Music of metagenomics—a review of its applications,analysis pipeline,and associated tools

Functional & Integrative Genomics - This humble effort highlights the intricate details of metagenomics in a simple, poetic, and rhythmic way. The paper enforces the significance of the...     

Antimicrobial peptides as effective tools for enhanced disease resistance in plants

Plant Cell, Tissue and Organ Culture (PCTOC) - Four serotypes of the dengue virus that can cause severe disease in humans greatly increases the complexity of vaccine development. In this study, we...     

Predicting subcellular localization of multi-label proteins by incorporating the sequence features into Chou's PseAAC

The emergence of numerous genome projects has made the experimental classification of the protein localization almost impossible due to the exponential increase in the number of protein samples. However, most of the applications are merely developed for single-plex and completely ignored the presence of one protein at two or more locations in a cell. In this regard, few attempts were carried out to target Multi-label protein localizations; consequently, undesirable accuracies are achieved. This paper presents a novel approach, in which a discrete feature extraction method is fused with physicochemical properties of amino acids by using Chou's general form of Pseudo Amino Acid Composition. The technique is tested on two benchmark datasets namely: Gpos-mploc and Virus-mPLoc. The empirical results demonstrated that the proposed method yields better results via two examined classifiers i.e. ML-KNN and Rank-SVM. It is established that the proposed model has improved values in all performance measures considered for the comparison.     

Immunomodulatory Expression of Cathelicidins Peptides in Pulp Inflammation and Regeneration: An Update

The role of inflammatory mediators in dental pulp is unique. The local environment of pulp responds to any changes in the physiology that are highly fundamental, like odontoblast cell differentiation and other secretory activity. The aim of this review is to assess the role of cathelicidins based on their capacity to heal wounds, their immunomodulatory potential, and their ability to stimulate cytokine production and stimulate immune-inflammatory response in pulp and periapex. Accessible electronic databases were searched to find studies reporting the role of cathelicidins in pulpal inflammation and regeneration published between September 2010 and September 2020. The search was performed using the following databases: Medline, Scopus, Web of Science, SciELO and PubMed. The electronic search was performed using the combination of keywords “cathelicidins” and “dental pulp inflammation”. On the basis of previous studies, it can be inferred that LL-37 plays an important role in odontoblastic cell differentiation and stimulation of antimicrobial peptides. Furthermore, based on these outcomes, it can be concluded that LL-37 plays an important role in reparative dentin formation and provides signaling for defense by activating the innate immune system.     

Pericellular proteolysis by leukocytes and tumor cells on substrates: focal activation and the role of urokinase-type plasminogen activator

Previous studies have shown that the urokinase-type plasminogen activator receptor (uPAR) is localized to the adherence sites of leukocytes and tumor cells suggesting that pericellular proteolysis may accompany focal activation of adherence. To assess for focused pericellular proteolytic activity, we prepared two-dimensional substrates coated with FITC-casein or Bodipy FL-BSA. These molecules are poorly fluorescent, but become highly fluorescent after proteolytic degradation. Fluorescent peptide products were observed at adherence sites of stationary human neutrophils and at lamellipodia of polarized neutrophils. During cell migration, multiple regions of proteolysis appeared sequentially beneath the cell. Similarly, proteolytic action was restricted to adherence sites of resting HT1080 tumor cells but localized to the invadopodia of active cells. Using an extracellular fluorescence quenching method, we demonstrate that these fluorescent peptide products are extracellular. The uPA/uPAR system played an important role in the observed proteolytic activation. Plasminogen activator inhibitor-1 significantly reduced focal proteolysis. Sites of focal proteolysis matched the membrane distribution of uPAR. When uPA was dissociated from uPAR by acid washing, substantially reduced pericellular proteolysis was found. uPAR-negative T47D tumor cells did not express significant levels of substrate proteolysis. However, transfectant clones expressing uPAR (for example, T47D-26) displayed high levels of fluorescence indicating proteolysis at adherence sites. To provide further evidence for the role of the uPA/uPAR system in pericellular proteolysis, peritoneal macrophages from uPA knock-out (uPA–/–) and control (uPA+/+) mice were studied. Pericellular proteolysis was dramatically reduced in uPA-negative peritoneal macrophages. Thus, we have: (1) developed a novel methodology to detect pericellular proteolytic function, (2) demonstrated focused activation of proteolytic enzymatic activity in several cell types, (3) demonstrated its usefulness in real-time studies of cell migration, and (4) showed that the uPA/uPAR system is an important contributor to focal pericellular proteolysis.     

CD8 alpha beta T cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats

The class I MHC allele HLA-B27 is highly associated with the human spondyloarthropathies, but the basis for this association remains poorly understood. Transgenic rats with high expression of HLA-B27 develop a multisystem inflammatory disease that includes arthritis and colitis. To investigate whether CD8alphabeta T cells are needed in this disease, we depleted these cells in B27 transgenic rats before the onset of disease by adult thymectomy plus short-term anti-CD8alpha mAb treatment. This treatment induced profound, sustained depletion of CD8alphabeta T cells, but failed to suppress either colitis or arthritis. To address the role of CD8alpha(+)beta(-) cells, we studied four additional groups of B27 transgenic rats treated with: 1) continuous anti-CD8alpha mAb, 2) continuous isotype-matched control mAb, 3) the thymectomy/pulse anti-CD8alpha regimen, or 4) no treatment. Arthritis occurred in approximately 40% of each group, but was most significantly reduced in severity in the anti-CD8alpha-treated group. In addition to CD8alphabeta T cells, two sizeable CD8alpha(+)beta(-) non-T cell populations were also reduced by the anti-CD8alpha treatment: 1) NK cells, and 2) a CD4(+)CD8(+)CD11b/c(+)CD161a(+)CD172a(+) monocyte population that became expanded in diseased B27 transgenic rats. These data indicate that HLA-B27-retricted CD8(+) T cells are unlikely to serve as effector cells in the transgenic rat model of HLA-B27-associated disease, in opposition to a commonly invoked hypothesis concerning the role of B27 in the spondyloarthropathies. The data also suggest that one or more populations of CD8alpha(+)beta(-) non-T cells may play a role in the arthritis that occurs in these rats.     

Multispectral imaging of tablets in blister packaging

This experiment tested the hypothesis that using near-infrared (IR) imaging spectrometry on tablets through blister packs permits the identification and composition of multiple individual tablets to be determined simultaneously. Aspirin was selected for this study because its breakdown mechanism is well understood. Near-IR cameras were used to collect thousands of spectra simultaneously from a field of packaged aspirin tablets. Tablets were selected by a principal component analysis selection alogorithm. Graphs of the columns of the transformation matrix showed that salicylic acid and acetylsalicylic acid in the samples were modeled by the principal components. The bootstrap error-adjusted single-sample technique chemometric-imaging algorithm was used to draw probability-density contour plots that revealed tablet composition. Choice of color was used to represent constituent identity, whereas intensity represented concentration. The percentage of usable pixels in the indium antimonide (InSb) array was 99.9%. The SEP was 0.06% of the tablet mass for both water uptake and salicylic acid production. The number of tablets that a typical near-IR camera can currently analyze simultaneously was also estimated to be approximately 1300.     

Effect of acidity on the enantiomeric resolution of thyroxine and tocainide by HPLC on a (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid column

Enantiomeric resolution of thyroxine and tocainide was achieved on a (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid column. The mobile phases were methanol/water (4:1, v/v) and methanol/water containing 5 mM sulfuric acid (4:1, v/v) for tocainide and thyroxine respectively. The flow rate was 0.5 ml/min. The effect of the acidity on the chiral resolution of these drugs was studied. Detection was at 220 nm for both drugs. The values of alpha and Rs were 2.08-3.11 and 1.00-2.60, respectively, for thyroxine while the values of alpha and Rs were 1.13-1.26 and 0.10-1.30, respectively, for tocainide.     

Oligosaccharide and sucrose complexes of amylosucrase. Structural implications for the polymerase activity

The glucosyltransferase amylosucrase is structurally quite similar to the hydrolase alpha-amylase. How this switch in functionality is achieved is an important and fundamental question. The inactive E328Q amylosucrase variant has been co-crystallized with maltoheptaose, and the structure was determined by x-ray crystallography to 2.2 A resolution, revealing a maltoheptaose binding site in the B'-domain somewhat distant from the active site. Additional soaking of these crystals with maltoheptaose resulted in replacement of Tris in the active site with maltoheptaose, allowing the mapping of the -1 to +5 binding subsites. Crystals of amylosucrase were soaked with sucrose at different concentrations. The structures at approximately 2.1 A resolution revealed three new binding sites of different affinity. The highest affinity binding site is close to the active site but is not in the previously identified substrate access channel. Allosteric regulation seems necessary to facilitate access from this binding site. The structures show the pivotal role of the B'-domain in the transferase reaction. Based on these observations, an extension of the hydrolase reaction mechanism valid for this enzyme can be proposed. In this mechanism, the glycogen-like polymer is bound in the widest access channel to the active site. The polymer binding introduces structural changes that allow sucrose to migrate from its binding site into the active site and displace the polymer.