Open AccessReview
Protein–Phospholipid Interaction Motifs: A Focus on Phosphatidic Acid
Biomolecules 2018, 8(2), 20; doi:10.3390/biom8020020 (registering DOI) -
Abstract
Cellular membranes are composed of thousands of different lipids usually maintained within a narrow range of concentrations. In addition to their well-known structural and metabolic roles, signaling functions for many lipids have also emerged over the last two decades. The latter largely depend
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Cellular membranes are composed of thousands of different lipids usually maintained within a narrow range of concentrations. In addition to their well-known structural and metabolic roles, signaling functions for many lipids have also emerged over the last two decades. The latter largely depend on the ability of particular classes of lipids to interact specifically with a great variety of proteins and to regulate their localization and activity. Among these lipids, phosphatidic acid (PA) plays a unique role in a large repertoire of cellular activities, most likely in relation to its unique biophysical properties. However, until recently, only incomplete information was available to model the interaction between PA and its protein partners. The development of new liposome-based assays as well as molecular dynamic simulation are now providing novel information. We will review the different factors that have shown to modulate the capacity of PA to interact with specific domains in target proteins. Full article
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Open AccessFeature PaperArticle
Improving the Activity of Trp-Rich Antimicrobial Peptides by Arg/Lys Substitutions and Changing the Length of Cationic Residues
Biomolecules 2018, 8(2), 19; doi:10.3390/biom8020019 -
Abstract
Antimicrobial peptides (AMPs) constitute a promising alternative for the development of new antibiotics that could potentially counteract the growing number of antibiotic-resistant bacteria. However, the AMP structure–function relationships remain unclear and detailed studies are still necessary. The positively charged amino acid residues (Arg
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Antimicrobial peptides (AMPs) constitute a promising alternative for the development of new antibiotics that could potentially counteract the growing number of antibiotic-resistant bacteria. However, the AMP structure–function relationships remain unclear and detailed studies are still necessary. The positively charged amino acid residues (Arg and Lys) play a crucial role in the activity of most AMPs due to the promotion of electrostatic interactions between the peptides and bacterial membranes. In this work we have analyzed the antimicrobial and structural properties of several Trp-rich AMPs containing exclusively either Arg or Lys as the positively charged residues. Their antimicrobial activity and mechanism of action were investigated, showing that Lys residues give rise to a reduced antimicrobial potency for most peptides, which was correlated, in turn, with a decrease in their ability to permeabilize the cytoplasmic membrane of Escherichia coli. Additionally, the presence of Arg and Lys renders the peptides susceptible to degradation by proteases, such as trypsin, limiting their therapeutic use. Therefore, modifications of the side chain length of Arg and Lys were investigated in an attempt to improve the protease resistance of AMPs. This approach resulted in enhanced stability to trypsin digestion, and in several cases, shorter sidechains conserved or even improved the antimicrobial activity. All together, these results suggest that Arg-to-Lys substitutions, coupled with side chain length modifications, can be extremely useful for improving the activity and stability of AMPs. Full article
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Open AccessReview
Biophysical Investigations Elucidating the Mechanisms of Action of Antimicrobial Peptides and Their Synergism
Biomolecules 2018, 8(2), 18; doi:10.3390/biom8020018 -
Abstract
Biophysical and structural investigations are presented with a focus on the membrane lipid interactions of cationic linear antibiotic peptides such as magainin, PGLa, LL37, and melittin. Observations made with these peptides are distinct as seen from data obtained with the hydrophobic peptide alamethicin.
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Biophysical and structural investigations are presented with a focus on the membrane lipid interactions of cationic linear antibiotic peptides such as magainin, PGLa, LL37, and melittin. Observations made with these peptides are distinct as seen from data obtained with the hydrophobic peptide alamethicin. The cationic amphipathic peptides predominantly adopt membrane alignments parallel to the bilayer surface; thus the distribution of polar and non-polar side chains of the amphipathic helices mirror the environmental changes at the membrane interface. Such a membrane partitioning of an amphipathic helix has been shown to cause considerable disruptions in the lipid packing arrangements, transient openings at low peptide concentration, and membrane disintegration at higher peptide-to-lipid ratios. The manifold supramolecular arrangements adopted by lipids and peptides are represented by the ‘soft membranes adapt and respond, also transiently’ (SMART) model. Whereas molecular dynamics simulations provide atomistic views on lipid membranes in the presence of antimicrobial peptides, the biophysical investigations reveal interesting details on a molecular and supramolecular level, and recent microscopic imaging experiments delineate interesting sequences of events when bacterial cells are exposed to such peptides. Finally, biophysical studies that aim to reveal the mechanisms of synergistic interactions of magainin 2 and PGLa are presented, including unpublished isothermal titration calorimetry (ITC), circular dichroism (CD) and dynamic light scattering (DLS) measurements that suggest that the peptides are involved in liposome agglutination by mediating intermembrane interactions. A number of structural events are presented in schematic models that relate to the antimicrobial and synergistic mechanism of amphipathic peptides when they are aligned parallel to the membrane surface. Full article
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Open AccessArticle
Association between Resistin Gene Polymorphisms and Atopic Dermatitis
Biomolecules 2018, 8(2), 17; doi:10.3390/biom8020017 -
Abstract
Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disorder. It is characterized by an inappropriate skin barrier function, allergen sensitization, and recurrent skin infections. Resistin is an adipokine expressed mainly in macrophages and monocytes; it has a role in the inflammatory
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Atopic dermatitis (AD) is a chronic, relapsing, and inflammatory skin disorder. It is characterized by an inappropriate skin barrier function, allergen sensitization, and recurrent skin infections. Resistin is an adipokine expressed mainly in macrophages and monocytes; it has a role in the inflammatory process and is associated with multiple inflammatory human diseases; however, only few studies linked resistin to atopic dermatitis. This study tested the association between G>A (rs3745367) and C>T (rs3219177) single nucleotide polymorphisms (SNPs) of the RETN gene with atopic dermatitis. In addition, it explored the relationship between serum resistin protein and atopic dermatitis. To achieve objectives of this study, 162 atopic dermatitis patients and 161 healthy participants were recruited in the study. A significant association was detected between rs3745367 and atopic dermatitis with age and gender specificity (p < 0.05), while no significant association between rs3219177 and atopic dermatitis was found (p > 0.05). For the serum resistin levels, a significant decrease was indicated in atopic dermatitis patients compared to healthy subjects (p < 0.05). In conclusion, rs3745367 may play a gender and age-specific role in atopic dermatitis. In addition, the significant decrease in the resistin protein level confirmed this association. Full article
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Open AccessMeeting Report
Role of Nutrition in Alcoholic Liver Disease: Summary of the Symposium at the ESBRA 2017 Congress
Biomolecules 2018, 8(2), 16; doi:10.3390/biom8020016 -
Abstract
The symposium, “Role of Nutrition in Alcoholic Liver Disease”, was held at the European Society for Biomedical Research on Alcoholism Congress on 9 October 2017 in Crete, Greece. The goal of the symposium was to highlight recent advances and developments in the field
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The symposium, “Role of Nutrition in Alcoholic Liver Disease”, was held at the European Society for Biomedical Research on Alcoholism Congress on 9 October 2017 in Crete, Greece. The goal of the symposium was to highlight recent advances and developments in the field of alcohol and nutrition. The symposium was focused on experimental and clinical aspects in relation to the role of different types of dietary nutrients and malnutrition in the pathogenesis of alcoholic liver disease (ALD). The following is a summary of key research presented at this session. The speakers discussed the role of dietary fats and carbohydrates in the development and progression of alcohol-induced multi-organ pathology in animal models of ALD, analyzed novel nutrition-related therapeutics (specifically, betaine and zinc) in the treatment of ALD, and addressed clinical relevance of malnutrition and nutrition support in ALD. This summary of the symposium will benefit junior and senior faculty currently investigating alcohol-induced organ pathology as well as undergraduate, graduate, and post-graduate students and fellows. Full article
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Open AccessArticle
An Arabidopsis Clathrin Assembly Protein with a Predicted Role in Plant Defense Can Function as an Adenylate Cyclase
Biomolecules 2018, 8(2), 15; doi:10.3390/biom8020015 -
Abstract
Adenylate cyclases (ACs), much like guanylate cyclases (GCs), are increasingly recognized as essential parts of many plant processes including biotic and abiotic stress responses. In order to identify novel ACs, we have applied a search motif derived from experimentally tested GCs and identified
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Adenylate cyclases (ACs), much like guanylate cyclases (GCs), are increasingly recognized as essential parts of many plant processes including biotic and abiotic stress responses. In order to identify novel ACs, we have applied a search motif derived from experimentally tested GCs and identified a number of Arabidopsis thaliana candidates including a clathrin assembly protein (AT1G68110; AtClAP). AtClAP contains a catalytic centre that can complement the AC-deficient mutant cyaA in E. coli, and a recombinant AtClAP fragment (AtClAP261–379) can produce cyclic adenosine 3′,5′ monophosphate (cAMP) from adenosine triphosphate (ATP) in vitro. Furthermore, an integrated analysis of gene expression and expression correlation implicate cAMP in pathogen defense and in actin cytoskeletal remodeling during endocytic internalization. Full article
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Open AccessReview
p53-Mediated Molecular Control of Autophagy in Tumor Cells
Biomolecules 2018, 8(2), 14; doi:10.3390/biom8020014 -
Abstract
Autophagy is an indispensable mechanism of the eukaryotic cell, facilitating the removal and renewal of cellular components and thereby balancing the cell’s energy consumption and homeostasis. Deregulation of autophagy is now regarded as one of the characteristic key features contributing to the development
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Autophagy is an indispensable mechanism of the eukaryotic cell, facilitating the removal and renewal of cellular components and thereby balancing the cell’s energy consumption and homeostasis. Deregulation of autophagy is now regarded as one of the characteristic key features contributing to the development of tumors. In recent years, the suppression of autophagy in combination with chemotherapeutic treatment has been approached as a novel therapy in cancer treatment. However, depending on the type of cancer and context, interference with the autophagic machinery can either promote or disrupt tumorigenesis. Therefore, disclosure of the major signaling pathways that regulate autophagy and control tumorigenesis is crucial. To date, several tumor suppressor proteins and oncogenes have emerged as eminent regulators of autophagy whose depletion or mutation favor tumor formation. The mammalian cell “janitor” p53 belongs to one of these tumor suppressors that are most commonly mutated in human tumors. Experimental evidence over the last decade convincingly reports that p53 can act as either an activator or an inhibitor of autophagy depending on its subcellular localization and its mode of action. This finding gains particular significance as p53 deficiency or mutant variants of p53 that accumulate in the cytoplasm of tumor cells enable activation of autophagy. Accordingly, we recently identified p53 as a molecular hub that regulates autophagy and apoptosis in histone deacetylase inhibitor-treated uterine sarcoma cells. In light of this novel experimental evidence, in this review, we focus on p53 signaling as a mediator of the autophagic pathway in tumor cells. Full article
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Open AccessArticle
Amyloid Assembly Endows Gad m 1 with Biomineralization Properties
Biomolecules 2018, 8(1), 13; doi:10.3390/biom8010013 -
Abstract
Acid proteins capable of nucleating Ca2+ and displaying aggregation capacity play key roles in the formation of calcium carbonate biominerals. The helix-loop helix EF-hands are the most common Ca2+-binding motifs in proteins. Calcium is bound by the loop region. These
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Acid proteins capable of nucleating Ca2+ and displaying aggregation capacity play key roles in the formation of calcium carbonate biominerals. The helix-loop helix EF-hands are the most common Ca2+-binding motifs in proteins. Calcium is bound by the loop region. These motifs are found in many proteins that are regulated by calcium. Gad m 1, an Atlantic cod β-parvalbumin isoform, is a monomeric EF-hand protein that acts as a Ca2+ buffer in fish muscle; the neutral and acid apo-forms of this protein can form amyloids. Since Ca2+-nucleating proteins have a propensity to form extended β-strand structures, we wondered whether amyloid assemblies of an EF-hand protein were able to influence calcium carbonate crystallization in vitro. Here, we used the Gad m 1 chain as a model to generate monomeric and amyloid assemblies and to analyze their effect on calcite formation in vitro. We found that only amyloid assemblies alter calcite morphology. Full article
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Open AccessFeature PaperArticle
The Impact of Protein Structure and Sequence Similarity on the Accuracy of Machine-Learning Scoring Functions for Binding Affinity Prediction
Biomolecules 2018, 8(1), 12; doi:10.3390/biom8010012 -
Abstract
It has recently been claimed that the outstanding performance of machine-learning scoring functions (SFs) is exclusively due to the presence of training complexes with highly similar proteins to those in the test set. Here, we revisit this question using 24 similarity-based training sets,
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It has recently been claimed that the outstanding performance of machine-learning scoring functions (SFs) is exclusively due to the presence of training complexes with highly similar proteins to those in the test set. Here, we revisit this question using 24 similarity-based training sets, a widely used test set, and four SFs. Three of these SFs employ machine learning instead of the classical linear regression approach of the fourth SF (X-Score which has the best test set performance out of 16 classical SFs). We have found that random forest (RF)-based RF-Score-v3 outperforms X-Score even when 68% of the most similar proteins are removed from the training set. In addition, unlike X-Score, RF-Score-v3 is able to keep learning with an increasing training set size, becoming substantially more predictive than X-Score when the full 1105 complexes are used for training. These results show that machine-learning SFs owe a substantial part of their performance to training on complexes with dissimilar proteins to those in the test set, against what has been previously concluded using the same data. Given that a growing amount of structural and interaction data will be available from academic and industrial sources, this performance gap between machine-learning SFs and classical SFs is expected to enlarge in the future. Full article
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Open AccessFeature PaperReview
DOT1L and H3K79 Methylation in Transcription and Genomic Stability
Biomolecules 2018, 8(1), 11; doi:10.3390/biom8010011 -
Abstract
The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA.
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The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA. Yeast Dot1 and the mammalian homologue DOT1L are methyltransferases that can add up to three methyl groups to histone H3 lysine 79 (H3K79). H3K79 methylation is implicated in several processes, including transcription elongation by RNA polymerase II, the DNA damage response and cell cycle checkpoint activation. DOT1L is also an important drug target for treatment of mixed lineage leukemia (MLL)-rearranged leukemia where aberrant transcriptional activation is promoted by DOT1L mislocalisation. This review summarizes what is currently known about the role of Dot1/DOT1L and H3K79 methylation in transcription and genomic stability. Full article
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Open AccessArticle
Bioconversion of Tyrosine and Tryptophan Derived Biogenic Amines by Neuropathogenic Bacteria
Biomolecules 2018, 8(1), 10; doi:10.3390/biom8010010 -
Abstract
The biochemical potential of pathogenic bacteria may cause alteration in the neurophysiological environment; consequently, neuroendocrine and immune responses of the host are modulated by endogenously produced metabolic products of neuropathogenic bacteria. The present study was designed to detect the derived biogenic amines in
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The biochemical potential of pathogenic bacteria may cause alteration in the neurophysiological environment; consequently, neuroendocrine and immune responses of the host are modulated by endogenously produced metabolic products of neuropathogenic bacteria. The present study was designed to detect the derived biogenic amines in spent culture media of Bacillus cereus (Bc), Clostridium tetani (Ct), Listeria monocytogenes (Lm), and Neisseria meningitidis (Nm). Overnight grown culture in different culture media i.e., Nutrient broth (NB), Luria basal broth (LB), Brain Heart Infusion broth (BHI), and human serum supplemented RPMI 1640 medium (RPMI) were used to prepare filter-sterilized, cell-free cultural broths (SCFBs) and subjected to high performance liquid chromatography with electrochemical detection (HPLC-EC) along with the control SCFBs. Comparative analysis of biogenic amines in neuropathogenic bacterial SCFBs with their respective control (SCFB) revealed the complete degradation of dopamine (DA) into its metabolic products by Bc, Ct, and Nm, whereas Lm showed negligible degradation of DA. A relatively high concentration of 5-hydroxyindol acetic acid (5HIAA) by Bc in NB and LB indicated the tryptophan metabolism by the serotonin (5HT) pathway. Our study suggests that microbial endocrinology could help unravel new perspectives to the progression of infectious diseases. Full article
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Open AccessFeature PaperArticle
Attenuation of Glucose-Induced Myoglobin Glycation and the Formation of Advanced Glycation End Products (AGEs) by (R)-α-Lipoic Acid In Vitro
Biomolecules 2018, 8(1), 9; doi:10.3390/biom8010009 -
Abstract
High-carbohydrate containing diets have become a precursor to glucose-mediated protein glycation which has been linked to an increase in diabetic and cardiovascular complications. The aim of the present study was to evaluate the protective effect of (R)-α-lipoic acid (ALA) against glucose-induced
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High-carbohydrate containing diets have become a precursor to glucose-mediated protein glycation which has been linked to an increase in diabetic and cardiovascular complications. The aim of the present study was to evaluate the protective effect of (R)-α-lipoic acid (ALA) against glucose-induced myoglobin glycation and the formation of advanced glycation end products (AGEs) in vitro. Methods: The effect of ALA on myoglobin glycation was determined via the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The extent of glycation-induced myoglobin oxidation was measured via the levels of protein carbonyl and thiol. Results: The results showed that the co-incubation of ALA (1, 2 and 4 mM) with myoglobin (1 mg/mL) and glucose (1 M) significantly decreased the levels of fructosamine, which is directly associated with the decrease in the formation of AGEs. Furthermore, ALA significantly reduced the release of free iron from myoglobin which is attributed to the protection of myoglobin from glucose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin from oxidative damage, as seen from the decreased protein carbonyls and increased protein thiols. Conclusion: The anti-glycation properties of ALA suggest that ALA supplementation may be beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications. Full article
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Open AccessCommunication
Elsinopirins A–D, Decalin Polyketides from the Ascomycete Elsinoё pyri
Biomolecules 2018, 8(1), 8; doi:10.3390/biom8010008 -
Abstract
In course of our screening for new secondary metabolites from ecological niche specialized, phytopathogenic fungi, the plant pathogen Elsinoё pyri, strain 2203C, was found to produce four novel compounds (14), which were named elsinopirins A–D, in addition to
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In course of our screening for new secondary metabolites from ecological niche specialized, phytopathogenic fungi, the plant pathogen Elsinoё pyri, strain 2203C, was found to produce four novel compounds (14), which were named elsinopirins A–D, in addition to the known metabolite elsinochrome A (5). After isolation by preparative high-performance liquid chromatography (HPLC), their structures, including relative stereochemistry, were elucidated by 1D and 2D nuclear magnetic resonance (NMR) and mass spectrometry (MS) data. Finally, absolute stereochemistry was assigned by chemical shifts of Mosher’s esters (α-methoxy-α-trifluoromethylphenylacetic acid; MTPA) derivatives of elsinopirin B (2). The compounds were found to be devoid of significant antibacterial, antifungal, and cytotoxic activities. Full article
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Open AccessReview
PIM Kinases and Their Relevance to the PI3K/AKT/mTOR Pathway in the Regulation of Ovarian Cancer
Biomolecules 2018, 8(1), 7; doi:10.3390/biom8010007 -
Abstract
Ovarian cancer is a medical term that includes a number of tumors with different molecular biology, phenotypes, tumor progression, etiology, and even different diagnosis. Some specific treatments are required to address this heterogeneity of ovarian cancer, thus molecular characterization may provide an important
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Ovarian cancer is a medical term that includes a number of tumors with different molecular biology, phenotypes, tumor progression, etiology, and even different diagnosis. Some specific treatments are required to address this heterogeneity of ovarian cancer, thus molecular characterization may provide an important tool for this purpose. On a molecular level, proviral-integration site for Moloney-murine leukemia virus (PIM) kinases are over expressed in ovarian cancer and play a vital role in the regulation of different proteins responsible for this tumorigenesis. Likewise, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is also a central regulator of the ovarian cancer. Interestingly, recent research has linked the PIM kinases to the PI3K/AKT/mTOR pathway in several types of cancers, but their connection in ovarian cancer has not been studied yet. Once the exact relationship of PIM kinases with the PI3K/AKT/mTOR pathway is acquired in ovarian cancer, it will hopefully provide effective treatments on a molecular level. This review mainly focuses on the role of PIM kinases in ovarian cancer and their interactions with proteins involved in its progression. In addition, this review suggests a connection between the PIM kinases and the PI3K/AKT/mTOR pathway and their parallel mechanism in the regulation of ovarian cancer. Full article
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Open AccessEditorial
Acknowledgement to Reviewers of Biomolecules in 2017
Biomolecules 2018, 8(1), 6; doi:10.3390/biom8010006 -
Abstract
Peer review is an essential part in the publication process, ensuring that Biomolecules maintains high quality standards for its published papers.[...] Full article
Open AccessArticle
The Functional Amyloid Curli Protects Escherichia coli against Complement-Mediated Bactericidal Activity
Biomolecules 2018, 8(1), 5; doi:10.3390/biom8010005 -
Abstract
Escherichia coli strains may be beneficial or pathogenic. Many E. coli strains that cause human disease, especially those responsible for bacteremia and sepsis, express virulence factors that impart resistance to the complement system. The bacterial amyloid curli functions in bacterial adherence and enhances
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Escherichia coli strains may be beneficial or pathogenic. Many E. coli strains that cause human disease, especially those responsible for bacteremia and sepsis, express virulence factors that impart resistance to the complement system. The bacterial amyloid curli functions in bacterial adherence and enhances the formation of biofilms. Survival of curli-producing parental and curli-deficient mutant E. coli in the context of a human complement response was evaluated using an in vivo murine model of bacteremia. Results showed that curli production enhanced E. coli survival, which suggests that curli defends against complement-mediated killing. This observation was supported by the results of in vitro assays comparing bacterial survival in human serum. Experiments in which the classical or alternative complement pathways were blocked indicated that the classical pathway is the major contributor to complement activation and that curli inhibits this activity. Our analyses indicate that curli does not appear to play a role in protecting E. coli against alternative pathway complement activation. We found that curli increases binding of E. coli cells to complement component Complement component 1q (C1q) but does not affect Complement component 3b (C3b) binding. We conclude that curli defends E. coli against complement-mediated killing via inhibition of the classical complement pathway. Full article
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Open AccessReview
Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo
Biomolecules 2018, 8(1), 4; doi:10.3390/biom8010004 -
Abstract
Antibiotic resistance is projected as one of the greatest threats to human health in the future and hence alternatives are being explored to combat resistance. Antimicrobial peptides (AMPs) have shown great promise, because use of AMPs leads bacteria to develop no or low
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Antibiotic resistance is projected as one of the greatest threats to human health in the future and hence alternatives are being explored to combat resistance. Antimicrobial peptides (AMPs) have shown great promise, because use of AMPs leads bacteria to develop no or low resistance. In this review, we discuss the diversity, history and the various mechanisms of action of AMPs. Although many AMPs have reached clinical trials, to date not many have been approved by the US Food and Drug Administration (FDA) due to issues with toxicity, protease cleavage and short half-life. Some of the recent strategies developed to improve the activity and biocompatibility of AMPs, such as chemical modifications and the use of delivery systems, are also reviewed in this article. Full article
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Open AccessReview
Rodent Models of Alcoholic Liver Disease: Role of Binge Ethanol Administration
Biomolecules 2018, 8(1), 3; doi:10.3390/biom8010003 -
Abstract
Both chronic and acute (binge) alcohol drinking are important health and economic concerns worldwide and prominent risk factors for the development of alcoholic liver disease (ALD). There are no FDA-approved medications to prevent or to treat any stage of ALD. Therefore, discovery of
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Both chronic and acute (binge) alcohol drinking are important health and economic concerns worldwide and prominent risk factors for the development of alcoholic liver disease (ALD). There are no FDA-approved medications to prevent or to treat any stage of ALD. Therefore, discovery of novel therapeutic strategies remains a critical need for patients with ALD. Relevant experimental animal models that simulate human drinking patterns and mimic the spectrum and severity of alcohol-induced liver pathology in humans are critical to our ability to identify new mechanisms and therapeutic targets. There are several animal models currently in use, including the most widely utilized chronic ad libitum ethanol (EtOH) feeding (Lieber–DeCarli liquid diet model), chronic intragastric EtOH administration (Tsukamoto–French model), and chronic-plus-binge EtOH challenge (Bin Gao—National Institute on Alcohol Abuse and Alcoholism (NIAAA) model). This review provides an overview of recent advances in rodent models of binge EtOH administration which help to recapitulate different features and etiologies of progressive ALD. These models include EtOH binge alone, and EtOH binge coupled with chronic EtOH intake, a high fat diet, or endotoxin challenge. We analyze the strengths, limitations, and translational relevance of these models, as well as summarize the liver injury outcomes and mechanistic insights. We further discuss the application(s) of binge EtOH models in examining alcohol-induced multi-organ pathology, sex- and age-related differences, as well as circadian rhythm disruption. Full article
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Open AccessArticle
Evaluation of the Simultaneous Production of Xylitol and Ethanol from Sisal Fiber
Biomolecules 2018, 8(1), 2; doi:10.3390/biom8010002 -
Abstract
Recent years have seen an increase in the use of lignocellulosic materials in the development of bioproducts. Because sisal fiber is a low cost raw material and is readily available, this work aimed to evaluate its hemicellulose fraction for the simultaneous production of
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Recent years have seen an increase in the use of lignocellulosic materials in the development of bioproducts. Because sisal fiber is a low cost raw material and is readily available, this work aimed to evaluate its hemicellulose fraction for the simultaneous production of xylitol and ethanol. The sisal fiber presented a higher hemicellulose content than other frequently-employed biomasses, such as sugarcane bagasse. A pretreatment with dilute acid and low temperatures was conducted in order to obtain the hemicellulose fraction. The highest xylose contents (0.132 g·g−1 of sisal fiber) were obtained at 120 °C with 2.5% (v/v) of sulfuric acid. The yeast Candida tropicalis CCT 1516 was used in the fermentation. In the sisal fiber hemicellulose hydrolysate, the maximum production of xylitol (0.32 g·g−1) and of ethanol (0.27 g·g−1) was achieved in 60 h. Thus, sisal fiber presents as a potential biomass for the production of ethanol and xylitol, creating value with the use of hemicellulosic liquor without detoxification and without the additional steps of alkaline pretreatment. Full article
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Open AccessReview
Emerging Roles for VEGF-D in Human Disease
Biomolecules 2018, 8(1), 1; doi:10.3390/biom8010001 -
Abstract
Blood vessels and lymphatic vessels are located in many tissues and organs throughout the body, and play important roles in a wide variety of prevalent diseases in humans. Vascular endothelial growth factor-D (VEGF-D) is a secreted protein that can promote the remodeling of
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Blood vessels and lymphatic vessels are located in many tissues and organs throughout the body, and play important roles in a wide variety of prevalent diseases in humans. Vascular endothelial growth factor-D (VEGF-D) is a secreted protein that can promote the remodeling of blood vessels and lymphatics in development and disease. Recent fundamental and translational studies have provided insight into the molecular mechanisms by which VEGF-D exerts its effects in human disease. Hence this protein is now of interest as a therapeutic and/or diagnostic target, or as a potential therapeutic agent, in a diversity of indications in cardiovascular medicine, cancer and the devastating pulmonary condition lymphangioleiomyomatosis. This has led to clinical trial programs to assess the effect of targeting VEGF-D signaling pathways, or delivering VEGF-D, in angina, cancer and ocular indications. This review summarizes our understanding of VEGF-D signaling in human disease, which is largely based on animal disease models and clinicopathological studies, and provides information about the outcomes of recent clinical trials testing agonists or antagonists of VEGF-D signaling. Full article
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