rDock: A Fast, Versatile and Open Source Program for Docking Ligands to Proteins and Nucleic Acids

Identification of chemical compounds with specific biological activities is an important step in both chemical biology and drug discovery. When the structure of the intended target is available, one approach is to use molecular docking programs to assess the chemical complementarity of small molecules with the target; such calculations provide a qualitative measure of affinity that can be used in virtual screening (VS) to rank order a list of compounds according to their potential to be active. rDock is a molecular docking program developed at Vernalis for high-throughput VS (HTVS) applications. Evolved from RiboDock, the program can be used against proteins and nucleic acids, is designed to be computationally very efficient and allows the user to incorporate additional constraints and information as a bias to guide docking. This article provides an overview of the program structure and features and compares rDock to two reference programs, AutoDock Vina (open source) and Schrodinger's Glide (commercial). In terms of computational speed for VS, rDock is faster than Vina and comparable to Glide. For binding mode prediction, rDock and Vina are superior to Glide. The VS performance of rDock is significantly better than Vina, but inferior to Glide for most systems unless pharmacophore constraints are used; in that case rDock and Glide are of equal performance. The program is released under the Lesser General Public License and is freely available for download, together with the manuals, example files and the complete test sets, at http://rdock.sourceforge.net

Changes in resting-state functionally connected parieto-frontal networks after videogame practice

Neuroimaging studies provide evidence for organized intrinsic activity under task-free conditions. This activity serves functionally relevant brain systems supporting cognition. Here, we analyze changes in resting-state functional connectivity after videogame practice applying a test–retest design. Twenty young females were selected from a group of 100 participants tested on four standardized cognitive ability tests. The practice and control groups were carefully matched on their ability scores. The practice group played during two sessions per week across 4 weeks (16 h total) under strict supervision in the laboratory, showing systematic performance improvements in the game. A group independent component analysis (GICA) applying multisession temporal concatenation on test–retest resting-state fMRI, jointly with a dual-regression approach, was computed. Supporting the main hypothesis, the key finding reveals an increased correlated activity during rest in certain predefined resting state networks (albeit using uncorrected statistics) attributable to practice with the cognitively demanding tasks of the videogame. Observed changes were mainly concentrated on parietofrontal networks involved in heterogeneous cognitive functions

Extragalactic magnetism with SOFIA (SALSA Legacy Program). VI. The magnetic fields in the multi-phase interstellar medium of the Antennae galaxies

Mergers are thought to be a fundamental channel for galaxy growth, perturbing the gas dynamics and the magnetic fields (B-fields) in the interstellar medium (ISM). However, the mechanisms that amplify and dissipate B-fields during a merger remain unclear. We characterize the morphology of the ordered B-fields in the multi-phase ISM of the closest merger of two spiral galaxies, the Antennae galaxies. We compare the inferred B-fields using $154~\mu$m thermal dust and $11$ cm radio synchrotron emission polarimetric observations. We find that the $154~\mu$m B-fields are more ordered across the Antennae galaxies than the $11$ cm B-fields. The turbulent-to-ordered $154~\mu$m B-field increases at the galaxy cores and star-forming regions. The relic spiral arm has an ordered spiral $154~\mu$m B-field, while the $11$ cm B-field is radial. The $154~\mu$m B-field may be dominated by turbulent dynamos with high $^{12}$CO(1-0) velocity dispersion driven by star-forming regions, while the $11$ cm B-field is cospatial with high HI velocity dispersion driven by galaxy interaction. This result shows the dissociation between the warm gas mainly disturbed by the merger, and the dense gas still following the dynamics of the relic spiral arm. We find a $\sim8.9$ kpc scale ordered B-field connecting the two galaxies. The base of the tidal tail is cospatial with the HI and $^{12}$CO(1-0) emission and has compressed and/or sheared $154~\mu$m and $11$ cm B-fields driven by the merger. We suggest that amplify B-fields, with respect to the rest of the system and other spiral galaxies, may be supporting the gas flow between both galaxies and the tidal tail.Comment: 11 pages, 5 figures, Accepted for publication in ApJ Letter

Structural changes after videogame practice related to a brain network associated with intelligence

Here gray and white matter changes after four weeks of videogame practice were analyzed using optimized voxel-based morphometry (VBM), cortical surface and cortical thickness indices, and white matter integrity computed from several projection, commissural, and association tracts relevant to cognition. Beginning with a sample of one hundred young females, twenty right handed participants were recruited for the study and assigned to a practice or a control group carefully matched by their general cognitive ability scores. After the first scan, the practice group played ‘Professor Layton and The Pandora's Box’ 4 h per week during four weeks. A second scan was obtained at the end of practice and intelligence was measured again. Image analyses revealed gray and white matter changes in the practice group. Gray matter changes theoretically relevant for intelligence were observed for the practice group mainly in frontal clusters (Brodmann areas 9 and 10) and also in smaller parietal and temporal regions. White matter findings were focused in the hippocampal cingulum and the inferior longitudinal fasciculus. These gray and white matter changes presumably induced by practice did not interact with intelligence tests' scores

Extragalactic magnetism with SOFIA (SALSA Legacy Program) -- V: First results on the magnetic field orientation of galaxies

We present the analysis of the magnetic field ($B$-field) structure of galaxies measured with far-infrared (FIR) and radio (3 and 6 cm) polarimetric observations. We use the first data release of the Survey on extragALactic magnetiSm with SOFIA (SALSA) of 14 nearby ($<20$ Mpc) galaxies with resolved (5 arcsec-18 arcsec; $90$ pc--$1$ kpc) imaging polarimetric observations using HAWC+/SOFIA from $53$ to $214$ \um. We compute the magnetic pitch angle ($\Psi_{B}$) profiles as a function of the galactrocentric radius. We introduce a new magnetic alignment parameter ($\zeta$) to estimate the disordered-to-ordered $B$-field ratio in spiral $B$-fields. We find FIR and radio wavelengths to not generally trace the same $B$-field morphology in galaxies. The $\Psi_{B}$ profiles tend to be more ordered with galactocentric radius in radio ($\zeta_{\rm{6cm}} = 0.93\pm0.03$) than in FIR ($\zeta_{\rm{154\mu m}} = 0.84\pm0.14$). For spiral galaxies, FIR $B$-fields are $2-75$\% more turbulent than the radio $B$-fields. For starburst galaxies, we find that FIR polarization is a better tracer of the $B$-fields along the galactic outflows than radio polarization. Our results suggest that the $B$-fields associated with dense, dusty, turbulent star-forming regions, those traced at FIR, are less ordered than warmer, less-dense regions, those traced at radio, of the interstellar medium. The FIR $B$-fields seem to be more sensitive to the activity of the star-forming regions and the morphology of the molecular clouds within a vertical height of few hundred pc in the disk of spiral galaxies than the radio $B$-fields.Comment: 26 pages, 13 figure

Mathematical modeling of SARS-CoV-2 variant substitutions in European countries: transmission dynamics and epidemiological insights

Background: Countries across Europe have faced similar evolutions of SARS-CoV-2 variants of concern, including the Alpha, Delta, and Omicron variants. Materials and methods: We used data from GISAID and applied a robust, automated mathematical substitution model to study the dynamics of COVID-19 variants in Europe over a period of more than 2 years, from late 2020 to early 2023. This model identifies variant substitution patterns and distinguishes between residual and dominant behavior. We used weekly sequencing data from 19 European countries to estimate the increase in transmissibility (Δβ) between consecutive SARS-CoV-2 variants. In addition, we focused on large countries with separate regional outbreaks and complex scenarios of multiple competing variants. Results: Our model accurately reproduced the observed substitution patterns between the Alpha, Delta, and Omicron major variants. We estimated the daily variant prevalence and calculated Δβ between variants, revealing that: (i) Δβ increased progressively from the Alpha to the Omicron variant; (ii) Δβ showed a high degree of variability within Omicron variants; (iii) a higher Δβ was associated with a later emergence of the variant within a country; (iv) a higher degree of immunization of the population against previous variants was associated with a higher Δβ for the Delta variant; (v) larger countries exhibited smaller Δβ, suggesting regionally diverse outbreaks within the same country; and finally (vi) the model reliably captures the dynamics of competing variants, even in complex scenarios. Conclusion: The use of mathematical models allows for precise and reliable estimation of daily cases of each variant. By quantifying Δβ, we have tracked the spread of the different variants across Europe, highlighting a robust increase in transmissibility trend from Alpha to Omicron. Additionally, we have shown that the geographical characteristics of a country, as well as the timing of new variant entrances, can explain some of the observed differences in variant substitution dynamics across countries

Production of recombinant enzymes of wide use for research

For biotechnological purposes, protein expression refers to the directed synthesis of large amounts of desired proteins. The aim of the present work was to produce reverse transcriptase Moloney murine Leukaemia Virus retro-transcriptase and Taq DNA polymerase, as bioactive products. In the present paper, we report the preparation of recombinant enzymes, expressed in E. coli strains. The enzymes produced exhibited quite good activity, compared with commercial enzymes, allowing us to replace the last ones for several lab applications. We are reporting changes and modifications to standard protocols described. The standard protocols were modified, i.e. for the purification step of Taq, a temperature dependent procedure was designed. The enzymes produced were used in different applications, such as PCR, RT-PCR, PCR Multiplex and RAPDs molecular markers

Production of recombinant enzymes of wide use for research

For biotechnological purposes, protein expression refers to the directed synthesis of large amounts of desired proteins. The aim of the present work was to produce reverse transcriptase Moloney murine Leukaemia Virus retro-transcriptase and Taq DNA polymerase, as bioactive products. In the present paper, we report the preparation of recombinant enzymes, expressed in E. coli strains. The enzymes produced exhibited quite good activity, compared with commercial enzymes, allowing us to replace the last ones for several lab applications. We are reporting changes and modifications to standard protocols described. The standard protocols were modified, i.e. for the purification step of Taq, a temperature dependent procedure was designed. The enzymes produced were used in different applications, such as PCR, RT-PCR, PCR Multiplex and RAPDs molecular markers

Transmissibility, hospitalization, and intensive care admissions due to omicron compared to delta variants of SARS-CoV-2 in Catalonia: A cohort study and ecological analysis

The transmissibility of omicron using variant screening data from primary care practices (PCP) and hospital admissions. In addition, we used this data from PCP to establish the two periods when delta and omicron were, respectively, dominant (above 95% of cases). After that, we performed a population-based cohort analysis to calculate the rates of hospital and intensive care unit (ICU) admissions for both periods and to estimate reduction in severity. Rate ratios (RR) and 95% confidence intervals (95% CI) were calculated and stratified by age and vaccination status. In a second analysis, the differential substitution model in primary care vs. hospitals allowed us to obtain a population-level average change in severity.We have included 48,874 cases during the delta period and 560,658 during the omicron period. During the delta period, on average, 3.8% of the detected cases required hospitalization for COVID-19. This percentage dropped to 0.9% with omicron [RR of 0.46 (95% CI: 0.43 to 0.49)]. For ICU admissions, it dropped from 0.8 to 0.1% [RR 0.25 (95% CI: 0.21 to 0.28)]. The proportion of cases hospitalized or admitted to ICU was lower in the vaccinated groups, independently of the variant. Omicron was associated with a reduction in risk of admission to hospital and ICU in all age and vaccination status strata. The differential substitution models showed an average RR between 0.19 and 0.50.Both independent methods consistently show an important decrease in severity for omicron relative to delta. The systematic reduction happens regardless of age. The severity is also reduced for non-vaccinated and vaccinated groups, but it remains always higher in the non-vaccinated population. This suggests an overall reduction in severity, which could be intrinsic to the omicron variant. The fact is that the RR in ICU admission is systematically smaller than in hospitalization points in the same direction.MC received funding from la Caixa Foundation ID 100010434, under agreement LCF/PR/GN17/50300003. MC, CP, and SA received funding from Ministerio de Ciencia, Innovación y Universidades and FEDER, with the project PGC2018-095456- B-I00.Objectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version