Papers by JUAN DAVID CASTRO BUSTAMANTE (ESTUDIANTE)
Ordered sets of chains and incidence algebras
Annales des Sciences Mathematiques du Quebec

Memórias do Instituto Oswaldo Cruz, 2015
Prevention of Trypanosoma cruzi infection in mammals likely depends on either prevention of the i... more Prevention of Trypanosoma cruzi infection in mammals likely depends on either prevention of the invading trypomastigotes from infecting host cells or the rapid recognition and killing of the newly infected cells by T. cruzispecific T cells. We show here that multiple rounds of infection and cure (by drug therapy) fails to protect mice from reinfection, despite the generation of potent T cell responses. This disappointing result is similar to that obtained with many other vaccine protocols used in attempts to protect animals from T. cruzi infection. We have previously shown that immune recognition of T. cruzi infection is significantly delayed both at the systemic level and at the level of the infected host cell. The systemic delay appears to be the result of a stealth infection process that fails to trigger substantial innate recognition mechanisms while the delay at the cellular level is related to the immunodominance of highly variable gene family proteins, in particular those of the trans-sialidase family. Here we discuss how these previous studies and the new findings herein impact our thoughts on the potential of prophylactic vaccination to serve a productive role in the prevention of T. cruzi infection and Chagas disease.

Biochemistry, 2014
The unique architecture of the active site of Thermobifida fusca truncated hemoglobin (Tf-trHb) a... more The unique architecture of the active site of Thermobifida fusca truncated hemoglobin (Tf-trHb) and other globins belonging to the same family has stimulated extensive studies aimed at understanding the interplay between ironbound ligands and distal amino acids. The behavior of the heme-bound hydroxyl, in particular, has generated much interest in view of the relationships between the spin-state equilibrium of the ferric iron atom and hydrogen-bonding capabilities (as either acceptor or donor) of the OH − group itself. The present investigation offers a detailed molecular dynamics and spectroscopic picture of the hydroxyl complexes of the WT protein and a combinatorial set of mutants, in which the distal polar residues, TrpG8, TyrCD1, and TyrB10, have been singly, doubly, or triply replaced by a Phe residue. Each mutant is characterized by a complex interplay of interactions in which the hydroxyl ligand may act both as a H-bond donor or acceptor. The resonance Raman stretching frequencies of the Fe−OH moiety, together with electron paramagnetic resonance spectra and MD simulations on each mutant, have enabled the identification of specific contributions to the unique ligandinclusive H-bond network typical of this globin family.
Stereotactic and Functional Neurosurgery, 2013

Drug-Induced Gynecomastia
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2012
Drugs account for about 20% of gynecomastia cases in men. As a number of factors can alter the es... more Drugs account for about 20% of gynecomastia cases in men. As a number of factors can alter the estrogen:androgen ratio, several pathophysiologic mechanisms are associated with drugs causing this disorder. Antiandrogens, protease inhibitors, and nucleoside reverse transcriptase inhibitors are the most common drug causes of gynecomastia, whereas first-generation antipsychotics, spironolactone, verapamil, and cimetidine are less common causes. Other drugs have been reported rarely as causes. Treatment may involve switching to an alternative agent or may require surgery or irradiation if the causative agent cannot be discontinued. We reviewed the literature on drug-induced gynecomastia and provided another perspective by reviewing data from the United States Food and Drug Administration's Adverse Event Reporting System. Epidemiologic studies are needed to provide a more accurate description of the frequency of drug-induced gynecomastia.
We provide a counter-example to Proposition 3.2 of "A note on the Fundamental Group of a Tri... more We provide a counter-example to Proposition 3.2 of "A note on the Fundamental Group of a Triangular Algebra", by F.Xu.

The Journal of Physical Chemistry B, 2014
Internal water molecules play an active role in ligand uptake regulation, since displacement of r... more Internal water molecules play an active role in ligand uptake regulation, since displacement of retained water molecules from protein surfaces or cavities by incoming ligands can promote favorable or disfavorable effects over the global binding process. Detection of these water molecules by X-ray crystallography is difficult given their positional disorder and low occupancy. In this work, we employ a combination of molecular dynamics simulations and ligand rebinding over a broad time range to shed light into the role of water molecules in ligand migration and binding. Computational studies on the unliganded structure of the thermostable truncated hemoglobin from Thermobif ida f usca (Tf-trHbO) show that a water molecule is in the vicinity of the iron heme, stabilized by WG8 with the assistance of YCD1, exerting a steric hindrance for binding of an exogenous ligand. Mutation of WG8 to F results in a significantly lower stabilization of this water molecule and in subtle dynamical structural changes that favor ligand binding, as observed experimentally. Water is absent from the fully hydrophobic distal cavity of the triple mutant YB10F-YCD1F-WG8F (3F), due to the lack of residues capable of stabilizing it nearby the heme. In agreement with these effects on the barriers for ligand rebinding, over 97% of the photodissociated ligands are rebound within a few nanoseconds in the 3F mutant case. Our results demonstrate the specific involvement of water molecules in shaping the energetic barriers for ligand migration and binding.

PROTEOMICS, 2009
Mass spectrometry was used to characterize the 24-kDa human growth hormone (hGH) glycoprotein iso... more Mass spectrometry was used to characterize the 24-kDa human growth hormone (hGH) glycoprotein isoform and determine the locus of O-linked oligosaccharide attachment, the oligosaccharide branching topology, and the monosaccharide sequence. MALDI-TOF/MS and ESI-MS/MS analyses of glycosylated 24-kDa hGH tryptic peptides showed that this hGH isoform is a product of the hGH normal gene (hGH-N). Analysis of the glycoprotein hydrolysate by highperformance anion-exchange chromatography with pulsed amperometric detection and HPLC with fluorescent detection for NeuAc, yielded the oligosaccharide composition (NeuAc 2 , GalNAc 1 , Gal 1). After β-elimination to release the oligosaccharide from glycosylated 24-kDa hGH, collision-induced dissociation of tryptic glycopeptide T6 indicated that there had been an O-linked oligosaccharide attached to Thr-60. The sequence and branching structure of the oligosaccharide were determined by ESI-MS/MS analysis of tryptic glycopeptide T6. The mucin-like Ooligosaccharide sequence linked to Thr-60 begins with GalNAc and branches in a bifurcated topology with one appendage consisting of Gal followed by NeuAc and the other consisting of a single NeuAc. The oligosaccharide moiety lies in the high-affinity binding site 1 structural epitope of hGH that interfaces with both the GH and prolactin receptors and is predicted to sterically affect receptor interactions and alter the biological actions of hGH.

PLoS ONE, 2012
CO recombination kinetics has been investigated in the type II truncated hemoglobin from Thermobi... more CO recombination kinetics has been investigated in the type II truncated hemoglobin from Thermobifida fusca (Tf-trHb) over more than 10 time decades (from 1 ps to ,100 ms) by combining femtosecond transient absorption, nanosecond laser flash photolysis and optoacoustic spectroscopy. Photolysis is followed by a rapid geminate recombination with a time constant of ,2 ns representing almost 60% of the overall reaction. An additional, small amplitude geminate recombination was identified at ,100 ns. Finally, CO pressure dependent measurements brought out the presence of two transient species in the second order rebinding phase, with time constants ranging from ,3 to ,100 ms. The available experimental evidence suggests that the two transients are due to the presence of two conformations which do not interconvert within the time frame of the experiment. Computational studies revealed that the plasticity of protein structure is able to define a branched pathway connecting the ligand binding site and the solvent. This allowed to build a kinetic model capable of describing the complete time course of the CO rebinding kinetics to Tf-trHb.
Journal of Pure and Applied Algebra, 2006

Journal of Infectious Diseases, 2013
The development of treatment protocols with reduced toxicity and equivalent or improved efficacy ... more The development of treatment protocols with reduced toxicity and equivalent or improved efficacy for Trypanosoma cruzi infection is a priority. We tested the effectiveness of benznidazole (BZ), nifurtimox (NFX), other prospective drugs in intermittent and combined treatment protocols to cure T. cruzi infection initiated with susceptible and drug-resistant parasite strains. A 40-day course of BZ, NFX, or the oxaborale AN4169 cured 100% of mice, whereas posaconazole (POS), and NTLA-1 (a nitro-triazole) cured approximately 90% and 20% of mice, respectively. Reducing the overall dosage of BZ or NFX by using an intermittent (once every 5 days) schedule or combining 5 daily doses of POS with 7 intermittent doses of BZ also provided approximately 100% cure. T. cruzi strains resistant to BZ were also found to be resistant to other drugs (POS), and extending the time of treatment or combining drugs did not increase cure rates with these isolates. Thus, dosing schedules for anti-T. cruzi compounds should be determined empirically, and compounds targeting different pathways may be combined to yield effective therapies with reduced toxicity. This work also suggests that standard treatment protocols using BZ and NFX may be significantly overdosing patients, perhaps contributing to the adverse events.
Journal of Algebra and Its Applications, 2006
In this note, we investigate how different fundamental groups of presentations of a fixed algebra... more In this note, we investigate how different fundamental groups of presentations of a fixed algebra A can be. For finitely many finitely presented groups Gi, we construct an algebra A such that all Gi appear as fundamental groups of presentations of A.
Journal of Algebra, 2010
In this paper, we study the covering theory of laura algebras. We prove that if a connected laura... more In this paper, we study the covering theory of laura algebras. We prove that if a connected laura algebra is standard (that is, has a standard connecting component), then it has Galois coverings associated to the coverings of the connecting component. As a consequence, the first Hochschild cohomology group of a standard laura algebra vanishes if and only if it has no proper Galois coverings.

Stereotactic and functional neurosurgery, 2012
Objective: To perform a preliminary study on the effects and safety of bilateral cingulotomy and ... more Objective: To perform a preliminary study on the effects and safety of bilateral cingulotomy and anterior capsulotomy in patients with aggressive behavior. Patients and Methods: Twenty-three psychiatric patients showing aggressive behavior refractory to conventional treatment were initially evaluated. The subjects were clinically selected using the Overt Aggression Scale (OAS) and the Global Assessment of Functioning Scale (GAF). Each case was carefully reviewed by the Ethics Committee of Mexico's General Hospital. Once selection criteria were met, stereotactic lesions were made using radiofrequency on the anterior limb of the internal capsule and supragenual cingulum. Statistical differences were evaluated with a Wilcoxon test at 6 months and at 4 years. Results: Ten patients underwent surgery. Their OAS and GAF scores decreased after the procedure at the 6-month (p < 0.05) and at the 4-year (p = 0.068) follow-up. Four patients showed mild and transitory postsurgical compli...
International Journal of Algebra and Computation, 2013
Given a cluster-tilted algebra B we study its first Hochschild cohomology group HH 1(B) with coef... more Given a cluster-tilted algebra B we study its first Hochschild cohomology group HH 1(B) with coefficients in the B–B-bimodule B. If C is a tilted algebra such that B is the relation extension of C by [Formula: see text], then we prove that HH 1(B) is isomorphic, as a vector space, to the direct sum of HH 1(C) with HH 1(B,E). This yields homological interpretations for results of the first and the fourth authors with M. J. Redondo.

Endocrinology, 2007
The prolactin (PRL) family of hormones/cytokines is involved in the maintenance of pregnancy and ... more The prolactin (PRL) family of hormones/cytokines is involved in the maintenance of pregnancy and adaptations to physiological stressors. In this report, we identify and characterize a new member of the rat PRL family, examine the impact of maternal hypoxia on placental PRL family gene expression, and investigate maternal adaptive responses to hypoxia. Perusal of the PRL gene family locus in the rat genome resulted in the identification of a putative new member of the rat PRL family. The new member is closely related to the previously reported PRL-like protein-F (PLP-F) and has been named PLP-Fβ and the originally characterized PLP-F, now termed PLP-Fα. The two proteins exhibit structural similarities but possess distinct cell- and temporal-specific expression profiles. In vivo hypoxia stimulates placental PLP-Fα and PLP-E mRNA expression in the rat and mouse, respectively. Rcho-1 trophoblast cells can differentiate into trophoblast giant cells, express PLP-Fα, and exhibit enhanced P...
On the Fundamental Group of a Schurian Algebra
Communications in Algebra, 2002
ABSTRACT We show that, for a class of schurian algebras, which we call schurian almost triangular... more ABSTRACT We show that, for a class of schurian algebras, which we call schurian almost triangular, the fundamental group of the algebra is isomorphic to the fundamental group of an associated simplicial complex. Moreover, we obtain a simple presentation of this group ...
Communications in Algebra, 2009
Colloquium Mathematicum, 2011
Let A be a special biserial algebra over an algebraically closed field. We show that the first Ho... more Let A be a special biserial algebra over an algebraically closed field. We show that the first Hohchshild cohomology group of A with coefficients in the bimodule A vanishes if and only if A is representation finite and simply connected (in the sense of Bongartz and Gabriel), if and only if the Euler characteristic of Q equals the number of indecomposable non uniserial projective injective A-modules (up to isomorphism). Moreover, if this is the case, then all the higher Hochschild cohomology groups of A vanish.
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Papers by JUAN DAVID CASTRO BUSTAMANTE (ESTUDIANTE)