuals but also in following generations. The co-analysis of multi-stressors with potential inter- and transgenerational effects is essential to allow researchers to perform long-term predictions on climate change impacts in wild populations and for establishing highly accurate monitoring tools and suitable mitigation strategies.
The features of 100 mixed-phenotype acute leukemias (MPALs), fulfilling WHO 2008 criteria, are documented. Myeloid and T-lineage features were demonstrated by cytoplasmic myeloperoxidase and CD3; ...B-lineage features were demonstrated by at least 2 B-lymphoid markers. There were 62 men and 38 women; 68% were adults. Morphology was consistent with acute lymphoblastic leukemia (ALL; 43%), acute myeloid leukemia (AML; 42%), or inconclusive (15%). Immunophenotyping disclosed B + myeloid (59%), T + myeloid (35%), B + T (4%), or trilineage (2%) combinations. Cytogenetics evidenced t(9;22)/(Ph+) (20%), 11q23/MLL rearrangements (8%), complex (32%), aberrant (27%), or normal (13%) karyotypes. There was no correlation between age, morphology, immunophenotype, or cytogenetics. Response to treatment and outcome were available for 67 and 70 patients, respectively; 27 received ALL, 34 AML, 5 a combination of ALL + AML therapy, and 1 imatinib. ALL treatment induced a response in 85%, AML therapy in 41%; 3 of 5 patients responded to the combination therapy. Forty (58%) patients died, 33 of resistant disease. Overall median survival was 18 months and 37% of patients are alive at 5 years. Age, Ph+, and AML therapy were predictors for poor outcome (P < .001; P = .002; P = .003). MPAL is confirmed to be a poor-risk disease. Adults and Ph+ patients should be considered for transplantation in first remission.
Folate is an essential vitamin for vertebrate embryo development. Methotrexate (MTX) is a folate antagonist that is widely prescribed for autoimmune diseases, blood and solid organ malignancies, and ...dermatologic diseases. Although it is highly contraindicated for pregnant women, because it is associated with an increased risk of multiple birth defects, the effect of paternal MTX exposure on their offspring has been largely unexplored. Here, we found MTX treatment of adult medaka male fish (Oryzias latipes) causes cranial cartilage defects in their offspring. Small non-coding RNA (sncRNAs) sequencing in the sperm of MTX treated males identify differential expression of a subset of tRNAs, with higher abundance for specific 5' tRNA halves. Sperm RNA methylation analysis on MTX treated males shows that m5C is the most abundant and differential modification found in RNAs ranging in size from 50 to 90 nucleotides, predominantly tRNAs, and that it correlates with greater testicular Dnmt2 methyltransferase expression. Injection of sperm small RNA fractions from MTX-treated males into normal fertilized eggs generated cranial cartilage defects in the offspring. Overall, our data suggest that paternal MTX exposure alters sperm sncRNAs expression and modifications that may contribute to developmental defects in their offspring.
Two oil shale layers are present in the Upper Cretaceous Nenjiang Formation of the Songliao Basin, representing excellent hydrocarbon source rocks. Their biomarker compositions provide evidence for a ...major contribution by aquatic organisms within the photic zone of the water column. Phytoplankton blooms were promoted by warm–humid climate, and lake eutrophication. Salinity stratification and anoxic bottom water conditions are indicated in the lower oil shale layer, whereas decreased salinity and partial oxygenation of the water column are evident in the upper oil shale layer. Moreover, an increase in sizes of alginite from the lower to the upper oil shale layer and enhanced telalginite concentrations is detected. Therefore, a stratified water column with high salinity and anoxic bottom water conditions contributes to organic matter (OM) preservation in the lower oil shale layer. In contrast, high bioproductivity in combination with OM preservation favored by enhanced algae sizes and telalginite concentrations are suggested as the OM enrichment mechanisms in the upper oil shale layer. In addition, factors such as clay minerals, microbial activity, and detrital matter input cannot be ignored for their influence on OM enrichment.
In this study, a preservation model within the lower oil shale layer and a productivity model within the upper oil shale layer are established. The models imply that excellent preservation is the major controlling factor for OM enrichment in the lower oil shale layer, whereas the high bioproductivity is the major controlling factor for OM enrichment in the upper oil shale layer. However, the combination of both factors for oil shale deposition must be considered.
•The Nenjiang Formation of the Songliao Basin hosts two oil shale layers.•Salinity stratification and anoxic bottom water occurred in the lower layer.•Brackish to fresh water and a partially oxygenation occurred in the upper layer.•Enhanced algae sizes and telalginite concentrations promote OM preservation.•Organic matter richness is due to excellent preservation or high bioproductivity.
Epitranscriptomic events such as adenosine‐to‐inosine (A‐to‐I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A ...(FLNA) mediates a Q‐to‐R transition in the interactive C‐terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient‐derived RNA‐Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases. Using mice with only impaired FLNA editing, we observed increased vascular contraction and diastolic hypertension accompanied by increased myosin light chain phosphorylation, arterial remodeling, and left ventricular wall thickening, which eventually causes cardiac remodeling and reduced systolic output. These results demonstrate a causal relationship between RNA editing and the development of cardiovascular disease indicating that a single epitranscriptomic RNA modification can maintain cardiovascular health.
Synopsis
RNA‐editing of Filamin A pre‐mRNA is decreased in human cardiac disease. A mouse model lacking this editing site shows altered smooth muscle contraction and diastolic blood pressure, illustrating that ADAR2‐dependent RNA editing plays a functional role outside the central nervous system.
The Filamin A (FLNA) pre‐mRNA is subject to RNA editing with the highest rates seen in the cardiovascular system.
FLNA editing rates are reduced in cardiovascular disease patients.
In mice, FLNA editing controls smooth muscle contraction of the dorsal aorta.
Mice deficient in FLNA editing show elevated diastolic blood pressure and cardiac remodeling.
Disrupting a single mRNA editing site in mice affects smooth muscle contraction and diastolic blood pressure, while reduced editing at the same site in human correlates with cardiac disease.
Background: Sleep disorders can cause tiredness. The relationship between sleep disorders and fatigue in patients with multiple sclerosis (MS) has not yet been investigated systematically.
Objective: ...To investigate the relationship between fatigue and sleep disorders in patients with MS.
Methods: Some 66 MS patients 20 to 66 years old were studied by overnight polysomnography. Using a cut-off point of 45 in the Modified Fatigue Impact Scale (MFIS), the entire cohort was stratified into a fatigued MS subgroup (n = 26) and a non-fatigued MS subgroup (n = 40).
Results: Of the fatigued MS patients, 96% (n = 25) were suffering from a relevant sleep disorder, along with 60% of the non-fatigued MS patients (n = 24) (p = 0.001). Sleep-related breathing disorders were more frequent in the fatigued MS patients (27%) than in the non-fatigued MS patients (2.5%). Significantly higher MFIS values were detected in all (fatigued and non-fatigued) patients with relevant sleep disorders (mean MFIS 42.8; SD 18.3) than in patients without relevant sleep disorders (mean MFIS 20.5; SD 17.0) (p < 0.001). Suffering from a sleep disorder was associated with an increased risk of fatigue in MS (odds ratio: 18.5; 95% CI 1.6–208; p = 0.018).
Conclusion: Our results demonstrate a clear and significant relationship between fatigue and sleep disorders.
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