Miracle-dz/UniFAR-FTUs huggingface dataset:
Genotypic variants of the tetrahydrobiopterin (BH4) biosynthesis genes in patients with hyperphenylalaninemia from different regions of Iran

Abstract Background Hyperphenylalaninemia (HPA) is a metabolic disorder classified into phenylalanine‐4‐hydroxylase (PAH) and non‐PAH deficiency. The latter is produced by mutations in genes involved in the tetrahydrobiopterin (BH4) biosynthesis pathway and DNAJC12 pathogenetic variants. The BH4 metabolism, including de novo biosynthesis involved genes (i.e., guanosine 5′‐triphosphate cyclohydrolase I (GTPCH/GCH1), sepiapterin reductase (SR/SPR), 6‐pyruvoyl‐tetrahydropterin synthase (PTPS/PTS)), and two genes that play roles in cofactor regeneration pathway (i.e., dihydropteridine reductase (DHPR/QDPR) and pterin‐4α‐carbinolamine dehydratase (PCD/PCBD1)). The subsequent systemic hyperphenylalaninemia and monoamine neurotransmitter deficiency lead to neurological consequences. The high rate of consanguineous marriages in Iran substantially increases the incidence of BH4 deficiency. Methods We utilized the Sanger sequencing technique in this study to investigate 14 Iranian patients with non‐PAH deficiency. All affected subjects in this study had HPA and no mutation was detected in their PAH gene. Results We successfully identified six mutant alleles in BH4‐deficiency‐associated genes, including three novel mutations: one in QDPR, one in PTS, and one in the PCBD1 gene, thus giving a definite diagnosis to these patients. Conclusion In this light, appropriate patient management may follow. The clinical effect of reported variants is essential for genetic counseling and prenatal diagnosis in the patients' families and significant for the improvement of precision medicine.
Scandinavia: A former Tibet?

The Himalaya and the Tibetan Plateau are uplifted by the ongoing northward underthrusting of the Indian continental lithosphere below Tibet resulting in lithospheric stacking. The layered structure of the Tibetan upper mantle is imaged by seismic methods, most detailed with the receiver function method. Tibet is considered as a place where the development of a future craton is currently under way. Here we study the upper mantle from Germany to northern Sweden with seismic S receiver functions and compare the structure below Scandinavia with that below Tibet. Below Proterozoic Scandinavia, we found two low‐velocity zones on top of each other, separated by a high‐velocity zone. The top of the upper low‐velocity zone at about 100 km depth extends from Germany to Archaean northern Sweden. It agrees with the lithosphere‐asthenosphere boundary (LAB) below Germany and Denmark. Below Sweden it is known as the 8°discontinuity, or as a mid‐lithospheric discontinuity (MLD), similar to observations in North America. Seismic tomography places the LAB near 200 km in Scandinavia, which is close to the top of our deeper low‐velocity zone. We also observed the bottom of the asthenosphere (the Lehmann discontinuity) deepening from 180 km in Germany to 260 km below Sweden. Remnants of old subduction in the upper about 100 km below Scandinavia and Finland are known from controlled source seismic experiments and local earthquake studies. Recent tomographic studies indicate delamination of the lithosphere below southern Scandinavia and northern Germany. We are suggesting that the large‐scale layered structure in the Scandinavian upper mantle may be caused by processes similar to the ongoing lithospheric stacking in Tibet.
METTL3-Mediated RNA m6A Modification Regulates the Angiogenic Behaviors of Retinal Endothelial Cells by Methylating MMP2 and TIE2

Purpose N6-methyladenosine (m6A) is a commonly occurring modification of mRNAs, catalyzed by a complex containing methyltransferase like 3 (METTL3). Our research aims to explore how METTL3-dependent m6A modification affects the functions of retinal endothelial cells (RECs). Methods An oxygen-induced retinopathy (OIR) mouse model was established, and RECs were isolated using magnetic beads method. Human retinal microvascular endothelial cells (HRMECs) were treated with normoxia (21% O2) or hypoxia (1% O2). Dot blot assay determined m6A modification levels. Quantitative RT-PCR and Western blot detected the mRNA and protein expression levels of the target candidates, respectively. Genes were knocked down by small interfering RNA transfection. Matrigel-based angiogenesis and transwell assays evaluated the abilities of endothelial tube formation and migration, respectively. Methylated RNA immunoprecipitation–qPCR determined the levels of m6A modification in the target genes. Results The m6A modification levels were significantly upregulated in the retinas and RECs of OIR mice. Exposure to hypoxia significantly elevated both METTL3 expression and m6A modification levels in HRMECs. METTL3 knockdown curtailed endothelial tube formation and migration in vitro under both normoxic and hypoxic conditions. Concurrently, this knockdown in HRMECs resulted in reduced m6A modification levels of MMP2 and TIE2 transcripts, subsequently leading to a decrease in their respective protein expressions. Notably, knockdown of MMP2 and TIE2 also markedly inhibited the angiogenic activities of HRMECs. Conclusions METTL3-mediated m6A modification promotes the angiogenic behaviors of RECs by targeting MMP2 and TIE2, suggesting its significance in retinal angiogenesis and METTL3 as a potential therapeutic target.
Multiplex analysis of inflammatory proteins associated with risk of coronary artery disease in type‐1 diabetes patients

Abstract Background Chronic uncontrolled hyperglycemia, a precursor to chronic low‐grade inflammation, is a leading cause of coronary artery disease (CAD) due to plaque buildup in type‐1 diabetes (T1D) patients. We evaluated levels of 22 inflammatory markers in cross‐sectional serum samples from 1222 subjects to evaluate their potential as risk factors for CAD in T1D patients. Hypothesis Circulating levels of markers of inflammation may be the risk factors for incident CAD. Methods The T1D subjects were divided into two groups: those without CAD (n = 1107) and with CAD (n = 115). Serum levels of proteins were assayed using multiplex immunoassays on a Luminex Platform. Differences between the two groups were made by univariate analysis. Multivariate logistic regression was used to ascertain the potential of proteins as risk factors for CAD. Influence of age, duration of diabetes, sex, hypertension, and dyslipidemia was determined in a stepwise manner. Serum levels of 22 proteins were combined into a composite score using Ridge regression for risk‐based stratification. Results Mean levels of CRP, IGFBP1, IGFBP2, insulin‐like growth factors binding protein‐6 (IGFBP6), MMP1, SAA, sTNFRI, and sTNFRII were elevated in CAD patients (n = 115) compared to T1D patients without CAD (nCAD, n = 1107). After adjusting for age, duration of diabetes, sex, hypertension, and dyslipidemia, higher levels of sTNFRI (odds ratio [OR] = 2.18, 1.1 × 10−3), sTNFRII (OR = 1.52, 1 × 10−2), and IGFBP6 (OR = 3.62, 1.8 × 10−3) were significantly associated with CAD. The composite score based on Ridge regression, was able to stratify CAD patients into low, medium, and high‐risk groups. Conclusions The results show activation of the TNF pathway in CAD patients. Evaluating these markers in serum can be a potential tool for identifying high‐risk T1D patients for intensive anti‐inflammatory therapeutic interventions.
A multicomponent propane monooxygenase catalyzes the initial degradation of methyl tert-butyl ether in Mycobacterium vaccae JOB5

ABSTRACT Methyl tert-butyl ether (MTBE) has been recognized as a groundwater contaminant due to its widespread distribution and potential threat to human health. The limited understanding of the enzymes catalyzing MTBE degradation restricts their application in MTBE bioremediation. In this study, an MTBE-degrading soluble di-iron monooxygenase that clusters phylogenetically with a known propane monooxygenase (PRM) encoded by the prmABCD gene cluster was identified and functionally characterized, revealing their role in MTBE metabolism by Mycobacterium vaccae JOB5. Transcriptome analysis demonstrated that the expression of prmABCD was upregulated when JOB5 was induced by MTBE. Escherichia coli Rosetta heterologously expressing prmABCD from JOB5 could transform MTBE, indicating that the PRM of JOB5 is capable of the initial degradation of MTBE. The loss of the gene encoding the oxygenase α-subunit or β-subunit, the coupling protein, or the reductase disrupted MTBE transformation by the recombinant E. coli Rosetta. In addition, the catalytic capacity of PRM is likely affected by residue G95 in the active site pocket and residues I84, P165, A269, and V270 in the substrate tunnel structure. Mutation of amino acids in the active site and substrate tunnel resulted in inefficiency or inactivation of MTBE degradation, and the activity in 1,4-dioxane (1,4-D) degradation was diminished less than that in MTBE degradation. IMPORTANCE Multicomponent monooxygenases catalyzing the initial hydroxylation of MTBE are important in MTBE biodegradation. Previous studies of MTBE degradation enzymes have focused on P450s, alkane monooxygenase and MTBE monooxygenase, but the vital role of soluble di-iron monooxygenases has rarely been reported. In this study, we deciphered the essential catalytic role of a PRM and revealed the key residues of the PRM in MTBE metabolism. Our findings provide new insight into the MTBE-degrading gene cluster and enzymes in bacteria. This characterization of the PRM associated with MTBE degradation expands our understanding of MTBE-degrading gene diversity and provides a novel candidate enzyme for the bioremediation of MTBE-contaminated sites. Multicomponent monooxygenases catalyzing the initial hydroxylation of MTBE are important in MTBE biodegradation. Previous studies of MTBE degradation enzymes have focused on P450s, alkane monooxygenase and MTBE monooxygenase, but the vital role of soluble di-iron monooxygenases has rarely been reported. In this study, we deciphered the essential catalytic role of a PRM and revealed the key residues of the PRM in MTBE metabolism. Our findings provide new insight into the MTBE-degrading gene cluster and enzymes in bacteria. This characterization of the PRM associated with MTBE degradation expands our understanding of MTBE-degrading gene diversity and provides a novel candidate enzyme for the bioremediation of MTBE-contaminated sites.
The impact of vertical resolution on regional model simulation of the west African summer monsoon

The RM3 regional climate model is used to simulate the west African summer monsoon for six June–September seasons using NCEP reanalysis data for lateral boundary forcing. The study compares the performance of the previously published 16‐level version with a newly tested 28‐level version, both running on a horizontal grid with 0.5° spacing, in order to determine what improvements in simulations are achieved by increased vertical resolution. Comparisons between the performances include diagnostics of seasonal mean precipitation rates and circulation, vertical profiles of cumulus heating rates, frequencies of shallow and deep convection and diagnostics related to transient African easterly waves (AEWs). The characteristics of a composite AEW simulated at both vertical resolutions are presented. Results show that the most significant impact of increasing the vertical resolution is stronger circulation, stronger vertical wind shear and higher amplitude AEWs. The simulations with higher vertical resolution also achieve higher peaks of cumulus latent heating rates. Spatial–temporal correlations between simulated daily 700 mb meridional winds versus corresponding NCEP reanalysis data and simulated daily precipitation versus estimates from the Tropical Rainfall Measurement Mission (TRMM) archive were equally high at both vertical resolutions. Copyright © 2007 Royal Meteorological Society
Particle sedimentation and diffusive convection in volcanic ash‐clouds

Understanding the longevity of volcanic ash‐clouds generated by powerful explosive eruptions is a long standing problem for assessing volcanic hazards and the nature and time scale of volcanic forcings on climate change. It is well known that the lateral spreading and longevity of these clouds is influenced by stratospheric winds, particle settling and turbulent diffusion. Observations of the recent 2010 Eyjafjallajökull and 2011 Grimsvötn umbrella clouds, as well as the structure of atmospheric aerosol clouds from the 1991 Mt Pinatubo event, suggest that an additional key process governing the cloud dynamics is the production of internal layering. Here, we use analog experiments on turbulent particle‐laden umbrella clouds to show that this layering occurs where natural convection driven by particle sedimentation and the differential diffusion of primarily heat and fine particles give rise to a large scale instability. Where umbrella clouds are particularly enriched in fine ash, this “particle diffusive convection” strongly influences the cloud longevity. More generally, cloud residence time will depend on fluxes due to both individual settling and diffusive convection. We develop a new sedimentation model that includes both sedimentation processes, and which is found to capture real‐time measurements of the rate of change of particle concentration in the 1982 El Chichon, 1991 Mt Pinatubo and 1992 Mt Spurr ash‐clouds. A key result is that these combined sedimentation processes enhance the fallout of fine particles relative to expectations from individual settling suggesting that particle aggregation is not the only mechanism required to explain volcanic umbrella longevity.
Assessment of Forest Growing Stock of Timergara Forest Subdivision, Dir Lower Forest Division

The present study was aimed to assess the growing stock of Timergara forest subdivision which was a part of Dir lower forest division (Pakistan). The study area was divided into two different climatic zones (i.e. sub-tropical sub humid and sub-humid temperate zones) on the basis of altitudinal considerations. A total of 43 sample plots are taken in the forest area of 8480 hectare with random sampling technique representing 0.5% of the total forest area. Each sample plot size was of one hectare. In each 100 × 100 m (1 ha plot), number of trees, diameter, age, height, increment, form factor and volume were measured. An interrelation between the diameter (independent variable) and all the other dependent variables (volume, increment and height) were found. At the end, volume tables were made which suited the local conditions as the ones used before were not suited to the local conditions.
Previsão do vento utilizando o modelo atmosférico WRF para o estado de Alagoas

This paper aim to analyses wind prediction over the Alagoas State (Brazil) using the WRF model. A 1-yr (August/2007 to July/2008) anemometer collected data is used to analyze wind pattern and the model predictions were statistically validated using stations located in the three State mesoregions: Backlands (Sertao), Rural (Agreste) and Coast (Litoral). The results showed that quality of WRF model prediction proved to be quite satisfactory especially in the interior of the State during the dry season. The wind predictions in the rainy season for coastal zones showed bias of 1.77 ms-1 and RMSE of 3.61 m.s-1, while in the dry season these ratios were 0.98 m.s-1 and 2.99 m.s-1, respectively. In the interior of the State, these indicators reached bias of -0.2 m.s-1 and RMSE of 2.75 m.s-1 for dry months, and bias of -0.1 m.s-1 and RMSE of 2.63 m.s-1 for rainy season. Some aspects of the WRF model must be further tested and analyzed to improve the prediction during the rainy period, especially the parameterizations of cumulus and clouds microphysics. The obtained statistical indexes were equivalent or better, in some cases, if compared to other similar studies, indicating that the WRF is a good tool for wind forecasting.
A scoping review, mapping, and prioritisation process for emergency obstetric and neonatal quality of care indicators: Focus on provision and experience of care

Background Globally, approximately 800 women and 6400 newborns die around the time of childbirth each day. Many of these deaths could be prevented with high-quality emergency obstetric and newborn care (EmONC). The Monitoring Emergency Obstetric Care: A handbook guides strengthening EmONC services. However, the handbook contains limited quality of care measures. Our study identified and prioritised quality of care indicators for potential inclusion in the handbook, which is undergoing revision. Methods We conducted a consultative scoping review, mapping, and prioritisation exercise to select a short list of indicators on facility-based maternal and newborn quality of care. Indicators were identified from literature searches and expert suggestions and organised by the categories of structure, process, and outcomes as defined in the World Health Organization’s Standards for Improving Quality of Maternal and Newborn Care in Health Facilities. We focused on process indicators, encompassing the provision of care and experience of care during the intrapartum period, and developed a priority list of indicators using the selection criteria of relevance and feasibility. Experience of care indicators were also mapped against the Person-Centered Maternity Care (PCMC) scale. Results We extracted a total of 3023 quality of care indicators. After removing out-of-scope and duplicate indicators and applying our selection criteria, we identified 20 provision of care indicators for possible inclusion in the revised EmONC handbook. We recommend including a score for experience of care that could be measured with the 30-item or the 13-item PCMC scale. We also identified 29 experience of care items not covered by the PCMC scale that could be used. Provider experience, patient safety, and quality of abortion care were identified as areas for which no or few indicators were found through our scoping review. Conclusions Through a rigorous, consultative, and multi-step process, we selected a short list of process-related, facility-based quality of care indicators for emergency obstetric and newborn care. This list could be included in the EmONC handbook or used for other monitoring purposes. Country consultations to assess the utility and feasibility of the proposed indicators and their adaptation to local contexts will support their refinement and uptake. Registration https://osf.io/msxbd (Open Science Framework)
Runoff to boreal lakes linked to land cover, watershed morphology and permafrost thaw: a 9‐year isotope mass balance assessment

Stable isotopes of oxygen and hydrogen were measured in water samples collected annually from a representative suite of 50 lakes in northeastern Alberta over a 9‐year period and are interpreted using a steady‐state isotope mass balance model to determine water yield and runoff ratios for the lake watersheds and residence time of the lakes. This isotopic perspective on hydrology of the region provides new insight into the role of land cover, watershed morphometry, climatic drivers and permafrost thaw on lakes. Bog cover, permafrost and presence of thaw features in bogs are found to be the dominant hydrologic drivers, although morphometric properties such as elevation, lake area and drainage basin area are also influential. In addition to quantifying the hydrologic fluxes, the analysis establishes contrasting conditions in more southerly lakes, located in the Stony Mountains and west of Fort McMurray, as compared with more northerly sites in the Birch Mountains, Caribou Mountains and northeast of Fort McMurray, mainly because of contributions from thawing permafrost at the northerly sites. Distinct hydrologic conditions are also noted for Shield systems north of Lake Athabasca where bogs and permafrost are absent. While permafrost thaw is not directly labelled by oxygen and hydrogen isotope composition, isotope mass balance calculations suggest that contributions of up to several hundred millimetres per year are occurring in 14 of the 50 lake watersheds under study. Several of these lakes have water yields in excess of precipitation in some years, and regional groups of lakes display significant correlations between water yield and percentage of bogs that have collapsed. Copyright © 2015 John Wiley & Sons, Ltd.
Polarizing Plates: Both Omnivores and Vegans Represent In-Group Foods With Eating Simulations.

In two pre-registered experiments, we assessed how people cognitively represent meat and plant-based foods, to examine processes underlying dietary polarization in society. Food descriptions from U.K.-based omnivores (NExp. 1 = 109; NExp. 2 = 436) and vegans (NExp. 1 = 111; NExp. 2 = 407) were coded for features about consumption and reward (e.g., "rich," "indulgent," and "treat") or features independent of the consumption situation (e.g., "healthy," "protein," and "eco-friendly"). Participants used more consumption and reward features for diet-congruent dishes (meat dishes for omnivores and plant-based dishes for vegans) than for diet-incongruent dishes (vice versa). Omnivores focused on abstract, long-term consequences of plant-based foods, whereas vegans focused on the socio-political associations with meat foods. Consumption and reward features also positively predicted attractiveness ratings, the likelihood of ordering a dish, and eating intentions. These findings indicate the cognitive processes of polarized dietary groups that may hinder the mainstream transition to more sustainable food choices.
Red blood cell alloimmunization in myelodysplastic syndromes: Associations with sex, DAT‐positivity, and increased transfusion needs

Many patients with myelodysplastic syndromes (MDS) need repeated red blood cell transfusions which entails a risk of immunization and antibody formation. Associations between alloantibodies, autoantibodies and increased transfusion requirements have been reported, but their relationship remains unclear. In this study, we analyzed factors potentially associated with red blood cell alloimmunization, as well as changes in transfusion intensity and post‐transfusion hemoglobin increments.
Needs Assessment and the Identification of Palliative Care Dimensions of the Essential Service Package for the Elderly with Alzheimer’s Disease: A Mixed Exploratory Study

Aim: This study was conducted with the aim of assessing the needs and determining the care dimensions of the essential palliative care service package for the elderly with Alzheimer’s disease. Method: The mixed exploratory study was conducted in three phases. The first phase of the study was conducted in the form of a qualitative study and a literature review. This qualitative research was done through in-depth and semi-structured interviews with 19 qualified caregivers (11 informal caregivers and 8 formal caregivers) The samples were selected using the purposive sampling method by referring to hospitals, nursing homes, and active branches of the Alzheimer’s Association in some provinces. In the second phase, the dimensions of palliative care were codified, and in the third phase, the prioritization and the validation of the dimensions of palliative care were performed in the form of two Delphi rounds. Results: Based on the results of the first phase of the study, the care dimensions of the service package were placed in eight categories based on National Consensus Project. In the second phase, the needs of Alzheimer’s patients were arranged in the form of a questionnaire consisting of 8 parts, with 180 indicators. Then, in the third phase, the dimensions of the palliative care essential package were designed with 74 items in the form of 4 dimensions. Conclusion: The dimensions of the essential service package of palliative care included a series of interventions as well as physical, psychological, cognitive, and spiritual support.