Homologous recombination (HR) is a high-fidelity DNA repair pathway responsible for the resolution of double-strand breaks, with the RAD51 recombinase playing a pivotal role through the formation of nucleoprotein filaments on single-stranded DNA. Overexpression of RAD51 is frequently observed in cancer cells, where it promotes genome stability under genotoxic stress and contributes to acquired resistance to DNA-damaging chemotherapeutic agents. In this study, we report the identification of a novel stilbene-derived compound, the disodium salt of 4,4'-diphenylcarbamate stilbene-2,2'-disulfonic acid (DPDS), as a novel compound that modulates RAD51 monomer-monomer interactions and reduces its binding to single-stranded DNA and ATP, processes that are critical for filament assembly and homologous recombination. Furthermore, DPDS enhances the cytotoxic effect of cisplatin in DU145 prostate cancer cells and was associated with reduced RAD51 nuclear foci formation and increased accumulation of DNA double-strand breaks. Notably, DPDS did not significantly affect cell viability in the four cellular models evaluated under our experimental conditions and displayed lower intrinsic cytotoxicity than DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) and emzadirib. Collectively, these findings support that DPDS as a chemical modulator of RAD51 activity may enhance cisplatin sensitivity in DU145 prostate cancer cells.
We have investigated the impact of obesity on the structural organization, morpho-mechanical properties of collagen fibers from rat tail tendon fascicles (RTTFs). Polarized Raman microspectroscopy showed that the collagen bands 855, 875, 938, and 960 cm-1 as well as those 1631 and 1660 cm-1 were affected by diet. Mechanical properties exhibited an increase in the yield strength from control (CTRL) to high fat (HF) diet (9.60 ± 1.71 and 13.09 ± 1.81 MPa) (p < 0.01) and ultimate tensile strength (13.12 ± 2.37 and 18.32 ± 2.83 MPa) (p < 0.05) with no significant change in the Young's Modulus. During mechanical, the band at 875 cm-1 exhibited the most relevant frequency shift (2 cm-1). The intensity of those at 855, 875, and 938 cm-1 in HF collagen displayed a comparable response to mechanical stress as compared to CTRL collagen with no significant diet-related changes in the Full Width at Half Maximum. Second harmonic generation technique revealed i) similar fiber straightness (0.963 ± 0.004 and 0.965 ± 0.003) and ii) significant changes in fibers diameter (1.48 ± 0.07 and 1.52 ± 0.08 μm) (p < 0.05) and length (22.06 ± 2.38 and 29.00 ± 3.76 μm) (p < 0.001) between CTRL and HF diet, respectively. The quantification of advanced glycation end products (AGEs) revealed an increase in both carboxymethyl-lysine and total fluorescence AGEs from CTRL to HF RTTFs.
AbstractThe first completed, circular mitochondrial genome and the first draft, linear chloroplastic genome of the blue diatom Haslea ostrearia (Simonsen 1974, Naviculaceae, Bacillariophyceae) were assembled from Illumina and PacBio sequencing. The mitochondrial genome was composed of 38,696 bases and contained 64 genes, including 31 protein-coding genes (CDS), 2 ribosomal RNA (rRNA) genes and 23 transfer RNA (tRNA) genes. For the chloroplast, the genome was composed of 130,200 bases with 169 genes (131 CDS, 6 rRNA genes, 31 tRNA genes, and 1 transfer messenger RNA gene). Phylogenetic trees, using the maximum-likehood method and partial genes currently available for Haslea ostrearia and other diatom species, suggested the proximity of all the Haslea ostrearia strains/isolates and the possibility of using these genomes as future references.
Abstract Objectives: Haslea ostrearia is a microalgae associated with the marrenine, a blue pigment known for its economic interest when it attaches to oyster gills. Complex to grow under axenic conditions, H. ostrearia probably needs its own bacterial procession to survive. Consequently, this important bacterial presence greatly complicates any study of its ecological, physiological and genomic content. Results: We therefore tested a first approach of a protocol to control the bacterial concentration without killing the microalgae, by growing four H. ostrearia NCC 532 cultures under two culture conditions: two with and two without antibiotic treatment. We also performed a first bacterial identification method by 16S sequencing adapted to the bacterial community of H. ostrearia. The V3V4 16S region allowed precise identification of bacteria present in H. ostrearia culture. An antibiotic treatment was found as necessary to stabilize the bacterial population of the cultures before the DNA extraction.
In this study, we focused on evaluating the responses of the cockle, Cerastoderma glaucum to in situ exposures to metals at three sites in the Gulf of Gabes in the coastal zone of Tunisia differing in levels of metal contamination. Firstly, we examined the general physiological state of the organisms. Secondly, we evaluated the bioaccumulation of several metals (Cd, Cu, Zn, Ni) in the cockles. Thirdly, we focused on evaluating histologically changes in gametogenesis and sexual maturity of the organisms. Finally, we determined the expression of seven key genes encoding enzymes or proteins involved in responses to different types of environmental stressors. Results showed a decrease in the general physiological status of the cockles, including a reduced condition index, sex ratios skewed to females (70% and 80% females in the intermediate and the contaminated site, respectively) and greater mortalities in tests under anoxic conditions (i.e., stress on stress test) in cockles collected from the most contaminated site (LT50 = 2.88 days) compared to the cockles from the intermediate site (LT50 = 5 days) and the less contaminated site (LT50 = 6 days). Results for metal bioaccumulation showed that the levels of Cd, Cu, Zn and Ni in cockles were consistent with the contaminant gradient, with the highest levels in cockles from the most contaminated site (1.04; 4.92; 52.76 and 13.81 µg/g dw, respectively), followed by those from the intermediate site (0.34; 2.94; 36.94; 17.40 µg/g dw, respectively) and then the less contaminated site (0.065; 1.27; 21.62 and 5.40 µg/g dw, respectively). Results from the gametogenesis and maturity index showed few differences in the reproductive cycle of cockles collected from the three study sites. There were different patterns of gene expression that were divided into three groups in terms of responses: (1) expression of genes involved in metal detoxification, ATP Binding Cassette Subfamily B Member 1 (ABCB1) and metallothionein MT) and genes for superoxide dismutases (i.e., Mn SOD and CuZn SOD), which did not show any difference in their levels of expression; (2) heat shock protein 70 (HSP70) gene expression, which decreased in cockles according to the pollution gradient, and (3) expression of catalase (CAT) and cytochrome oxidase subunit 1 (COI) genes was threefold and 1000-fold higher in cockles from intermediate and most contaminated sites compared to the less contaminated site. Therefore, changes in overall physiological condition, sex ratios and expression of HSP70, CAT and COI genes may be appropriate biomarkers for in situ studies of the impacts of metals in cockles. However, these biomarkers should be coupled to proteomics studies.
Abstract Background: The pigment produced by Haslea ostrearia , the marennine, is of an important medical and economic interest. Unfortunately this microalgae is complex to grow under axenic conditions, and H. ostrearia probably needs its own bacterial procession to survive. Consequently, this important bacterial presence greatly complicates any study of its ecological, physiological and genomic content. We have therefore tested a first approach of a protocol to control the bacterial concentration without killing the microalgae, by growing four H. ostrearia NCC 532 cultures under two culture conditions: two with and two without antibiotic treatment. We also sought a first bacterial identification method by 16S sequencing adapted to the bacterial community of H. ostrearia. Results: The V3V4 16S region allowed precise identification of bacteria present in H. ostrearia culture. Also, an antibiotic treatment was found necessary to stabilize the bacterial population of the cultures before the DNA extraction. Conclusions: These first results will allow the testing of other antibiotic treatments specific to these bacteria, as well as a wider study of other H. ostrearia isolates to determine the essential bacterial community of this microalga.
Nowadays, diet and breast cancer are studied at different levels, particularly in tumor prevention and progression. Thus, the molecular mechanisms leading to better knowledge are deciphered with a higher precision. Among the molecules implicated in a preventive and anti-progressive way, n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs) are good candidates. These molecules, like docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, are generally found in marine material, such as fat fishes or microalgae. EPA and DHA act as anti-proliferative, anti-invasive, and anti-angiogenic molecules in breast cancer cell lines, as well as in in vivo studies. A better characterization of the cellular and molecular pathways involving the action of these fatty acids is essential to have a realistic image of the therapeutic avenues envisaged behind their use. This need is reinforced by the increase in the number of clinical trials involving more and more n-3 LC-PUFAs, and this, in various pathologies ranging from obesity to a multitude of cancers. The objective of this review is, therefore, to highlight the new elements showing the preventive and beneficial effects of n-3 LC-PUFAs against the development and progression of breast cancer.
Transposable elements (TEs) are genetically mobile units that move from one site to another within a genome. These units can mediate regulatory changes that can result in massive changes in genes expression. In fact, a precise identification of TEs can allow the detection of the mechanisms involving these elements in gene regulation and genome evolution. In the present study, a genome-wide analysis of the Hemipteran pest Bemisia tabaci was conducted using bioinformatics tools to identify, annotate and estimate the age of TEs, in addition to their insertion sites, within or near of the defensome genes involved in insecticide resistance. Overall, 1,292,393 TE copies were identified in the B. tabaci genome grouped into 4872 lineages. A total of 699 lineages were found to belong to Class I of TEs, 1348 belong to Class II, and 2825 were uncategorized and form the largest part of TEs (28.81%). The TE age estimation revealed that the oldest TEs invasion happened 14 million years ago (MYA) and the most recent occurred 0.2 MYA with the insertion of Class II TE elements. The analysis of TE insertion sites in defensome genes revealed 94 insertions. Six of these TE insertions were found within or near previously identified differentially expressed insecticide resistance genes. These insertions may have a potential role in the observed insecticide resistance in these pests.
Miniature inverted-repeat transposable elements MITEs are ubiquitous, non-autonomous class II transposable elements. The moths, Helicoverpa armigera and Helicoverpa zea, are recognized as the two most serious pest species within the genus. Moreover, these pests have the ability to develop insecticide resistance. In the present study, we conducted a genome-wide analysis of MITEs present in H. armigera and H. zea genomes using the bioinformatics tool, MITE tracker. Overall, 3570 and 7405 MITE sequences were identified in H. armigera and H. zea genomes, respectively. Comparative analysis of identified MITE sequences in the two genomes led to the identification of 18 families, comprising 140 MITE members in H. armigera and 161 MITE members in H. zea. Based on target site duplication (TSD) sequences, the identified families were classified into three superfamilies (PIF/harbinger, Tc1/mariner and CACTA). Copy numbers varied from 6 to 469 for each MITE family. Finally, the analysis of MITE insertion sites in defensome genes showed intronic insertions of 11 MITEs in the cytochrome P450, ATP-binding cassette transporter (ABC) and esterase genes in H. armigera whereas for H. zea, only one MITE was retrieved in the ABC-C2 gene. These insertions could thus be involved in the insecticide resistance observed in these pests.
Long-chain polyunsaturated fatty acids n-3 series (n-3 LC-PUFAs), especially eicosapentaenoic and docosahexaenoic acids, are known to exert preventive effects on obesity and metabolic syndrome. Mainly consumed in the form of fish oil, LC-PUFAs n-3 are also found in significant quantities in other sources such as certain microalgae. The aim of this study was to evaluate the effects of Diacronema lutheri (Dia), a microalga rich in n-3 LC-PUFAs, on metabolic disorders associated with obesity. Three groups of male Wistar rats (n = 6 per group) were submitted for eight weeks to a standard diet or high-fat and high-fructose diet (HF), supplemented or not with 12% of Dia (HF-Dia). Compared to HF rats, HF-Dia rats showed a 41% decrease in plasma triacylglycerol (TAG) and an increase in plasma cholesterol (+35%) as well as in high-density lipoprotein cholesterol (+51%) without change to low-density lipoprotein cholesterol levels. Although fasting glycemia did not change, glucose and insulin tolerance tests highlighted an improvement in glucose and insulin homeostasis. Dia supplementation restored body weight and fat mass, and decreased levels of liver TAG (−75%) and cholesterol (−84%). In HF-Dia rats, leptin was decreased (−30%) below the control level corresponding to a reduction of 68% compared to HF rats. Similarly, the anti-inflammatory cytokines interleukin-4 (IL-4) and IL-10 were restored up to control levels, corresponding to a 74% and 58% increase in HF rats, respectively. In contrast, the level of IL-6 remained similar in the HF and HF-Dia groups and about twice that of the control. In conclusion, these results indicated that the D. lutheri microalga may be beneficial for the prevention of weight gain and improvement in lipid and glucose homeostasis.
Transposable elements (TEs) are recognized as major players in genome plasticity and evolution. The high abundance of TEs in the human genome, especially the Alu and Long Interspersed Nuclear Element-1 (LINE-1) repeats, makes them responsible for the molecular origin of several diseases. This involves several molecular mechanisms that are presented in this review: insertional mutation, DNA recombination and chromosomal rearrangements, modification of gene expression, as well as alteration of epigenetic regulations. This literature review also presents some of the more recent and/or more classical examples of human diseases in which TEs are involved. Whether through insertion of LINE-1 or Alu elements that cause chromosomal rearrangements, or through epigenetic modifications, TEs are widely implicated in the origin of human cancers. Many other human diseases can have a molecular origin in TE-mediated chromosomal recombination or alteration of gene structure and/or expression. These diseases are very diverse and include hemoglobinopathies, metabolic and neurological diseases, and common diseases. Moreover, TEs can also have an impact on aging. Finally, the exposure of individuals to stresses and environmental contaminants seems to have a non-negligible impact on the epigenetic derepression and mobility of TEs, which can lead to the development of diseases. Thus, improving our knowledge of TEs may lead to new potential diagnostic markers of diseases.
Blossoming advancements and implementation of technologies in nanosciences have thrown open avenues for the nano-revolution, which divulge the contribution of microorganisms in bio and green synthesis of nanomaterials (NMs), which seemed to have drawn indisputable attention of researchers towards this new area of research. However, many approaches based on physiochemical methods are being implemented these days for nanoparticle synthesis. Microorganism-based biological approaches for the reduction of metals to corresponding nanoscale particles are frequently used for biological and medical applications due to their environmental friendliness, cost effectiveness, energy efficiency, and lack of chemical contaminants. Biological synthesis of various metallic NMs via different microorganisms such as bacteria, cyanobacteria, microalgae, fungi, yeasts, actinomycetes, and viruses are reported. This review highlights the literature found on the approaches to synthesize inorganic NMs by microorganisms, either through intracellular or extracellular pathways. It also presents several examples of the various biological applications of these NMs in the fields of agriculture, bioremediation, food industry, biotechnology and the vast biomedical sector (antibacterial, anticancer, cosmetic, drug delivery). Finally, the development of improved NMs bioproduction technology will open many new and exciting possibilities in the use of NMs in every sphere of life, which may become a boon to society.
ABSTRACTThe first completed, circular mitochondrial genome and the first draft chloroplastic genome of Northern Atlantic blue diatomHaslea ostrearia(Naviculaceae, Bacillariophyceae) are described. The mitochondrial genome is composed of 38,696 bases and contains 64 genes, including 31 protein-coding genes (CDS), 2 ribosomal RNA (rRNA) genes and 23 transfer RNA (tRNA) genes. For the chloroplast, the genome is composed of 130,200 bases with 169 genes (131 CDS, 6 rRNA genes, 31 tRNA genes, and 1 transfermessenger RNA (tmRNA) gene). Phylogenetic trees suggest the proximity of allH. ostreariastrains yet available and the possibility to use these genomes as future references.
Cyanobacteria (blue-green microalgae) are ubiquitous, Gram-negative photoautotrophic prokaryotes. They are considered as one of the most efficient sources of bioactive secondary metabolites. More than 50% of cyanobacteria are cultivated on commercial platforms to extract bioactive compounds, which have bene shown to possess anticancer activity. The chemically diverse natural compounds or their analogues induce cytotoxicity and potentially kill a variety of cancer cells via the induction of apoptosis, or altering the activation of cell signaling, involving especially the protein kinase-C family members, cell cycle arrest, mitochondrial dysfunctions and oxidative damage. These therapeutic properties enable their use in the pharma and healthcare sectors for the betterment of future generations. This review provides a baseline overview of the anti-cancerous cyanobacterial bioactive compounds, along with recently introduced nanomaterials that could be used for the development of new anticancer drugs to build a healthy future for mankind.
Long-chain polyunsaturated fatty acids n-3 series and especially docosahexaenoic acid are known to exert preventive effects on metabolic disturbances associated with obesity and decrease cardiovascular disease risk. n-3 LC-PUFAs are mainly consumed in the form of fish oil, while other sources, such as certain microalgae, may contain a high content of these fatty acids. The aim of this study was to evaluate the effects of Tisochrysis lutea (Tiso), a microalga rich in DHA, on metabolic disorders associated with obesity. Three male Wistar rat groups were submitted for eight weeks to a standard diet or high-fat and high fructose diet (HF), supplemented or not with 12% of T. lutea (HF-Tiso). The supplementation did not affect plasma alanine aminotransferase (ALAT). Bodyweight, glycemia and insulinemia decreased in HF-Tiso rats (ANOVA, p < 0.001), while total plasma cholesterol, high-density lipoprotein-cholesterol (HDL-C) increased (ANOVA, p < 0.001) without change of low-density lipoprotein-cholesterol (LDL-C) and triacylglycerol (TAG) levels. Tiso supplementation decreased fat mass and leptinemia as well as liver TAG, cholesterol and plasma tumor necrosis factor-alpha levels (ANOVA, p < 0.001) while it did not affect interleukin 6 (IL-6), IL-4 and lipopolysaccharides levels. HF-Tiso rats showed an increase of IL-10 level in abdominal adipose tissue (ANOVA, p < 0.001). In conclusion, these results indicated that DHA-rich T. lutea might be beneficial for the prevention of obesity and improvement of lipid and glucose metabolism.
Algae are organisms with an enormous biodiversity and contain manifold fatty acid molecular structures and ratios. This chapter presents information about the structure and distribution of fatty acids in algae whether microalgae or macroalgae. The parameters affecting lipid and fatty acid contents as well as distribution are also discussed. Methods for isolation and purification of fatty acids from algae to obtain highly pure fatty acid or fatty acid fractions with good overall yields are presented. Algal fatty acids are known as sources of bioactive compounds for health promotion and wellness. Lipid fractions and fatty acids act as bioactives or additives for cosmeceutical applications. For health promotion, preventive effects of n-3 polyunsaturated fatty acids on cardiovascular disease, metabolic syndrome, and cancer are discussed. The role of n-3 fatty acids in cancer therapy and antiviral activities of lipids are also discussed. Furthermore, potential commercial application domains and concepts are discussed in this chapter.
Homologous recombination (HR) is involved in repairing DNA double-strand breaks (DSB), the most harmful for the cell. Regulating HR is essential for maintaining genomic stability. In many forms of cancer, overactivation of HR increases tumor resistance to DNA-damaging treatments. RAD51, HR's core protein, is very often over-expressed in these cancers and plays a critical role in cancer cell development and survival. Targeting RAD51 directly to reduce its activity and its expression is therefore one strategy to sensitize and overcome resistance cancer cells to existing DNA-damaging therapies which remains the limiting factor for the success of targeted therapy. This review describes the structure and biological roles of RAD51, summarizes the different targeted sites of RAD51 and its inhibitory compounds discovered and described in the last decade.
The whitefly, Bemisia tabaci is a hemipteran pest of vegetable crops vectoring a broad category of viruses. Currently, this insect pest showed a high adaptability and resistance to almost all the chemical compounds commonly used for its control. In many cases, transposable elements (TEs) contributed to the evolution of host genomic plasticity. This study focuses on the annotation of Mariner-like elements (MLEs) and their derived Miniature Inverted repeat Transposable Elements (MITEs) in the genome of B. tabaci. Two full-length MLEs belonging to mauritiana and irritans subfamilies were detected and named Btmar1.1 and Btmar2.1, respectively. Additionally, 548 defective MLE sequences clustering mainly into 19 different Mariner lineages of mauritiana and irritans subfamilies were identified. Each subfamily showed a significant variation in MLE copy number and size. Furthermore, 71 MITEs were identified as MLEs derivatives that could be mobilized via the potentially active transposases encoded by Btmar 1.1 and Btmar2.1. The vast majority of sequences detected in the whitefly genome present unusual terminal inverted repeats (TIRs) of up to 400 bp in length. However, some exceptions are sequences without TIRs. This feature of the MLEs and their derived MITEs in B. tabaci genome that distinguishes them from all the other MLEs so far described in insects, which have TIRs size ranging from 20 to 40 bp. Overall, our study provides an overview of MLEs, especially those with large TIRs, and their related MITEs, as well as diversity of their families, which will provide a better understanding of the evolution and adaptation of the whitefly genome.
The algae and microalgae are an extremely diverse group of organisms that contain many bioactive molecules, including pigments, polyunsaturated fatty acids, polysaccharides, polyphenol, etc [...]