Miracle-dz/UniFAR-FTUs huggingface dataset:
The contribution of Saccharomyces cerevisiae cap binding complex to small nuclear and small nucleolar RNA processing

5’ end of RNA polymerase II (Pol II) transcripts, including small nuclear and nucleolar RNAs (sn/snoRNAs) is modified at the early stage of their transcription by mGMP addidion that leads to mG cap structure. This structure serves as a barrier for 5’-3’ exonucleases and is specifically recognized by nuclear cap binding complex (CBC) immediately after its synthesis. CBC is a heterodimer that consists of Cbp20 i Cbp80 subunits. In the case of sn/snoRNA, after transcription termination dependent on noncoding RNA (ncRNA) specific Nrd1/Nab3/Sen1 (NNS) complex, their extended 3’ ends are trimmed exonucleolytically by the exosome. For snRNA and some snoRNA precursors endonucleolytic cleavage of the 3’ end by Rnt1 nuclease proceeds exosome trimming. 5’ ends of some snoRNA (especially box C/D class) is also cleaved by Rnt1, which removes cap structure and enable further exonucleolytic processing by Rat1. Alternatively, the 5’ mG cap becomes hypermethylated by methyltransferase Tgs1. The aim of this PhD project was to investigate the connection between both pre-sn/snoRNA termini and its role in maturation of these molecules in yeast Saccharomyces cerevisiae. Realization of the project involved the analysis of the interaction between protein complexes binding both termini of pre-sn/snoRNA: CBC at the 5’ end and NNS at the 3’ end, examination of the recruitment of CBC, Rnt1 and Nrd1 to sn/snoRNA genes, and studies of the pre-snoRNA 3’ and 5’ end status in the absence of factors responsible for 5’ end maturation (Rnt1, CBC, Tgs1).
Using the NIH Toolbox to Assess Cognition in Adolescents and Young Adults with Autism Spectrum Disorders

Despite the clinically significant impact of executive dysfunction on the outcomes of adolescents and young adults with autism spectrum disorders (ASD), we lack a clear understanding of its prevalence, profile, and development. To address this gap, we administered the NIH Toolbox Cognition Battery to a cross‐sectional Intelligence Quotient (IQ) case‐matched cohort with ASD (n = 66) and typical development (TD; n = 66) ages 12–22. We used a general linear model framework to examine group differences in task performance and their associations with age. Latent profile analysis (LPA) was used to identify subgroups of individuals with similar cognitive profiles. Compared to IQ case‐matched controls, ASD demonstrated poorer performance on inhibitory control (P < 0.001), cognitive flexibility (P < 0.001), episodic memory (P < 0.02), and processing speed (P < 0.001) (components of Fluid Cognition), but not on vocabulary or word reading (components of Crystallized Cognition). There was a significant positive association between age and Crystallized and Fluid Cognition in both groups. For Fluid (but not Crystallized) Cognition, ASD performed more poorly than TD at all ages. A four‐group LPA model based on subtest scores best fit the data. Eighty percent of ASD belonged to two groups that exhibited relatively stronger Crystallized versus Fluid Cognition. Attention deficits were not associated with Toolbox subtest scores, but were lowest in the group with the lowest proportion of autistic participants. Adaptive functioning was poorer in the groups with the greatest proportion of autistic participants. Autistic persons are especially impaired on Fluid Cognition, and this more flexible form of thinking remains poorer in the ASD group through adolescence.
Role of SARS-CoV-2 in Altering the RNA-Binding Protein and miRNA-Directed Post-Transcriptional Regulatory Networks in Humans

The outbreak of a novel coronavirus SARS-CoV-2 responsible for COVID-19 pandemic has caused worldwide public health emergency. Due to the constantly evolving nature of the coronaviruses, SARS-CoV-2 mediated alteration on post-transcriptional gene regulation across human tissues remains elusive. In this study, we analyze publicly available genomic datasets to systematically dissect the crosstalk and dysregulation of human post-transcriptional regulatory networks governed by RNA binding proteins (RBPs) and micro-RNAs (miRs), due to SARS-CoV-2 infection. We uncovered that 13 out of 29 SARS-CoV-2 encoded proteins directly interact with 51 human RBPs of which majority of them were abundantly expressed in gonadal tissues and immune cells. We further performed a functional analysis of differentially expressed genes in mock-treated versus SARS-CoV-2 infected lung cells that revealed enrichment for immune response, cytokine-mediated signaling, and metabolism associated genes. This study also characterized the alternative splicing events in SARS-CoV-2 infected cells compared to control demonstrating that skipped exons and mutually exclusive exons were the most abundant events that potentially contributed to differential outcomes in response to viral infection. Motif enrichment analysis on the RNA genomic sequence of SARS-CoV-2 clearly revealed the enrichment for RBPs such as SRSFs, PCBPs, ELAVs, and HNRNPs suggesting the sponging of RBPs by SARS-CoV-2 genome. A similar analysis to study the interactions of miRs with SARS-CoV-2 revealed functionally important miRs that were highly expressed in immune cells, suggesting that these interactions may contribute to the progression of the viral infection and modulate host immune response across other human tissues. Given the need to understand the interactions of SARS-CoV-2 with key post-transcriptional regulators in the human genome, this study provides a systematic computational analysis to dissect the role of dysregulated post-transcriptional regulatory networks controlled by RBPs and miRs, across tissues types during SARS-CoV-2 infection.
Effects of beta-tricalcium phosphate nanoparticles on theproperties of athermosensitive chitosan/collagen hydrogel and controlled release of quercetin.

In the present study, an inorganic matrix of beta-tricalcium phosphate (bTCP) nanoparticles and quercetin was incorporatedinto an organic matrix of 2:1 (w/w) chitosan/collagen composite to fabricate thermosensitive bTCP-chitosan/collagen-quercetin hydrogels. A sol-gel transition of the hydrogels was stimulated by beta-glycerophosphate (bGP) and temperature changes at physiological temperature and pH levels. Thereafter, the effects of 1%-3% (w/v) bTCP on properties of the bTCP-bGP-2:1 (w/w) chitosan/collagen hydrogels were investigated. Notably, the incorporation of 1%-3% (w/v) bTCP in the hydrogels did not interfere with thegelation process and time of the hydrogels at physiological temperature and pH levels. The bTCP-hydrogels exhibited a porous structure, interconnecting pore architecture, and median pore size of 100-200 μm. The incorporation of 3% bTCP increased the mechanical strengthbut decreased the swelling and degradation rates, pore size, permeability, and quercetin release rate of the hydrogels. The hydrogels were noncytotoxic and able to support cell encapsulation. A sustained quercetin release profile of the 3% bTCP-hydrogel further suggested the applicability of the hydrogel as a delivery vehicle of natural flavonoids for bone regeneration. This article is protected by copyright. All rights reserved.
Use of Alternative Containers for Long- and Short-term Greenhouse Crop Production

S UMMARY . While research on the use of alternative containers for greenhouse production is growing, most studies have focused on a limited number of types of alternative containers and primarily on short-term greenhouse crops. With the recent release of several new bioplastic alternatives, comparisons to established alternative containers and production of longer rotation ornamental crops should be investigated. Our work, therefore, investigates the performance of ten commercially available alternative containers and their effects on both a short-term ‘Sunpatiens Compacta’ impatiens ( Impatiens · hybrida ) and a long-term greenhouse crop ‘Elegans Ice’ lavender ( Lavendula angustifolia ) at four different locations. Results indicated that plant growth in terms of dry weight differed by container at most locations. Combined analysis of all locations showed that only straw and a bioplastic sleeve outperformed plastic pots in terms of shoot dry weight and then only after 12 weeks of production. Leachate pH, but not electrical conductivity (EC), varied by container in both the short- and long-term crop with alternative containers made from composted cow manure and peat showing consistently higher and lower pH readings, respectively. Postharvest container strength varied signif-icantly by container, with the plastic control maintaining the highest puncture resistance after both 6 and 12 weeks, in some instances matched by the puncture strength of coconut ﬁber pots. Some alternative containers, in particular, wood, manure, and peat showed algal growth after 6 and 12 weeks of greenhouse production. We conclude that while some alternative containers were linked to increased growth, most showed growth equal to the plastic control, and could therefore make appropriate alternatives to plastic pots. However, changes in pH, low puncture strengths after production, higher denesting times, and algal growth on manure, wood, and peat may make these pots less desirable alternatives than other pots under investigation. However, other factors not studied here, such as compostability, biodegradability in the landscape, water use, consumer preference, aesthetics, compatibility with mechanized operations, and cost may also need to be taken into account when deciding on an appropriate container for greenhouse production.
Extensive Dynamics of Aneurysms and Long-term Prognosis in IRVAN Syndrome: A Case Series

ABSTRACT Objectives To report the extensive dynamic clinical condition and long-term therapeutic prognosis in three cases of idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome. Methods Retrospective, interventional case series. Results Data of the three IRVAN syndrome patients were retrospectively reviewed at study enrollment and during the follow-up period. The mean follow-up time was 60 months. All three patients manifested the typical characteristics of IRVAN syndrome with bilateral eye involvement. The good long-term visual acuity has been maintained after treatment. The aneurysms showed extensive dynamic changes and regressed mostly. Conclusion IRVAN syndrome is a rare condition that may progress rapidly and cause severe vision loss without treatment. The photocoagulation is beneficial and should be performed in the early phase. The aneurysms presented extensive dynamic changes through multimodal imaging which suggested a migratory inflammatory process involving retinal arterioles.
Induction of Redox-Mediated Cell Death in ER-Positive and ER-Negative Breast Cancer Cells by a Copper(II)-Phenolate Complex: An In Vitro and In Silico Study

This research was aimed at finding the cytotoxic potential of the mixed ligand copper(II) complex [Cu(tdp)(phen)](ClO4)—where H(tdp) is the tetradentate ligand 2-[(2-(2-hydroxyethylamino)-ethylimino)methyl]phenol, and phen is 1,10-phenanthroline—to two genotypically different breast cancer cells, MCF-7 (p53+ and ER+) and MDA-MB-231 (p53- and ER-). The complex has been already shown to be cytotoxic to ME180 cervical carcinoma cells. The special focus in this study was the induction of cell death by apoptosis and necrosis, and its link with ROS. The treatment brought about nuclear fragmentation, phosphatidylserine externalization, disruption of mitochondrial trans-membrane potential, DNA damage, cell cycle arrest at sub-G1 phase, and increase of ROS generation, followed by apoptotic death of cells during early hours and a late onset of necrosis in the cells surviving the apoptosis. The efficacy of the complex against genotypically different breast cancer cells is attributed to a strong association through p53-mitochondrial redox—cell cycle junction. The ADMET properties and docking of the complex at the active site of Top1 are desirable attributes of a lead molecule for development into a therapeutic. Thus, it is shown that the copper(II)–phenolate complex[Cu(tdp)(phen)]+ offers potential to be developed into a therapeutic for breast cancers in general and ER-negative ones in particular.
Lifestyle, metabolism and environmental adaptation in Lactococcus lactis.

Lactococcus lactis serves as a paradigm organism for the lactic acid bacteria (LAB). Extensive research into the molecular biology, metabolism and physiology of several model strains of this species has been fundamental for our understanding of the LAB. Genomic studies have provided new insights in the species L. lactis, including the resolution of the genetic basis of its subspecies division, as well as the control mechanisms involved in the fine-tuning of growth-rate and energy metabolism. In addition, it has enabled novel approaches to study lactococcal lifestyle adaptations to the dairy application environment, including its adjustment to near-zero growth rates that are particularly relevant in the context of cheese ripening. This review highlights various insights in these areas and exemplifies the strength of combining experimental evolution with functional genomics and bacterial physiology research to expand our fundamental understanding of the L. lactis lifestyle under different environmental conditions.
Network Code DGNSS Positioning for Faster L1–L5 GPS Ambiguity Initialization

This paper presents DGNSS network code positioning using permanent geodetic networks, commonly used in GNSS measurements. Using several reference stations at the same time allows for the independent control of GNSS positioning and facilitates the more realistic estimation of accuracy. Test calculations were made on the basis of real GPS data, using one TRIMBLE mobile receiver and four nearest reference stations of the ASG-EUPOS geodetic system. In addition, DGNSS positioning computational simulations were performed for a case where one mobile GNSS receiver would be able to be used with two (e.g., GPS + Galileo or GPS + GLONASS) or four different positioning systems and different GNSS reference station systems at the same time. To reduce the deviations of the DGPS positioning from a true value, the Kalman filtering for horizontal coordinates and vertical ones was used. The result shows a significant improvement in DGPS positioning accuracy. Based on the numerical analysis carried out, it can be seen that when four GNSS systems are used, it is possible to achieve a DGNSS accuracy of 0.1 m and 0.2 m for horizontal and height coordinates, respectively, using only code measurements. Additionally, the paper presents the impact of the DGNSS code positioning accuracy on the effectiveness of determining ambiguities of phase observations on individual measurement epochs, using the L1–L5 observations of the GPS system and the precise and fast method of ambiguity resolution (PREFMAR). The developed DGNSS positioning methodology can be applied for reliable GNSS navigation using at least two independent GNSS systems.
Single-Cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns in Control and Aneurysmal Human Aortic Tissue

Supplemental Digital Content is available in the text. Background: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of the aortic wall and can lead to aortic dissection, rupture, and other life-threatening complications. To improve our understanding of ATAA pathogenesis, we aimed to comprehensively characterize the cellular composition of the ascending aortic wall and to identify molecular alterations in each cell population of human ATAA tissues. Methods: We performed single-cell RNA sequencing analysis of ascending aortic tissues from 11 study participants, including 8 patients with ATAA (4 women and 4 men) and 3 control subjects (2 women and 1 man). Cells extracted from aortic tissue were analyzed and categorized with single-cell RNA sequencing data to perform cluster identification. ATAA-related changes were then examined by comparing the proportions of each cell type and the gene expression profiles between ATAA and control tissues. We also examined which genes may be critical for ATAA by performing the integrative analysis of our single-cell RNA sequencing data with publicly available data from genome-wide association studies. Results: We identified 11 major cell types in human ascending aortic tissue; the high-resolution reclustering of these cells further divided them into 40 subtypes. Multiple subtypes were observed for smooth muscle cells, macrophages, and T lymphocytes, suggesting that these cells have multiple functional populations in the aortic wall. In general, ATAA tissues had fewer nonimmune cells and more immune cells, especially T lymphocytes, than control tissues did. Differential gene expression data suggested the presence of extensive mitochondrial dysfunction in ATAA tissues. In addition, integrative analysis of our single-cell RNA sequencing data with public genome-wide association study data and promoter capture Hi-C data suggested that the erythroblast transformation-specific related gene(ERG) exerts an important role in maintaining normal aortic wall function. Conclusions: Our study provides a comprehensive evaluation of the cellular composition of the ascending aortic wall and reveals how the gene expression landscape is altered in human ATAA tissue. The information from this study makes important contributions to our understanding of ATAA formation and progression.
Choice of methods can determine which behavioral determinates are identified for targeting in future behavior change interventions: Increasing antibiotic adherence in Pakistan

When developing a behavioral intervention, formative research should be conducted to determine which behavioral barriers and facilitators to target. This is often done using qualitative interviews, but quantitative surveys may also be used. The current study examines the consequences of applying descriptive (rank order and t-tests) versus predictive (regression) quantitative analyses on intervention development, specifically for increasing antibiotic course completion. For demonstrative purposes, 1892 adults in Pakistan completed a cross-sectional survey that measures a comprehensive set of barriers/facilitators to their course completion. The descriptive and predictive analyses disagreed regarding which barriers/facilitators to prioritize. Reasons to prefer predictive analyses are discussed.
A novel NIR-image segmentation method for the precise estimation of above-ground biomass in rice crops

Traditional methods to measure spatio-temporal variations in biomass rely on a labor-intensive destructive sampling of the crop. In this paper, we present a high-throughput phenotyping approach for the estimation of Above-Ground Biomass Dynamics (AGBD) using an unmanned aerial system. Multispectral imagery was acquired and processed by using the proposed segmentation method called GFKuts, that optimally labels the plot canopy based on a Gaussian mixture model, a Montecarlo based K-means, and a guided image filtering. Accurate plot segmentation results enabled the extraction of several canopy features associated with biomass yield. Machine learning algorithms were trained to estimate the AGBD according to the growth stages of the crop and the physiological response of two rice genotypes under lowland and upland production systems. Results report AGBD estimation correlations with an average of r = 0.95 and R2 = 0.91 according to the experimental data. We compared our segmentation method against a traditional technique based on clustering. A comprehensive improvement of 13% in the biomass correlation was obtained thanks to the segmentation method proposed herein.
Impact of PI-RADS 3 lesions on the diagnostic accuracy of MRI for detecting prostate cancer and the prevalence of prostate cancer within each PI-RADS category: A systematic review and Meta-Analysis.

OBJECTIVE To evaluateProstate Imaging Reporting and Data System (PI-RADS) category three lesions impact on diagnostic test accuracy (DTA) of MRI for prostate cancer (PC) and to derive prevalence of PC within each PI-RADS category. METHODS MEDLINE and Embase were searched for studies reporting on the DTA of MRI by PI-RADS category. Accuracy metrics were calculated using a bivariate random-effects meta-analysis with PI-RADS three lesions treated as a positive test, negative test, and excluded from the analysis. Differences in DTA were assessed utilizing meta-regression.PC prevalenceby PI-RADS category was estimated with proportional meta-analysis. RESULTS Twenty-six studies reporting on 12,913 patients (4,853 with PC) were included.Sensitivity for PC in the positive, negative, and excluded test groups was 96% (95%-confidence interval [CI]92-98), 82% (CI75-87), and 95% (CI91-97), respectively. Specificity for the positive, negative, and excluded test groups were 33%(CI23-44), 71% (CI62-79),and 52% (CI37-66), respectively. Meta-regression demonstrated higher sensitivity (p < 0.001) and lower specificity (p < 0.001) in the positive test group compared to the negative group. Clinically significant PC prevalence was 5.9% (CI0-17.1), 11.4% (CI 6.5-17.3), 24.9% (CI18.4-32.0), 55.7% (CI47.8-63.5), and 81.4% (CI75.9-86.4)for PI-RADS categories 1, 2, 3, 4, and 5, respectively. CONCLUSION PI-RADS three lesions can significantly impact the DTA of MRI for PC detection. A low prevalence of clinically significant PC is noted in PI-RADS category1 and 2 cases. ADVANCES IN KNOWLEDGE Inclusion or exclusion of PI-RADS category three lesions impacts the DTA of MRI for PC detection.
Some Aspects of the Liquid Water Thermodynamic Behavior: From The Stable to the Deep Supercooled Regime

Liquid water is considered to be a peculiar example of glass forming materials because of the possibility of giving rise to amorphous phases with different densities and of the thermodynamic anomalies that characterize its supercooled liquid phase. In the present work, literature data on the density of bulk liquid water are analyzed in a wide temperature-pressure range, also including the glass phases. A careful data analysis, which was performed on different density isobars, made in terms of thermodynamic response functions, like the thermal expansion αP and the specific heat differences CP−CV, proves, exclusively from the experimental data, the thermodynamic consistence of the liquid-liquid transition hypothesis. The study confirms that supercooled bulk water is a mixture of two liquid “phases”, namely the high density (HDL) and the low density (LDL) liquids that characterize different regions of the water phase diagram. Furthermore, the CP−CV isobars behaviors clearly support the existence of both a liquid–liquid transition and of a liquid–liquid critical point.