Mining microsatellite markers from public expressed sequence tags databases for the study of threatened plants

Background: Simple Sequence Repeats (SSRs) are widely used in population genetic studies but their classical development is costly and time-consuming. The ever-increasing available DNA datasets generated by high-throughput techniques offer an inexpensive alternative for SSRs discovery. Expressed Sequence Tags (ESTs) have been widely used as SSR source for plants of economic relevance but their application to non-model species is still modest. Methods: Here, we explored the use of publicly available ESTs (GenBank at the National Center for Biotechnology Information-NCBI) for SSRs development in non-model plants, focusing on genera listed by the International Union for the Conservation of Nature (IUCN). We also search two model genera with fully annotated genomes for EST-SSRs, Arabidopsis and Oryza, and used them as controls for genome distribution analyses. Overall, we downloaded 16 031 555 sequences for 258 plant genera which were mined for SSRsand their primers with the help of QDD1. Genome distribution analyses in Oryza and Arabidopsis were done by blasting the sequences with SSR against the Oryza sativa and Arabidopsis thaliana reference genomes implemented in the Basal Local Alignment Tool (BLAST) of the NCBI website. Finally, we performed an empirical test to determine the performance of our EST-SSRs in a few individuals from four species of two eudicot genera, Trifolium and Centaurea. Results: We explored a total of 14 498 726 EST sequences from the dbEST database (NCBI) in 257 plant genera from the IUCN Red List. We identify a very large number (17 102) of ready-to-test EST-SSRs in most plant genera (193) at no cost. Overall, dinucleotide and trinucleotide repeats were the prevalent types but the abundance of the various types of repeat differed between taxonomic groups. Control genomes revealed that trinucleotide repeats were mostly located in coding regions while dinucleotide repeats were largely associated with untranslated regions. Our results from the empirical test revealed considerable amplification success and transferability between congenerics. Conclusions: The present work represents the first large-scale study developing SSRs by utilizing publicly accessible EST databases in threatened plants. Here we provide a very large number of ready-to-test EST-SSR (17 102) for 193 genera. The cross-species transferability suggests that the number of possible target species would be large. Since trinucleotide repeats are abundant and mainly linked to exons they might be useful in evolutionary and conservation studies. Altogether, our study highly supports the use of EST databases as an extremely affordable and fast alternative for SSR developing in threatened plants

Tailoring the frictional properties of granular media

A method of modifying the roughness of soda-lime glass spheres is presented, with the purpose of tuning inter-particle friction. The effect of chemical etching on the surface topography and the bulk frictional properties of grains is systematically investigated. The surface roughness of the grains is measured using white light interferometry and characterised by the lateral and vertical roughness length scales. The underwater angle of repose is measured to characterise the bulk frictional behaviour. We observe that the co-efficient of friction depends on the vertical roughness length scale. We also demonstrate a bulk surface roughness measurement using a carbonated soft drink.Comment: 10 pages, 17 figures, submitted to Phys. Rev.

Potential Inhibitors for Novel Coronavirus Protease Identified by Virtual Screening of 606 Million Compounds

The rapid outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China followed by its spread around the world poses a serious global concern for public health. To this date, no specific drugs or vaccines are available to treat SARS-CoV-2 despite its close relation to the SARS-CoV virus that caused a similar epidemic in 2003. Thus, there remains an urgent need for the identification and development of specific antiviral therapeutics against SARS-CoV-2. To conquer viral infections, the inhibition of proteases essential for proteolytic processing of viral polyproteins is a conventional therapeutic strategy. In order to find novel inhibitors, we computationally screened a compound library of over 606 million compounds for binding at the recently solved crystal structure of the main protease (M; pro; ) of SARS-CoV-2. A screening of such a vast chemical space for SARS-CoV-2 M; pro; inhibitors has not been reported before. After shape screening, two docking protocols were applied followed by the determination of molecular descriptors relevant for pharmacokinetics to narrow down the number of initial hits. Next, molecular dynamics simulations were conducted to validate the stability of docked binding modes and comprehensively quantify ligand binding energies. After evaluation of potential off-target binding, we report a list of 12 purchasable compounds, with binding affinity to the target protease that is predicted to be more favorable than that of the cocrystallized peptidomimetic compound. In order to quickly advise ongoing therapeutic intervention for patients, we evaluated approved antiviral drugs and other protease inhibitors to provide a list of nine compounds for drug repurposing. Furthermore, we identified the natural compounds (-)-taxifolin and rhamnetin as potential inhibitors of M; pro; . Rhamnetin is already commercially available in pharmacies

Gender influences on brain responses to errors and post-error adjustments

Sexual dimorphisms have been observed in many species, including humans, and extend to the prevalence and presentation of important mental disorders associated with performance monitoring malfunctions. However, precisely which underlying differences between genders contribute to the alterations observed in psychiatric diseases is unknown. Here, we compare behavioural and neural correlates of cognitive control functions in 438 female and 436 male participants performing a flanker task while EEG was recorded. We found that males showed stronger performance-monitoring-related EEG amplitude modulations which were employed to predict subjects’ genders with ~72% accuracy. Females showed more post-error slowing, but both samples did not differ in regard to response-conflict processing and coupling between the error-related negativity (ERN) and consecutive behavioural slowing. Furthermore, we found that the ERN predicted consecutive behavioural slowing within subjects, whereas its overall amplitude did not correlate with post-error slowing across participants. These findings elucidate specific gender differences in essential neurocognitive functions with implications for clinical studies. They highlight that within- and between-subject associations for brain potentials cannot be interpreted in the same way. Specifically, despite higher general amplitudes in males, it appears that the dynamics of coupling between ERN and post-error slowing between men and women is comparable

Two- and three-point functions in two-dimensional Landau-gauge Yang-Mills theory: Continuum results

We investigate the Dyson-Schwinger equations for the gluon and ghost propagators and the ghost-gluon vertex of Landau-gauge gluodynamics in two dimensions. While this simplifies some aspects of the calculations as compared to three and four dimensions, new complications arise due to a mixing of different momentum regimes. As a result, the solutions for the propagators are more sensitive to changes in the three-point functions and the ansaetze used for them at the leading order in a vertex a expansion. Here, we therefore go beyond this common truncation by including the ghost-gluon vertex self-consistently for the first time, while using a model for the three-gluon vertex which reproduces the known infrared asymptotics and the zeros at intermediate momenta as observed on the lattice. A separate computation of the three-gluon vertex from the results is used to confirm the stability of this behavior a posteriori. We also present further arguments for the absence of the decoupling solution in two dimensions. Finally, we show how in general the infrared exponent kappa of the scaling solutions in two, three and four dimensions can be changed by allowing an angle dependence and thus an essential singularity of the ghost-gluon vertex in the infrared.Comment: 24 pages; added references, improved choices of parameters for vertex models; identical to version published in JHE

Immune responses upon Campylobacter jejuni infection of secondary abiotic mice lacking nucleotide-oligomerization-domain-2

Background Campylobacter jejuni infections are of rising importance worldwide. Given that innate immune receptors including nucleotide-oligomerization- domain-2 (Nod2) are essentially involved in combating enteropathogenic infections, we here surveyed the impact of Nod2 in murine campylobacteriosis. Methods and results In order to overcome physiological colonization resistance preventing from C. jejuni infection, we generated secondary abiotic Nod2−/− and wildtype (WT) mice by broad-spectrum antibiotic treatment. Mice were then perorally infected with C. jejuni strain 81-176 on 2 consecutive days and could be stably colonized by the pathogen at high loads. Notably, Nod2 deficiency did not affect gastrointestinal colonization properties of C. jejuni. Despite high intestinal pathogenic burdens mice were virtually uncompromised and exhibited fecal blood in single cases only. At day 7 postinfection (p.i.) similar increases in numbers of colonic epithelial apoptotic cells could be observed in mice of either genotype, whereas C. jejuni infected Nod2−/− mice displayed more distinct regenerative properties in the colon than WT controls. C. jejuni infection was accompanied by increases in distinct immune cell populations such as T lymphocytes and regulatory T cells in mice of either genotype. Increases in T lymphocytes, however, were less pronounced in large intestines of Nod2−/− mice at day 7 p.i. when compared to WT mice, whereas colonic numbers of B lymphocytes were elevated in WT controls only upon C. jejuni infection. At day 7 p.i., colonic pro-inflammatory mediators including nitric oxide, TNF, IFN-γ and IL-22 increased more distinctly in Nod2−/− as compared to WT mice, whereas C. jejuni induced IL-23p19 and IL-18 levels were lower in the large intestines of the former. Converse to the colon, however, ileal concentrations of nitric oxide, TNF, IFN-γ, IL-6 and IL-10 were lower in Nod2−/− as compared to WT mice at day 7 p.i. Even though MUC2 was down-regulated in C. jejuni infected Nod2−/− mice, this did not result in increased pathogenic translocation from the intestinal tract to extra-intestinal compartments. Conclusion In secondary abiotic mice, Nod2 signaling is involved in the orchestrated host immune responses upon C. jejuni infection, but does not control pathogen loads in the gastrointestinal tract

Entanglement correlations, Bell inequalities, and the concurrence

Probabilities of measurement outcomes of two-particle entangled states give a physically transparent interpretation of the concurrence and of the I-concurrence as entanglement measures. The (I)-concurrence can thus be measured experimentally. The tight connection between these measures and Bell inequalities is highlighted.Comment: Updated version of quant-ph/0110139, with extension to mixed states. To appear in Phys. Lett.

Studies on mechanisms of augmentation of liver regeneration by cyclosporine and FK 506

Evidence could not be found of immune modulation of liver regeneration. The powerful immunosuppressive drug FK 506, which augments the response after partial hepatectomy in normal rats, had the same effect in T cell—deficient nude rats. The cytotoxicity of natural killer cells in treated nude rats was not significantly changed by FK 506 therapy. However, the serum of FK 506—treated nude rats increased hepatocyte proliferation when added to third‐party hepatocyte cultures, suggesting that FK 506 had induced a serum growth factor in the nude rats or had suppressed an inhibitory factor. A hypothesis was advanced that FK 506 (and cyclosporine) affects hepatic growth by nonimmunological pathways. (HEPATOLOGY 1991;14:140–143.) Copyright © 1991 American Association for the Study of Liver Disease