Prebiotic potential of new sweeteners based on the simultaneous biosynthesis of galactooligosaccharides and enzymatically modified steviol glycosides.

Prebiotics are known for their health-promoting functions associated with the modulation of the colonic microbiota and the products of fermentation. Recently, single-pot syntheses of galactooligosaccharides in combination with steviol glycosides (mSG-GOS) have been developed. This work was conducted to evaluate their prebiotic effect by using faecal inoculum from healthy human donors during in vitro batch fermentations.

Molecular recognition of a membrane-anchored HIV-1 pan-neutralizing epitope.

Antibodies against the carboxy-terminal section of the membrane-proximal external region (C-MPER) of the HIV-1 envelope glycoprotein (Env) are considered as nearly pan-neutralizing. Development of vaccines capable of producing analogous broadly neutralizing antibodies requires deep understanding of the mechanism that underlies C-MPER recognition in membranes. Here, we use the archetypic 10E8 antibody and a variety of biophysical techniques including single-molecule approaches to study the molecular recognition of C-MPER in membrane mimetics.

Identification of 1,2,3-triazolium salt-based inhibitors of Leishmania infantum trypanothione disulfide reductase with enhanced antileishmanial potency in cellulo and increased selectivity.

N-methylation of the triazole moiety present in our recently described triazole-phenyl-thiazole dimerization disruptors of Leishmania infantum trypanothione disulfide reductase (LiTryR) led to a new class of potent inhibitors that target different binding sites on this enzyme. Subtle structural changes among representative library members modified their mechanism of action, switching from models of classical competitive inhibition to time-dependent mixed noncompetitive inhibition. X-ray crystallography and molecular modeling results provided a rationale for this distinct behavior.

Nucleus-translocated mitochondrial cytochrome c liberates nucleophosmin-sequestered ARF tumor suppressor by changing nucleolar liquid-liquid phase separation.

The regular functioning of the nucleolus and nucleus-mitochondria crosstalk are considered unrelated processes, yet cytochrome c (Cc) migrates to the nucleus and even the nucleolus under stress conditions. Nucleolar liquid-liquid phase separation usually serves the cell as a fast, smart mechanism to control the spatial localization and trafficking of nuclear proteins. Actually, the alternative reading frame (ARF), a tumor suppressor protein sequestered by nucleophosmin (NPM) in the nucleoli, is shifted out from NPM upon DNA damage.

Examining Topoisomers of a Snake-Venom-Derived Peptide for Improved Antimicrobial and Antitumoral Properties.

Ctn[15-34], the C-terminal section of crotalicidin (Ctn), a cathelicidin from a South American pit viper, is an antimicrobial and antitumoral peptide with remarkably longer stability in human serum than the parent Ctn. In this work, a set of topoisomers of both Ctn and Ctn[15-34], including the retro, enantio, and retroenantio versions, were synthesized and tested to investigate the structural requirements for activity. All topoisomers were as active as the cognate sequences against Gram-negative bacteria and tumor cells while slightly more toxic towards normal cells.

Prebiotic Potential of a New Sweetener Based on Galactooligosaccharides and Modified Mogrosides.

This study was conducted to investigate the sweetness intensity and the potential fecal microbiome modulation of galactooligosaccharides in combination with enzymatically modified mogrosides (mMV-GOS), both generated through a patented single-pot synthesis. Sweetness intensity was performed by trained sensory panelists. The impact on the human fecal microbiome was evaluated by pH-controlled batch fermentation, and bacterial populations and organic acid concentrations were measured by qPCR and GC-FID, respectively.

Major shrimp allergen peptidomics signatures and potential biomarkers of heat processing.

It is important to develop tools that can be used to understand the effects of processing on allergenic foods in order to achieve personalized food labeling. To evaluate the effect of heating on the allergy-relevant structural properties of tropomyosin (TM), arginine kinase (AK), myosin light chain (MLC) and sarcoplasmic calcium-binding protein (SCP) shrimp allergens, trypsin digests of raw, fried and baked shrimp extracts were analyzed by peptidomics and epitope correlations. Processing altered the number of peptides released from the distinct allergens, and each treatment generated a specific epitope-matched peptide allergen fingerprint.

Identification of the Dominant T-Cell Epitopes of Lit v 1 Shrimp Major Allergen and Their Functional Overlap with Known B-Cell Epitopes.

Development of efficient peptide-based immunotherapy for shrimp allergy relies on the identification of the dominant T-cell epitopes of its major allergen, tropomyosin. In this study, immunoinformatic tools, T-cell proliferation, cytokine release, IgG/IgE binding, and degranulation assays were used to identify and characterize the T-cell epitopes in Lit v 1 in comparison with previously validated B-cell epitopes. The results showed that of the six in silico predicted T-cell epitopes only one (T2: VQESLLKANIQLVEK, 60-74) promoted T-cell proliferation, the release of IL-2, and upregulated secretion of Th2-associated cytokines in the absence of IgG/IgE binding and degranulation activities.

Penetrating the Blood-Brain Barrier with New Peptide-Porphyrin Conjugates Having anti-HIV Activity.

Passing through the blood-brain barrier (BBB) to treat neurological conditions is one of the main hurdles in modern medicine. Many drugs with promising in vitro profiles become ineffective in vivo due to BBB restrictive permeability. In particular, this includes drugs such as antiviral porphyrins, with the ability to fight brain-resident viruses causing diseases such as HIV-associated neurocognitive disorders (HAND).

High-Yield Synthesis of Transglycosylated Mogrosides Improves the Flavor Profile of Monk Fruit Extract Sweeteners.

Luo Han Guo fruit extract (), mainly composed of mogroside V (50%), could be considered a suitable alternative to free sugars; however, its commercial applications are limited by its unpleasant off-notes. In the present work, a central composite design method was employed to optimize the transglycosylation of a mogroside extract using cyclodextrin glucosyltransferases (CGTases) from three different bacteriological sources (, sp., and sp.

Transglycosylation of Steviol Glycosides and Rebaudioside A: Synthesis Optimization, Structural Analysis and Sensory Profiles.

To improve flavor profiles, three cyclodextrin glucosyltransferases (CGTases) from different bacteriological sources, , sp. and sp., were used with an extract of steviol glycosides (SVglys) and rebaudioside A (RebA) as acceptor substrates in two parallel sets of reactions.

Plasticisers and preservatives in commercial milk products: A comprehensive study on packages used in the Spanish market.

A comprehensive study on packaging used in commercially available milk products from Spanish markets has been presented. Concentrations of four phthalates, seven parabens and BPA were determined in forty-two milk products. Eleven brands and five types of packaging (metallic aluminium bag, carton, high-density polyethylene, metal pail and polyethylene terephthalate) were included in the study.

Proteomics-Based Methodologies for the Detection and Quantification of Seafood Allergens.

Seafood is considered one of the main food allergen sources by the European Food Safety Authority (EFSA). It comprises several distinct groups of edible aquatic animals, including fish and shellfish, such as crustacean and mollusks. Recently, the EFSA recognized the high risk of food allergy over the world and established the necessity of developing new methodologies for its control.

Congener-specific determination of hydroxylated polychlorinated biphenyls by polar-embedded reversed-phase liquid chromatography-tandem mass spectrometry.

This paper reports the development of an LC-ESI-MS method for the sensitive determination of hydroxylated polychlorinated biphenyls (OH-PCBs) in human serum samples. Congener-specific separation was achieved by using a polar-embedded stationary phase, previously optimized for the working group, which provided better separation of isobaric compounds than the common octadecylsilane phases. MS fragmentation patterns and energies showed differences among OH-PCB congeners, mainly depending on the position of OH-group and the number of chlorine atoms in the molecule, although the most intense transitions were always those corresponding to the neutral loss of an HCl group from the quasi-molecular ion cluster.

Disulfide Engineered Lipase to Enhance the Catalytic Activity: A Structure-Based Approach on BTL2.

Enhancement, control, and tuning of hydrolytic activity and specificity of lipases are major goals for the industry. Thermoalkaliphilic lipases from the I.5 family, with their native advantages such as high thermostability and tolerance to alkaline pHs, are a target for biotechnological applications.

Pyrrolopyrimidine vs Imidazole-Phenyl-Thiazole Scaffolds in Nonpeptidic Dimerization Inhibitors of Leishmania infantum Trypanothione Reductase.

Disruption of protein-protein interactions of essential oligomeric enzymes by small molecules represents a significant challenge. We recently reported some linear and cyclic peptides derived from an α-helical region present in the homodimeric interface of Leishmania infantum trypanothione reductase ( Li-TryR) that showed potent effects on both dimerization and redox activity of this essential enzyme. Here, we describe our first steps toward the design of nonpeptidic small-molecule Li-TryR dimerization disruptors using a proteomimetic approach.

Direct quantification of inorganic iodine in seawater by mixed-mode liquid chromatography-electrospray ionization-mass spectrometry.

Atmospheric iodine plays a relevant role in climate change. Bearing in mind that most of this iodine comes from the oceans, analytical methods capable of determining iodine in a challenging matrix as seawater are necessary. In this work, the first method capable of direct determination of total inorganic iodine in seawater at subnanomolar level based on mixed-mode liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) without any sample treatment is presented.

Structure-Related Roles for the Conservation of the HIV-1 Fusion Peptide Sequence Revealed by Nuclear Magnetic Resonance.

Despite extensive characterization of the human immunodeficiency virus type 1 (HIV-1) hydrophobic fusion peptide (FP), the structure-function relationships underlying its extraordinary degree of conservation remain poorly understood. Specifically, the fact that the tandem repeat of the FLGFLG tripeptide is absolutely conserved suggests that high hydrophobicity may not suffice to unleash FP function. Here, we have compared the nuclear magnetic resonance (NMR) structures adopted in nonpolar media by two FP surrogates, wtFP-tag and scrFP-tag, which had equal hydrophobicity but contained wild-type and scrambled core sequences LFLGFLG and FGLLGFL, respectively.

Stabilization of Telomeric I-Motif Structures by (2'S)-2'-Deoxy-2'-C-Methylcytidine Residues.

G-quadruplexes and i-motifs are tetraplex structures present in telomeres and the promoter regions of oncogenes. The possibility of producing nanodevices with pH-sensitive functions has triggered interest in modified oligonucleotides with improved structural properties. We synthesized C-rich oligonucleotides carrying conformationally restricted (2'S)-2'-deoxy-2'-C-methyl-cytidine units.

Histone chaperone activity of Arabidopsis thaliana NRP1 is blocked by cytochrome c.

Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone chaperone-mediated nucleosome disassembly/reassembly is essential for DNA to be accessible to repair machinery. However, little is known about the specific role and modulation of histone chaperones in the context of DNA damage in plants.

Structural basis for broad neutralization of HIV-1 through the molecular recognition of 10E8 helical epitope at the membrane interface.

The mechanism by which the HIV-1 MPER epitope is recognized by the potent neutralizing antibody 10E8 at membrane interfaces remains poorly understood. To solve this problem, we have optimized a 10E8 peptide epitope and analyzed the structure and binding activities of the antibody in membrane and membrane-like environments. The X-ray crystal structure of the Fab-peptide complex in detergents revealed for the first time that the epitope of 10E8 comprises a continuous helix spanning the gp41 MPER/transmembrane domain junction (MPER-N-TMD; Env residues 671-687).

Structural Basis for a Unique ATP Synthase Core Complex from Nanoarcheaum equitans.

ATP synthesis is a critical and universal life process carried out by ATP synthases. Whereas eukaryotic and prokaryotic ATP synthases are well characterized, archaeal ATP synthases are relatively poorly understood. The hyperthermophilic archaeal parasite, Nanoarcheaum equitans, lacks several subunits of the ATP synthase and is suspected to be energetically dependent on its host, Ignicoccus hospitalis.

Random Coordinate Descent with Spinor-matrices and Geometric Filters for Efficient Loop Closure.

Protein loop closure constitutes a critical step in loop and protein modeling whereby geometrically feasible loops must be found between two given anchor residues. Here, a new analytic/iterative algorithm denoted random coordinate descent (RCD) to perform protein loop closure is described. The algorithm solves loop closure through minimization as in cyclic coordinate descent but selects bonds for optimization randomly, updates loop conformations by spinor-matrices, performs loop closure in both chain directions, and uses a set of geometric filters to yield efficient conformational sampling.