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Nucleic Acids Research May 2024Emerging evidence indicates that arginine methylation promotes the stability of arginine-glycine-rich (RGG) motif-containing RNA-binding proteins (RBPs) and regulates...
Emerging evidence indicates that arginine methylation promotes the stability of arginine-glycine-rich (RGG) motif-containing RNA-binding proteins (RBPs) and regulates gene expression. Here, we report that post-translational modification of FXR1 enhances the binding with mRNAs and is involved in cancer cell growth and proliferation. Independent point mutations in arginine residues of FXR1's nuclear export signal (R386 and R388) and RGG (R453, R455 and R459) domains prevent it from binding to RNAs that form G-quadruplex (G4) RNA structures. Disruption of G4-RNA structures by lithium chloride failed to bind with FXR1, indicating its preference for G4-RNA structure containing mRNAs. Furthermore, loss-of-function of PRMT5 inhibited FXR1 methylation both in vivo and in vitro, affecting FXR1 protein stability, inhibiting RNA-binding activity and cancer cell growth and proliferation. Finally, the enhanced crosslinking and immunoprecipitation (eCLIP) analyses reveal that FXR1 binds with the G4-enriched mRNA targets such as AHNAK, MAP1B, AHNAK2, HUWE1, DYNC1H1 and UBR4 and controls its mRNA expression in cancer cells. Our findings suggest that PRMT5-mediated FXR1 methylation is required for RNA/G4-RNA binding, which promotes gene expression in cancer cells. Thus, FXR1's structural characteristics and affinity for RNAs preferentially G4 regions provide new insights into the molecular mechanism of FXR1 in oral cancer cells.
PubMed: 38709899
DOI: 10.1093/nar/gkae319 -
Acta Crystallographica Section B,... Oct 2023Five different electron density datasets obtained from conventional and synchrotron single crystal X-ray diffraction experiments are compared. The general aim of the...
Five different electron density datasets obtained from conventional and synchrotron single crystal X-ray diffraction experiments are compared. The general aim of the study is to investigate the quality of data for electron density analysis from current state-of-the-art conventional sources, and to see how the data perform in comparison with high-quality synchrotron data. A molecular crystal of melamine was selected as the test compound due to its ability to form excellent single crystals, the light atom content, and an advantageous suitability factor of 3.6 for electron density modeling. These features make melamine an optimal system for conventional X-ray diffractometers since the inherent advantages of synchrotron sources such as short wavelength and high intensity are less critical in this case. Data were obtained at 100 K from new in-house diffractometers Rigaku Synergy-S (Mo and Ag source, HyPix100 detector) and Stoe Stadivari (Mo source, EIGER2 1M CdTe detector), and an older Oxford Diffraction Supernova (Mo source, Atlas CCD detector). The synchrotron data were obtained at 25 K from BL02B1 beamline at SPring-8 in Japan (λ = 0.2480 Å, Pilatus3 X 1M CdTe detector). The five datasets were compared on general quality parameters such as resolution, ⟨I/σ⟩, redundancy and R factors, as well as the more model specific fractal dimension plot and residual density maps. Comparison of the extracted electron densities reveals that all datasets can provide reliable multipole models, which overall convey similar chemical information. However, the new laboratory X-ray diffractometers with advanced pixel detector technology clearly measure data with significantly less noise and much higher reliability giving densities of higher quality, compared to the older instrument. The synchrotron data have higher resolution and lower measurement temperature, and they allow for finer details to be modeled (e.g. hydrogen κ parameters).
PubMed: 37669152
DOI: 10.1107/S2052520623006625 -
International Journal of Law and... 2023The Italian mafia organizations represent a subculture with values, beliefs and goals that are antithetical to and undermining of the predominant society. The conduct of...
The Italian mafia organizations represent a subculture with values, beliefs and goals that are antithetical to and undermining of the predominant society. The conduct of individual members includes such extreme violence for material gain, it may at least superficially suggest a severe personality disorder. Since the first edition of the DSM and into the 21st century, various terms have been used, sometimes interchangeably, but over time inconsistently, to designate the mentality and practices of mafia members. Only recently has the psychology of mafia members become a focus of serious scientific study. Following broader national multicenter research, the present study aimed at investigating the possible differences in psychopathy between those mafia associates who had been convicted only of mafia association (Group A, bosses), and those who were also convicted of violent crimes (Group B, soldiers). The Psychopathy Checklist-Revised (PCL-R) was administered to n = 48 male inmates convicted of mafia association (M 45.0 years, SD 10.9, range 20-80 years); Group A consisted of n = 26 (54%) subjects, Group B n = 22 (46%). Most of the sample (73%) did not manifest psychopathy (PCL-R ≥ 25) nor Mann-Whitney U test disclosed significant differences in the total PCL-R scores between the study groups. We found significantly higher scores of PCR-R factor 1 (interpersonal / affective) in the members of the mafia association also convicted of violent crimes (PCL-R F1, group A: 5.8 ± 3.7; group B: 7.9 ± 3.5; p < 0.05), this difference appeared explainable on the basis of a higher component of affective psychopathy. These initial results add to the limited literature on mafia and psychopathy and seem to suggest the existence of a specific component of psychopathy in the subgroup of mafiosi with overtly violent conduct.
Topics: Humans; Male; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Socialization; Antisocial Personality Disorder; Violence; Personality Disorders; Aggression
PubMed: 37441856
DOI: 10.1016/j.ijlp.2023.101907 -
Journal of Trace Elements in Medicine... Dec 2023CeONPs and ZnONPs can curb the increase of cholesterol and triglycerides observed in rats with non-alcoholic fatty liver disease. It was suggested that CeO NPs could...
Nano cerium oxide and cerium/zinc nanocomposites characterization and therapeutic role in combating obesity via controlling oxidative stress and insulin resistance in rat model.
BACKGROUND
CeONPs and ZnONPs can curb the increase of cholesterol and triglycerides observed in rats with non-alcoholic fatty liver disease. It was suggested that CeO NPs could potentially have an insulin-sensitizing effect, specifically on adipose tissue and skeletal muscle. It was reported that ZnONPs combat the increase of insulin resistance observed in obese rats and could be beneficial value in NAFLD. In our previous work, ZnO-NPs manifested valuable anti-obesity effects via lowering body weight gain, oxidative stress, BMI, lipids, and insulin resistance.
METHODS
In the present study, cerium oxide nanoparticles (A-1) and cerium/zinc nanocomposites (A-2 and A-3) were synthesized by solgel to investigate their role on oxidative stress, adipocyte hormones, and insulin resistance in an obese rat model. X-ray diffraction, HRTEM, SEM, and XPS were carried out to confirm the crystal structure, the particle size, the morphology of the nanoparticles and the oxidation states.
RESULTS
The Rietveld refinement has also been executed on A-1 (chi = 1.00; average Bragg = 2.92%; R-factor = 2.45%) and on A-2 (R = 9.87%, R= 9.68%, χ = 1.04, G = 1.02). The XPS spectra indicated the presence of Ce in + 4 and + 3 oxidation states and Zn as ZnO and ZnO.OH. Cerium oxide and ZnO crystal sizes lie in the range 40.53-45.01 and 40.53-45.01 nm, respectively. The results indicated that treating obese rats with any of the tested nano compounds (5 mg or 10 mg/Kg) lowered plasma cholesterol, triglycerides, LDL, insulin resistance, glucose, and BMI significantly relative to obese group values. On the other hand, HDL increased significantly in obese rats after treatment with either A-2 or A-3 compared to obese rats. The current investigation showed antioxidant activities for A-1, A-2, and A3 as evidenced by the significant increase in GSH level and a significant decrease in MDA.
CONCLUSION
It was found that A-1, A-2, and A-3 have an efficient therapeutic role in treating of obesity-related hyperlipidemia, oxidative stress and insulin resistance. The results of A-2 and A-3 were more pronounced than those of A-1. The use of Zn/Ce nanocomposite (that have positive characteristics) in combating obesity and its complications could be become a new trend in therapeutic application for a management of obesity.
Topics: Rats; Animals; Insulin Resistance; Zinc; Zinc Oxide; Obesity; Oxidative Stress; Cerium; Nanoparticles; Cholesterol; Non-alcoholic Fatty Liver Disease; Triglycerides; Nanocomposites
PubMed: 37804595
DOI: 10.1016/j.jtemb.2023.127312 -
Advances in Health Sciences Education :... Dec 2023Q methodology is a unique, yet underutilized methodology designed specifically to scientifically study subjectivity. Q, as it is most often referred to, is an...
Q methodology is a unique, yet underutilized methodology designed specifically to scientifically study subjectivity. Q, as it is most often referred to, is an appropriate methodology whenever a researcher is interested in uncovering and describing the multiple divergent viewpoints on any topic. Such discovery of viewpoints provides insight into the subjectivities related to policies, values, priorities, judgements, opinions, and decisions. The disciplines where Q has been used for research are many, and include health sciences, education, and other social science / behavioral science fields. Because of its rather idiosyncratic place in research, however, many Q methodologists are self-taught or seek education through a few select universities that offer graduate level Q courses. The key to successfully approaching a Q study is to embrace its unique approach to studying subjectivity such that it is a powerful tool in health science education and other fields. It is common to find inconsistencies related to Q terminology, analyses, and decision making across studies. There is often an over reliance on concepts that come from purely quantitative methodologies such as R factor analysis rather than embracing the qualitative-quantitative hybridity of Q. This article is written as a primer with a focus on understanding Q at a deeper level rather than a step-by-step guide.
Topics: Health Education; Research Design
PubMed: 37071262
DOI: 10.1007/s10459-023-10214-1 -
IEEE Transactions on Medical Imaging Jan 2024Our lab at the University of Pennsylvania (UPenn) is investigating novel designs for digital breast tomosynthesis. We built a next-generation tomosynthesis system with a...
Our lab at the University of Pennsylvania (UPenn) is investigating novel designs for digital breast tomosynthesis. We built a next-generation tomosynthesis system with a non-isocentric geometry (superior-to-inferior detector motion). This paper examines four metrics of image quality affected by this design. First, aliasing was analyzed in reconstructions prepared with smaller pixelation than the detector. Aliasing was assessed with a theoretical model of r -factor, a metric calculating amplitudes of alias signal relative to input signal in the Fourier transform of the reconstruction of a sinusoidal object. Aliasing was also assessed experimentally with a bar pattern (illustrating spatial variations in aliasing) and 360°-star pattern (illustrating directional anisotropies in aliasing). Second, the point spread function (PSF) was modeled in the direction perpendicular to the detector to assess out-of-plane blurring. Third, power spectra were analyzed in an anthropomorphic phantom developed by UPenn and manufactured by Computerized Imaging Reference Systems (CIRS), Inc. (Norfolk, VA). Finally, calcifications were analyzed in the CIRS Model 020 BR3D Breast Imaging Phantom in terms of signal-to-noise ratio (SNR); i.e., mean calcification signal relative to background-tissue noise. Image quality was generally superior in the non-isocentric geometry: Aliasing artifacts were suppressed in both theoretical and experimental reconstructions prepared with smaller pixelation than the detector. PSF width was also reduced at most positions. Anatomic noise was reduced. Finally, SNR in calcification detection was improved. (A potential trade-off of smaller-pixel reconstructions was reduced SNR; however, SNR was still improved by the detector-motion acquisition.) In conclusion, the non-isocentric geometry improved image quality in several ways.
Topics: Humans; Image Processing, Computer-Assisted; Breast; Mammography; Computer Simulation; Models, Theoretical; Calcinosis; Phantoms, Imaging; Algorithms
PubMed: 37603482
DOI: 10.1109/TMI.2023.3307004 -
The Science of the Total Environment May 2024The water sector is facing unprecedented pressures as increased environmental and anthropogenic challenges, such as climate change and rapid urbanization, impact the... (Review)
Review
The water sector is facing unprecedented pressures as increased environmental and anthropogenic challenges, such as climate change and rapid urbanization, impact the availability and predictability of safe drinking water. There is a need for practitioners and policymakers to integrate water security and resilience (WS&R) factors into programming to sustain investments in drinking water systems to support associated economic, security, and public health benefits. In response to intensifying impacts from WS&R risks, communities around the world are developing adaptive strategies, and a critical review of these strategies may provide lessons that can be implemented at scale. In this critical review, we systematically screened over 9000 peer-reviewed and grey literature articles and extracted data from relevant studies that propose, pilot, and/or evaluate adaptations in low- and middle-income countries (LMICs) and evaluated the suitability of each adaptation for different contexts. We created a portfolio of adaptive strategies from over 75 LMICs to inform practitioners and policymakers in enhancing the resilience of drinking water systems. Over 20 adaptations were identified, including strategies such as stormwater management, wastewater reuse, non-revenue water reductions, water pricing, and public awareness campaigns. We categorized adaptations by function (improving water management, augmenting existing supplies, reducing water demand) and scale (household, municipal, regional) to provide recommendations tailored to local needs. For each adaptation, we highlighted associated strengths, weaknesses, barriers to adoption, and enabling environments for successful implementation. We propose a novel decision-support tool, called STEP WS&R, that provides a consistent and replicable process for informing high-level investment and policy choices around WS&R. This critical review presents recommendations for practitioners and policymakers to invest in WS&R adaptations, catered to shared risks and contexts.
PubMed: 38460697
DOI: 10.1016/j.scitotenv.2024.171520 -
British Journal of Cancer Nov 2023Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR...
BACKGROUND
Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC).
METHODS
We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS).
RESULTS
One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively.
CONCLUSION
Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies.
Topics: Humans; Neoadjuvant Therapy; Retrospective Studies; DNA Mismatch Repair; R Factors; Neoplasm Staging; Rectal Neoplasms; Chemoradiotherapy; Adenocarcinoma; Protein Deficiency
PubMed: 37749283
DOI: 10.1038/s41416-023-02444-2 -
Frontiers in Microbiology 2023Metaproteomics is a subfield in meta-omics that is used to characterize the proteome of a microbial community. Despite its importance and the plethora of publications in...
BACKGROUND
Metaproteomics is a subfield in meta-omics that is used to characterize the proteome of a microbial community. Despite its importance and the plethora of publications in different research area, scientists struggle to fully comprehend its functional impact on the study of microbiomes. In this study, bibliometric analyses are used to evaluate the current state of metaproteomic research globally as well as evaluate the specific contribution of Africa to this burgeoning research area. In this study, we use bibliometric analyses to evaluate the current state of metaproteomic research globally, identify research frontiers and hotspots, and further predict future trends in metaproteomics. The specific contribution of Africa to this research area was evaluated.
METHODS
Relevant documents from 2004 to 2022 were extracted from the Scopus database. The documents were subjected to bibliometric analyses and visualization using VOS viewer and Biblioshiny package in R. Factors such as the trends in publication, country and institutional cooperation networks, leading scientific journals, author's productivity, and keywords analyses were conducted. The African publications were ranked using Field-Weighted Citation Impact (FWCI) scores.
RESULTS
A total of 1,138 documents were included and the number of publications increased drastically from 2004 to 2022 with more publications (170) reported in 2021. In terms of publishers, had the highest number of total publications (62). The United States of America (USA), Germany, China, and Canada, together with other European countries were the most productive. Institution-wise, the Helmholtz Zentrum für Umweltforschung, Germany had more publications while Max Plank Institute had the highest total collaborative link strength. Jehmlich N. was the most productive author whereas Hettich RL had the highest h-index of 63. Regarding Africa, only 2.2% of the overall publications were from the continent with more publication outputs from South Africa. More than half of the publications from the continent had an FWCI score ≥ 1.
CONCLUSION
The scientific outputs of metaproteomics are rapidly evolving with developed countries leading the way. Although Africa showed prospects for future progress, this could only be accelerated by providing funding, increased collaborations, and mentorship programs.
PubMed: 37476667
DOI: 10.3389/fmicb.2023.1217727 -
Environmental Monitoring and Assessment Oct 2023The Soil and Water Assessment Tool (SWAT) is a computational hydrological model extensively utilised for developing sustainable strategies and viable approaches for...
The Soil and Water Assessment Tool (SWAT) is a computational hydrological model extensively utilised for developing sustainable strategies and viable approaches for prudent management of water resources. The central emphasis of this study is on the utilisation of SWAT model along with SWAT-CUP (SWAT calibration toolbox) to simulate streamflow in the upper Jhelum basin, the North West Himalayas, for a period of 20 years from 2000 to 2019. The global sensitivity analysis algorithm, Sequential Uncertainty Fitting 2 (SUFI-2) of SWAT-CUP, is used for sensitivity and uncertainty analysis. The optimised parameter set estimated by SUFI-2 constitutes 11 parameters that are found to be sensitive with soil conservation service (SCS) curve number (CN) being the most influential parameter followed by snowmelt base temperature. Autocorrelation analysis using the autocorrelation function was conducted on the temperature and precipitation time series data, followed by a pre-whitening procedure to remove any autocorrelation effects. Subsequently, the modified Mann-Kendall (MMK) test was applied to examine trends in the annual temperature and precipitation data. The results indicated statistically significant positive trends in both datasets on an annual scale. The results for the calibration period (2003-2014) for monthly simulation displayed good model performance at three gauging stations, Rambiara, Sangam and Ram Munshi Bagh with R values of 0.83, 0.847, 0.829, P factor values of 0.73, 0.76, 0.75 and R factor values of 0.61, 0.58, 0.63, respectively. The validation results for monthly simulation for the 2015-2019 period showed good model agreement with R values of 0.817, 0.853, and 0.836, P factor values of 0.76, 0.8, and 0.75 and R factor values of 0.62, 0.53, and 0.65, respectively. The study concludes that the SWAT hydrological model can perform satisfactorily in high mountainous catchments and can be employed to analyse the impact of land use-land cover changes and the effect of climate variation on streamflow dynamics.
Topics: Soil; Water; Uncertainty; Environmental Monitoring; Models, Theoretical; Algorithms
PubMed: 37874405
DOI: 10.1007/s10661-023-11916-0