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African dust incursions in the Caribbean Region: dust concentrations, chemical composition, and fungal spore concentrations
(2021-05-18)
African dust can be transported over thousands of kilometers through the Atlantic Ocean reaching the Caribbean region, Central América, and parts of the southern USA mostly in the summer months. Dust emissions from ...
Development of targeted formulations for the delivery of a cytochrome c-based drug for application in cancer therapy
(2021-05-13)
The progression of a cell toward apoptosis, upon cellular stress, is accompanied by a set of characteristic events which includes permeabilization of the mitochondrial outer membrane and release of cytochrome c into the ...
Exploring the formation of guanosine-based colloidal particles and their affinity towards targeted molecules
(2021-06-30)
The ultimate goal of stimuli-responsive drug delivery systems is the encapsulation and release of biologically relevant molecules (e.g., drugs, proteins) with spatiotemporal control. In order to do this, delivery systems ...
Biologically relevant formulation and expansion of responsive properties of guanine based supramolecular particles.
(2021-01-14)
Colloidal particles ranging from the nano to the microscale show great promise in the delivery and enhancement of therapeutic agents. The formulation of many of these particles usually includes crosslinkers, non-biocompatible ...
Single entity electrochemistry of hard and soft nanoparticles using direct particle coulometry, blocking, and catalytic amplification methods.
(2021-05-10)
In the last decades, single entity electrochemistry (SEE) has emerged as a powerful technique allowing for characterization of nanoparticles, detection of molecules, enzymes, cells, viruses, and even one single atom at a ...
From environmental remediation to photoelectrochemical cell applications: Fe0/ FexOy, CdFe2O4, and NiFe2O4 nanoparticles and the development of an electrochemical system for ammonia oxidation reaction at the international space station
(2021-05-14)
Contaminated water bodies have been identified in the industrialized area of the north area of Puerto Rico. The excessive construction without considering the diversity of the ecosystem that encompasses the north area has ...
Improving the packing density of an enzyme/block-copolymer conjugate as a reactive layer to design an anti-endotoxin water purification membrane
(2021-07-07)
<p>Purified water is the most abundant raw material used in the formulation, cleaning, and manufacturing of pharmaceutical products, analytical reagents, intermediates, biomedical devices, and active pharmaceutical ingredients (API). The United State Pharmacopeia monograph <1231> establishes distinct classifications of water quality that must be used in a biotechnological facility. Membrane technology is an important application employed to produce water with a high-standard quality level.</p>
<p>The membrane separation field for water purification applications are evolving toward developing bio-functional interfaces. The permi-selective barrier that separates the unclean to the clean passage is primarily driven by the size exclusion principle in most filtration systems. In addition to this approach, we aimed to design an in-situ response of the membrane to biodegrade unwanted molecules, particularly those from bacterial origin (i.e. endotoxins), using an active interface at the surface of a nano-porous barrier. In pursuit of that vision, we fostered path-breaking scientific discovery via working with bio-reactive membrane separation sciences to address this challenge and thus provide water with a higher quality level.</p>
<p>This research sought to understand the fundamental aspects related to the packing density of a nano-porous polymeric active layer. The porous layer results from the self-assembly properties of the di-block copolymer (BCP) polystyrene-b-poly(4 vinyl pyridine) (PS-bP4VP) that results in cylindrical domains. The PS<sub>40.5K</sub>-b-P4VP<sub>16.5K</sub> and PS<sub>17K</sub>-b-P4VP<sub>49K</sub> forms supramolecular immiscible assemblies that have been previously studied in the bulk. Additionally, in recent studies, the complexes of this system have been also investigated ix via phase inversion and as thin films by spin coating techniques to produce thin-porous layers. Moreover, we looked forward to attaching lipase b from Candida Antarctica (CALB) enzyme within the polymeric matrix prepared from the aforementioned methods to add functional properties by means of an enzymatic reaction activity. In this work, CALB was initially attached via physical adsorption and later covalently attached to the self-assembled PS-b-P4VP block copolymer thin-film. The attachment was then characterized via atomic force microscopy (AFM), scanning electron microscopy (SEM), FTIR, hydrolytic activity, among other techniques. For the adsorbed lipase above the thinfilm model, the adsorption of the enzyme was successfully achieved onto the polymeric matrix with average pore size of 19.4 ± 2.0 nm. Results also demonstrated a relative activity of the immobilized enzyme up to 90.5 ± 3.7 %. For the covalently attached method, the immobilized enzyme was able to retain 97% of its enzymatic activity when using 4- nitrophenyl acetate (pNPA) and up to 74% when biodegrading LPS. The observed average pore size at the final constructed enzymatic thin-film composite (E-TFC) membrane was 91.8 ± 29.6 nm. The prepared reactive enzymatic active layer serves as a model and proofof-concept to develop further reactive layers for TFC membranes that finds suitability in water purification applications.</p>...
Development of a novel series of vinylic halogenated fatty acids and their potential biomedical applications.
(2021-01-29)
Marine sponges and anemones have provided most of the naturally occurring halogenated vinylic fatty acids (FA) known to date. Red algae such as A. taxiformis and Bonnemaisonia nootkana biosynthesize interesting brominated and chlorinated FA. Some of these compounds exhibit antifungal activity but their antiprotozoal and antibacterial activity remain unexplored. <br />
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In this work we report the synthesis and characterization of a novel series of halogenated vinylic FA with different chain lengths: 2-allyl-3-bromo-2E-nonadecenoic acid (1a), 2-allyl-3-chloro-2E-nonadecenoic acid (2a), 2-allyl-3-bromo-2E-dodecenoic acid (1b), 2-allyl-3-chloro-2E-dodecenoic acid (2b), 2-allyl-3-bromo-2E-hexadecenoic acid (1c), and 2-allyl-3-chloro-2E-hexadecenoic acid (2c) in synthetically useful yields (38-83%), which allow us to study their potential as antileishmanial and antibacterial agents. <br />
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The inhibitory effect of the FA’s with the longest chain (19 carbons) 1a and 2a, and the ones with the shortest chain (12 carbons) 1b and 2b on LTopIB and hTopIB was explored. The brominated FA 1a displayed a higher inhibitory potential to both enzymes than the chlorinated analog (LTopIB EC<sub>50</sub> = 7.4 ± 0.2 μM, hTopIB EC<sub>50</sub> = 12.7 ± 0.0 μM). The reduction of the carbon chain length from 19 to 12 carbons (1b and 2b) proved detrimental. The mechanism of the inhibition of LTopIB by the halogenated vinylic FA 1a and 2a follows a Gimatecan-independent mechanism. The long-chain FA 1a and 2a also displayed higher toxicity towards amastigotes than towards promastigotes demonstrating that these FA can distinguish between the different stages of the leishmanial parasite and display differential toxicities towards each stage. Molecular modeling studies of 1a and 2a determined, that in fact, the brominated FA 1a forms a halogen bond (binding energy = -4.85 kcal/mol) with a DNA phosphate group and an ionic interaction between the carboxylate and Lys 262, which supports the higher potency of 1a (IC<sub>50</sub> = 7.4 μM) over its chlorinated analog 2a (IC<sub>50</sub> = 25.7 μM). <br />
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The shorter chain FA’s antibacterial potential was also studied (1b, 2b, 1c, and 2c) against 5 clinical isolates of methicillin-resistant Staphylococcus aureus (CIMRSA) strains. Using microdilution susceptibility testing, we determined that the most significant inhibition was obtained with brominated FA 1c for all five CIMRSA strains studied. Moreover, 1c showed inhibitory effects comparable to, and- on some occasions (as with CIMRSA XII and XIII), even better than Ciprofloxacin (Cipro). The brominated hexadecenoic acid 1c also displayed a 19% cytotoxicity against Vero Cells at 100 μg/mL and in kinetic growth assays demonstrated to be toxic to CIMRSA XIII at a significantly lower concentration than Cipro (31.2 μg/mL of 1c vs 250 μg/mL of Cipro), which reveals the potency of 1c as an antibacterial agent towards CIMRSA strains. Our results indicate that the mechanism of action of 1c on the inhibition of these CIMRSA involves disrupting of the cell wall. We also determined that the brominated hexadecenoic FA inhibited the norB expression in S. aureus, suggesting that the bacteria is not resistant to 1c, which makes it a great antibacterial candidate....
Bacterial outer membrane vesicles as mediators of colibactin toxicity
(2021-09-27)
Colibactin is the product of a hybrid non-ribosomal peptide/polyketide synthase complex (pks island) found in some strains of Escherichia coli. Bacterial strains harboring the pks island show peculiar toxicity toward mammalian cells in culture with a distinctive phenotype that includes DNA damage, cell cycle arrest, and megalocytosis of the infected cells. It has been shown by our group that the pks island can be found in the normal gut microflora and its presence is positively correlated with colorectal cancer (CRC). Despite the notable interest in elucidating the mode of action of colibactin, its structure, the detailed mechanism of action, and the mechanism by which colibactin is transported to host cells remains unknown. The broad objective of this investigation was to develop molecular strategies towards the isolation of colibactin in pursuance of its structure and eventually, its mode of action. To do so, we first made a variant strain of the pks+ E. coli IHE3034 deficient of clbP gene, a key enzyme involved in the activation of colibactin. In our strain, removal of clbP did not cause a complete decrease in the megalocytosis phenotype (toxicity) on infected cells as expected but caused the accumulation of an unknown product of 994 Da. In addition, since the production of colibactin takes place in the space between the inner and outer membranes, we explored the involvement of bacterial outer membrane vesicles (OMVs) in colibactin toxicity. In all cases, we compared a natural producer of colibactin, strain IHE3034 with the mutant ΔclbP. We further found that (1) colibactin production does not have any detectable effects on the chemical composition, size, and amount of bacterial OMVs, (2) OMVs were sufficient to elicit the colibactin hallmarks of genotoxicity, including megalocytosis and DNA Damages on treated cells. However, we also found that (3) OMVs from both the pks+ strain and the ΔclbP mutant did not cause interstrand crosslinks, contrary to what was expected based on the proposed genotoxic mode of action of colibactin. Interestingly and an unforeseen outcome, we found that OMVs from the strain incapable to produce the active colibactin ΔclbP mutant, caused a substantial amount of toxicity towards cells. From these efforts, we conclude that OMVs vesicles are involved in the genotoxicity of colibactin although we have yet to find the compound in these vesicles....
The potential of natural polysaccharides: chemical approaches for bone tissue regeneration
(2021-11-16)
There are approximately 44 million people in the United States alone who suffer from diseases that cause bone density loss; and as life expectancy increases, so do the probabilities of being inflicted with such diseases. ...