Miracle-dz/UniFAR-FTUs huggingface dataset:
Exosomes transfer miRNAs from cell-to-cell to inhibit autophagy during infection with Crohn’s disease-associated adherent-invasive E. coli

ABSTRACT Adherent-invasive E. coli (AIEC), which abnormally colonize the intestinal mucosa of Crohn’s disease (CD) patients, are able to adhere to and invade intestinal epithelial cells (IECs), survive and replicate within macrophages and induce a pro-inflammatory response. AIEC infection of IECs induces secretion of exosomes that increase AIEC replication in exosome-receiving IECs and macrophages. Here, we investigated the mechanism underlying the increased AIEC replication in cells receiving exosomes from AIEC-infected cells. Exosomes released by uninfected human intestinal epithelial T84 cells (Exo-uninfected) or by T84 cells infected with the clinical AIEC LF82 strain (Exo-LF82), the nonpathogenic E. coli K12 strain (Exo-K12) or the commensal E. coli HS strain (Exo-HS) were purified and used to stimulate T84 cells. Stimulation of T84 cells with Exo-LF82 inhibited autophagy compared with Exo-uninfected, Exo-K12 and Exo-HS. qRT-PCR analysis revealed increased levels of miR-30c and miR-130a in Exo-LF82 compared to Exo-uninfected, Exo-K12 and Exo-HS. These miRNAs were transferred via exosomes to recipient cells, in which they targeted and inhibited ATG5 and ATG16L1 expression and thereby autophagy response, thus favoring AIEC intracellular replication. Inhibition of these miRNAs in exosome-donor cells infected with AIEC LF82 abolished the increase in miR-30c and miR-130a levels in the released Exo-LF82 and in Exo-LF82-receiving cells, thus suppressing the inhibitory effect of Exo-LF82 on ATG5 and ATG16L1 expression and on autophagy-mediated AIEC clearance in Exo-LF82-receiving cells. Our study shows that upon AIEC infection, IECs secrete exosomes that can transfer specific miRNAs to recipient IECs, inhibiting autophagy-mediated clearance of intracellular AIEC.
Characterization of a Type II-A CRISPR-Cas System in Streptococcus mutans

CRISPR-Cas is one of the mechanisms used by bacteria to defend against viral predation. Increasing our knowledge of the biology and diversity of CRISPR-Cas systems will also improve our understanding of virus-bacterium interactions. As CRISPR-Cas systems acquiring novel immunities under laboratory conditions are rare, Streptococcus mutans strain P42S provides an alternative model to study the adaptation step, which is still the least understood step in CRISPR-Cas biology. Furthermore, the availability of a natural Cas9 protein recognizing an AT-rich PAM opens up new avenues for genome editing purposes. ABSTRACT Streptococcus mutans and its virulent phages are important members of the human oral microbiota. S. mutans is also the primary causal agent of dental caries. To survive in this ecological niche, S. mutans must encode phage defense mechanisms, which include CRISPR-Cas systems. Here, we describe the CRISPR-Cas type II-A system of S. mutans strain P42S, which was found to display natural adaptation and interference activity in response to phage infection and plasmid transformation. Newly acquired spacers were integrated both at the 5′ end of the CRISPR locus and ectopically. In comparisons of the cas genes of P42S to those of other strains of S. mutans, cas1, cas2, and csn2 appear to be highly conserved within the species. However, more diversity was observed with cas9. While the nuclease domains of S. mutans Cas9 (SmCas9) are conserved, the C terminus of the protein, including the protospacer adjacent motif (PAM) recognition domain, is less conserved. In support of these findings, we experimentally demonstrated that the PAMs associated with SmCas9 of strain P42S are NAA and NGAA. These PAMs are different from those previously reported for the CRISPR-Cas system of the model strain S. mutans UA159. This study illustrates the diversity of CRISPR-Cas type II-A systems that can be found within the same bacterial species. IMPORTANCE CRISPR-Cas is one of the mechanisms used by bacteria to defend against viral predation. Increasing our knowledge of the biology and diversity of CRISPR-Cas systems will also improve our understanding of virus-bacterium interactions. As CRISPR-Cas systems acquiring novel immunities under laboratory conditions are rare, Streptococcus mutans strain P42S provides an alternative model to study the adaptation step, which is still the least understood step in CRISPR-Cas biology. Furthermore, the availability of a natural Cas9 protein recognizing an AT-rich PAM opens up new avenues for genome editing purposes.
Characterization of alkaline phosphatase activity in the North and South Pacific Subtropical Gyres: Implications for phosphorus cycling

We characterized alkaline phosphatase (AP) activity (APA) and report AP kinetic parameters in the North and South Pacific Subtropical Gyres (NPSG and SPSG, respectively) to evaluate the relative importance of APA in dissolved organic P (DOP) remineralization. APA potential hydrolysis rates were low but measurable (0.10 ± 0.06 nmol L−1 h−1, n = 12, and 0.13 ± 0.08 nmol L−1 h−1, n = 6) in surface samples from the NPSG and central SPSG, respectively. When compared to dissolved inorganic P (DIP) uptake rates, the potential utilization of DOP by APA may be important for microbial communities in these oligotrophic habitats. Assuming an upper (80%) and a lower (10%) fraction of the DOP to be AP‐hydrolyzable, APA could represent 25% ± 18% (n = 11) and 4% ± 3% (n = 11) of the DIP uptake, respectively, in surface waters of the NPSG and 147% ± 86% (n = 6) and 20% ± 12% (n = 6), respectively, in surface waters of the central SPSG. The ratio of APA to DIP uptake was significantly larger in the SPSG compared to the NPSG despite having higher DIP and lower DOP. The half‐saturation constant (Km) was in the range of DOP concentrations measured in the two gyres, meaning that microorganisms can adjust their DOP utilization according to DOP availability. Dissolved APA was a large fraction of total APA in the NPSG, contributing between 12% and 100% (41 ± 23%, n = 23) of total APA at Sta. ALOHA. Utilization of the AP‐hydrolyzable fraction of the DOP probably contributes to production in the extensive Pacific oligotrophic gyres.
The role of transposable elements for gene expression in Capsella hybrids and allopolyploids

The formation of an allopolyploid species involves the merger of two genomes with separate evolutionary histories. In allopolyploids, genes derived from one progenitor species are often expressed at higher levels than those from the other progenitor. It has been suggested that this could be due to differences in transposable element (TE) content among progenitors, as silencing of TEs can affect expression of nearby genes. Here, we examine the role of TEs for expression biases in the widespread allotetraploid Capsella bursa-pastoris and in diploid F1 hybrids generated by crossing Capsella orientalis and Capsella rubella, two close relatives of the progenitors of C. bursa-pastoris. As C. rubella harbors more TEs than C. orientalis, we expect C. orientalis alleles to be expressed at higher levels if TE content is key for expression biases. To test this hypothesis, we quantified expression biases at approximately 5800 genes in flower buds and leaves, while correcting for read mapping biases using genomic data. While three of four C. bursa-pastoris accessions exhibited a shift toward higher relative expression of C. orientalis alleles, the fourth C. bursa-pastoris accession had the opposite direction of expression bias, as did diploid F1 hybrids. Associations between TE polymorphism and expression bias were weak, and the effect of TEs on expression bias was small. These results suggest that differences in TE content alone cannot fully explain expression biases in these species. Future studies should investigate the role of differences in TE silencing efficacy, as well as a broader set of other factors. Our results are important for a more general understanding of the role of TEs for cis-regulatory evolution in plants.
The Presence of Plant-Associated Bacteria Alters Responses to N-acyl Homoserine Lactone Quorum Sensing Signals that Modulate Nodulation in Medicago Truncatula

Bacteria use quorum sensing signaling for cell-to-cell communication, which is also important for their interactions with plant hosts. Quorum sensing via N-acyl-homoserine lactones (AHLs) is important for successful symbioses between legumes and nitrogen-fixing rhizobia. Previous studies have shown that plant hosts can recognize and respond to AHLs. Here, we tested whether the response of the model legume Medicago truncatula to AHLs from its symbiont and other bacteria could be modulated by the abundance and composition of plant-associated microbial communities. Temporary antibiotic treatment of the seeds removed the majority of bacterial taxa associated with M. truncatula roots and significantly altered the effect of AHLs on nodule numbers, but lateral root density, biomass, and root length responses were much less affected. The AHL 3-oxo-C14-HSL (homoserine lactone) specifically increased nodule numbers but only after the treatment of seeds with antibiotics. This increase was associated with increased expression of the early nodulation genes RIP1 and ENOD11 at 24 h after infection. A 454 pyrosequencing analysis of the plant-associated bacteria showed that antibiotic treatment had the biggest effect on bacterial community composition. However, we also found distinct effects of 3-oxo-C14-HSL on the abundance of specific bacterial taxa. Our results revealed a complex interaction between plants and their associated microbiome that could modify plant responses to AHLs.
Analysis of Magneto-Mechanical Response for Magnetization-Graded Ferromagnetic Material in Magnetoelectric Laminate

This paper analyzes the dynamic magneto-mechanical response in magnetization-graded ferromagnetic materials (MGFM) comprised of high-permeability Finemet and traditional magnetostrictive materials. The theoretical modeling of the piezomagnetic coefficient that depends on the bias magnetic field of MGFM is proposed by using the nonlinear constitutive model of a piezomagnetic material, the magnetoelectric equivalent circuit method, and the simulation software Ansoft. The theoretical variation of piezomagnetic coefficients of MGFM on the bias magnetic field is in good agreement with the experiment. Using the piezomagnetic coefficient in the magnetoelectric voltage model, the theoretical longitudinal resonant magnetoelectric voltage coefficients have also been calculated, which are consistent with the experimental values. This theoretical analysis is beneficial to comprehensively understand the self-biased piezomagnetic response of MGFM, and to design magnetoelectric devices with MGFM.
Isoleucine 44 Hydrophobic Patch Controls Toxicity of Unanchored, Linear Ubiquitin Chains through NF-κB Signaling

Ubiquitination is a post-translational modification that regulates cellular processes by altering the interactions of proteins to which ubiquitin, a small protein adduct, is conjugated. Ubiquitination yields various products, including mono- and poly-ubiquitinated substrates, as well as unanchored poly-ubiquitin chains whose accumulation is considered toxic. We previously showed that transgenic, unanchored poly-ubiquitin is not problematic in Drosophila melanogaster. In the fruit fly, free chains exist in various lengths and topologies and are degraded by the proteasome; they are also conjugated onto other proteins as one unit, eliminating them from the free ubiquitin chain pool. Here, to further explore the notion of unanchored chain toxicity, we examined when free poly-ubiquitin might become problematic. We found that unanchored chains can be highly toxic if they resemble linear poly-ubiquitin that cannot be modified into other topologies. These species upregulate NF-κB signaling, and modulation of the levels of NF-κB components reduces toxicity. In additional studies, we show that toxicity from untethered, linear chains is regulated by isoleucine 44, which anchors a key interaction site for ubiquitin. We conclude that free ubiquitin chains can be toxic, but only in uncommon circumstances, such as when the ability of cells to modify and regulate them is markedly restricted.
Patient Characteristics and Outcomes of Nonmetastatic Breast Cancer in Haiti: Results from a Retrospective Cohort

Abstract Background There are few studies on breast cancer outcomes in the Caribbean region. This study identified a retrospective cohort of female patients with nonmetastatic breast cancer in Haiti and conducted survival analyses to identify prognostic factors that may affect patient outcomes. Methods The cohort included 341 patients presenting between June 2012 and December 2016. The primary endpoint was event‐free survival (EFS), defined as time to disease progression, recurrence, or death. Descriptive summaries of patient characteristics and treatments were reported. Survival curves were plotted using Kaplan‐Meier estimation. Multivariate survival analyses were performed using Cox proportional hazards regression. Results Median age at diagnosis was 49 years, with 64.2% being premenopausal. Most patients (55.1%) were staged as locally advanced. One hundred and sixty patients received neoadjuvant therapy: 33.3% of patients with early stage disease and 61.2% of those with locally advanced stage disease. Curative‐intent surgery was performed in 278 (81.5%) patients, and 225 patients received adjuvant therapy. Adjuvant endocrine therapy was used in 82.0% of patients with estrogen receptor–positive disease. During the follow‐up period, 28 patients died, 77 had disease recurrence, and 10 had progressive disease. EFS rates at 2 years and 3 years were 80.9% and 63.4%, respectively. After controlling for multiple confounders, the locally advanced stage group had a statistically significant adjusted hazard ratio for EFS of 3.27 compared with early stage. Conclusion Patients with nonmetastatic breast cancer in Haiti have more advanced disease, poorer prognostic factors, and worse outcomes compared with patients in high‐income countries. Despite several limitations, curative treatment is possible in Haiti. Implications for Practice Patients with breast cancer in Haiti have poor outcomes. Prior studies show that most Haitian patients are diagnosed at later stages. However, there are no rigorous studies describing how late‐stage diagnosis and other prognostic factors affect outcomes in this population. This study presents a detailed analysis of survival outcomes and assessment of prognostic factors in patients with nonmetastatic breast cancer treated in Haiti. In addition to late‐stage diagnosis, other unfavorable prognostic factors identified were young age and estrogen receptor‐negative disease. The study also highlights that the availability of basic breast cancer treatment in Haiti can lead to promising early patient outcomes.
A Review of Genomic Models for the Analysis of Livestock Crossbred Data

Livestock breeding has shifted during the past decade toward genomic selection. For the estimation of breeding values in purebred breeding schemes, genomic best linear unbiased prediction has become the method of choice. Systematic crossbreeding with the aim to utilize heterosis and breed complementary effects is widely used in livestock breeding, especially in pig and poultry breeding. The goal is to improve the performance of the crossbred animals. Due to genotype-by-environment interactions, imperfect linkage disequilibrium, and the existence of dominance and imprinting, purebred and crossbred performances are not perfectly correlated. Hence, more complex genomic models are required for crossbred populations. This study reviews and compares such models. Compared to purebred genomic models, the reviewed models were of much higher complexity due to the inclusion of dominance effects, breed-specific effects, imprinting effects, and the joint evaluation of purebred and crossbred performance data. With the model assessment work conducted until now, it is not possible to come to a clear recommendation as to which existing method is most suitable for a specific breeding program and a specific genetic trait architecture. Since it is expected that a superior method includes all the different genetic effects in a single model, a dominance model with imprinting and breed-specific SNP effects is proposed. Further progress could be made by assuming realistic covariance structures between the genetic effects of the different breeding lines, and by using larger marker panels and mixture distributions for the SNP effects.
Scientific Reasoning: Theory Evidence Coordination in Physics-based and Non-physics-based Tasks

Scientific reasoning is crucial to any scientific discipline. One sub-skill particularly relevant to the scientific enterprise is theory evidence coordination. This study, underpinned by Kuhn's framework for scientific reasoning, investigates how university students coordinate their self-generated theory and evidence in a physics topic (energy) and in non-content specific (non-physics-based) situations. Twenty-seven students completed five written reasoning tasks, three of which deal with energy concepts (physics-based) and two tasks concern with non-physics-based situations. The analysis focused on: (a) the completeness and correctness of the theory; (b) the source of the evidence; (c) theory evidence coordination or non-coordination; and (d) if coordination occurs, whether the evidence supports or refutes the theory, and the quality of students’ explanations. The outcomes revealed that the students tended to coordinate theory and evidence for non-physics tasks as opposed to physics problems. When theory evidence coordination occurred, regardless of the type of scenarios, the evidence primarily supported the theory in the form of a poor explanation. The importance of content knowledge for scientific reasoning is discussed. The implications for applying scientific reasoning as an assessment tool in science are also highlighted.
Attempting to synthesize lasso peptides using high pressure

Lasso peptides are unique in that the tail of the lasso peptide threads through its macrolactam ring. The unusual structure and biological activity of lasso peptides have generated increased interest from the scientific community in recent years. Because of this, many new types of lasso peptides have been discovered. These peptides can be synthesized by microorganisms efficiently, and yet, their chemical assembly is challenging. Herein, we investigated the possibility of high pressure inducing the cyclization of linear precursors of lasso peptides. Unlike other molecules like rotaxanes which mechanically interlock at high pressure, the threaded lasso peptides did not form, even at pressures the high pressure up to 14 000 kbar.
Drug Repositioning for Noonan and LEOPARD Syndromes by Integrating Transcriptomics With a Structure-Based Approach

Noonan and LEOPARD syndromes (NS and LS) belong to a group of related disorders called RASopathies characterized by abnormalities of multiple organs and systems including hypertrophic cardiomyopathy and dysmorphic facial features. There are no approved drugs for these two rare diseases, but it is known that a missense mutation in PTPN11 genes is associated with approximately 50% and 70% of NS and LS cases, respectively. In this study, we implemented a hybrid computational drug repositioning framework by integrating transcriptomic and structure-based approaches to explore potential treatment options for NS and LS. Specifically, disease signatures were derived from the transcriptomic profiles of human induced pluripotent stem cells (iPSCs) from NS and LS patients and reverse correlated to drug transcriptomic signatures from CMap and L1000 projects on the basis that if disease and drug transcriptomic signatures are reversely correlated, the drug has the potential to treat that disease. The compounds that were ranked top based on their transcriptomic profiles were docked to mutated and wild-type 3D structures of PTPN11 by an adjusted Induced Fit Docking (IFD) protocol. In addition, we prioritized repositioned candidates for NS and LS by a consensus ranking strategy. Network analysis and phenotypic anchoring of the transcriptomic data could discriminate the two diseases at the molecular level. Furthermore, the adjusted IFD protocol was able to recapitulate the binding specificity of potential drug candidates to mutated 3D structures, revealing the relevant amino acids. Importantly, a list of potential drug candidates for repositioning was identified including 61 for NS and 43 for LS and was further verified from literature reports and on-going clinical trials. Altogether, this hybrid computational drug repositioning approach has highlighted a number of drug candidates for NS and LS and could be applied to identifying drug candidates for other diseases as well.
Changes in fish assemblage in the Hungarian section of River Szamos/Somes after a massive cyanide and heavy metal pollution

The main objective of this study was to investigate the regeneration potential of the fish fauna of River Szamos/Somes after a massive cyanide and heavy metal pollution in 2000. The investigation of the fish fauna was started in 2004 in the Hungarian part of the river. Fish samples were taken with electrofishing equipment three times a year, from river sections of the same size. From the spring of 2004 to the autumn of 2009 we carried out 18 samplings; caught and identified 18,751 individuals of 37 fish species. Beside fish sampling, the main water quality parameters of the Hungarian section of the river were measured. The number of fish species increased from the initial 23 to 29; they re-appeared year by year, including some common and typically sensitive species. Our results highlight that the river's fish community has recovered from the shocking effect of the pollution, owing to the significant improvements in water quality. The concentration of more heavy metals reduced significantly, but significant increase were found in concentration of copper (Cu), so it seems copper is the less limiting element for fish of R. Szamos/Somes. From all these results, it can be concluded that the structure and assemblage of the investigated area's fish community had slowly changed.
Morphological Observations by Electron Microscopy of the Virus (Tucker Strain) of a Chronic Respiratory Disease in Chickens

Abstract ELECTRON microscope studies of the virus producing a chronic respiratory disease in turkeys prevously reported by the authors describe the virus as having an average mean diameter of 60 millimicrons with oblong heads and filamentous projections which seem to be flatter than the projections observed in bronchitis virus (Reagan et al., 1948). The virus of the chronic respiratory disease in chickens used in these studies was isolated by one of the authors (J. P. Delaplane). The virus was subjected to 26 serial passages in 10-day embryonated eggs before use in electron microscope studies. Approximately 25 percent of the embryos of the 26th passage were dead or appeared sluggish within 96 to 168 hours. The allantoic fluid from these eggs was harvested and filtered through a Type ST size L3 Seitz filter. The filtered virus suspension was then subjected to centrifugation in a Spinco Ultracentrifuge at 44,400 r.p.m. for 2 hours, .