BUSCADOR RECOLECTA

Results of the computational study of the new series of 2-acylpyrrole derivatives., In this work, the SOFT.PTML tool has been used to pre-process a ChEMBL dataset of pre-clinical assays of antileishmanial compound candidates. A comparative study of different ML algorithms, such as logistic regression (LOGR), support vector machine (SVM), and random forests (RF), has shown that the IFPTML-LOGR model presents excellent values of specificity and sensitivity (81–98%) in training and validation series. The use of this software has been illustrated with a practical case study focused on a series of 28 derivatives of 2-acylpyrroles 5a,b, obtained through a Pd­(II)-catalyzed C–H radical acylation of pyrroles. Their in vitro leishmanicidal activity against visceral (L. donovani) and cutaneous (L. amazonensis) leishmaniasis was evaluated finding that compounds 5bc (IC50 = 30.87 μM, SI > 10.17) and 5bd (IC50 = 16.87 μM, SI > 10.67) were approximately 6-fold more selective than the drug of reference (miltefosine) in in vitro assays against L. amazonensis promastigotes. In addition, most of the compounds showed low cytotoxicity, CC50 > 100 μg/mL in J774 cells. Interestingly, the IFPMTL-LOGR model predicts correctly the relative biological activity of these series of acylpyrroles. A computational high-throughput screening (cHTS) study of 2-acylpyrroles 5a,b has been performed calculating >20,700 activity scores vs a large space of 647 assays involving multiple Leishmania species, cell lines, and potential target proteins. Overall, the study demonstrates that the SOFT.PTML all-in-one strategy is useful to obtain IFPTML models in a friendly interface making the work easier and faster than before. The present work also points to 2-acylpyrroles as new lead compounds worthy of further optimization as antileishmanial hits., Peer reviewed

The controversy about intracellular local temperature increments; materials and methods; experimental setup for magnetic-induced heating and optical microscope temperature imaging; calibration of the thermal probes, relative thermal sensitivity, and temperature uncertainty; temperature imaging of living cells; cell cultures; intracellular temperature evolution over time during exposure to an AMF., Peer reviewed

27 pages. -- Includes: Strains construction. -- Experimental setup. -- Image processing. -- The definition of repression. -- Characterizing background fluorescence signals. -- Signal-to-noise ratio and the amplitude of pulses. -- A probabilistic inference algorithm. -- Correlation between promoter activity and gene dosage during cell growth. -- Robustness of the repression to temperature change. -- CRP and glucose experiments. -- Modeling the effects of DNA looping in gene regulation. -- Simulations with cell division., Peer reviewed

See Supplemental Material for (i) the derivations of the CMM equations for a real metal, (ii) the justification for the minimal model used in the text, (iii) the validity of the small-hole approximation, and (iv) the experimental set-up for Mueller polarimetry., Peer reviewed

Raw microscopy data for Fig5E (.lif files) in a single zip file., Resources available on the publisher's site: https://doi.org/10.25452/figshare.plus.18348926.v1, Marie Skłodowska-Curie grant agreement No. 754510 Ministry of Science, Innovation and Universities PGC2018-095616-B-I00 Ministry of Science, Innovation and Universities PGC2018-099562-B-I00, Peer reviewed

Screening of exfoliation conditions (dispersion solvent, prewetting solvent, microwave power, microwave irradiation time, MoS2–NMP ratio, and % yield); UV–vis analyses, optical and electronic microscopy analyses; thermogravimetric analysis of bulk and exfoliated MoS2, X-ray photoelectron spectroscopy analysis, electron transport measurements., Peer reviewed

Raw microscopy data for Fig7A-B, C and D-G (.lif and .jpg files) in a single zip file., Resources available on the publisher's site: https://doi.org/10.25452/figshare.plus.18316226.v1, Deutsche Forschungsgemeinschaft DFG PH144/4-1 and PH144/6-1, Peer reviewed

Tables; Table S1. Search Strategy, Table S2. Full text of excluded articles, Table S3a. Genetic model studies, Table S3b. Environmental model studies, Table S3c Gene x environmental model studies, Quality assessment procedures S4., Reelin is an extracellular matrix glycoprotein reduced in brain regions (the prefrontal cortex and the hippocampus) of patients with schizophrenia. There are diverse rodent models of schizophrenia that mimic patient symptoms based on various causal theories; however, likely shared reelin alterations have not yet been systematically assessed in those models. A systematic review of the literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model. Articles focused on psychotic disorders or schizophrenia and their relationship with reelin in rodent models were selected. Data (first author, publication year, results, both open field and prepulse inhibition test results, and type of reelin alteration) were extracted in duplicate by two independent reviewers. The 37 reviewed articles reported about various schizophrenia models and their reelin alterations, brain morphology, and behavioral defects. We conclude that reelin is an altered preclinical biomarker common to all models included, mainly prenatal or genetic models, and a key protein in schizophrenia disease, making the reelin signaling pathway in prenatal stages a target of special interest for future preclinical and clinical studies. All models presented at least one of the four described reelin alteration types. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021210568], identifier [CRD42021210568]., Peer reviewed

The appearance of synapses was a crucial step in the creation of the variety of nervous systems that are found in the animal kingdom. With increased complexity of the organisms came a greater number of synaptic proteins. In this review we describe synaptic proteins that contain the structural domains CUB, CCP, or TSP-1. These domains are found in invertebrates and vertebrates, and CUB and CCP domains were initially described in proteins belonging to the complement system of innate immunity. Interestingly, they are found in synapses of the nematode C. elegans, which does not have a complement system, suggesting an ancient function. Comparison of the roles of CUB-, CCP-, and TSP-1 containing synaptic proteins in various species shows that in more complex nervous systems, these structural domains are combined with other domains and that there is partial conservation of their function. These three domains are thus basic building blocks of the synaptic architecture. Further studies of structural domains characteristic of synaptic proteins in invertebrates such as C. elegans and comparison of their role in mammals will help identify other conserved synaptic molecular building blocks. Furthermore, this type of functional comparison across species will also identify structural domains added during evolution in correlation with increased complexity, shedding light on mechanisms underlying cognition and brain diseases., Peer reviewed

Table S1. Checklist of items according to STROBE document. Table S2. Definitions of the key variables used. Table S3. Summary of outcomes for the different analyses. Table S4. Characteristics of patients who underwent debridement, antibiotic therapy, and implant retention (DAIR) treated with and without rifampicin. Table S5. Approval of the ethics committee of all participating centers. Figure S1. Cumulative proportion of SA-PJIs occurring after primary arthroplasty., Peer reviewed