Strong nucleosomes reside in meiotic centromeres of C. elegans

Recently discovered strong nucleosomes (SNs) are characterized by strongly periodical DNA sequence, with visible rather than hidden sequence periodicity. In a quest for possible functions of the SNs, it has been found that the SNs concentrate within centromere regions of A. thaliana chromosomes . They, however, have been detected in Caenorhabditis elegans as well, although the holocentric chromosomes of this species do not have centromeres. Scrutinizing the SNs of C. elegans and their distributions along the DNA sequences of the chromosomes, we have discovered that the SNs are located mainly at the ends of the chromosomes of C. elegans. This suggests that, perhaps, the ends of the chromosomes fulfill some function(s) of centromeres in this species, as also indicated by the cytogenetic studies on meiotic chromosomes in spermatocytes of C. elegans, where the end-to-end association is observed. The centromeric involvement of the SNs, also found in A. thaliana, opens new horizons for the chromosome and centromere structure studies.     

Synthesis and anti-Trypanosoma cruzi activity of naphthoquinone-containing triazoles: Electrochemical studies on the effects of the quinoidal moiety

In our continued search for novel trypanocidal compounds, twenty-six derivatives of para- and ortho-naphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17–24, 28–30 and 36–38 are described herein for the first time. Three of these novel compounds (28–30) were found to be more potent than the standard drug benznidazole, with IC₅₀/24 h values between 6.8 and 80.8 μM. Analysis of the toxicity to heart muscle cells led to LC₅₀/24 h of <125, 63.1 and 281.6 μM for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent.     

Metabotropic Glutamate Receptor 1 Expression and Its Polymorphic Variants Associate with Breast Cancer Phenotypes

Several epidemiological studies have suggested a link between melanoma and breast cancer. Metabotropic glutamate receptor 1 (GRM1), which is involved in many cellular processes including proliferation and differentiation, has been implicated in melanomagenesis, with ectopic expression of GRM1 causing malignant transformation of melanocytes. This study was undertaken to evaluate GRM1 expression and polymorphic variants in GRM1 for associations with breast cancer phenotypes. Three single nucleotide polymorphisms (SNPs) in GRM1 were evaluated for associations with breast cancer clinicopathologic variables. GRM1 expression was evaluated in human normal and cancerous breast tissue and for in vitro response to hormonal manipulation. Genotyping was performed on genomic DNA from over 1,000 breast cancer patients. Rs6923492 and rs362962 genotypes associated with age at diagnosis that was highly dependent upon the breast cancer molecular phenotype. The rs362962 TT genotype also associated with risk of estrogen receptor or progesterone receptor positive breast cancer. In vitro analysis showed increased GRM1 expression in breast cancer cells treated with estrogen or the combination of estrogen and progesterone, but reduced GRM1 expression with tamoxifen treatment. Evaluation of GRM1 expression in human breast tumor specimens demonstrated significant correlations between GRM1 staining with tissue type and molecular features. Furthermore, analysis of gene expression data from primary breast tumors showed that high GRM1 expression correlated with a shorter distant metastasis-free survival as compared to low GRM1 expression in tamoxifen-treated patients. Additionally, induced knockdown of GRM1 in an estrogen receptor positive breast cancer cell line correlated with reduced cell proliferation. Taken together, these findings suggest a functional role for GRM1 in breast cancer.     

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form.     

Breaking the state of the heart: meshless model for cardiac mechanics

Biomechanics and Modeling in Mechanobiology - Cardiac modeling has recently emerged as a promising tool to study pathophysiology mechanisms and to predict treatment outcomes for personalized...     

An Optimal Au Grating Structure for Light Absorption in Amorphous Silicon Thin Film Solar Cell

Plasmonics - Effect of different gold (Au) grating structures on light absorption in solar cell is investigated by finite elemental analysis using COMSOL multiphysics-RF module. The geometry of the...     

A conserved GH17 glycosyl hydrolase from plant pathogenic Dothideomycetes releases a DAMP causing cell death in tomato

To facilitate infection, pathogens deploy a plethora of effectors to suppress basal host immunity induced by exogenous microbe-associated or endogenous damage-associated molecular patterns (DAMPs). In this study, we have characterized family 17 glycosyl hydrolases of the tomato pathogen Cladosporium fulvum (CfGH17) and studied their role in infection. Heterologous expression of CfGH17-1 to 5 by potato virus X in different tomato cultivars showed that CfGH17-1 and CfGH17-5 enzymes induce cell death in Cf-0, Cf-1 and Cf-5 but not in Cf-Ecp3 tomato cultivars or tobacco. Moreover, CfGH17-1 orthologues from other phytopathogens, including Dothistroma septosporum and Mycosphaerella fijiensis, also trigger cell death in tomato. CfGH17-1 and CfGH17-5 are predicted to be β-1,3-glucanases and their enzymatic activity is required for the induction of cell death. CfGH17-1 hydrolyses laminarin, a linear 1,3-β-glucan with 1,6-β linkages. CfGH17-1 expression is down-regulated during the biotrophic phase of infection and up-regulated during the necrotrophic phase. Deletion of CfGH17-1 in C. fulvum did not reduce virulence on tomato, while constitutive expression of CfGH17-1 decreased virulence, suggesting that abundant presence of CfGH17-1 during biotrophic growth may release a DAMP that activates plant defence responses. Under natural conditions CfGH17-1 is suggested to play a role during saprophytic growth when the fungus thrives on dead host tissue, which is in line with its high levels of expression at late stages of infection when host tissues have become necrotic. We suggest that CfGH17-1 releases a DAMP from the host cell wall that is recognized by a yet unknown host plant receptor.     

Modifying bio-catalytic properties of enzymes for efficient biocatalysis: a review from immobilization strategies viewpoint

Enzyme-based catalysis has become one of the most important disciplines in organic synthesis and plays a noteworthy role in the establishment of many chemical industries, e.g. fine chemicals, food or energy, textiles, agricultural, cosmeceutical, medicinal and pharmaceutical industries. However, pristine enzymes fail to demonstrate requisite functionalities for an industrial setting where extremely specific and stable catalysts are required. Immobilization enhances the catalytic stability and activity of enzymes and trims the overall cost burden of the enzyme. Therefore, it widely endeavours for proficient, sustainable, and environmentally responsive catalytic processes. Amongst several immobilization strategies, e.g. (1) supports-assisted, i.e. physical or covalent coupling and (2) supports-free techniques, i.e. cross-linked enzyme crystals (CLECs) or aggregates are the most promising ones and widely pursued for enzyme immobilization purposes. This perspective review focuses on up-to-date developments in the area of enzyme immobilization and presents their potentialities to upgrade and/or modify enzyme properties. Both types of immobilization strategies, i.e. supports-assisted and supports-free techniques are discussed with particular reference to CLECs or aggregates and protein-coated microcrystals. Also, several useful traits achieved after immobilization are also discussed in the second half of the review.     

Resolving the pathogenicity factors of a novel opportunistic fungus Schizophyllum commune at molecular level

Molecular Biology Reports - Schizophyllum commune is a well-known mushroom forming fungi which is an edible one due to its nutritive value. It exhibits a special wood degrading mechanism to grow in...     

Acaricidal properties of essential oils from agro‐industrial waste products from citric fruit against Tetranychus urticae

Tetranychus urticae is a major agricultural pest with worldwide distribution that has caused considerable damage to vegetable crops in north‐eastern Brazil. The aim of the present study was to investigate the chemical and lethal/sublethal effects of essential oils from the peels of the lime (Citrus aurantiifolia), lemon (C. limon), mandarin orange (C. reticulata) and (C. reticulata × C. sinensis) as well as selected constituents (linalool, α‐terpineol, α‐pinene, β‐pinene, terpinolene and limonene) against T. urticae. The greatest yield was achieved with the mandarin and tangerine peel oils. The chemical analysis (gas chromatography‐mass spectrometry) of the essential oils from the Citrus fruit peels enabled the identification of 127 compounds, revealing a predominance of monoterpenes. Limonene was the major constituent, and α‐pinene, β‐pinene, linalool and α‐terpineol were found in substantial quantities. Regarding the susceptibility of T. urticae, the Citrus oils and selected constituents were more effective by fumigation than residual contact. The C. reticulata oil was the most toxic by fumigation, and the C. limon oil was the most toxic by residual contact. The constituent α‐terpineol exhibited the highest toxicity with both methods. At a sublethal concentration, the oils and selected constituents had significant effects on the fecundity, feeding preference and oviposition of the mite. Citrus oils and their constituents are potentially useful for the future integrated management of T. urticae due to their lethal and sublethal properties. However, further studies are needed to evaluate the action of these essential oils against non‐target organisms and determine the cost–benefit ratio for the formulation of an acaricide harvested from agro‐industrial waste from citric fruit processing activities for use in the integrated control of T. urticae.