Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycosuria Alters Uropathogenic Escherichia coli Global Gene Expression and Virulence

Uropathogenic Escherichia coli (UPEC) is an important causative agent of urinary tract infections in diabetic humans. We examined the effects of in vitro exposure to glycosuria (presence of glucose in urine) on the virulence and gene expression by UPEC. Our results show that glycosuria rapidly (in 2 h) alters UPEC gene expression, induces biofilm formation, and suppresses type 1 piliation. These results offer novel insights into the pathogenesis of UPEC in the urinary tract. ABSTRACT Uropathogenic Escherichia coli (UPEC) is the principal etiology of more than half of urinary tract infections (UTI) in humans with diabetes mellitus. Epidemiological data and studies in mouse model of ascending UTI have elucidated various host factors responsible for increasing the susceptibility of diabetic hosts to UPEC-UTI. In contrast, diabetic urinary microenvironment-mediated alterations in UPEC physiology and its contributions to shaping UPEC-UTI pathogenesis in diabetes have not been examined. To address our central hypothesis that glycosuria directly induces urinary virulence of UPEC, we compared virulence characteristics and gene expression in human UPEC strains UTI89 (cystitis) and CFT073 (pyelonephritis), exposed for 2 h in vitro to urine from either male or female donors that was either plain or supplemented with glucose to mimic glycosuria. Compared to control UPEC exposed to nutrient-rich culture medium, lysogeny broth, glycosuria-exposed UPEC exhibited significant increase in biofilm formation and reduction in the hemagglutination of Guinea pig erythrocytes (a measure of type 1 piliation). In addition, the analysis of UTI89 transcriptome by RNA sequencing revealed that 2-h-long, in vitro exposure to glycosuria also significantly alters expression of virulence and metabolic genes central to urinary virulence of UPEC. Addition of galactose as an alternative carbon source affected biofilm formation and gene expression profile of UPEC to an extent similar to that observed with glucose exposure. In summary, our results provide novel insights into how glycosuria-mediated rapid changes in UPEC fitness may facilitate UTI pathogenesis in the diabetic urinary microenvironment. IMPORTANCE Uropathogenic Escherichia coli (UPEC) is an important causative agent of urinary tract infections in diabetic humans. We examined the effects of in vitro exposure to glycosuria (presence of glucose in urine) on the virulence and gene expression by UPEC. Our results show that glycosuria rapidly (in 2 h) alters UPEC gene expression, induces biofilm formation, and suppresses type 1 piliation. These results offer novel insights into the pathogenesis of UPEC in the urinary tract.
Somatic mutation detection: a critical evaluation through simulations and reanalyses in oaks

Mutation, the source of genetic diversity, is the raw material of evolution; however, the mutation process remains understudied, especially in plants. Using both a simulation and reanalysis framework, we set out to explore and demonstrate the improved performance of variant callers developed for cancer research compared to single nucleotide polymorphism (SNP) callers in detecting de novo somatic mutations. In an in silico experiment, we generated Illumina-like sequence reads spiked with simulated mutations at different allelic fractions to compare the performance of seven commonly-used variant callers to recall them. More empirically, we then reanalyzed two of the largest datasets available for plants, both developed for identifying within-individual variation in long-lived pedunculate oaks. Based on the in silico experiment, variant callers developed for cancer research outperform SNP callers regarding plant mutation recall and precision, especially at low allele frequency. Such variants at low allelic fractions are typically expected for within-individual de novo plant mutations, which initially appear in single cells. Reanalysis of published oak data with Strelka2, the best-performing caller based on our simulations, identified up to 3.4x more candidate somatic mutations than reported in the original studies. Our results advocate the use of cancer research callers to boost de novo mutation research in plants, and to reconcile empirical reports with theoretical expectations. This version of the article has been peer-reviewed and recommended by Peer Community in Genomics https://doi.org/10.24072/pci.genomics. 100024
Development of a novel rodent rapid serial visual presentation task reveals dissociable effects of stimulant vs non-stimulant treatments on attention

The rapid serial visual presentation (RSVP) task and continuous performance tasks (CPT) are used to assess attentional impairments in patients with psychiatric and neurological conditions. This study developed a novel touchscreen task for rats based on the structure of a human RSVP task and used pharmacological manipulations to investigate their effects on different performance measures. Normal animals were trained to respond to a target image and withhold responding to distractor images presented within a continuous sequence. In a second version of the task a false-alarm image was included so performance could be assessed relative to two types of non-target distractors. The effects of acute administration of the stimulant and non-stimulant treatments for ADHD (amphetamine and atomoxetine) were tested in both tasks. Methylphenidate, ketamine and nicotine were tested in the first task only. Amphetamine made animals more impulsive and decreased overall accuracy but increased accuracy when the target was presented early in the image sequence. Atomoxetine improved accuracy overall with a specific reduction in false-alarm responses and a shift in the attentional curve reflecting improved accuracy for targets later in the image sequence. However, atomoxetine also slowed responding and increased omissions. Ketamine, nicotine and methylphenidate had no specific effects at the doses tested. These results suggest that stimulant versus non-stimulant treatments have different effects on attention and impulsive behaviour in this rat version of an RSVP task. These results also suggest that RSVP-like tasks have the potential to be used to study attention in rodents.
Adee: Bringing Accessibility Right Inside Design Tools

According to the world bank organization report, about 15 percent of the world’s population (equal to 1 billion people) experience some form of disability [3]. However, designers can easily forget to take account of disabilities such as colorblindness, as most designers are not colorblind and tools for accessibility are not integrated into design tools. In this work, we introduce and evaluate Adee, an accessibility testing tool that has been integrated into widely used design tools Adobe XD, Figma and Sketch. Adee aims to make accessibility part of the design process, to create inclusive and ethical products.
New from old: discovery of the novel antibiotic actinomycin L in Streptomyces sp. MBT27

Streptomycetes are major producers of bioactive natural products, including the majority of the antibiotics. While much if the low-hanging fruit has been discovered, it is predited that less than 5% of the chemical space has been mined. Here, we describe the novel actinomycins L1 and L2, which are produced by Streptomyces sp. MBT27. The molecules were discovered via metabolic analysis combined with molecular networking of cultures grown with different combinations of carbon sources. Actinomycins L1 and L2 are diastereoisomers, and the structure of actinomycin L2 was resolved using NMR and single crystal X-ray crystallography. Actinomycin L is formed via a unique spirolinkage of anthranilamide to the 4-oxoproline moiety of actinomycin X2, prior to the condensation of the actinomycin halves. Feeding anthranilamide to cultures of Streptomyces antibioticus, which has the same biosynthetic gene cluster as Streptomyces sp. MBT27 but only produces actinomycin X2, resulted in the production of actinomycin L. This shows that actinomycin L results from joining two distinct metabolic pathways, namely those for actinomycin X2 and for anthranilamide. Actinomycins L1 and L2 showed significant antimicrobial activity against Gram- positive bacteria. Our work shows how new molecules can still be identified even in the oldest of natural product families. IMPORTANCE Actinomycin was the first antibiotic discovered in an actinobacterium by Selman Waksman and colleagues, as early as 1940. This period essentially marks the start of the ‘golden era’ of antibiotic discovery. Over time, emerging antimicrobial resistance (AMR) and the declining success rate of antibiotic discovery resulted in the current antibiotic crisis. We surprisingly discovered that under some growth conditions, Streptomyces sp. MBT27 can produce actinomycins that are significantly different from those that have been published so far. The impact of this work is not only that we have discovered a novel molecule with very interesting chemical modifications in one of the oldest antibiotics ever described, but also that this requires the combined action of primary and secondary metabolic pathways, namely the biosynthesis of anthranilamide and of actinomycin X2, respectively. The implication of the discovery is that even the most well-studied families of natural products may still have surprises in store for us.
Deep Learning Genome-wide Linkage Association Study for Wheat Fusarium Head Blight Resistance Genes Discovery

Background Fusarium head blight (FHB) is one of the most devastating diseases of wheat worldwide and artificial intelligence can assist with understanding resistance to the disease. Considering different sample populations, marker types, reference maps, and statistical methods, we developed a Deep Learning Genome-wide Linkage Association Study (dpGLAS) of FHB resistance in wheat. Results The dpGLAS was first applied to two bi-parental population datasets in which the cultivar AC Barrie was a common parent for FHB resistance. Eight candidate gene markers were discovered in the one AC Barrie population and 10 in the other associated with FHB resistance. Eight of these markers were also supported by the conventional QTL mapping. Most of these candidate marker genes were found associated with the Reactive Oxygen Species (ROS) and Abscisic acid (ABA) axes. These ROS and ABA pathways were further supported by RNA-seq transcriptome data of FHB resistant cv. AAC Tenacious, a parent of the third bi-parental population. In this dataset, the ROS-centered Panther protein families were significantly enriched in those genes that had most different response to FHB when compared the resistance Tenacious and the susceptible Roblin. Conclusions This study developed the framework of dpGLAS and identified candidate genes for FHB resistance in the Canadian spring wheat cultivars AC Barrie and AAC Tenacious.
Angiomotin isoform 2 promotes binding of PALS1 to KIF13B at the base of primary cilia and suppresses ciliary elongation

The kinesin-3 motor KIF13B functions in endocytosis, vesicle transport, and regulation of ciliary length and signaling. Direct binding of the membrane-associated guanylate kinase (MAGUK) DLG1 to KIF13B’s MAGUK-binding stalk (MBS) domain relieves motor autoinhibition and promotes microtubule plus end-directed cargo transport. Here we characterize Angiomotin isoform 2 (Ap80) as a novel KIF13B interactor that promotes binding of another MAGUK, the polarity protein and Crumbs complex component PALS1, to KIF13B. Live cell imaging analysis indicated that Ap80 is concentrated at the base of primary cilia and recruits PALS1 to this site, but is not itself a cargo of KIF13B. Consistent with a ciliary function for Ap80, its depletion led to elongated primary cilia while its overexpression caused ciliary shortening. Our results suggest that Ap80 may specifically activate KIF13B cargo binding at the base of primary cilia to regulate ciliary length.
Gastrointestinal Development and Microbiota Responses of Geese to Honeycomb Flavonoids Supplementation

Background: Geese are conventionally considered to be herbivorous, which could also be raised with concentrate feeding diets without green grass because of the similar gastrointestinal tract with other poultry. However, the geese gut microbiota profiles and their interactions with epithelial cells are still of limited study. Flavonoids were well-documented to shape gut microbiota and promote epithelial barrier functions individually or cooperatively with other metabolites. Therefore, in the present study, honeycomb flavonoids (HF) were supplemented to investigate the effects on growth performances, intestinal development, and gut microbiome of geese. Material and Methods: A total of 400 1-day-old male lion-head geese with similar birth weight (82.6 ± 1.4 g) were randomly divided into five treatments: the control treatment (CON) and the HF supplementation treatments, HF was supplemented arithmetically to increase from 0.25 to 1%. Growth performance, carcass performances, and intestines' development parameters were measured to determine the optimum supplement. Junction proteins including ZO-1 and ZO-2 and cecal microbiota were investigated to demonstrate the regulatory effects of HF on both microbiota and intestinal epithelium. Results: Results showed that 0.5% of HF supplement had superior growth performance, carcass performance, and the total parameters of gastrointestinal development to other treatments. Further research showed that tight junction proteins including ZO-1 and ZO-2 significantly up-regulated, while Firmicutes and some probiotics including Clostridiales, Streptococcus, Lachnoclostridium, and Bifidobacterium, remarkably proliferated after HF supplement. In conclusion, HF supplement in concentrate-diet feeding geese effectively increased the growth performances by regulating the gut microbiota to increase the probiotic abundance to promote the nutrient digestibility and fortify the epithelial development and barrier functions to facilitate the nutrient absorption and utilization.
Psychological Status Associated With Low Quality of Life in School-Age Children With Neurodevelopmental Disorders During COVID-19 Stay-At-Home Period

Background: This study seeks to ascertain how the COVID-19 stay-at-home period has affected the quality of life (QOL) of children with neurodevelopmental disorders (NDDs) who had experienced sleep schedules alteration and clarify what psychological status predicted low QOL in children with and without altered sleep patterns. Materials and Methods: Study participants were 86 children between 8 and 17 years of age (mean age, 11.7 years; 70 boys, 16 girls; mean intellectual quotient, 83.6). QOL was evaluated using the self-assessment KINDLR. Participants answered questions regarding depression and anxiety on a visual analog scale (VAS) for temporary mood. Their parents answered questionnaires regarding their maladaptive behaviors and differences in sleep patterns before and during the COVID-19 pandemic. The student's t-test was performed to examine the presence or absence of sleep changes in the children, which affected QOL, temporary mood, and maladaptive behaviors. Multiple or simple linear regression analyses were also performed to identify the psychogenic factors that significantly affected decreased QOL for each group with and without changes in sleep schedule. Results: During the COVID-19 stay-at-home period, 46.5% of participants experienced changes in sleep patterns. These changes were associated with decreased QOL as well as internalized symptoms. The decreased QOL of children with sleep patterns changed was predicted by a high level of depression. In addition, low QOL in children with unchanged sleep patterns was predicted by a high level of depression and low current mood status. Conclusions: Almost half of the participants experienced a poor sleep schedule during the stay-at-home period. These alterations in sleep patterns were associated with a low QOL. The QOL of children with a stable life schedule was affected not only by depressive tendencies but also temporary moods. Therefore, they need to live a fulfilling life to maintain their QOL. However, the QOL of children with poor sleep patterns was affected only by depressive tendencies. Hence, clinicians need to ensure that children with NDDs are well-diagnosed with depression and treated for sleep problems.
Characterization of Reproductive Microbiota of Primiparous Cows During Early Postpartum Periods in the Presence and Absence of Endometritis

Endometritis has a major impact on fertility in postpartum dairy cows. Since previous studies showed an association between reproductive microbiota and perinatal disease, we monitored both bovine uterine and vaginal microbiota in primiparous cows to elucidate the effect of early postpartum microbiota on endometritis. Uterine and vaginal samples were collected at time points from pre-calving to 35 days postpartum (DPP), and analyzed by 16S rRNA sequencing, combined with ancillary bacterial culture. A total of seven healthy cows and seven cows diagnosed with endometritis on 35 DPP were used in the current study. The uterine and vaginal microbiota showed a maximum of 20.1% shared amplicon sequence variants (ASVs) at linked time points. 16S rRNA based analysis and traditional culture methods revealed that Trueperella showed a higher abundance in both uterus and vagina of the endometritis group compared to the healthy group on 21 DPP (U-test p < 0.05). Differential abundance analysis of the uterine microbiota showed that Enterococcus and six bacterial genera including Bifidobacterium were unique to the healthy group on the day of calving (0 DPP) and 28 DPP, respectively. In contrast, Histophilus and Mogibacteriaceae were characteristic bacteria in the vagina pre-calving in cows that later developed endometritis, suggesting that these bacteria could be valuable to predict clinical outcomes. Comparing the abundances of bacterial genera in the uterine microbiota, a negative correlation was observed between Trueperella and several bacteria including Lactobacillus. These results suggest that building an environment where there is an increase in bacteria that are generally recognized as beneficial, such as Lactobacillus, may be one possible solution to reduce the abundance of Trueperella and control endometritis.
Mesenchymal Stem Cells With Cancer-Associated Fibroblast-Like Phenotype Stimulate SDF-1/CXCR4 Axis to Enhance the Growth and Invasion of B-Cell Acute Lymphoblastic Leukemia Cells Through Cell-to-Cell Communication

Background: Bone marrow mesenchymal stem cells (BM-MSCs) are the stromal cells in the leukemia microenvironment, and can obtain cancer-associated fibroblast (CAF)-like phenotype under certain conditions to further promote leukemia progression. However, the mechanism of MSCs with CAF-like phenotype interacting with leukemia cells in B-cell acute lymphoblastic leukemia (B-ALL) and promoting the progression of B-ALL remains unclear. Methods: Mesenchymal stem cells with CAF-like phenotype were obtained by treating MSCs with recombinant human transforming growth factor-β (rhTGF-β), hereafter referred to as TGF-β conditioned MSCs. In vivo mouse model experiments, in vitro transwell chamber experiments, three-dimensional (3D) cell culture models, lentiviral transfection and other experimental methods were used to investigate the possible mechanism of the interaction between TGF-β conditioned MSCs and leukemia cells in promoting the growth, migration and invasion of B-ALL cells. Results: Compared with untreated MSCs, TGF-β conditioned MSCs significantly promoted the growth and proliferation of leukemia cells in mice, and increased the expression of CXCR4 in tumor tissues. In vitro cell experiments, TGF-β conditioned MSCs obviously promoted the migration and invasion of Nalm-6/RS4;11 cells, which were effectively blocked by the CXCR4 inhibitor AMD3100, thereby inhibiting the secretion of MMP-9 in TGF-β conditioned MSCs and inhibiting the activation of the PI3K/AKT signaling pathway in leukemia cells. Further, findings were made that the interaction between TGF-β conditioned MSCs and leukemia cells were mediated by the interaction between the integrin receptor α5β1 on the surface of leukemia cells and the increased expression of fibronectin on TGF-β conditioned MSCs. AMD3100 could weaken such effect by reducing the expression of integrin α5β1 on leukemia cells. Further regulation of integrin β1 could effectively interfere with the interaction between TGF-β conditioned MSCs and leukemia cells. Conclusion: Mesenchymal stem cells with CAF-like phenotype could be a key factor in promoting the growth and invasion of B-ALL cells, and the SDF-1/CXCR4 axis might be a significant factor in mediating the communication of MSCs with CAF-like phenotype and leukemia cells. To prevent the progression of B-ALL cells, blocking the SDF-1/CXCR4 axis with AMD3100 or targeting integrin β1 might be a potential therapeutic strategy.
Shot Characteristics Based on Match Period in Elite Table Tennis Matches

This study aimed to compare the shot characteristics amongst different match periods in table tennis matches. For the shot characteristics of position, type, placement and efficacy, 13 men’s singles matches comprising 72 sets from a round of 16 to the final in the 2019 World Table Tennis Championships were selected for notational analysis. Kruskal–Wallis and Mann–Whitney tests were conducted to quantify the differences in various categories of each variable amongst the initial, intermediate and ending match periods. There are no significant differences in each distribution between initial and intermediate periods. From intermediate to ending periods, significant decreases were found in chop type (p < 0.01) and middle long placement (p < 0.01), whereas a significant increase was found in backhand half placement (p < 0.05). By comparing the initial and ending periods, significant decreases were found in middle backhand turn position (p < 0.05), middle long placement (p < 0.01), chop (p < 0.01), and poor shots (p < 0.05). Therefore, shot characteristics in table tennis matches are match period related, and the main differences existed between the beginning and the ending period. From initial to ending period, the frequency of applying the middle long placements is decreasing. At the end of every set, the players adopted a safe stroke position, performed offensive stroke types and deployed flexible stroke placement. Results suggested that coaches can establish different scenarios on the basis of varying match periods for players’ training.