Miracle-dz/UniFAR-FTUs huggingface dataset:
Induced Mutations through EMS Treatment and In Vitro Screening for Salt Tolerance Plant of Petunia × atkinsiana D. Don

In vitro culture is a practical plant breeding tool in developing plant resistant to different abiotic stresses such as salinity. In this study, the focus is on inducing mutations for salt tolerance using ethyl methane sulphonate (EMS) in calli of petunia ( Petunia × atkinsiana D. Don ‘Prism Red’), followed by cell line selection and subsequent plant regeneration. Callus cultures were initiated from leaf fragments soaked in mutagen solution in two concentrations 0.5 and 5.0 mM for 60, 120 and 180 min, respectively. Then, the callus was rinsed three times in deionized, sterile water and was transferred onto embryo formation medium Murashige and Skoog (MS) supplemented with 2.0 mg l -1 1-napthaleneaceticacid (NAA) and 5.0 mg l -1 (6-benzyloaminopurine) BAP. After 28 days, somatic embryos were transferred onto MS medium supplemented with 4.0 mg l -1 BAP for regeneration. Results of our studies showed that the callus immersion in the 5.0 mM EMS solution caused damage to the cells, and indicated by the change in callus colour into brown. The plants regenerated from the somatic embryos induced from callus treated with 0.5 mM solution of mutagen for 60 and 120 min were determined as M1 and M2 mutant variants, respectively. After the multiplication of the obtained plants, their tolerance to salinity stress was determined. The obtained results have showed that the M1 and M2 mutant lines were characterized by elevated tolerance to the stress factor in comparison to non-mutated plants.
Overexpression of PLIN1 Promotes Lipid Metabolism in Bovine Adipocytes

Simple Summary In bovine preadipocytes, the overexpression of the PLIN1 gene promotes the expression of FASN, PPARγ, ACC, LPL, FABP4, DGAT2, and C/EBPβ at the mRNA level, inhibiting the expression of fat metabolism genes such as PLIN2 and ATGL. Furthermore, after overexpression of PLIN1, the oil red O-staining results showed that the number of lipid droplets (LDs) in fat cells, their volume and triglyceride content were increased. The elevation in triglyceride content indicates that PLIN1 can promote the accumulation of triglyceride in bovine preadipocytes and has an important regulatory role in fat metabolism. After transfection with the adenovirues Ad-PLIN1 and Ad-NC (empty virus), RNA-seq was used to analyze the differentially expressed genes in bovine preadipocytes. A total of 1923 differentially expressed genes were detected, and GO and KEGG signaling pathways were analyzed for differentially expressed genes. Abstract Perilipin 1 (PLIN1) is a protein encoded by the PLIN1 gene in eukaryotes. PLIN1 is a member of the PAT protein family, a family of proteins related to lipid droplet (LD) surface proteins. PLIN1 phosphorylation plays a vital role during fat metabolism of adipose tissue lipolysis and fat storage in adipocytes. However, to further explore the regulation of the PLIN1 gene on the proliferation, differentiation and lipid metabolism of bovine adipocytes. In this study, the mRNA expression of PLIN1, at day six, was the highest during bovine adipocyte differentiation. Moreover, PLIN1 can promote the proliferation and differentiation of preadipocytes in cattle. On the sixth day, after transfection with, and overexpression of, the PLIN1 gene in bovine preadipocytes via adenovirus, cell samples were collected, and transcriptome sequencing was performed. A total of 1923 differentially expressed genes were detected. Through GO and KEGG pathway analysis, the differentially expressed genes were established to be mainly enriched in the AMPK, Wnt, and PPAR signaling pathways related to fat proliferation and differentiation. In conclusion, at the transcriptional level, PLIN1 plays an important role in regulating fat proliferation and metabolism. Additionally, the sequencing results screened new differentially expressed genes related to fat metabolism, providing theoretical support for molecular breeding of Qinchuan beef cattle.
Insights into the composition of ancient Egyptian red and black inks on papyri achieved by synchrotron-based microanalyses

Significance Ink, invented in ancient Egypt circa 5,000 y ago, is the established and time-honored medium wherewith humankind commits words to writing. A comprehensive synchrotron-based microanalysis of a considerable corpus of ancient Egyptian papyri from the Roman period, inscribed with red and black inks, reveal a hitherto undetected complex composition of inks. Highlighted by the presence of iron, the red color can be attributed to the use of ocher. Unexpectedly, lead is regularly present in both the red and black inks and is associated to phosphate, sulfate, chloride, and carboxylate ions. The analysis shows that lead was probably used as a drier rather than as a pigment, similar to its usage in 15th century Europe during the development of oil paintings. A hitherto unknown composition is highlighted in the red and black inks preserved on ancient Egyptian papyri from the Roman period (circa 100 to 200 CE). Synchrotron-based macro–X-ray fluorescence (XRF) mapping brings to light the presence of iron (Fe) and lead (Pb) compounds in the majority of the red inks inscribed on 12 papyrus fragments from the Tebtunis temple library. The iron-based compounds in the inks can be assigned to ocher, notably due to the colocalization of Fe with aluminum, and the detection of hematite (Fe2O3) by micro–X-ray diffraction. Using the same techniques together with micro-Fourier transform infrared spectroscopy, Pb is shown to be associated with fatty acid phosphate, sulfate, chloride, and carboxylate ions. Moreover, micro-XRF maps reveal a peculiar distribution and colocalization of Pb, phosphorus (P), and sulfur (S), which are present at the micrometric scale resembling diffused “coffee rings” surrounding the ocher particles imbedded in the red letters, and at the submicrometric scale concentrated in the papyrus cell walls. A similar Pb, P, and S composition was found in three black inks, suggesting that the same lead components were employed in the manufacture of carbon-based inks. Bearing in mind that pigments such as red lead (Pb3O4) and lead white (hydrocerussite [Pb3(CO3)2(OH)2] and/or cerussite [PbCO3]) were not detected, the results presented here suggest that the lead compound in the ink was used as a drier rather than as a pigment. Accordingly, the study calls for a reassessment of the composition of lead-based components in ancient Mediterranean pigments.
Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study

Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis-related cardiovascular diseases (CVD) share common metabolic pathways. We explored the association between three NAFLD-associated single nucleotide polymorphisms (SNPs) rs738409, rs10401969, and rs1260326 with sub-clinical atherosclerosis estimated by the carotid intima-media thickness (c-IMT) and the inter-adventitia common carotid artery diameter (ICCAD) in patients free from clinically overt NAFLD and CVD. The study population is the IMPROVE, a multicenter European study (n = 3711). C-IMT measures and ICCAD were recorded using a standardized protocol. Linear regression with an additive genetic model was used to test for association of the three SNPs with c-IMT and ICCAD. In secondary analyses, the association of the three SNPs with c-IMT and ICCAD was tested after stratification by alanine aminotransferase levels (ALT). No associations were found between rs738409, rs1260326, rs10401969, and c-IMT or ICCAD. Rs738409-G and rs10401969-C were associated with ALT levels (p < 0.001). In patients with ALT levels above 28 U/L (highest quartile), we observed an association between rs10401969-C and c-IMT measures of c-IMTmax and c-IMTmean-max (p = 0.018 and 0.021, respectively). In conclusion, NAFLD-associated SNPs do not associate with sub-clinical atherosclerosis measures. However, our results suggest a possible mediating function of impaired liver function on atherosclerosis development.
A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.
On the many‐body nature of intramolecular forces in FFLUX and its implications

FFLUX is a biomolecular force field under construction, based on Quantum Chemical Topology (QCT) and machine learning (kriging), with a minimalistic and physically motivated design. A detailed analysis of the forces within the kriging models as treated in FFLUX is presented, taking as a test example a liquid water model. The energies of topological atoms are modeled as 3Natoms‐6 dimensional potential energy surfaces, using atomic local frames to represent the internal degrees of freedom. As a result, the forces within the kriging models in FFLUX are inherently N‐body in nature where N refers to Natoms. This provides a fuller picture that is closer to a true quantum mechanical representation of interactions between atoms. The presented computational example quantitatively showcases the non‐negligible (as much as 9%) three‐body nature of bonded forces and angular forces in a water molecule. We discuss the practical impact on the pressure calculation with N‐body forces and periodic boundary conditions (PBC) in molecular dynamics, as opposed to classical force fields with two‐body forces. The equivalence between the PBC‐related correction terms in the general virial equation is shown mathematically.
Immersive Virtual Reality as Analgesia during Dressing Changes of Hospitalized Children and Adolescents with Burns: A Systematic Review with Meta-Analysis

Children and adolescents with severe burns require medical and nursing interventions, associated with pain. As immersive virtual reality (VR) gained prominence as non-pharmacological adjuvant analgesia, we conducted a systematic review and meta-analysis on the efficacy of full immersive VR on pain experienced during dressing changes in hospitalized children and adolescents with severe burns. This exercise included quality and risk of bias assessment. The systematic review resulted in eight studies and 142 patients. Due to missing data, four studies were excluded from the meta-analysis. Fixed effects meta-analysis of the four included studies (n = 104) revealed a large effect size (ES) (Standardized Mean Difference = 0.94; 95% Confidence Interval = 0.62, 1.27; Z = 5.70; p < 0.00001) for adjuvant full immersive VR compared to standard care (SC). In conclusion, adjuvant full immersive VR significantly reduces pain experienced during dressing changes in children and adolescents with burns. We therefore recommend implementing full immersive VR as an adjuvant in this specific setting and population. However, this requires further research into the hygienic use of VR appliances in health institutions. Furthermore, due to the high cost of the hardware, a cost–benefit analysis is required. Finally, research should also verify the long term physical and psychological benefits of VR.
Listeria monocytogenes Infection of Bat Pipistrellus nathusii Epithelial cells Depends on the Invasion Factors InlA and InlB

L. monocytogenes is a widespread facultative intracellular pathogen. The range of natural hosts that supporting L. monocytogenes persistence in the environment has not been fully established yet. In this study, we were interested in the potential of L. monocytogenes to infect cells of bats, which are being increasingly recognized as a reservoir for microorganisms that are pathogenic to humans and domestic animals. A stable epithelial cell line was developed from the kidneys of Pipistrellus nathusii, a small bat widely distributed across Europe. The wild-type L. monocytogenes strain EGDe infected this cell line with an invasion efficiency of 0.0078 ± 0.0009%. Once it entered bat cells, L. monocytogenes doubled within about 70 min. When L. monocytogenes lacked either of the major invasion factors, InlA and InlB, invasion efficiency decreased by a factor of 10 and 25 respectively (p < 0.000001). The obtained results suggest that bat epithelial cells are susceptible to L. monocytogenes infection and that L. monocytogenes invasion of bat cells depends on the major invasion factors InlA and InlB. These results constitute the first report on in vitro studies of L. monocytogenes infection in bats.
Myh6-driven Cre recombinase activates the DNA damage response and the cell cycle in the myocardium in the absence of loxP sites

ABSTRACT Regeneration of muscle in the damaged myocardium is a major objective of cardiovascular research, for which purpose many investigators utilize mice containing transgenes encoding Cre recombinase to recombine loxP-flanked target genes. An unfortunate side effect of the Cre-loxP model is the propensity of Cre recombinase to inflict off-target DNA damage, which has been documented in various eukaryotic cell types including cardiomyocytes (CMs). In the heart, reported effects of Cre recombinase include contractile dysfunction, fibrosis, cellular infiltration and induction of the DNA damage response (DDR). During experiments on adult mice containing a widely used Myh6-merCremer transgene, the protein product of which is activated by tamoxifen, we observed large, transient, off-target effects of merCremer, some of which have not previously been reported. On Day 3 after the first of three daily tamoxifen injections, immunofluorescent microscopy of heart sections revealed that the presence of merCremer protein in myonuclei was nearly uniform, thereafter diminishing to near extinction by Day 6; during this time, cardiac function was depressed as determined by echocardiography. On Day 5, peaks of apoptosis and expression of DDR-regulatory genes were observed, highlighted by >25-fold increased expression of Brca1. Concomitantly, the expression of genes encoding cyclin-A2, cyclin-B2 and cyclin-dependent kinase 1, which regulate the G2/S cell-cycle transition, were dramatically increased (>50- to 100-fold). Importantly, immunofluorescent staining revealed that this was accompanied by peaks in Ki67, 5′-bromodeoxyuridine and phosphohistone H3 labeling in non-CMs, as well as CMs. We further document that tamoxifen-induced activation of merCremer exacerbates cardiac dysfunction following myocardial infarction. These findings, when considered in the context of previous reports, indicate that the presence of merCremer in the nucleus induces DNA damage and unscheduled cell-cycle activation. Although these effects are transient, the inclusion of appropriate controls, coupled with an awareness of the defects caused by Cre recombinase, are required to avoid misinterpreting results when using Cre-loxP models for cardiac regeneration studies. This article has an associated First Person interview with the first author of the paper. Summary: The presence of tamoxifen-induced Cre recombinase (merCremer) in the nucleus of cardiomyocytes induces DNA damage and unscheduled cell-cycle activation, indicating the requirement for appropriate controls when using Cre-loxP models for cardiac regeneration studies.
InstaDock: A single-click graphical user interface for molecular docking-based virtual high-throughput screening

Exploring protein-ligand interactions is a subject of immense interest, as it provides deeper insights into molecular recognition, mechanism of interaction and subsequent functions. Predicting an accurate model for a protein-ligand interaction is a challenging task. Molecular docking is a computational method used for predicting the preferred orientation, binding conformations and the binding affinity of a ligand to a macromolecular target, especially protein. It has been applied in 'virtual high-throughput screening' of chemical libraries containing millions of compounds to find potential leads in drug design and discovery. Here, we have developed InstaDock, a free and open access Graphical User Interface (GUI) program that performs molecular docking and high-throughput virtual screening efficiently. InstaDock is a single-click GUI that uses QuickVina-W, a modified version of AutoDock Vina for docking calculations, made especially for the convenience of non-bioinformaticians and for people who are not experts in using computers. InstaDock facilitates onboard analysis of docking and visual results in just a single click. To sum up, InstaDock is the easiest and more interactive interface than ever existing GUIs for molecular docking and high-throughput virtual screening. InstaDock is freely available for academic and industrial research purposes via https://hassanlab.org/instadock.
The NICE MEDLINE and Embase (Ovid) health apps search filters: development of validated filters to retrieve evidence about health apps

Abstract Objectives Health apps are software programs that are designed to prevent, diagnose, monitor, or manage conditions. Inconsistent terminology for apps is used in research literature and bibliographic database subject headings. It can therefore be challenging to retrieve evidence about them in literature searches. Information specialists at the United Kingdom's National Institute for Health and Care Excellence (NICE) have developed novel validated search filters to retrieve evidence about apps from MEDLINE and Embase (Ovid). Methods A selection of medical informatics journals was hand searched to identify a “gold standard” (GS) set of references about apps. The GS set was divided into a development and validation set. The filters’ search terms were derived from and tested against the development set. An external development set containing app references from published NICE products was also used to inform the development of the filters. The filters were then validated using the validation set. Target recall was >90 percent. The filters’ overall recall, specificity, and precision were calculated using all the references identified from the hand search. Results Both filters achieved 98.6 percent recall against their validation sets. Overall, the MEDLINE filter had 98.8 percent recall, 71.3 percent specificity, and 22.6 percent precision. The Embase filter had 98.6 percent recall, 74.9 percent specificity, and 24.5 percent precision. Conclusions The NICE health apps search filters retrieve evidence about apps from MEDLINE and Embase with high recall. They can be applied to literature searches to retrieve evidence about the interventions by information professionals, researchers, and clinicians.
Lysis of cells of diverse bacteria by l,d‐peptidases of Escherichia coli bacteriophages RB43, RB49 and T5

The objective of this work was to study the antibacterial specificity and antibacterial effect of endolysins isolated from colibacteriophages RB43, RB49 and T5—as manifested on the exponential and stationary cell cultures of diverse bacteria depending on the growth stage, structure of peptidoglycan (PG) and antibiotic resistance.
Spatial Variation in Long-Term Trends in a Metapopulation of the Globally Threatened Aquatic Warbler Acrocephalus paludicola in Poland

Abstract. The Polish breeding population (3,200–3,250 males) of the globally threatened Aquatic Warbler Acrocephalus paludicola represents almost 25% of the global population. Except for the relatively stable large population in the Biebrza valley in north-east Poland less is known about population trends of peripheral populations in western, central and south-eastern regions of the country and whether trends differ depending on region. We investigated the long-term population dynamics in 38 small populations between 1969–2013 in the four Polish regions. Summarizing the trends of all small populations of Aquatic Warblers showed a significant decline in total number of individuals and declining number of populations over time. However, population trends were distinctly different in the different regions, with stable dynamics in south-east, moderate decline in north-east and sharp decline in the central and western regions. During the study period 19 out of 38 populations became extinct (11 populations in the western region, two in central region, four in north-east region and none in the south-east region). Five of these populations were later recolonised thus suggesting a pattern of metapopulation dynamics. To mitigate the negative trends and increased risk of local and regional extinction in the western and central parts of Poland effort should be put to increasing dispersal among populations by increasing the number of stepping stone patches between the viable large eastern populations and the smaller central and western ones.
SHOC2 Is a Critical Modulator of Sensitivity to EGFR–TKIs in Non–Small Cell Lung Cancer Cells

EGFR mutation-positive patients with non–small cell lung cancer (NSCLC) respond well to treatment with EGFR–tyrosine kinase inhibitors (EGFR–TKI); however, treatment with EGFR–TKIs is not curative, owing to the presence of residual cancer cells with intrinsic or acquired resistance to this class of drugs. Additional treatment targets that may enhance the efficacy of EGFR–TKIs remain elusive. Using a CRISPR/Cas9-based screen, we identified the leucine-rich repeat scaffold protein SHOC2 as a key modulator of sensitivity to EGFR–TKI treatment. On the basis of in vitro assays, we demonstrated that SHOC2 expression levels strongly correlate with the sensitivity to EGFR–TKIs and that SHOC2 affects the sensitivity to EGFR–TKIs in NSCLC cells via SHOC2/MRAS/PP1c and SHOC2/SCRIB signaling. The potential SHOC2 inhibitor celastrol phenocopied SHOC2 depletion. In addition, we confirmed that SHOC2 expression levels were important for the sensitivity to EGFR–TKIs in vivo. Furthermore, IHC showed the accumulation of cancer cells that express high levels of SHOC2 in lung cancer tissues obtained from patients with NSCLC who experienced acquired resistance to EGFR–TKIs. These data indicate that SHOC2 may be a therapeutic target for patients with NSCLC or a biomarker to predict sensitivity to EGFR–TKI therapy in EGFR mutation-positive patients with NSCLC. Our findings may help improve treatment strategies for patients with NSCLC harboring EGFR mutations. Implications: This study showed that SHOC2 works as a modulator of sensitivity to EGFR–TKIs and the expression levels of SHOC2 can be used as a biomarker for sensitivity to EGFR–TKIs.