Publications by authors named "F Castello"

86 Publications

Structure and thermodynamics of two-dimensional Yukawa liquids.

Phys Rev E 2021 Jun;103(6-1):063205

Space and Plasma Physics, Royal Institute of Technology, Stockholm, SE-100 44, Sweden.

The thermodynamic and structural properties of two-dimensional dense Yukawa liquids are studied with molecular dynamics simulations. The "exact" thermodynamic properties are simultaneously employed in an advanced scheme for the determination of an equation of state that shows an unprecedented level of accuracy for the internal energy, pressure, and isothermal compressibility. The "exact" structural properties are utilized to formulate a novel empirical correction to the hypernetted-chain approach that leads to a very high accuracy level in terms of static correlations and thermodynamics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1103/PhysRevE.103.063205DOI Listing
June 2021

From Genome to Drugs: New Approaches in Antimicrobial Discovery.

Front Pharmacol 2021 9;12:647060. Epub 2021 Jun 9.

Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.

Decades of successful use of antibiotics is currently challenged by the emergence of increasingly resistant bacterial strains. Novel drugs are urgently required but, in a scenario where private investment in the development of new antimicrobials is declining, efforts to combat drug-resistant infections become a worldwide public health problem. Reasons behind unsuccessful new antimicrobial development projects range from inadequate selection of the molecular targets to a lack of innovation. In this context, increasingly available omics data for multiple pathogens has created new drug discovery and development opportunities to fight infectious diseases. Identification of an appropriate molecular target is currently accepted as a critical step of the drug discovery process. Here, we review how diverse layers of multi-omics data in conjunction with structural/functional analysis and systems biology can be used to prioritize the best candidate proteins. Once the target is selected, virtual screening can be used as a robust methodology to explore molecular scaffolds that could act as inhibitors, guiding the development of new drug lead compounds. This review focuses on how the advent of omics and the development and application of bioinformatics strategies conduct a "big-data era" that improves target selection and lead compound identification in a cost-effective and shortened timeline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.647060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219968PMC
June 2021

Five-year microevolution of a multidrug-resistant Mycobacterium tuberculosis strain within a patient with inadequate compliance to treatment.

BMC Infect Dis 2021 Apr 29;21(1):394. Epub 2021 Apr 29.

Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Buenos Aires, Argentina.

Background: Whole-genome sequencing has shown that the Mycobacterium tuberculosis infection process can be more heterogeneous than previously thought. Compartmentalized infections, exogenous reinfections, and microevolution are manifestations of this clonal complexity. The analysis of the mechanisms causing the microevolution -the genetic variability of M. tuberculosis at short time scales- of a parental strain into clonal variants with a patient is a relevant issue that has not been yet completely addressed. To our knowledge, a whole genome sequence microevolution analysis in a single patient with inadequate adherence to treatment has not been previously reported.

Case Presentation: In this work, we applied whole genome sequencing analysis for a more in-depth analysis of the microevolution of a parental Mycobacterium tuberculosis strain into clonal variants within a patient with poor treatment compliance in Argentina. We analyzed the whole-genome sequence of 8 consecutive Mycobacterium tuberculosis isolates obtained from a patient within 57-months of intermittent therapy. Nineteen mutations (9 short-term, 10 fixed variants) emerged, most of them associated with drug resistance. The first isolate was already resistant to isoniazid, rifampicin, and streptomycin, thereafter the strain developed resistance to fluoroquinolones and pyrazinamide. Surprisingly, isolates remained susceptible to the pro-drug ethionamide after acquiring a frameshift mutation in ethA, a gene required for its activation. We also found a novel variant, (T-54G), in the 5' untranslated region of whiB7 (T-54G), a region allegedly related to kanamycin resistance. Notably, discrepancies between canonical and phage-based susceptibility testing to kanamycin were previously found for the isolate harboring this mutation. In our patient, microevolution was mainly driven by drug selective pressure. Rare short-term mutations fixed together with resistance-conferring mutations during therapy.

Conclusions: This report highlights the relevance of whole-genome sequencing analysis in the clinic for characterization of pre-XDR and MDR resistance profile, particularly in patients with incomplete and/or intermittent treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-021-06069-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082761PMC
April 2021

Protein -Fucosyltransferase 1 Undergoes Interdomain Flexibility in Solution.

Molecules 2021 Apr 7;26(8). Epub 2021 Apr 7.

Institute of Biocomputation and Physics of Complex Systems (BIFI), University of Zaragoza, 50018 Zaragoza, Spain.

Protein -fucosyltransferase 1 (PoFUT1) is a GT-B fold enzyme that fucosylates proteins containing EGF-like repeats. GT-B glycosyltransferases have shown a remarkable grade of plasticity adopting closed and open conformations as a way of tuning their catalytic cycle, a feature that has not been observed for PoFUT1. Here, we analyzed PoFUT1 (PoFUT1) conformational behavior in solution by atomic force microscopy (AFM) and single-molecule fluorescence resonance energy transfer (SMF-FRET). Our results show that this enzyme is very flexible and adopts mainly compact conformations and to a lesser extend a highly dynamic population that oscillates between compact and highly extended conformations. Overall, our experiments illustrate the inherent complexity of PoFUT1 dynamics, which might play a role during its catalytic cycle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26082105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067585PMC
April 2021

Cyanobacterial NOS expression improves nitrogen use efficiency, nitrogen-deficiency tolerance and yield in Arabidopsis.

Plant Sci 2021 Jun 28;307:110860. Epub 2021 Feb 28.

Instituto de Investigaciones Biológicas-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Deán Funes 3350, CC 1245, 7600 Mar del Plata, Argentina. Electronic address:

Developing strategies to improve nitrogen (N) use efficiency (NUE) in plants is a challenge to reduce environmental problems linked to over-fertilization. The nitric oxide synthase (NOS) enzyme from the cyanobacteria Synechococcus PCC 7335 (SyNOS) has been recently identified and characterized. SyNOS catalyzes the conversion of arginine to citrulline and nitric oxide (NO), and then approximately 75 % of the produced NO is rapidly oxidized to nitrate by an unusual globin domain in the N-terminus of the enzyme. In this study, we assessed whether SyNOS expression in plants affects N metabolism, NUE and yield. Our results showed that SyNOS-expressing transgenic Arabidopsis plants have greater primary shoot length and shoot branching when grown under N-deficient conditions and higher seed production both under N-sufficient and N-deficient conditions. Moreover, transgenic plants showed significantly increased NUE in both N conditions. Although the uptake of N was not modified in the SyNOS lines, they showed an increase in the assimilation/remobilization of N under conditions of low N availability. In addition, SyNOS lines have greater N-deficiency tolerance compared to control plants. Our results support that SyNOS expression generates a positive effect on N metabolism and seed production in Arabidopsis, and it might be envisaged as a strategy to improve productivity in crops under adverse N environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.plantsci.2021.110860DOI Listing
June 2021
-->