Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein adhesin that interacts with salivary components within the salivary pellicle. AgI/II contributes to virulence and has been studied as an immunological and structural target, but a fundamental understanding of its underlying architecture has been lacking. Here we report a high-resolution (1.8 Å) crystal structure of the A 3 VP 1 fragment of S. mutans AgI/II that demonstrates a unique fibrillar form (155 Å) through the interaction of two noncontiguous regions in the primary sequence. The A 3 repeat of the alanine-rich domain adopts an extended α-helix that intertwines with the P 1 repeat polyproline type II (PPII) helix to form a highly extended stalk-like structure heretofore unseen in prokaryotic or eukaryotic protein structures. Velocity sedimentation studies indicate that fulllength AgI/II that contains three A/P repeats extends over 50 nanometers in length. Isothermal titration calorimetry revealed that the high-affinity association between the A 3 and P 1 helices is enthalpically driven. Two distinct binding sites on AgI/II to the host receptor salivary agglutinin (SAG) were identified by surface plasmon resonance (SPR). The current crystal structure reveals that AgI/II family proteins are extended fibrillar structures with the number of alanine-and proline-rich repeats determining their length.bacterial adhesion | dental caries | Streptococcus | x-ray crystallography | fibrous proteins S treptococcus mutans is the causative agent of human dental caries (1) and its protein adhesin antigen I/II (AgI/II) is a known target of protective immunity (2). AgI/II family molecules are expressed by numerous oral streptococci (3) and homologs have also been identified in the invasive pathogens Streptococcus pyogenes and Streptococcus agalactiae (4) (Fig. S1). In addition to mediating adhesion to the tooth surface (5), AgI/II influences biofilm formation (6), promotes collagen-dependent bacterial invasion of dentin (7), and mediates adherence to human epithelial cells (8). Elimination of AgI/II results in decreased virulence (9), but despite three decades of study, a mechanistic understanding of the functional properties of the molecule has been stymied by a lack of understanding of its structure.Originally identified as AgI/II (10) (also called P1, PAc, or SpaP), members of this protein family contain between 1310 and 1653 amino acids (aa) beginning with an amino-terminal signal motif that directs secretion, followed by the A, V, and P regions (Fig. 1A). The A region typically consists of 3-4 alanine-rich repeats (82 residues each) with 23-30% alanine content. The P region has 3-4 proline-rich repeats (39 residues each) with ∼35% proline content. Nested between the A and P repeats is a segment commonly referred to as the V or variable region, which contains within it a stretch of ∼100 amino acids where most of the sequence variation among S. mutans AgI/II molecules is clustered (11). The crystal structure of the V region adopts a globular β-s...

A series of disubstituted acridine ligands have been cocrystallized with a bimolecular DNA G-quadruplex. The ligands have a range of cyclic amino end groups of varying size. The crystal structures show that the diagonal loop in this quadruplex results in a large cavity for these groups, in contrast to the steric constraints imposed by propeller loops in human telomeric quadruplexes. We conclude that the nature of the loop has a significant influence on ligand selectivity for particular quadruplex folds.

Participating in TC for 16 weeks led to significant improvements in functional fitness and components of physical and mental health among older adults with self-reported arthritis. Tai Chi seems to be a valuable mode of physical activity for this population.

The effects of methyl jasmonate (MeJA), an elicitor of plant defense mechanisms, on the biosynthesis of diosgenin, a steroidal saponin, were investigated in six fenugreek (Trigonella foenum-graecum) varieties (Gujarat Methi-2, Kasuri-1, Kasuri-2, Pusa Early Branching, Rajasthan Methi and Maharashtra Methi-5). Treatment with 0.01% MeJA increased diosgenin levels, in 12 days old seedlings, from 0.5%–0.9% to 1.1%–1.8%. In addition, MeJA upregulated the expression of two pivotal genes of the mevalonate pathway, the metabolic route leading to diosgenin: 3-hydroxy-3-methylglutaryl-CoA reductase (HMG) and sterol-3-β-glucosyl transferase (STRL). In particular, MeJA increased the expression of HMG and STRL genes by 3.2- and 22.2-fold, respectively, in the Gujarat Methi-2 variety, and by 25.4- and 28.4-fold, respectively, in the Kasuri-2 variety. Therefore, MeJA may be considered a promising elicitor for diosgenin production by fenugreek plants.

The aim of this research was to advance solid lipid nanoparticle (SLN) preparation methodology by preparing glyceryl monostearate (GMS) nanoparticles using a temperature-modulated solidification process. The technique was reproducible and prepared nanoparticles without the need of organic solvents. An anticancer agent, 5-fluorouracil (5-FU), was incorporated in the SLNs. The SLNs were characterized by particle size analysis, zeta potential analysis, differential scanning calorimetry (DSC), infrared spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), drug encapsulation efficiency, in vitro drug release, and in vitro cell viability studies. Particle size of the SLN dispersion was below 100 nm, and that of redispersed lyophilizates was ~500 nm. DSC and infrared spectroscopy suggested that the degree of crystallinity did not decrease appreciably when compared to GMS. TEM and AFM images showed well-defined spherical to oval particles. The drug encapsulation efficiency was found to be approximately 46%. In vitro drug release studies showed that 80% of the encapsulated drug was released within 1 h. In vitro cell cultures were biocompatible with blank SLNs but demonstrated concentration-dependent changes in cell viability to 5-FU-loaded SLNs. The 5-FU-loaded SLNs can potentially be utilized in an anticancer drug delivery system.

No abstract

Background Hidradenitis suppurativa (HS) is a chronic inflammatory disease influenced by genetics, non‐genetic and environmental factors that modulate miRNA expression. Currently, no miRNA data are available for HS. In this study, we profiled DNA methylation patterns of miRNA genes associated with HS susceptibility. Objectives Identify miRNA gene methylation profiles associated with HS susceptibility. This study examined the methylation patterns of DNAs from 24 healthy controls and 24 patients with HS using Illumina Infinium MethylationEPIC BeadChip array analysis. Methylation patterns of miRNA genes were analysed using KEGG pathway analysis to explore the inversely correlated pathways regulated by miRNAs. Results We identified 60 CpG sites representing 65 unique microRNA genes including 54 hypomethylated and 6 hypermethylated CpGs as potentially associated with HS. Some of these CpGs were found to be critical for skin function, such as miR‐29, miR‐200, miR‐205, miR‐548 and miR‐132. The miR‐192 is implicated in non‐alcoholic fatty liver disease. The miR‐200c gene was identified as a vital determinant in regulating skin repair after injury and may contribute to age‐associated alterations in wound repair. miR‐132 was significantly upregulated during the inflammation phase of wound repair, enhancing the activity of STAT3 and ERK pathways that promote keratinocyte proliferation. Conclusions Epigenetically altered microRNA genes are implicated in wound healing, inflammation, keratinocyte proliferation and wound modulation. This is the first study to analyse methylation profiles of miRNA genes in the HS population, highlighting the unique role that miRNAs might play in diagnosing and treating HS.

Bacopa monnieri known as 'Brahmi' is a well-known medicinal plant belonging to Scrophulariaceae family for its nootropic properties. To the best of our knowledge, no characterization data is available on the potential role of micro RNAs (miRNAs) from this plant till date. We present here the first report of computational characterizations of miRNAs from B. monnieri. Owing to the high conservation of miRNAs in nature, new and potential miRNAs can be identified in plants using in silico techniques. Using the plant miRNA sequences present in the miRBase repository, a total of 12 miRNAs were identified from B. monnieri which pertained to 11 miRNA families from the shoot and root transcriptome data. Furthermore, gene ontology analysis of the identified 68 human target genes exhibited significance in various biological processes. These human target genes were associated with signaling pathways like NF-kB and MAPK with TRAF2, CBX1, IL1B, ITGA4 and ITGB1BP1 as the top five hub nodes. This crosskingdom study provides initial insights about the potential of miRNA-mediated cross-kingdom regulation and unravels the essential target genes of human with implications in numerous human diseases including cancer.