Next Issue
Previous Issue

E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Table of Contents

Int. J. Mol. Sci., Volume 19, Issue 2 (February 2018)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
Cover Story (view full-size image) The IL-23/IL-17 axis mediates the initiation and persistence of inflammation during Psoriasis and [...] Read more.
View options order results:
result details:
Displaying articles 1-327
Export citation of selected articles as:
Open AccessArticle Fine Physical Bin Mapping of the Powdery Mildew Resistance Gene Pm21 Based on Chromosomal Structural Variations in Wheat
Int. J. Mol. Sci. 2018, 19(2), 643; https://doi.org/10.3390/ijms19020643
Received: 31 January 2018 / Revised: 19 February 2018 / Accepted: 22 February 2018 / Published: 24 February 2018
Viewed by 829 | PDF Full-text (342 KB) | HTML Full-text | XML Full-text
Abstract
Pm21, derived from wheat wild relative Dasypyrum villosum, is one of the most effective powdery mildew resistance genes and has been widely applied in wheat breeding in China. Mapping and cloning Pm21 are of importance for understanding its resistance mechanism. In
[...] Read more.
Pm21, derived from wheat wild relative Dasypyrum villosum, is one of the most effective powdery mildew resistance genes and has been widely applied in wheat breeding in China. Mapping and cloning Pm21 are of importance for understanding its resistance mechanism. In the present study, physical mapping was performed using different genetic stocks involving in structural variations of chromosome 6VS carrying Pm21. The data showed that 6VS could be divided into eight distinguishable chromosomal bins, and Pm21 was mapped to the bin FLb4–b5/b6 closely flanked by the markers 6VS-08.6 and 6VS-10.2. Comparative genomic mapping indicated that the orthologous regions of FLb4–b5/b6 carrying Pm21 were narrowed to a 117.7 kb genomic region harboring 19 genes in Brachypodium and a 37.7 kb region harboring 5 genes in rice, respectively. The result was consistent with that given by recent genetic mapping in diploid D. villosum. In conclusion, this study demonstrated that physical mapping based on chromosomal structural variations is an efficient method for locating alien genes in wheat background. Full article
(This article belongs to the Section Molecular Plant Sciences)
Figures

Graphical abstract

Open AccessArticle Refining the Results of a Classical SELEX Experiment by Expanding the Sequence Data Set of an Aptamer Pool Selected for Protein A
Int. J. Mol. Sci. 2018, 19(2), 642; https://doi.org/10.3390/ijms19020642
Received: 9 January 2018 / Revised: 9 February 2018 / Accepted: 19 February 2018 / Published: 24 February 2018
Cited by 1 | Viewed by 1154 | PDF Full-text (3337 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
New, as yet undiscovered aptamers for Protein A were identified by applying next generation sequencing (NGS) to a previously selected aptamer pool. This pool was obtained in a classical SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiment using the FluMag-SELEX procedure followed
[...] Read more.
New, as yet undiscovered aptamers for Protein A were identified by applying next generation sequencing (NGS) to a previously selected aptamer pool. This pool was obtained in a classical SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiment using the FluMag-SELEX procedure followed by cloning and Sanger sequencing. PA#2/8 was identified as the only Protein A-binding aptamer from the Sanger sequence pool, and was shown to be able to bind intact cells of Staphylococcus aureus. In this study, we show the extension of the SELEX results by re-sequencing of the same aptamer pool using a medium throughput NGS approach and data analysis. Both data pools were compared. They confirm the selection of a highly complex and heterogeneous oligonucleotide pool and show consistently a high content of orphans as well as a similar relative frequency of certain sequence groups. But in contrast to the Sanger data pool, the NGS pool was clearly dominated by one sequence group containing the known Protein A-binding aptamer PA#2/8 as the most frequent sequence in this group. In addition, we found two new sequence groups in the NGS pool represented by PA-C10 and PA-C8, respectively, which also have high specificity for Protein A. Comparative affinity studies reveal differences between the aptamers and confirm that PA#2/8 remains the most potent sequence within the selected aptamer pool reaching affinities in the low nanomolar range of KD = 20 ± 1 nM. Full article
(This article belongs to the Section Biochemistry)
Figures

Graphical abstract

Open AccessReview Plant Mitochondrial Inner Membrane Protein Insertion
Int. J. Mol. Sci. 2018, 19(2), 641; https://doi.org/10.3390/ijms19020641
Received: 2 February 2018 / Revised: 20 February 2018 / Accepted: 22 February 2018 / Published: 24 February 2018
Cited by 4 | Viewed by 1087 | PDF Full-text (776 KB) | HTML Full-text | XML Full-text
Abstract
During the biogenesis of the mitochondrial inner membrane, most nuclear-encoded inner membrane proteins are laterally released into the membrane by the TIM23 and the TIM22 machinery during their import into mitochondria. A subset of nuclear-encoded mitochondrial inner membrane proteins and all the mitochondrial-encoded
[...] Read more.
During the biogenesis of the mitochondrial inner membrane, most nuclear-encoded inner membrane proteins are laterally released into the membrane by the TIM23 and the TIM22 machinery during their import into mitochondria. A subset of nuclear-encoded mitochondrial inner membrane proteins and all the mitochondrial-encoded inner membrane proteins use the Oxa machinery—which is evolutionarily conserved from the endosymbiotic bacterial ancestor of mitochondria—for membrane insertion. Compared to the mitochondria from other eukaryotes, plant mitochondria have several unique features, such as a larger genome and a branched electron transport pathway, and are also involved in additional cellular functions such as photorespiration and stress perception. This review focuses on the unique aspects of plant mitochondrial inner membrane protein insertion machinery, which differs from that in yeast and humans, and includes a case study on the biogenesis of Cox2 in yeast, humans, two plant species, and an algal species to highlight lineage-specific similarities and differences. Interestingly, unlike mitochondria of other eukaryotes but similar to bacteria and chloroplasts, plant mitochondria appear to use the Tat machinery for membrane insertion of the Rieske Fe/S protein. Full article
(This article belongs to the Special Issue Plant Mitochondria)
Figures

Figure 1

Open AccessArticle Non-Native Conformational Isomers of the Catalytic Domain of PCSK9 Induce an Immune Response, Reduce Lipids and Increase LDL Receptor Levels
Int. J. Mol. Sci. 2018, 19(2), 640; https://doi.org/10.3390/ijms19020640
Received: 11 January 2018 / Revised: 16 February 2018 / Accepted: 19 February 2018 / Published: 24 February 2018
Viewed by 777 | PDF Full-text (3383 KB) | HTML Full-text | XML Full-text
Abstract
PCSK9 (Proprotein convertase subtilisin/kexin type 9) increases plasma cholesterol levels by promoting LDL receptor degradation. Current antibody inhibitors block the interaction between PCSK9 and LDL receptors, significantly decrease plasma cholesterol levels, and provide beneficial clinical outcomes. To reduce the action of PCSK9 in
[...] Read more.
PCSK9 (Proprotein convertase subtilisin/kexin type 9) increases plasma cholesterol levels by promoting LDL receptor degradation. Current antibody inhibitors block the interaction between PCSK9 and LDL receptors, significantly decrease plasma cholesterol levels, and provide beneficial clinical outcomes. To reduce the action of PCSK9 in plasma, a novel strategy that will produce a panel of non-native, conformationally-altered isomers of PCSK9 (X-PCSK9) to develop active immunotherapy targeting of native PCSK9 and inhibiting/blocking the interaction of PCSK9 with LDL receptor, thus decreasing plasma cholesterol levels is proposed. The authors used the scrambled disulfide bond technique to generate conformationally-altered isomers of the catalytic domain of mouse PCSK9. The focus was on the immune response of four X-isomers and their effects on plasma cholesterol and triglyceride levels in both C57BL/6J and Apoe−/− mice. The authors showed that the four immunogens produced significant immunogenicity against native PCSK9 to day 120 after immunization of C57BL/6J and Apoe−/− mice. This resulted in significantly decreased plasma cholesterol levels in C57BL/6J mice, and to a lesser degree in Apoe−/− mice. The X-PCSK9-B1 treated mice had increased LDL receptor mRNA and protein levels at day 120 after treatment. Thus, this study provides a new, potentially promising approach that uses long-term immunotherapy for a treatment of hypercholesterolemia. Full article
(This article belongs to the Special Issue Cholesterol and Lipoprotein Metabolism)
Figures

Figure 1

Open AccessReview Ten Prominent Host Proteases in Plant-Pathogen Interactions
Int. J. Mol. Sci. 2018, 19(2), 639; https://doi.org/10.3390/ijms19020639
Received: 2 February 2018 / Revised: 17 February 2018 / Accepted: 17 February 2018 / Published: 24 February 2018
Cited by 4 | Viewed by 1052 | PDF Full-text (677 KB) | HTML Full-text | XML Full-text
Abstract
Proteases are enzymes integral to the plant immune system. Multiple aspects of defence are regulated by proteases, including the hypersensitive response, pathogen recognition, priming and peptide hormone release. These processes are regulated by unrelated proteases residing at different subcellular locations. In this review,
[...] Read more.
Proteases are enzymes integral to the plant immune system. Multiple aspects of defence are regulated by proteases, including the hypersensitive response, pathogen recognition, priming and peptide hormone release. These processes are regulated by unrelated proteases residing at different subcellular locations. In this review, we discuss 10 prominent plant proteases contributing to the plant immune system, highlighting the diversity of roles they perform in plant defence. Full article
(This article belongs to the Special Issue Plant Defense Genes Against Biotic Stresses)
Figures

Graphical abstract

Open AccessArticle Arabidopsis RETICULON-LIKE3 (RTNLB3) and RTNLB8 Participate in Agrobacterium-Mediated Plant Transformation
Int. J. Mol. Sci. 2018, 19(2), 638; https://doi.org/10.3390/ijms19020638
Received: 31 January 2018 / Revised: 21 February 2018 / Accepted: 21 February 2018 / Published: 24 February 2018
Viewed by 1135 | PDF Full-text (2903 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Agrobacterium tumefaciens can genetically transform various eukaryotic cells because of the presence of a resident tumor-inducing (Ti) plasmid. During infection, a defined region of the Ti plasmid, transfer DNA (T-DNA), is transferred from bacteria into plant cells and causes plant cells to abnormally
[...] Read more.
Agrobacterium tumefaciens can genetically transform various eukaryotic cells because of the presence of a resident tumor-inducing (Ti) plasmid. During infection, a defined region of the Ti plasmid, transfer DNA (T-DNA), is transferred from bacteria into plant cells and causes plant cells to abnormally synthesize auxin and cytokinin, which results in crown gall disease. T-DNA and several virulence (Vir) proteins are secreted through a type IV secretion system (T4SS) composed of T-pilus and a transmembrane protein complex. Three members of Arabidopsis reticulon-like B (RTNLB) proteins, RTNLB1, 2, and 4, interact with VirB2, the major component of T-pilus. Here, we have identified that other RTNLB proteins, RTNLB3 and 8, interact with VirB2 in vitro. Root-based A. tumefaciens transformation assays with Arabidopsis rtnlb3, or rtnlb5-10 single mutants showed that the rtnlb8 mutant was resistant to A. tumefaciens infection. In addition, rtnlb3 and rtnlb8 mutants showed reduced transient transformation efficiency in seedlings. RTNLB3- or 8 overexpression transgenic plants showed increased susceptibility to A. tumefaciens and Pseudomonas syringae infection. RTNLB1-4 and 8 transcript levels differed in roots, rosette leaves, cauline leaves, inflorescence, flowers, and siliques of wild-type plants. Taken together, RTNLB3 and 8 may participate in A. tumefaciens infection but may have different roles in plants. Full article
(This article belongs to the Special Issue Plant Innate Immunity 2.0)
Figures

Graphical abstract

Open AccessArticle Phosphate-Catalyzed Succinimide Formation from Asp Residues: A Computational Study of the Mechanism
Int. J. Mol. Sci. 2018, 19(2), 637; https://doi.org/10.3390/ijms19020637
Received: 6 February 2018 / Revised: 22 February 2018 / Accepted: 22 February 2018 / Published: 24 February 2018
Cited by 1 | Viewed by 784 | PDF Full-text (2811 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Aspartic acid (Asp) residues in proteins and peptides are prone to the non-enzymatic reactions that give biologically uncommon l-β-Asp, d-Asp, and d-β-Asp residues via the cyclic succinimide intermediate (aminosuccinyl residue, Suc). These abnormal Asp residues are known to have relevance
[...] Read more.
Aspartic acid (Asp) residues in proteins and peptides are prone to the non-enzymatic reactions that give biologically uncommon l-β-Asp, d-Asp, and d-β-Asp residues via the cyclic succinimide intermediate (aminosuccinyl residue, Suc). These abnormal Asp residues are known to have relevance to aging and pathologies. Despite being non-enzymatic, the Suc formation is thought to require a catalyst under physiological conditions. In this study, we computationally investigated the mechanism of the Suc formation from Asp residues that were catalyzed by the dihydrogen phosphate ion, H2PO4. We used Ac–l-Asp–NHMe (Ac = acetyl, NHMe = methylamino) as a model compound. The H2PO4 ion (as a catalyst) and two explicit water molecules (as solvent molecules stabilizing the negative charge) were included in the calculations. All of the calculations were performed by density functional theory with the B3LYP functional. We revealed a phosphate-catalyzed two-step mechanism (cyclization–dehydration) of the Suc formation, where the first step is predicted to be rate-determining. In both steps, the reaction involved a proton relay mediated by the H2PO4 ion. The calculated activation barrier for this mechanism (100.3 kJ mol−1) is in reasonable agreement with an experimental activation energy (107 kJ mol−1) for the Suc formation from an Asp-containing peptide in a phosphate buffer, supporting the catalytic mechanism of the H2PO4 ion that is revealed in this study. Full article
(This article belongs to the Section Molecular Biophysics)
Figures

Figure 1

Open AccessArticle Phytochemical Analysis by HPLC–HRESI-MS and Anti-Inflammatory Activity of Tabernaemontana catharinensis
Int. J. Mol. Sci. 2018, 19(2), 636; https://doi.org/10.3390/ijms19020636
Received: 22 November 2017 / Revised: 7 January 2018 / Accepted: 13 January 2018 / Published: 24 February 2018
Viewed by 1183 | PDF Full-text (3085 KB) | HTML Full-text | XML Full-text
Abstract
Tabernaemontana catharinensis (Apocynaceae) has been popularly used by folk medicine because of its anti-inflammatory, analgesic, and antiophidic properties. This study aims to analyze the flavonoids composition of the hydroethanolic extract and of the ethyl acetate (EtOAc) and butanol (BuOH) fractions of T. catharinensis
[...] Read more.
Tabernaemontana catharinensis (Apocynaceae) has been popularly used by folk medicine because of its anti-inflammatory, analgesic, and antiophidic properties. This study aims to analyze the flavonoids composition of the hydroethanolic extract and of the ethyl acetate (EtOAc) and butanol (BuOH) fractions of T. catharinensis leaves, as well as to evaluate their anti-inflammatory activity using in vivo models. The phytochemical profile, determined by High-Performance Liquid Chromatography–High-Resolution Electrospray Ionization-Mass Spectrometry (HPLC–HRESI-MS), showed the presence of flavonoids mainly having an isorhamnetin nucleus. The anti-inflammatory activity was evaluated in carrageenan-induced paw edema (pre- and post-treatment) with oral administration of a T. catharinensis hydroethanolic extract (50, 100, and 150 mg/kg) and of organic fractions (50 mg/kg). The extract and fractions showed antiedematogenic activity by decreasing myeloperoxidase (MPO) production. In the zymosan-air-pouch model, the extract and fractions inhibited leukocyte migration and significantly decreased the levels of various proteins, such as MPO, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α. The cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, which revealed no cytotoxicity of the extract and the fractions. These results suggest that the hydroethanolic extract and organic fractions of T. catharinensis leaves have sufficient anti-inflammatory activity to support the popular use of this plant in the treatment of inflammatory disorders. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
Figures

Graphical abstract

Open AccessArticle The In Vitro Effects of Enzymatic Digested Gliadin on the Functionality of the Autophagy Process
Int. J. Mol. Sci. 2018, 19(2), 635; https://doi.org/10.3390/ijms19020635
Received: 22 January 2018 / Revised: 16 February 2018 / Accepted: 19 February 2018 / Published: 23 February 2018
Viewed by 993 | PDF Full-text (9573 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Gliadin, the alcohol-soluble protein fraction of wheat, contains the factor toxic for celiac disease (CD), and its toxicity is not reduced by digestion with gastro-pancreatic enzymes. Importantly, it is proved that an innate immunity to gliadin plays a key role in the development
[...] Read more.
Gliadin, the alcohol-soluble protein fraction of wheat, contains the factor toxic for celiac disease (CD), and its toxicity is not reduced by digestion with gastro-pancreatic enzymes. Importantly, it is proved that an innate immunity to gliadin plays a key role in the development of CD. The immune response induces epithelial stress and reprograms intraepithelial lymphocytes into natural killer (NK)-like cells, leading to enterocyte apoptosis and an increase in epithelium permeability. In this contribution, we have reported that in Caco-2 cells the administration of enzymatically digested gliadin (PT-gliadin) reduced significantly the expression of the autophagy-related marker LC3-II. Furthermore, electron and fluorescent microscope analysis suggested a compromised functionality of the autophagosome apparatus. The rescue of the dysregulated autophagy process, along with a reduction of PT-gliadin toxicity, was obtained with a starvation induction protocol and by 3-methyladenine administration, while rapamycin, a well-known autophagy inducer, did not produce a significant improvement in the clearance of extra- and intra-cellular fluorescent PT-gliadin amount. Altogether, our results highlighted the possible contribution of the autophagy process in the degradation and in the reduction of extra-cellular release of gliadin peptides and suggest novel molecular targets to counteract gliadin-induced toxicity in CD. Full article
Figures

Graphical abstract

Open AccessArticle Sinus Bradycardia in Carriers of the SCN5A-1795insD Mutation: Unraveling the Mechanism through Computer Simulations
Int. J. Mol. Sci. 2018, 19(2), 634; https://doi.org/10.3390/ijms19020634
Received: 8 January 2018 / Revised: 13 February 2018 / Accepted: 19 February 2018 / Published: 23 February 2018
Cited by 3 | Viewed by 714 | PDF Full-text (2722 KB) | HTML Full-text | XML Full-text
Abstract
The SCN5A gene encodes the pore-forming α-subunit of the ion channel that carries the cardiac fast sodium current (INa). The 1795insD mutation in SCN5A causes sinus bradycardia, with a mean heart rate of 70 beats/min in mutation carriers vs. 77
[...] Read more.
The SCN5A gene encodes the pore-forming α-subunit of the ion channel that carries the cardiac fast sodium current (INa). The 1795insD mutation in SCN5A causes sinus bradycardia, with a mean heart rate of 70 beats/min in mutation carriers vs. 77 beats/min in non-carriers from the same family (lowest heart rate 41 vs. 47 beats/min). To unravel the underlying mechanism, we incorporated the mutation-induced changes in INa into a recently developed comprehensive computational model of a single human sinoatrial node cell (Fabbri–Severi model). The 1795insD mutation reduced the beating rate of the model cell from 74 to 69 beats/min (from 49 to 43 beats/min in the simulated presence of 20 nmol/L acetylcholine). The mutation-induced persistent INa per se resulted in a substantial increase in beating rate. This gain-of-function effect was almost completely counteracted by the loss-of-function effect of the reduction in INa conductance. The further loss-of-function effect of the shifts in steady-state activation and inactivation resulted in an overall loss-of-function effect of the 1795insD mutation. We conclude that the experimentally identified mutation-induced changes in INa can explain the clinically observed sinus bradycardia. Furthermore, we conclude that the Fabbri–Severi model may prove a useful tool in understanding cardiac pacemaker activity in humans. Full article
(This article belongs to the Special Issue Ion Transporters and Channels in Physiology and Pathophysiology)
Figures

Graphical abstract

Open AccessReview On the Metal Cofactor in the Tyrosinase Family
Int. J. Mol. Sci. 2018, 19(2), 633; https://doi.org/10.3390/ijms19020633
Received: 26 January 2018 / Revised: 13 February 2018 / Accepted: 13 February 2018 / Published: 23 February 2018
Cited by 6 | Viewed by 611 | PDF Full-text (852 KB) | HTML Full-text | XML Full-text
Abstract
The production of pigment in mammalian melanocytes requires the contribution of at least three melanogenic enzymes, tyrosinase and two other accessory enzymes called the tyrosinase-related proteins (Trp1 and Trp2), which regulate the type and amount of melanin. The last two proteins are paralogues
[...] Read more.
The production of pigment in mammalian melanocytes requires the contribution of at least three melanogenic enzymes, tyrosinase and two other accessory enzymes called the tyrosinase-related proteins (Trp1 and Trp2), which regulate the type and amount of melanin. The last two proteins are paralogues to tyrosinase, and they appeared late in evolution by triplication of the tyrosinase gene. Tyrosinase is a copper-enzyme, and Trp2 is a zinc-enzyme. Trp1 has been more elusive, and the direct identification of its metal cofactor has never been achieved. However, due to its enzymatic activity and similarities with tyrosinase, it has been assumed as a copper-enzyme. Recently, recombinant human tyrosinase and Trp1 have been expressed in enough amounts to achieve for the first time their crystallization. Unexpectedly, it has been found that Trp1 contains a couple of Zn(II) at the active site. This review discusses data about the metal cofactor of tyrosinase and Trps. It points out differences in the studied models, and it proposes some possible points accounting for the apparent discrepancies currently appearing. Moreover, some proposals about the possible flexibility of the tyrosinase family to uptake copper or zinc are discussed. Full article
(This article belongs to the Special Issue Melanins and Melanogenesis: From Nature to Applications)
Figures

Graphical abstract

Open AccessReview Alternative mRNA Splicing in the Pathogenesis of Obesity
Int. J. Mol. Sci. 2018, 19(2), 632; https://doi.org/10.3390/ijms19020632
Received: 5 January 2018 / Revised: 21 February 2018 / Accepted: 21 February 2018 / Published: 23 February 2018
Viewed by 1005 | PDF Full-text (1828 KB) | HTML Full-text | XML Full-text
Abstract
Alternative mRNA splicing is an important mechanism in expansion of proteome diversity by production of multiple protein isoforms. However, emerging evidence indicates that only a limited number of annotated protein isoforms by alternative splicing are detected, and the coding sequence of alternative splice
[...] Read more.
Alternative mRNA splicing is an important mechanism in expansion of proteome diversity by production of multiple protein isoforms. However, emerging evidence indicates that only a limited number of annotated protein isoforms by alternative splicing are detected, and the coding sequence of alternative splice variants usually is only slightly different from that of the canonical sequence. Nevertheless, mis-splicing is associated with a large array of human diseases. Previous reviews mainly focused on hereditary and somatic mutations in cis-acting RNA sequence elements and trans-acting splicing factors. The importance of environmental perturbations contributed to mis-splicing is not assessed. As significant changes in exon skipping and splicing factors expression levels are observed with diet-induced obesity, this review focuses on several well-known alternatively spliced metabolic factors and discusses recent advances in the regulation of the expressions of splice variants under the pathophysiological conditions of obesity. The potential of targeting the alternative mRNA mis-splicing for obesity-associated diseases therapies will also be discussed. Full article
(This article belongs to the Special Issue Pre-mRNA Splicing 2017)
Figures

Figure 1

Open AccessReview Temporospatial Analysis and New Players in the Immunology of Amyotrophic Lateral Sclerosis
Int. J. Mol. Sci. 2018, 19(2), 631; https://doi.org/10.3390/ijms19020631
Received: 1 February 2018 / Revised: 18 February 2018 / Accepted: 21 February 2018 / Published: 23 February 2018
Cited by 1 | Viewed by 1171 | PDF Full-text (2945 KB) | HTML Full-text | XML Full-text
Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss of lower and upper motor neurons (MN) leading to muscle weakness, paralysis and eventually death. Although a highly varied etiology results in ALS, it broadly manifests itself as sporadic and familial
[...] Read more.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss of lower and upper motor neurons (MN) leading to muscle weakness, paralysis and eventually death. Although a highly varied etiology results in ALS, it broadly manifests itself as sporadic and familial forms that have evident similarities in clinical symptoms and disease progression. There is a tremendous amount of knowledge on molecular mechanisms leading to loss of MNs and neuromuscular junctions (NMJ) as major determinants of disease onset, severity and progression in ALS. Specifically, two main opposing hypotheses, the dying forward and dying back phenomena, exist to account for NMJ denervation. The former hypothesis proposes that the earliest degeneration occurs at the central MNs and proceeds to the NMJ, whereas in the latter, the peripheral NMJ is the site of precipitating degeneration progressing backwards to the MN cell body. A large body of literature strongly indicates a role for the immune system in disease onset and progression via regulatory involvement at the level of both the central and peripheral nervous systems (CNS and PNS). In this review, we discuss the earliest reported immune responses with an emphasis on newly identified immune players in mutant superoxide dismutase 1 (mSOD1) transgenic mice, the gold standard mouse model for ALS. Full article
(This article belongs to the collection Neuroprotective Strategies)
Figures

Figure 1

Open AccessArticle Molecular Modeling Study for the Design of Novel Peroxisome Proliferator-Activated Receptor Gamma Agonists Using 3D-QSAR and Molecular Docking
Int. J. Mol. Sci. 2018, 19(2), 630; https://doi.org/10.3390/ijms19020630
Received: 30 January 2018 / Revised: 17 February 2018 / Accepted: 18 February 2018 / Published: 23 February 2018
Cited by 2 | Viewed by 955 | PDF Full-text (2406 KB) | HTML Full-text | XML Full-text
Abstract
Type 2 diabetes is becoming a global pandemic disease. As an important target for the generation and development of diabetes mellitus, peroxisome proliferator-activated receptor γ (PPARγ) has been widely studied. PPARγ agonists have been designed as potential anti-diabetic agents. The advanced development of
[...] Read more.
Type 2 diabetes is becoming a global pandemic disease. As an important target for the generation and development of diabetes mellitus, peroxisome proliferator-activated receptor γ (PPARγ) has been widely studied. PPARγ agonists have been designed as potential anti-diabetic agents. The advanced development of PPARγ agonists represents a valuable research tool for diabetes therapy. To explore the structural requirements of PPARγ agonists, three-dimensional quantitative structure–activity relationship (3D-QSAR) and molecular docking studies were performed on a series of N-benzylbenzamide derivatives employing comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and surflex-dock techniques. The generated models of CoMFA and CoMSIA exhibited a high cross-validation coefficient (q2) of 0.75 and 0.551, and a non-cross-validation coefficient (r2) of 0.958 and 0.912, respectively. The predictive ability of the models was validated using external validation with predictive factor (r2pred) of 0.722 and 0.682, respectively. These results indicate that the model has high statistical reliability and good predictive power. The probable binding modes of the best active compounds with PPARγ active site were analyzed, and the residues His323, Tyr473, Ser289 and Ser342 were found to have hydrogen bond interactions. Based on the analysis of molecular docking results, and the 3D contour maps generated from CoMFA and CoMSIA models, the key structural features of PPARγ agonists responsible for biological activity could be determined, and several new molecules, with potentially higher predicted activity, were designed thereafter. This work may provide valuable information in further optimization of N-benzylbenzamide derivatives as PPARγ agonists. Full article
(This article belongs to the Special Issue PPARs in Cellular and Whole Body Energy Metabolism)
Figures

Graphical abstract

Open AccessReview Indispensable Role of Proteases in Plant Innate Immunity
Int. J. Mol. Sci. 2018, 19(2), 629; https://doi.org/10.3390/ijms19020629
Received: 5 February 2018 / Revised: 14 February 2018 / Accepted: 19 February 2018 / Published: 23 February 2018
Cited by 2 | Viewed by 1146 | PDF Full-text (2217 KB) | HTML Full-text | XML Full-text
Abstract
Plant defense is achieved mainly through the induction of microbe-associated molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and RNA silencing. Plant immunity is a highly complex phenomenon with its own unique features that have
[...] Read more.
Plant defense is achieved mainly through the induction of microbe-associated molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and RNA silencing. Plant immunity is a highly complex phenomenon with its own unique features that have emerged as a result of the arms race between plants and pathogens. However, the regulation of these processes is the same for all living organisms, including plants, and is controlled by proteases. Different families of plant proteases are involved in every type of immunity: some of the proteases that are covered in this review participate in MTI, affecting stomatal closure and callose deposition. A large number of proteases act in the apoplast, contributing to ETI by managing extracellular defense. A vast majority of the endogenous proteases discussed in this review are associated with the programmed cell death (PCD) of the infected cells and exhibit caspase-like activities. The synthesis of signal molecules, such as salicylic acid, jasmonic acid, and ethylene, and their signaling pathways, are regulated by endogenous proteases that affect the induction of pathogenesis-related genes and SAR or ISR establishment. A number of proteases are associated with herbivore defense. In this review, we summarize the data concerning identified plant endogenous proteases, their effect on plant-pathogen interactions, their subcellular localization, and their functional properties, if available, and we attribute a role in the different types and stages of innate immunity for each of the proteases covered. Full article
(This article belongs to the Special Issue Plant Innate Immunity 2.0)
Figures

Figure 1

Open AccessArticle Epigallocatechin Gallate Reduces Ischemia/Reperfusion Injury in Isolated Perfused Rabbit Hearts
Int. J. Mol. Sci. 2018, 19(2), 628; https://doi.org/10.3390/ijms19020628
Received: 26 January 2018 / Revised: 14 February 2018 / Accepted: 19 February 2018 / Published: 23 February 2018
Viewed by 873 | PDF Full-text (4206 KB) | HTML Full-text | XML Full-text
Abstract
Cardioplegic arrest during heart operations is often used in cardiac surgery. During cardioplegia, the heart is subjected to a global ischemia/reperfusion-injury. (−)-epigallocatechin gallate (EGCG), one of the main ingredients of green tea, seems to be beneficial in various cardiac diseases. Therefore, the aim
[...] Read more.
Cardioplegic arrest during heart operations is often used in cardiac surgery. During cardioplegia, the heart is subjected to a global ischemia/reperfusion-injury. (−)-epigallocatechin gallate (EGCG), one of the main ingredients of green tea, seems to be beneficial in various cardiac diseases. Therefore, the aim of our study was to evaluate EGCG in a rabbit model of cardioplegic arrest. Twenty four mature Chinchilla rabbits were examined. Rabbit hearts were isolated and perfused according to Langendorff. After induction of cardioplegia (without and with 20 µmol/L EGCG, n = 6 each) the hearts maintained arrested for 90-min. Thereafter, the hearts were re-perfused for 60 min. During the entire experiment hemodynamic and functional data were assessed. At the end of each experiment, left ventricular samples were processed for ATP measurements and for histological analysis. Directly after cessation of cardioplegia, all hearts showed the same decline in systolic and diastolic function. However, hearts of the EGCG-group showed a significantly faster and better hemodynamic recovery during reperfusion. In addition, tissue ATP-levels were significantly higher in the EGCG-treated hearts. Histological analysis revealed that markers of nitrosative and oxidative stress were significantly lower in the EGCG group. Thus, addition of EGCG significantly protected the cardiac muscle from ischemia/reperfusion injury. Full article
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention 2017)
Figures

Graphical abstract

Open AccessArticle “Nano-Ginseng” for Enhanced Cytotoxicity AGAINST Cancer Cells
Int. J. Mol. Sci. 2018, 19(2), 627; https://doi.org/10.3390/ijms19020627
Received: 23 January 2018 / Revised: 6 February 2018 / Accepted: 11 February 2018 / Published: 23 February 2018
Viewed by 791 | PDF Full-text (3133 KB) | HTML Full-text | XML Full-text
Abstract
Panax ginseng has high medicinal and health values. However, the various and complex components of ginseng may interact with each other, thus reducing and even reversing therapeutic effects. In this study, we designed and fabricated a novel “nano-ginseng” with definite ingredients, ginsenoside Rb1/protopanaxadiol
[...] Read more.
Panax ginseng has high medicinal and health values. However, the various and complex components of ginseng may interact with each other, thus reducing and even reversing therapeutic effects. In this study, we designed and fabricated a novel “nano-ginseng” with definite ingredients, ginsenoside Rb1/protopanaxadiol nanoparticles (Rb1/PPD NPs), completely based on the protopanaxadiol-type extracts. The optimized nano-formulations demonstrated an appropriate size (~110 nm), high drug loading efficiency (~96.8%) and capacity (~27.9 wt %), long half-time in systemic circulation (nine-fold longer than free PPD), better antitumor effects in vitro and in vivo, higher accumulation at the tumor site and reduced damage to normal tissues. Importantly, this process of “nano-ginseng” production is a simple, scalable, green economy process. Full article
(This article belongs to the collection Bioactive Nanoparticles)
Figures

Graphical abstract

Open AccessArticle Identification and Evaluation of Cytotoxicity of Peptide Liposome Incorporated Citron Extracts in an in Vitro System
Int. J. Mol. Sci. 2018, 19(2), 626; https://doi.org/10.3390/ijms19020626
Received: 11 January 2018 / Revised: 12 February 2018 / Accepted: 19 February 2018 / Published: 22 February 2018
Cited by 1 | Viewed by 876 | PDF Full-text (3022 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Citrons have been widely used for medicinal purposes for a long time, but the application of citron in the food industry is still restricted. The extensive advantages of nanotechnology in the food industry have greatly broadened the application of foods. In this study,
[...] Read more.
Citrons have been widely used for medicinal purposes for a long time, but the application of citron in the food industry is still restricted. The extensive advantages of nanotechnology in the food industry have greatly broadened the application of foods. In this study, by employing nanotechnology, we prepared citron-extract nanoparticle with an average size of 174.11 ± 3.89 nm, containing protein peptide and/or liposome. In order to evaluate the toxicity of nanoparticles and to ensure food safety, biological cytotoxicity at the cell and genomic levels was also identified to examine the toxicity of citron extracts by using an in vitro system. Our results demonstrated that the cytotoxicity of citronliposome was dependent on cell type in high concentrations (1 and 5 mg/mL), selectively against primary human cardiac progenitor cells (hCPCs), and human endothelial progenitor cells (hEPCs) in MTT and lactate dehydrogenase (LDH) assays. Interestingly, for the NIH-3T3 and H9C2 cell lines, cell cytotoxicity was observed with slight genotoxicity, especially from citronpeptide extract for both cell lines. Taken together, our study provides cytotoxicity data on nanoengineered citron extracts according to different cell type as is crucial for further applications. Full article
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine) Printed Edition available
Figures

Graphical abstract

Open AccessArticle Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis
Int. J. Mol. Sci. 2018, 19(2), 625; https://doi.org/10.3390/ijms19020625
Received: 1 February 2018 / Revised: 18 February 2018 / Accepted: 19 February 2018 / Published: 22 February 2018
Cited by 1 | Viewed by 1004 | PDF Full-text (6095 KB) | HTML Full-text | XML Full-text
Abstract
Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically
[...] Read more.
Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene. Most JNCL patients exhibit a 1.02 kb genomic deletion removing exons 7 and 8 of this gene, which results in a truncated CLN3 protein carrying an aberrant C-terminus. A genetically accurate mouse model (Cln3Δex7/8 mice) for this deletion has been generated. Using cerebellar precursor cell lines generated from wildtype and Cln3Δex7/8 mice, we have here analyzed the consequences of the CLN3 deletion on levels of cellular gangliosides, particularly GM3, GM2, GM1a and GD1a. The levels of GM1a and GD1a were found to be significantly reduced by both biochemical and cytochemical methods. However, quantitative high-performance liquid chromatography analysis revealed a highly significant increase in GM3, suggesting a metabolic blockade in the conversion of GM3 to more complex gangliosides. Quantitative real-time PCR analysis revealed a significant reduction in the transcripts of the interconverting enzymes, especially of β-1,4-N-acetyl-galactosaminyl transferase 1 (GM2 synthase), which is the enzyme converting GM3 to GM2. Thus, our data suggest that the complex a-series gangliosides are reduced in Cln3Δex7/8 mouse cerebellar precursor cells due to impaired transcription of the genes responsible for their synthesis. Full article
(This article belongs to the Special Issue Molecular Features of Lysosomal Storage Disorders)
Figures

Figure 1

Open AccessReview Neurophysiological Assessment of Abnormalities of the Neuromuscular Junction in Children
Int. J. Mol. Sci. 2018, 19(2), 624; https://doi.org/10.3390/ijms19020624
Received: 24 October 2017 / Revised: 16 January 2018 / Accepted: 17 January 2018 / Published: 22 February 2018
Viewed by 709 | PDF Full-text (1202 KB) | HTML Full-text | XML Full-text
Abstract
The function of the neuromuscular junction in children is amenable to electrophysiological testing. Of the two tests available, repetitive nerve stimulation is uncomfortable and has a reduced sensitivity compared with single-fibre methodology. The latter is the method of choice, recording the variability in
[...] Read more.
The function of the neuromuscular junction in children is amenable to electrophysiological testing. Of the two tests available, repetitive nerve stimulation is uncomfortable and has a reduced sensitivity compared with single-fibre methodology. The latter is the method of choice, recording the variability in neuromuscular transmission as a value called jitter. It can be performed by voluntary activation of the muscle being examined, which is not suitable in children, or by stimulation techniques. A modification of these techniques, called Stimulated Potential Analysis with Concentric needle Electrodes (SPACE), is well tolerated and can be performed while the child is awake. It has a high sensitivity (84%) for the diagnosis of neuromuscular transmission disorders, the majority of which are myasthenic syndromes, and a moderate specificity (70%). The latter can be improved by the exclusion of neurogenic causes and the determination of the degree of jitter abnormality. Minor jitter abnormalities, under 115% of the upper limit of normal, are usually caused by myopathies with an associated neuromuscular transmission disorder, whereas levels higher than this value are usually associated with one of the myasthenic conditions. Full article
(This article belongs to the Special Issue The Neuromuscular Synapse in Health and Disease)
Figures

Figure 1

Open AccessReview Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy
Int. J. Mol. Sci. 2018, 19(2), 623; https://doi.org/10.3390/ijms19020623
Received: 28 January 2018 / Revised: 11 February 2018 / Accepted: 16 February 2018 / Published: 22 February 2018
Cited by 2 | Viewed by 1123 | PDF Full-text (2251 KB) | HTML Full-text | XML Full-text
Abstract
Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly
[...] Read more.
Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly prone to developing age-related changes. Changes in articular cartilage that take place in the course of aging include the acquisition of the senescence-associated secretory phenotype by chondrocytes, a decrease in the sensitivity of chondrocytes to growth factors, a destructive effect of chronic production of reactive oxygen species and the accumulation of the glycation end products. All of these factors affect the mechanical properties of articular cartilage. A better understanding of the underlying mechanisms in the process of articular cartilage aging may help to create new therapies aimed at slowing or inhibiting age-related modifications of articular cartilage. This paper presents the causes and consequences of cellular aging of chondrocytes and the biological therapeutic outlook for the regeneration of age-related changes of articular cartilage. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Aging and Age-Related Disorders)
Figures

Figure 1

Open AccessArticle Belowground Interactions Impact the Soil Bacterial Community, Soil Fertility, and Crop Yield in Maize/Peanut Intercropping Systems
Int. J. Mol. Sci. 2018, 19(2), 622; https://doi.org/10.3390/ijms19020622
Received: 12 December 2017 / Revised: 11 February 2018 / Accepted: 15 February 2018 / Published: 22 February 2018
Cited by 2 | Viewed by 1164 | PDF Full-text (4292 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Intercropping has been widely used to control disease and improve yield in agriculture. In this study, maize and peanut were used for non-separation intercropping (NS), semi-separation intercropping (SS) using a nylon net, and complete separation intercropping (CS) using a plastic sheet. In field
[...] Read more.
Intercropping has been widely used to control disease and improve yield in agriculture. In this study, maize and peanut were used for non-separation intercropping (NS), semi-separation intercropping (SS) using a nylon net, and complete separation intercropping (CS) using a plastic sheet. In field experiments, two-year land equivalent ratios (LERs) showed yield advantages due to belowground interactions when using NS and SS patterns as compared to monoculture. In contrast, intercropping without belowground interactions (CS) showed a yield disadvantage. Meanwhile, in pot experiments, belowground interactions (found in NS and SS) improved levels of soil-available nutrients (nitrogen (N) and phosphorus (P)) and enzymes (urease and acid phosphomonoesterase) as compared to intercropping without belowground interactions (CS). Soil bacterial community assay showed that soil bacterial communities in the NS and SS crops clustered together and were considerably different from the CS crops. The diversity of bacterial communities was significantly improved in soils with NS and SS. The abundance of beneficial bacteria, which have the functions of P-solubilization, pathogen suppression, and N-cycling, was improved in maize and peanut soils due to belowground interactions through intercropping. Among these bacteria, numbers of Bacillus, Brevibacillus brevis, and Paenibacillus were mainly increased in the maize rhizosphere. Burkholderia, Pseudomonas, and Rhizobium were mainly increased in the peanut rhizosphere. In conclusion, using maize and peanut intercropping, belowground interactions increased the numbers of beneficial bacteria in the soil and improved the diversity of the bacterial community, which was conducive to improving soil nutrient (N and P) supply capacity and soil microecosystem stability. Full article
(This article belongs to the Special Issue Plant Microbe Interaction 2017) Printed Edition available
Figures

Figure 1

Open AccessReview Major Histocompatibility Complex and Hematopoietic Stem Cell Transplantation: Beyond the Classical HLA Polymorphism
Int. J. Mol. Sci. 2018, 19(2), 621; https://doi.org/10.3390/ijms19020621
Received: 17 January 2018 / Revised: 11 February 2018 / Accepted: 20 February 2018 / Published: 22 February 2018
Cited by 1 | Viewed by 1141 | PDF Full-text (251 KB) | HTML Full-text | XML Full-text
Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) represents a curative treatment for many patients with hematological malignant or non-malignant disorders. Evaluation of potential donors for HSCT includes a rigorous assessment of the human leukocyte antigens (HLA) match status of family members, and the identification
[...] Read more.
Allogeneic hematopoietic stem cell transplantation (HSCT) represents a curative treatment for many patients with hematological malignant or non-malignant disorders. Evaluation of potential donors for HSCT includes a rigorous assessment of the human leukocyte antigens (HLA) match status of family members, and the identification of suitable unrelated donors. Genes encoding transplantation antigens are placed both within and outside the major histocompatibility complex (MHC). The human MHC is located on the short arm of chromosome 6 and contains a series of genes encoding two distinct types of highly polymorphic cell surface glycoproteins. Donors for HSCT are routinely selected based on the level of matching for HLA-A, -B, -C, -DRB1, and -DQB1 loci. However, disease relapse, graft-versus-host-disease, and infection remain significant risk factors of morbidity and mortality. In the same breath, in high-risk patients, graft-versus-leukemia effects inherent in HLA mismatching play a substantial immunological role to limit the recurrence of post-transplant disease. The definition of a suitable donor is ever changing, shaped not only by current typing technology, but also by the specific transplant procedure. Indeed, a more complete understanding of permissible HLA mismatches and the role of Killer Immunoglobulin-like receptors’ genes increases the availability of HLA-haploidentical and unrelated donors. Full article
(This article belongs to the Section Biochemistry)
Open AccessArticle 3,5,6,7,8,3′,4′-Heptamethoxyflavone, a Citrus Flavonoid, Inhibits Collagenase Activity and Induces Type I Procollagen Synthesis in HDFn Cells
Int. J. Mol. Sci. 2018, 19(2), 620; https://doi.org/10.3390/ijms19020620
Received: 12 January 2018 / Revised: 26 January 2018 / Accepted: 21 February 2018 / Published: 22 February 2018
Viewed by 909 | PDF Full-text (1812 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Citrus fruits contain various types of flavonoids with powerful anti-aging and photoprotective effects on the skin, and have thus been attracting attention as potential, efficacious skincare agents. Here, we aimed to investigate the chemical composition of Citrus unshiu and its protective effects on
[...] Read more.
Citrus fruits contain various types of flavonoids with powerful anti-aging and photoprotective effects on the skin, and have thus been attracting attention as potential, efficacious skincare agents. Here, we aimed to investigate the chemical composition of Citrus unshiu and its protective effects on photoaging. We isolated and identified a bioactive compound, 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), from C. unshiu peels using ethanol extraction and hexane fractionation. HMF inhibited collagenase activity and increased type I procollagen content in UV-induced human dermal fibroblast neonatal (HDFn) cells. HMF also suppressed the expression of matrix metalloproteinases 1 (MMP-1) and induced the expression of type I procollagen protein in UV-induced HDFn cells. Additionally, HMF inhibited ultraviolet B (UVB)-induced phosphorylation of the mitogen-activated protein kinases (MAPK) cascade signaling components—ERK, JNK, and c-Jun—which are involved in the induction of MMP-1 expression. Furthermore, HMF affected the TGF-β/Smad signaling pathway, which is involved in the regulation of type I procollagen expression. In particular, HMF induced Smad3 protein expression and suppressed Smad7 protein expression in UV-induced HDFn cells in a dose-dependent manner. These findings suggest a role for Citrus unshiu in the preparation of skincare products in future. Full article
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols 2018)
Figures

Graphical abstract

Open AccessArticle Stroke-Like Episodes and Cerebellar Syndrome in Phosphomannomutase Deficiency (PMM2-CDG): Evidence for Hypoglycosylation-Driven Channelopathy
Int. J. Mol. Sci. 2018, 19(2), 619; https://doi.org/10.3390/ijms19020619
Received: 10 January 2018 / Revised: 15 February 2018 / Accepted: 18 February 2018 / Published: 22 February 2018
Viewed by 1473 | PDF Full-text (2561 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Stroke-like episodes (SLE) occur in phosphomannomutase deficiency (PMM2-CDG), and may complicate the course of channelopathies related to Familial Hemiplegic Migraine (FHM) caused by mutations in CACNA1A (encoding CaV2.1 channel). The underlying pathomechanisms are unknown. We analyze clinical variables to detect risk
[...] Read more.
Stroke-like episodes (SLE) occur in phosphomannomutase deficiency (PMM2-CDG), and may complicate the course of channelopathies related to Familial Hemiplegic Migraine (FHM) caused by mutations in CACNA1A (encoding CaV2.1 channel). The underlying pathomechanisms are unknown. We analyze clinical variables to detect risk factors for SLE in a series of 43 PMM2-CDG patients. We explore the hypothesis of abnormal CaV2.1 function due to aberrant N-glycosylation as a potential novel pathomechanism of SLE and ataxia in PMM2-CDG by using whole-cell patch-clamp, N-glycosylation blockade and mutagenesis. Nine SLE were identified. Neuroimages showed no signs of stroke. Comparison of characteristics between SLE positive versus negative patients’ group showed no differences. Acute and chronic phenotypes of patients with PMM2-CDG or CACNA1A channelopathies show similarities. Hypoglycosylation of both CaV2.1 subunits (α1A and α) induced gain-of-function effects on channel gating that mirrored those reported for pathogenic CACNA1A mutations linked to FHM and ataxia. Unoccupied N-glycosylation site N283 at α1A contributes to a gain-of-function by lessening CaV2.1 inactivation. Hypoglycosylation of the α2δ subunit also participates in the gain-of-function effect by promoting voltage-dependent opening of the CaV2.1 channel. CaV2.1 hypoglycosylation may cause ataxia and SLEs in PMM2-CDG patients. Aberrant CaV2.1 N-glycosylation as a novel pathomechanism in PMM2-CDG opens new therapeutic possibilities. Full article
(This article belongs to the Special Issue Calcium Signaling in Human Health and Diseases)
Figures

Graphical abstract

Open AccessArticle Preparation of Fish Skin Gelatin-Based Nanofibers Incorporating Cinnamaldehyde by Solution Blow Spinning
Int. J. Mol. Sci. 2018, 19(2), 618; https://doi.org/10.3390/ijms19020618
Received: 23 January 2018 / Revised: 12 February 2018 / Accepted: 13 February 2018 / Published: 22 February 2018
Cited by 1 | Viewed by 1111 | PDF Full-text (4622 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cinnamaldehyde, a natural preservative that can non-specifically deactivate foodborne pathogens, was successfully incorporated into fish skin gelatin (FSG) solutions and blow spun into uniform nanofibers. The effects of cinnamaldehyde ratios (5–30%, w/w FSG) on physicochemical properties of fiber-forming emulsions (FFEs) and
[...] Read more.
Cinnamaldehyde, a natural preservative that can non-specifically deactivate foodborne pathogens, was successfully incorporated into fish skin gelatin (FSG) solutions and blow spun into uniform nanofibers. The effects of cinnamaldehyde ratios (5–30%, w/w FSG) on physicochemical properties of fiber-forming emulsions (FFEs) and their nanofibers were investigated. Higher ratios resulted in higher values in particle size and viscosity of FFEs, as well as higher values in diameter of nanofibers. Loss of cinnamaldehyde was observed during solution blow spinning (SBS) process and cinnamaldehyde was mainly located on the surface of resultant nanofibers. Nanofibers all showed antibacterial activity by direct diffusion and vapor release against Escherichia coli O157:H7, Salmonella typhimurium, and Listeria monocytogenes. Inhibition zones increased as cinnamaldehyde ratio increased. Nanofibers showed larger inhibition effects than films prepared by casting method when S. typhimurium was exposed to the released cinnamaldehyde vapor, although films had higher remaining cinnamaldehyde than nanofibers after preparation. Lower temperature was favorable for cinnamaldehyde retention, and nanofibers added with 10% cinnamaldehyde ratio showed the highest retention over eight-weeks of storage. Results suggest that FSG nanofibers can be prepared by SBS as carriers for antimicrobials. Full article
Figures

Graphical abstract

Open AccessReview A Metabolomic Approach to Predict Breast Cancer Behavior and Chemotherapy Response
Int. J. Mol. Sci. 2018, 19(2), 617; https://doi.org/10.3390/ijms19020617
Received: 30 November 2017 / Revised: 29 January 2018 / Accepted: 31 January 2018 / Published: 21 February 2018
Cited by 1 | Viewed by 1336 | PDF Full-text (714 KB) | HTML Full-text | XML Full-text
Abstract
Although the classification of breast carcinomas into molecular or immunohistochemical subtypes has contributed to a better categorization of women into different therapeutic regimens, breast cancer nevertheless still progresses or recurs in a remarkable number of patients. Identifying women who would benefit from chemotherapy
[...] Read more.
Although the classification of breast carcinomas into molecular or immunohistochemical subtypes has contributed to a better categorization of women into different therapeutic regimens, breast cancer nevertheless still progresses or recurs in a remarkable number of patients. Identifying women who would benefit from chemotherapy could potentially increase treatment effectiveness, which has important implications for long-term survival. Metabolomic analyses of fluids and tissues from cancer patients improve our knowledge of the reprogramming of metabolic pathways involved in resistance to chemotherapy. This review evaluates how recent metabolomic approaches have contributed to understanding the relationship between breast cancer and the acquisition of resistance. We focus on the advantages and challenges of cancer treatment and the use of new strategies in clinical care, which helps us comprehend drug resistance and predict responses to treatment. Full article
(This article belongs to the Special Issue Tumor Microenvironment)
Figures

Figure 1

Open AccessReview Expression of Lectins in Heterologous Systems
Int. J. Mol. Sci. 2018, 19(2), 616; https://doi.org/10.3390/ijms19020616
Received: 4 December 2017 / Revised: 24 December 2017 / Accepted: 27 December 2017 / Published: 21 February 2018
Cited by 1 | Viewed by 813 | PDF Full-text (2361 KB) | HTML Full-text | XML Full-text
Abstract
Lectins are proteins that have the ability to recognize and bind in a reversible and specific way to free carbohydrates or glycoconjugates of cell membranes. For these reasons, they have been extensively used in a wide range of industrial and pharmacological applications. Currently,
[...] Read more.
Lectins are proteins that have the ability to recognize and bind in a reversible and specific way to free carbohydrates or glycoconjugates of cell membranes. For these reasons, they have been extensively used in a wide range of industrial and pharmacological applications. Currently, there is great interest in their production on a large scale. Unfortunately, conventional techniques do not provide the appropriate platform for this purpose and therefore, the heterologous production of lectins in different organisms has become the preferred method in many cases. Such systems have the advantage of providing better yields as well as more homogeneous and better-defined properties for the resultant products. However, an inappropriate choice of the expression system can cause important structural alterations that have repercussions on their biological activity since the specificity may lay in their post-translational processing, which depends largely on the producing organism. The present review aims to examine the most representative studies in the area, exposing the four most frequently used systems (bacteria, yeasts, plants and animal cells), with the intention of providing the necessary information to determine the strategy to follow in each case as well as their respective advantages and disadvantages. Full article
(This article belongs to the Special Issue Recombinant Proteins)
Figures

Figure 1

Open AccessReview Sarcoma Spheroids and Organoids—Promising Tools in the Era of Personalized Medicine
Int. J. Mol. Sci. 2018, 19(2), 615; https://doi.org/10.3390/ijms19020615
Received: 29 December 2017 / Revised: 13 February 2018 / Accepted: 16 February 2018 / Published: 21 February 2018
Cited by 1 | Viewed by 2130 | PDF Full-text (795 KB) | HTML Full-text | XML Full-text
Abstract
Cancer treatment is rapidly evolving toward personalized medicine, which takes into account the individual molecular and genetic variability of tumors. Sophisticated new in vitro disease models, such as three-dimensional cell cultures, may provide a tool for genetic, epigenetic, biomedical, and pharmacological research, and
[...] Read more.
Cancer treatment is rapidly evolving toward personalized medicine, which takes into account the individual molecular and genetic variability of tumors. Sophisticated new in vitro disease models, such as three-dimensional cell cultures, may provide a tool for genetic, epigenetic, biomedical, and pharmacological research, and help determine the most promising individual treatment. Sarcomas, malignant neoplasms originating from mesenchymal cells, may have a multitude of genomic aberrations that give rise to more than 70 different histopathological subtypes. Their low incidence and high level of histopathological heterogeneity have greatly limited progress in their treatment, and trials of clinical sarcoma are less frequent than trials of other carcinomas. The main advantage of 3D cultures from tumor cells or biopsy is that they provide patient-specific models of solid tumors, and they overcome some limitations of traditional 2D monolayer cultures by reflecting cell heterogeneity, native histologic architectures, and cell–extracellular matrix interactions. Recent advances promise that these models can help bridge the gap between preclinical and clinical research by providing a relevant in vitro model of human cancer useful for drug testing and studying metastatic and dormancy mechanisms. However, additional improvements of 3D models are expected in the future, specifically the inclusion of tumor vasculature and the immune system, to enhance their full ability to capture the biological features of native tumors in high-throughput screening. Here, we summarize recent advances and future perspectives of spheroid and organoid in vitro models of rare sarcomas that can be used to investigate individual molecular biology and predict clinical responses. We also highlight how spheroid and organoid culture models could facilitate the personalization of sarcoma treatment, provide specific clinical scenarios, and discuss the relative strengths and limitations of these models. Full article
(This article belongs to the Special Issue Current Advances in Soft Tissue and Bone Sarcoma)
Figures

Graphical abstract

Open AccessReview Can Plant Defence Mechanisms Provide New Approaches for the Sustainable Control of the Two-Spotted Spider Mite Tetranychus urticae?
Int. J. Mol. Sci. 2018, 19(2), 614; https://doi.org/10.3390/ijms19020614
Received: 28 December 2017 / Revised: 2 February 2018 / Accepted: 18 February 2018 / Published: 21 February 2018
Cited by 3 | Viewed by 1510 | PDF Full-text (902 KB) | HTML Full-text | XML Full-text
Abstract
Tetranychus urticae (T. urticae) Koch is a cosmopolitan, polyphagous mite which causes economic losses in both agricultural and ornamental plants. Some traits of T. urticae hamper its management, including a short life cycle, arrhenotokous parthenogenesis, its haplodiploid sex determination system, and
[...] Read more.
Tetranychus urticae (T. urticae) Koch is a cosmopolitan, polyphagous mite which causes economic losses in both agricultural and ornamental plants. Some traits of T. urticae hamper its management, including a short life cycle, arrhenotokous parthenogenesis, its haplodiploid sex determination system, and its extraordinary ability to adapt to different hosts and environmental conditions. Currently, the use of chemical and biological control are the major control methods used against this mite. In recent years, some studies have focused on plant defence mechanisms against herbivores. Various families of plant compounds (such as flavonoids, glucosinolates, or acyl sugars) have been shown to behave as acaricides. Plants can be induced upon appropriate stimuli to increase their resistance against spider mites. This knowledge, together with the understanding of mechanisms by which T. urticae detoxifies and adapts to pesticides, may complement the control of this pest. Herein, we describe plant volatile compounds (VOCs) with repellent activity, and new findings about defence priming against spider mites, which interfere with the T. urticae performance. The use of VOCs and defence priming can be integrated into current management practices and reduce the damage caused by T. urticae in the field by implementing new, more sustainable crop management tools. Full article
(This article belongs to the Special Issue Plant Defense Genes Against Biotic Stresses)
Figures

Figure 1

Back to Top