Miracle-dz/UniFAR-FTUs huggingface dataset:
Reactive oxygen species are major contributors to SOS-mediated mutagenesis induced by fluoroquinolones

Certain antibiotics, particularly fluoroquinolones, induce the mutagenic SOS response and increase the levels of intracellular reactive oxygen species (ROS), which have been correlated with antibiotic lethality. Both SOS and ROS increase mutagenesis in treated bacteria, likely resulting in the appearance of resistant mutants during antibiotic treatments. However, the relative contribution of ROS and SOS on this antibiotic-mediated mutagenesis is currently unknown. We used the antioxidant molecule N-acetylcysteine (NAC) to study the contribution of ROS on the SOS response and mutagenesis mediated by the fluoroquinolone antibiotic ciprofloxacin (CIP). We show that NAC is able to reduce intracellular ROS levels, mitigating as well the SOS response caused by treatment with subinhibitory concentrations of CIP. This effect leads to the reduction of antibiotic-induced mutagenesis to levels comparable to a translesion DNA-polymerases (TLS) deficient strain, suggesting that ROS play a major role in SOS-induced mutagenesis. Collectively, our results shed light on the mechanisms underlying antibiotic-induced mutagenesis and pave the way for the use of NAC as a safe adjuvant in antibiotic therapy to inhibit antibiotic-induced mutagenesis, hence augmenting our capacity to fight against threatening bacterial infections.
Susceptibilidad antimicrobiana de enterobacterias identificadas en infección urinaria adquirida en la comunidad, en gestantes en nueve hospitales de Colombia

Objective: To identify sensitivity profiles of the main anti-microbial agents used in the management of community-acquired urinary tract infection in pregnant women, and to make the molecular characterisation in order to confirm the existence of bacterial resistance in this population group.Materials and methods: Descriptive cross-sectional study that included pregnant women with community-acquired urinary tract infection requiring admission to hospital. They were part of a study conducted in the general population. The microbiological results of the urine cultures were analysed. Isolates of Escherichia coli, Klebsiella spp. And Proteus mirabilis were identified over a period of 12 months in 9 Colombian hospitals, and their sensitivity profiles were determined using microdilution broth and gradient diffusion tests, and the presence of extended spectrum beta-lactamases was characterised using microbiological and molecular methods. The sociodemographic and clinical characteristics of these patients are presented.Results: Overall, 74 isolates were collected (64 E. coli, 7 Klebsiella spp. and 3 P. mirabilis isolates) in 73 patients. Prior use of antibiotics was documented in 58% of the patients. Resistance to ampicillin/sulbactam, cefazolin and ceftriaxone was 15.6%, 17.2% and 4.7%, respectively. There was extended spectrum beta-lactamase expression in three of the isolates, 2 of E. coli and 1 of Klebsiella spp. (3.1% E. coli and 14.3% Klebsiella spp.) One E. coli isolate expressed enzymes of the AmpC type.Conclusion: The presence of resistant strains to antibiotics used as first-line empirical treatment and to third-generation cephalosporins was confirmed in enterobacteria responsible for community-acquired urinary tract infection in pregnant women, produced by type CTX M-15 and AmpC extended spectrum betalactamase enzymes.
Spatio-temporal reconstruction of emergent flash synchronization in firefly swarms via stereoscopic 360-degree cameras

During mating season, males of synchronous firefly species flash in unison within swarms of thousands of individuals. These strongly-correlated collective displays have inspired numerous mathematical models to explain how global synchronous patterns emerge from local interactions. Yet, experimental data to validate these models remains sparse. To address this gap, we develop a method for three-dimensional tracking of firefly flashes, using a stereoscopic setup of 360-degree cameras. We apply this method to record flashing displays of the North American synchronous species Photinus carolinus in its natural habitat as well as within controlled environments, and obtain the 3D reconstruction of flash occurrences in the swarm. Our results show that even a small number of interacting males synchronize their flashes; however, periodic flash bursts only occur in groups larger than 15 males. Moreover, flash occurrences are correlated over several meters, indicating long-range interactions. While this suggests emergent collective behaviour and cooperation, we identify distinct individual trajectories that hint at additional competitive mechanisms. These reveal possible behavioural differentiation with early flashers being more mobile and flashing longer than late followers. Our experimental technique is inexpensive and easily implemented. It is extensible to tracking light communication in various firefly species and flight trajectories in other insect swarms.
Global Landscape of Native Protein Complexes in Synechocystis sp. PCC 6803

Synechocystis sp. PCC 6803 is a model organism for studying photosynthesis, energy metabolism, and environmental stress. Though known as the first fully sequenced phototrophic organism, Synechocystis sp. PCC 6803 still has almost half of its proteome without functional annotations. In this study, we obtained 291 protein complexes, including 24,092 protein-protein interactions (PPIs) among 2,062 proteins by using co–fractionation and LC/MS/MS. The additional level of PPIs information not only revealed the roles of photosynthesis in metabolism, cell motility, DNA repair, cell division, and other physiological processes, but also showed how protein functions vary from bacteria to higher plants due to the changed interaction partner. It also allows us to uncover functions of hypothetical proteins, such as Sll0445, Sll0446, Sll0447 participating in photosynthesis and cell motility, and Sll1334 regulating the expression of fatty acid. Here we presented the most extensive protein interaction data in Synechocystis so far, which might provide critical insights into the fundamental molecular mechanism in Cyanobacterium.
A selective inference approach for FDR control using multi-omics covariates yields insights into disease risk

To correct for a large number of hypothesis tests, most researchers rely on simple multiple testing corrections. Yet, new methodologies of selective inference could potentially improve power while retaining statistical guarantees, especially those that enable exploration of test statistics using auxiliary information (covariates) to weight hypothesis tests for association. We explore one such method, adaptive p-value thresholding (Lei & Fithian 2018, AdaPT), in the framework of genome-wide association studies (GWAS) and gene expression/coexpression studies, with particular emphasis on schizophrenia (SCZ). Selected SCZ GWAS association p-values play the role of the primary data for AdaPT; SNPs are selected because they are gene expression quantitative trait loci (eQTLs). This natural pairing of SNPs and genes allow us to map the following covariate values to these pairs: GWAS statistics from genetically-correlated bipolar disorder, the effect size of SNP genotypes on gene expression, and gene-gene coexpression, captured by subnetwork (module) membership. In all 24 covariates per SNP/gene pair were included in the AdaPT analysis using flexible gradient boosted trees. We demonstrate a substantial increase in power to detect SCZ associations using gene expression information from the developing human prefontal cortex (Werling et al. 2019). We interpret these results in light of recent theories about the polygenic nature of SCZ. Importantly, our entire process for identifying enrichment and creating features with independent complementary data sources can be implemented in many different high-throughput settings to ultimately improve power.
Novel linguistic evaluation of prefrontal synthesis (LEPS) test measures prefrontal synthesis acquisition in neurotypical children and predicts high-functioning versus low-functioning class assignment in individuals with autism

Abstract In order to grasp the difference between “the cat on the mat” and “the mat on the cat,” understanding the words and the grammar is not enough. Rather it is essential to visualize the cat and the mat together to appreciate their relations. This type of imagination, which involves juxtaposition of mental objects is conducted by the prefrontal cortex and is therefore called Prefrontal Synthesis (PFS). PFS acquisition has a strong experience-dependent critical period putting children with language delay in danger of never acquiring PFS and, consequently, not mastering complex language comprehension. In typical children, the timeline of PFS acquisition correlates with vocabulary expansion. Conversely, atypically developing children may learn many words but never acquire PFS. In these individuals, intelligence tests based on vocabulary assessment may miss the profound deficit in PFS. Accordingly, we developed a test specific for PFS — Linguistic Evaluation of Prefrontal Synthesis or LEPS — and administered it to 50 neurotypical children, age 4.1 ± 1.3 years and to 23 individuals with impairments, age 16.4 ± 3.0 years. All neurotypical children older than 4 years received the LEPS score 7/10 or greater indicating good PFS ability. Among individuals with impairments only 39% received the LEPS score 7/10 or greater. LEPS was 90% correct in predicting high-functioning vs. low-functioning class assignment in individuals with impairments.
Contrasting Responses of Protistan Plant Parasites and Phagotrophs to Ecosystems, Land Management and Soil Properties

Functional traits are increasingly used in ecology to link the structure of microbial communities to ecosystem processes. We investigated two important protistan lineages, Cercozoa and Endomyxa (Rhizaria) in soil using Illumina sequencing and analysed their diversity and functional traits along with their responses to environmental factors in grassland and forest across Germany. From 600 soil samples, we obtained 2,101 Operational Taxonomy Units representing ~18 million Illumina reads (region V4, 18S rRNA gene). All major taxonomic and functional groups were present, dominated by small bacterivorous flagellates (Glissomonadida). Endomyxan plant parasites were absent from forest. In grassland, they were promoted by more intensive land use management. Grassland and forest strikingly differed in community composition. Relative abundances of bacterivores and eukaryvores were contrastingly influenced by environmental factors, indicating bottom-up regulation by food resources. These patterns provide new insights into the functional organization of soil biota and indications for a more sustainable land-use management. Highlights Protistan plant parasites of worldwide importance (Phytomyxea) are absent from forest Protistan plant parasites are enhanced by land use intensification in grassland Opposite responses of protistan trophic guilds to environmental conditions in forest Drastic differences in protistan community composition between grassland and forest
Conformational catalysis of cataract-associated aggregation in a human eye lens crystallin occurs via interface stealing

Human γD-crystallin (HγD) is an abundant and highly stable two-domain protein in the core region of the eye lens. Destabilizing mutations and post-translational modifications in this protein are linked to onset of aggregation that causes cataract disease (lens turbidity). Wild-type HγD greatly accelerates aggregation of the cataract-related W42Q variant, without itself aggregating. The mechanism of this “inverse prion” catalysis of aggregation remained unknown. Here we provide evidence that an early unfolding intermediate with an opened domain interface enables transient dimerization of the C-terminal domains of wild-type and mutant, or mutant and mutant, HγD molecules, which deprives the mutant’s N-terminal domain of intramolecular stabilization by the native domain interface and thus accelerates its misfolding to a distinct, aggregation-prone intermediate. A detailed kinetic model predicts universal power-law scaling relationships for lag time and rate of the resulting aggregation, which are in excellent agreement with the data. The mechanism reported here, which we term interface stealing, can be generalized to explain how common domain-domain interactions can have surprising consequences, such as conformational catalysis of unfolding, in multidomain proteins. Significance Most known proteins in nature consist of multiple domains. Interactions between domains may lead to unexpected folding and misfolding phenomena. This study of human γD-crystallin, a two-domain protein in the eye lens, revealed one such surprise: conformational catalysis of misfolding via intermolecular domain interface “stealing. ” An intermolecular interface between the more stable domains outcompetes the native intramolecular domain interface. Loss of the native interface in turn promotes misfolding and subsequent aggregation, especially in cataract-related γD-crystallin variants. This phenomenon is likely a contributing factor in the development of cataract disease, the leading worldwide cause of blindness. However, interface stealing likely occurs in many proteins composed of two or more interacting domains.
Cutting tree branches to pick OTUs: a novel method of provisional species delimitation

Delimitation of species is crucial in all studies of biodiversity, its geographic patterns and evolutionary dynamics as well as in the corresponding conservation applications. In practice, operational taxonomic units (OTUs) are often used as provisional surrogates of the species, whose evidence-based and robust delimitation requires too extensive data and complex analyses. The novel method for this provisional species delimitation is suggested, which uses any phylogenetic tree with meaningful branch lengths as an input and delimits OTUs on it by identification of branches whose removal significantly changes structure of the tree. Such branches are considered to reflect interspecific differentiation that is assumed generally more erratic than intraspecific branching. It is called branch-cutting method as it evaluates structural importance of the branch by its cutting (shrinking to zero length) and inspecting impact of this operation on the average pairwise distances between tree tips. Tree tips can be also constrained to be either conspecific or heterospecific which allows the method to achieve more robust and informed delimitations and to focus on particular phylogenetic scale. Usefulness of the method is demonstrated on four empirical examples and comparison with similar methods is performed.
Tratamiento con ciclosfamida de la tumefacción parotídea del síndrome de Sjögren

Se presenta una paciente de 67 años con síndrome de sicca de 10 años de evolución y tumefacción parotídea bilateral de curso crónico durante 4 años. Mediante el tratamiento con ciclofosfamida se consiguió la desaparición de la tumefacción parotídea, sin recidiva a los 4 meses de interrumpido el tratamiento. Los autores señalan que un tratamiento apropiado para el síndrome de Sjögren puede ser la administración de citostáticos, indicando la necesidad de realizar ensayos terapéuticos controlados.
Low variability of dynamical functional connectivity in cerebellar networks

Brain networks can be defined and explored using different types of connectivity. Here, we studied P=48 healthy participants with neuroimaging state-of-the-art techniques and analyzed the relationship between the actual structural connectivity (SC) networks (between 2514 regions of interest covering the entire brain and brainstem) and the dynamical functional connectivity (DFC) among the same regions. To do so, we focused on a combination of two metrics: the first one measures the degree of SC-DFC similarity –i.e. how much functional correlations can be explained by structural pathways– and the second one, the intrinsic variability of DFC networks across time. Overall, we found that cerebellar networks have smaller DFC variability than other networks in the cerebrum. Moreover, our results clearly evidence the internal structure of the cerebellum, which is divided in two differentiated networks, the posterior and anterior parts, the latter also being connected to the brain stem. The mechanism for keeping the DFC variability low in the posterior part of the cerebellum is consistent with another finding, namely, it exhibits the highest SC-DFC similarity among all other sub-networks, i.e. its structure constrains very strongly its dynamics. On the other hand, the anterior part of the cerebellum, which also exhibits a low level of DFC variability, has the lowest SC-DFC similarity, suggesting very different dynamical mechanisms. It is likely that its connections with the brain stem –which regulates sleep cycles, cardiac and respiratory functioning– might have a critical role in DFC variations in the anterior part. A lot is known about cerebellar networks, such as having extremely rich and complex anatomy and functionality, connecting to the brainstem, and cerebral hemispheres, and participating in a large variety of cognitive functions, such as movement control and coordination, executive function, visual-spatial cognition, language processing, and emotional regulation. However, as far as we know, our findings of low variability in the dynamical functional connectivity of cerebellar networks and its possible relation with the above functions, have not been reported so far. Further research is still needed to shed light on these findings.
Study of the binding mechanism of dasatinib to c-Src kinase using an efficient molecular dynamics method

10 Small molecules such as metabolites and drugs play essential roles in biological processes and 11 pharmaceutical industry. Knowing their interactions with biomacromolecular targets demands a 12 deep understanding of binding mechanisms. Dozens of papers have suggested that discovering of 13 the binding event by means of conventional unbiased molecular dynamics simulation urges 14 considerable amount of computational resources, therefore, only one who holds a cluster or a 15 supercomputer can afford such extensive simulations. Thus, many researchers who do not own 16 such resources are reluctant to take the benefits of running unbiased molecular dynamics 17 simulation, in full atomistic details, when studying a ligand binding pathway. Many researchers 18 are impelled to be content with biased molecular dynamics simulations which seek its validation 19 due to its intrinsic preconceived framework. In this work, we have presented a workable 20 stratagem to encourage everyone to perform unbiased (unguided) molecular dynamics 21 simulations, in this case a protein-ligand binding process, by typical desktop computers and so 22 achieve valuable results in nanosecond time scale. Here, we have described a dynamical 23 binding’s process of an anticancer drug, the dasatinib, to the c-Src kinase in full atomistic details 24 for the first time, without applying any biasing force or potential which may lead the drug to 25 artificial interactions with the protein. We have attained multiple independent binding events 26 which occurred in the nano-second timescales, surprisingly as little as ~30 ns. Both the 27 protonated and deprotonated forms of the dasatinib reached the crystallographic binding mode 28 without having any major intermediate state during induction. 29 not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was this version posted February 28, 2020. ; https://doi.org/10.1101/650440 doi: bioRxiv preprint
Specialised functions of two common plasmid mediated toxin-antitoxin systems, ccdAB and pemIK, in Enterobacteriaceae

Toxin-antitoxin systems (TAS) are commonly found on bacterial plasmids and are involved in plasmid maintenance. Even though the same TAS are present in a variety of plasmid types and bacterial species, differences in their sequences, expression and functions are not well defined. Here, we aimed to identify commonly occurring plasmid TAS in Escherichia coli and Klebsiella pneumoniae and compare the sequence, expression and plasmid stability function of their variants. 27 putative type II TAS were identified from 1063 plasmids of Klebsiella pneumoniae in GenBank. Among these, ccdAB and pemIK were found to be most common, also occurring in plasmids of E. coli. Comparisons of ccdAB variants, taken from E. coli and K. pneumoniae, revealed sequence differences, while pemIK variants from IncF and IncL/M plasmids were almost identical. Similarly, the expression and plasmid stability functions of ccdAB variants varied according to the host strain and species, whereas the expression and functions of pemIK variants were consistent among host strains. The specialised functions of some TAS may determine the host specificity and epidemiology of major antibiotic resistance plasmids.
Expression of E. coli glycogen branching enzyme in an Arabidopsis mutant devoid of endogenous starch branching enzymes induces the synthesis of starch-like polyglucans

Starch synthesis requires several enzymatic activities including branching enzymes (BEs) responsible for the formation of α(1→6) linkages. Distribution and number of these linkages are further controlled by debranching enzymes (DBEs) that cleave some of them, rendering the polyglucan water-insoluble and semi-crystalline. Although the activity of BEs and DBEs is mandatory to sustain normal starch synthesis, the relative importance of each in the establishment of the plant storage polyglucan (i.e. water-insolubility, crystallinity, presence of amylose) is still debated. Here, we have substituted the activity of BEs in Arabidopsis with that of the Escherichia coli glycogen branching enzyme (GlgB). The latter is the BE counterpart in the metabolism of glycogen, a highly branched water-soluble and amorphous storage polyglucan. GlgB was expressed in the be2 be3 double mutant of Arabidopsis that is devoid of BE activity and consequently free of starch. The synthesis of a water-insoluble, partly crystalline, amylose-containing starch-like polyglucan was restored in GlgB-expressing plants, suggesting that BEs origin only have a limited impact on establishing essential characteristics of starch. Moreover, the balance between branching and debranching is crucial for the synthesis of starch, as an excess of branching activity results in the formation of highly branched, water-soluble, poorly crystalline polyglucan.
Testing the phylogenetic gambit: how much functional diversity can we reliably conserve if we prioritize phylogenetic diversity?

In the face of the biodiversity crisis, it is argued that we should prioritize species in order to capture high functional diversity (FD). Because species traits often reflect shared evolutionary history, many researchers have advocated for a “phylogenetic gambit”: maximizing phylogenetic diversity (PD) should indirectly capture FD. For the first time, we empirically test this gambit using data from >15,000 vertebrate species and ecologically-relevant traits. Maximizing PD results in an average gain of 18% of FD relative to random choice. However, this average gain hides the fact that in over 1/3 of the comparisons, maximum PD sets contain less FD than randomly chosen sets of species. These results suggest that, while maximizing PD protection can help to protect FD, it represents a risky strategy. Statement of authorship FM, MP, MC, SD, GVDR, RG, AOM, CT and WP conceived the design of the study. FM and GVDR conducted the analysis. FM, RG, MP and WP interpreted the results and wrote the first draft of the manuscript. All authors edited the final version. Data accessibility statement Most of the data is publicly available (see methods). The Fish data is available upon request. Code accessibility statement R functions developed in this paper are available at https://github.com/FloMazel/FD_PD_Max