DISTRIBUTION OF DINOCYSTS IN THE SURFACE SEDIMENTS OF SIDI MOUSSA LAGOON : (ATLANTIC COAST-MOROCCO)

The Sidi Moussa lagoon, (32°52′0″ N / 8° 51′05″ W) is located on the Moroccan Atlantic coast between the cities of El Jadida and Safi about 15 km South of the Jorf Lasfar industrial complex, The climate of the lagoon is classified as hot temperate. It is characterised by an oceanic influence. This study of dinoflagellate cyst mapping is the first of its kind from the Sidi Moussa lagoon. the objectives of the present survey were (i) to evaluate to the spatial variation of dinoflagellate cyst assemblages in the sediment along the Sidi Moussa lagoon (ii) to assess the densities of its cysts (iii) to compare the cyst assemblages in this study with that of other sites. The data were collected in a scientific campaign by zodiac carried out from in April 2018 by core following a sampling network of 21 stations distributed randomly in the study area. The surface layer of the sediment cores (3 cm) was sliced and kept at 4° C until analysis. The highest total cyst abundance was 194 cysts. g−1 dry sediment. The Pearson statistical test revealed a positive and significant correlation between cyst abundance and water content, organic matter and of fine sediment. Our study showed the presence of morphotypes of potentially toxic species. The cysts of these species present in the sediment of the Sidi Moussa lagoon could germinate, when environmental conditions become favorable, and in turn could inoculate the water column with the subsequent bloom formation. This study confirms the usefulness of cyst analysis in the assessment of harmful bloom risk in this area important for oyster’s culture.

A Chemical Chaperone That Prevents Insulin Fibrillation

Insulin, a peptide hormone, is susceptible to amyloid formation upon exposure to aberrant physiological conditions, result-ing in a loss of its bioactivity. For mitigating insulin aggregation, we report a molecule called PAD-S, which completely inhibit-ed insulin fibril formation, and preserved insulin in its soluble form. Circular Dichroism spectroscopy showed that PAD-S was able to maintain the native structure of insulin, thus acting as a chemical chaperone. Seeded aggregation kinetics suggest that PAD-S inhibited primary nucleation events during aggregation. This is consistent with molecular docking results which suggest that PAD-S binds strongly to native insulin monomers/dimers. Through a competitive binding experiment with ‘LVEALYL’ peptide, we conclude that PAD-S likely binds to the amyloid prone B11-B17 residues of insulin thereby prevent-ing its aggregation. PAD-S was also effective in disaggregating preformed insulin fibrils to non-toxic species. PAD-S treated insulin was functional as indicated by its ability to phosphorylate Akt. PAD-S was also highly effective in preventing the ag-gregation of insulin biosimilars. The low cellular cytotoxicity of PAD-S, and amelioration of aggregation-induced toxicity by PAD-S treated insulin further highlights its potential as an effective chemical chaperone.

Cyanobacteria in freshwater Lake Dikoye (Pribaikalsky district, Buryatia, Siberia) under intensive eutrophication

We studied freshwater Lake Dikoye located in the coastal zone of Lake Baikal. Negative changes associated with cyanobacterial bloom were observed in the lake. Phototrophs were represented by cyanobacteria, green algae, and diatoms. In the microbial community, Cyanobacteria were the dominant phylum and accounted for up to 48% of the total diversity. Cyanobacteria were represented by 7 genera and 9 species. Microcystis aeruginosa, a potentially toxic species, was dominant among cyanobacteria. According to chlorophyll a content, the lake should be assigned to eutrophic ones. The bacterial eutrophication index for the lake studied varied from 1.17 (middle eutrophic) to 28.2 (hypereutrophic) during cyanobacterial bloom.

Members of the GADD45 Protein Family Show Distinct Propensities to form Toxic Amyloid-Like Aggregates in Physiological Conditions

The three members (GADD45α, GADD45β, and GADD45γ) of the growth arrest and DNA damage-inducible 45 (GADD45) protein family are involved in a myriad of diversified cellular functions. With the aim of unravelling analogies and differences, we performed comparative biochemical and biophysical analyses on the three proteins. The characterization and quantification of their binding to the MKK7 kinase, a validated functional partner of GADD45β, indicate that GADD45α and GADD45γ are strong interactors of the kinase. Despite their remarkable sequence similarity, the three proteins present rather distinct biophysical properties. Indeed, while GADD45β and GADD45γ are marginally stable at physiological temperatures, GADD45α presents the Tm value expected for a protein isolated from a mesophilic organism. Surprisingly, GADD45α and GADD45β, when heated, form high-molecular weight species that exhibit features (ThT binding and intrinsic label-free UV/visible fluorescence) proper of amyloid-like aggregates. Cell viability studies demonstrate that they are endowed with a remarkable toxicity against SHSY-5Y and HepG2 cells. The very uncommon property of GADD45β to form cytotoxic species in near-physiological conditions represents a puzzling finding with potential functional implications. Finally, the low stability and/or the propensity to form toxic species of GADD45 proteins constitute important features that should be considered in interpreting their many functions.

All-or-none amyloid disassembly via chaperone-triggered fibril unzipping favors clearance of α-synuclein toxic species

α-synuclein aggregation is present in Parkinson’s disease and other neuropathologies. Among the assemblies that populate the amyloid formation process, oligomers and short fibrils are the most cytotoxic. The human Hsc70-based disaggregase system can resolve α-synuclein fibrils, but its ability to target other toxic assemblies has not been studied. Here, we show that this chaperone system preferentially disaggregates toxic oligomers and short fibrils, while its activity against large, less toxic amyloids is severely impaired. Biochemical and kinetic characterization of the disassembly process reveals that this behavior is the result of an all-or-none abrupt solubilization of individual aggregates. High-speed atomic force microscopy explicitly shows that disassembly starts with the destabilization of the tips and rapidly progresses to completion through protofilament unzipping and depolymerization without accumulation of harmful oligomeric intermediates. Our data provide molecular insights into the selective processing of toxic amyloids, which is critical to identify potential therapeutic targets against increasingly prevalent neurodegenerative disorders.

Transforming growth factor β3 deficiency promotes defective lipid metabolism and fibrosis in kidney

Glomerulosclerosis and tubulointerstitial fibrosis are pathological features of chronic kidney disease. Transforming growth factor β (TGFβ) is a key player in the development of fibrosis. However, of the three known TGFβ isoforms, only TGFβ1 has an established role in fibrosis, and the pathophysiological relevance of TGFβ2 and TGFβ3 is unknown. Because Tgfβ3 deficiency in mice results in early postnatal lethality, we analyzed the kidney phenotype of heterozygous Tgfβ3-knockout mice (Tgfβ3+/-) and compared it with that of matched wild-type mice. Four-month-old Tgfβ3+/- mice exhibited incipient renal fibrosis with epithelial-to-mesenchymal transition, in addition to glomerular basement membrane thickening and podocyte foot process effacement associated with albuminuria. Also evident was insulin resistance and oxidative stress at the renal level together with aberrant renal lipid metabolism and mitochondrial function. Omics analysis showed toxic species such as diacylglycerides and ceramides in Tgfβ3+/- mice, and dysregulated mitochondrial metabolism. Kidney of Tgfβ3+/- mice showed morphological alterations of mitochondria and overactivation of non-canonical MAPK ERK1/2 and JNK cascades. Our study shows that renal TGFβ3 might have antifibrotic and renoprotective properties, opposing or counteracting the activity of TGFβ1.

The Stabilization of Waste Funnel Glass of CRT by SiO2 Film Coating Technique

The funnel glass of the CRT monitor contains about 22–28% of lead oxide, of which lead is a highly toxic species and hazardous to the environment. This study proposes a process to form a protective layer of SiO2 film coating on the funnel glass to reduce the hazardous effect of lead leaching to the environment. The film coating benefits from the advantages of the sol–gel method. There are two key procedures of the stabilization technique, including the alkaline treatment and the formation of SiO2 coating from TEOS. The results show that the funnel glass powder treated with 10 M NaOH can produce a mushy layer on the surface. The mushy layer, which comprises OH− and water, can promote the formation of the SiO2 film layer on the surface of funnel glass powder. The conditions of the SiO2 film coating proposed in this study are: alkaline treatment by 10 M NaOH, the addition ratio of TEOS and funnel glass powder 2: 1, reaction temperature 40 °C, and reaction time 1.3 h. The EDS and ESCA results show that the Pb peak intensity on the surface of funnel glass decreases with the film coating. In the TCLP test, the leaching amount for Pb of the SiO2 film coated funnel glass powders is 0.7 mg/L, which is far lower than the standard in Taiwan EPA. Based on the experimental results, the formation mechanism of the SiO2 film layer on the surface of waste funnel glass powder is proposed. This study demonstrates that the SiO2 film coating is a potentially effective method to solve the problem of the waste funnel glass.