Centromere binding specificity in assembly of the F plasmid partition complex

The segregation of plasmid F of Escherichia coli is highly reliable. The Sop partition locus, responsible for this stable maintenance, is composed of two genes, sopA and sopB and a centromere, sopC, consisting of 12 direct repeats of 43 bp. Each repeat carries a 16-bp inverted repeat motif to which SopB binds to form a nucleoprotein assembly called the partition complex. A database search for sequences closely related to sopC revealed unexpected features that appeared highly conserved. We have investigated the requirements for specific SopB–sopC interactions using a surface plasmon resonance imaging technique. We show that (i) only 10 repeats interact specifically with SopB, (ii) no base outside the 16-bp sopC sites is involved in binding specificity, whereas five bases present in each arm are required for interactions, and (iii) the A-C central bases contribute to binding efficiency by conforming to a need for a purine–pyrimidine dinucleotide. We have refined the SopB–sopC binding pattern by electro-mobility shift assay and found that all 16 bp are necessary for optimal SopB binding. These data and the model we propose, define the basis of the high binding specificity of F partition complex assembly, without which, dispersal of SopB over DNA would result in defective segregation

Non-target effects of three formulated pesticides on microbially-mediated processes in a clay-loam soil

An experiment was performed to study non-target effects of difenoconazole (fungicide), deltamethrin (insecticide) and ethofumesate (herbicide) on microbial parameters in a clay-loam soil. Pesticides were applied as commercial formulations to soil samples at different concentrations (5, 50 and 500 mg kg−1 DW soil) and then incubated under laboratory conditions for 3 months. Throughout the incubation period, microbial parameters were determined at days 7, 30, 60 and 90. At 5 mg kg−1 DW soil, none of the three pesticides caused significant changes in soil microbial parameters. In contrast, at 500 mg kg−1 DW soil, pesticide application decreased overall soil microbial activity, negatively affecting the activity of soil enzymes. Similarly, at 500 mg kg−1 DW soil, difenoconazole and ethofumesate, but not deltamethrin, caused a pesticide-induced stress on soil microbial communities, as reflected by the respiratory quotient. Besides, deltamethrin and ethofumesate at 50 and 500 mg kg−1 DW soil resulted in lower values of denitrification potential. It was concluded that, although pesticide concentration had a somewhat inconsistent and erratic effect on soil microbial parameters, pesticide application at 500 mg kg−1 DW soil did have an impact on many of the microbial parameters studied here

Effects of herbicide mixtures on freshwater microalgae with the potential effect of a safener

International audienceFreshwater microalgae are primary producers and cosmopolitan species subjected to the effects of herbicides. In this work, the in vitro algal growth inhibitory effects of 11 agrochemicals (9 herbicides, 1 metabolite, and 1 safener) were quantified. Chemical compounds were applied singly and in specific mixtures. Three species were used in axenic condition: the green alga Desmodesmus subspicatus (Chodat), the diatoms Nitzschia palea (Kützing) W. Smith and Navicula pelliculosa (Kützing) Hilse. When exposed to single compounds, N. palea and N. pelliculosa were only sensitive to atrazine/desethylatrazine and the safener benoxacor (BE), respectively. D. subspicatus was equally sensitive to four herbicides including atrazine and its metabolite and significantly more sensitive to iodosulfuron-methyl-sodium (IODO). The mixture of these five compounds induced a significantly higher growth inhibition of about 1.5-fold than IODO alone, which could be attributed to the four other herbicides. The mixture of all compounds was twofold less toxic than IODO on D. subspicatus. A halogen atom is present in IODO as in the herbicides to which the safener BE À known to induce glutathione-S-transferases À is associated in agrochemical preparations. We then showed that IODO was less toxic when combined with non-toxic concentrations of BE. These results indicated that the toxicity of the most active herbicide studied was decreased by a non-herbicide compound present in agrochemical formulations of other herbicides. These results suggest the importance to take into account the chemistry and the mechanisms of action for each compound in a risk assessment approach of a complex mixture

Nanocrystalline cellulose reinforced poly(ethylene oxide) electrolytes for lithium-metal batteries with excellent cycling stability

Polyethylene oxide (PEO) based polymer electrolytes are still the state of the art for commercial lithium-metal batteries (LMBs) despite their remaining challenges such as the limited ionic conductivity at ambient temperature. Accordingly, the realization of thin electrolyte membranes and, thus, higher conductance is even more important, but this requires a sufficiently high mechanical strength. Herein, the incorporation of nanocrystalline cellulose into PEO-based electrolyte membranes is investigated with a specific focus on the electrochemical properties and the compatibility with lithium-metal and LiFePO$_4$-based electrodes. The excellent cycling stability of symmetric Li||Li cells, including the complete stripping of lithium from one electrode to the other, and Li||LiFePO$_4$ cells renders this approach very promising for eventually yielding thin high-performance electrolyte membranes for LMBs

A new DFM approach to combine machining and additive manufacturing

Design For Manufacturing (DFM) approaches aim to integrate manufacturability aspects during the design stage. Most of DFM approaches usually consider only one manufacturing process, but products competitiveness may be improved by designing hybrid modular products, in which products are seen as 3-D puzzles with modules realized aside by the best manufacturing process and further gathered. A new DFM system is created in order to give quantitative information during the product design stage of which modules will benefit in being machined and which ones will advantageously be realized by an additive process (such as Selective Laser Sintering or laser deposition). A methodology for a manufacturability evaluation in case of a subtractive or an additive manufacturing process is developed and implemented in a CAD software. Tests are carried out on industrial products from automotive industry

Reduction of Matrix Metallopeptidase 13 and Promotion of Chondrogenesis by Zeel T in Primary Human Osteoarthritic Chondrocytes

Objectives: Zeel T (Ze14) is a multicomponent medicinal product. Initial preclinical data suggested a preventive effect on cartilage degradation. Clinical observational studies demonstrated that Ze14 reduced symptoms of osteoarthritis (OA), including stiffness and pain. This study aimed to explore these effects further to better understand the mode of action of Ze14 on human OA chondrocytes in vitro. Methods: Primary chondrocytes were obtained from the knees of 19 OA patients and cultured either as monolayers or in alginate beads. The cultures were treated with 20% or 10% (v/v) Ze14 or placebo. For RNA-seq, reads were generated with Illumina NextSeq5000 sequencer and aligned to the human reference genome (UCSC hg19). Differential expression analysis between Ze14 and placebo was performed in R using the DESeq2 package. Protein quantification by ELISA was performed on selected genes from the culture medium and/or the cellular fractions of primary human OA chondrocyte cultures. Results: In monolayer cultures, Ze14 20% (v/v) significantly modified the expression of 13 genes in OA chondrocytes by at least 10% with an adjusted p-value < 0.05: EGR1, FOS, NR4A1, DUSP1, ZFP36, ZFP36L1, NFKBIZ, and CCN1 were upregulated and ATF7IP, TXNIP, DEPP1, CLEC3A, and MMP13 were downregulated after 24 h Ze14 treatment. Ze14 significantly increased (mean 2.3-fold after 24 h, p = 0.0444 and 72 h, p = 0.0239) the CCN1 protein production in human OA chondrocytes. After 72 h, Ze14 significantly increased type II collagen pro-peptide production by mean 27% (p = 0.0147). For both time points CCN1 production by OA chondrocytes was correlated with aggrecan (r = 0.66, p = 0.0004) and type II collagen pro-peptide (r = 0.64, p = 0.0008) production. In alginate beads cultures, pro-MMP-13 was decreased by Ze14 from day 7–14 (from −16 to −25%, p < 0.05) and from day 17–21 (−22%, p = 0.0331) in comparison to controls. Conclusion: Ze14 significantly modified the expression of DUSP1, DEPP1, ZFP36/ZFP36L1, and CLEC3A, which may reduce MMP13 expression and activation. Protein analysis confirmed that Ze14 significantly reduced the production of pro-MMP-13. As MMP-13 is involved in type II collagen degradation, Ze14 may limit cartilage degradation. Ze14 also promoted extracellular matrix formation arguably through CCN1 production, a growth factor well correlated with type II collagen and aggrecan production

Curcuma longa and Boswellia serrata Extracts Modulate Different and Complementary Pathways on Human Chondrocytes In Vitro: Deciphering of a Transcriptomic Study

peer reviewedObjectives:Curcuma longa (CL) and Boswellia serrata (BS) extracts are used to relieve osteoarthritis symptoms. The aim of this in vitro study was to investigate their mechanisms of action at therapeutic plasmatic concentrations on primary human osteoarthritic (OA) chondrocytes.Methods: BS (10–50 μg/ml) and CL (0.4–2 μg/ml corresponding to 1–5 µM of curcumin) were evaluated separately or in combination on primary chondrocytes isolated from 17 OA patients and cultured in alginate beads. Ten patients were used for RNA-sequencing analysis. Proteomic confirmation was performed either by immunoassays in the culture supernatant or by flow cytometry for cell surface markers after 72 h of treatment.Results: Significant gene expression modifications were already observed after 6 h of treatment at the highest dose of CL (2 μg/ml) while BS was significantly effective only after 24 h of treatment irrespective of the concentration tested. The most over-expressed genes by CL were anti-oxidative, detoxifying, and cytoprotective genes involved in the Nrf2 pathway. Down-regulated genes were principally pro-inflammatory cytokines and chemokines. Inversely, BS anti-oxidant/detoxifying activities were related to the activation of Nrf1 and PPARα pathways. BS anti-inflammatory effects were associated with the increase in GDF15, decrease in cholesterol cell intake and fatty acid metabolism-involved genes, and down-regulation of Toll-like receptors (TLRs) activation. Similar to CL, BS down-regulated ADAMTS1, 5, and MMP3, 13 genes expression. The combination of both CL and BS was significantly more effective than CL or BS alone on many genes such as IL-6, CCL2, ADAMTS1, and 5.Conclusion: BS and CL have anti-oxidative, anti-inflammatory, and anti-catabolic activities, suggesting a protective effect of these extracts on cartilage. Even if they share some mechanism of action, the two extracts act mainly on distinct pathways, and with different time courses, justifying their association to treat osteoarthritis

Intrinsic Capacity Defined Using Four Domains and Mortality Risk: A 5-Year Follow-Up of the SarcoPhAge Cohort

peer reviewedObjectives: The concept of 'intrinsic capacity' (IC) offers a new way to approach another concept, that of 'healthy aging'. The first objective of the present study was to assess the ability of the construct of 'intrinsic capacity' to predict death. The second objective was to assess whether deteriorations in intrinsic capacity, measured over 1 and 2 years, are predictive of death. Design: The present analysis was based on a prospective cohort study. Setting: Community-dwelling participants. Participants: The study recruited older adults aged 65 years and older. Measurements: Intrinsic capacity (IC) encompasses five domains: sensorial (not evaluated here), cognition (Mini-Mental State Examination), nutrition (Mini-Nutritional Assessment), mobility (Short Physical Performance Battery), and psychological (Geriatric Depression Scale). Each domain was considered satisfactory when its assessment, for an individual, was above the threshold defined by the initial validation of the domain assessment tool. To explore the relationship between IC and mortality risk, a Cox model was applied. The predictive value of the dynamic aspects (i.e., changes over 1 year and 2 years) was investigated using the following categorization of IC: stable, deteriorated, improved. Results: The sample was composed of 481 volunteers aged 73.4±6.12 years (60.1% women). Two satisfactory IC domains appeared to be significantly associated with reduced mortality risk: the satisfactory mobility domain (adjusted HR=0.45 [0.26-0.79]) and the satisfactory psychological domain (adjusted HR = 0.56 [1.04-3.09]). When considering intrinsic capacity as a whole construct, using a composite Z-score, we noticed that the risk of death was decreased by 49% for an increase of 1 standard deviation in IC. Changes in intrinsic capacity in the mobility and psychological domains led to an increased risk of death (from 2.74 to 4.18-fold). Conclusion: The concept of intrinsic capacity seems highly relevant in order to assess older adults' health and well-being. This concept should be considered for integration into clinical practice

Paleomagnetism of the ~860 Ma Manso dyke swarm, West Africa: implications for the assembly of Rodinia

The West African Craton (WAC) is one of the major cratons in the Rodinia jigsaw puzzle (~1000?750Ma). In the Rodinian models, the position of West Africa is mainly constrained by the assumptionthat it had been a partner of Amazonia since the Paleoproterozoic. Unfortunately, nopaleomagnetic data are available for these cratons when the Rodina supercontinent is consideredtectonically stable (~1000-750 Ma). Thus, every new reliable paleomagnetic pole for the WestAfrican Craton during the Neoproterozoic times is of paramount importance to constrain itsposition and testing the Rodinia models. In this study we present a combined paleomagnetic andgeochronological investigation for the Manso dyke swarm in the Leo-Man Shield, southern WestAfrica (Ghana). The ~860 Ma emplacement age for the NNW-trending Manso dykes is thus wellconstrainedby two new U-Pb apatite ages of 857.2 ± 8.5 Ma and 855 ± 16 Ma, in agreement withbaddeleyite data. Remanence of these coarse-to-fine grained dolerite dykes is carried by stablesingle to pseudo-single domain (SD-PSD) magnetite. A positive baked-contact test, associated to apositive reversal test (Class-C), support the primary remanence obtained for these dykes (13 sites).Moreover, our new paleomagnetic dataset satisfy all the seven R-criteria (R=7). The ~860 MaManso pole can thus be considered as the first key Tonian paleomagnetic pole for West Africa. Wepropose that the West Africa-Baltica-Amazonia-Congo-São Francisco were associated in a longlivedWABAMGO juxtaposition (~1100?800 Ma).Fil: Antonio, Paul Yves Jean. National Research Institute of Science and Technology. Centre de Montpellier; FranciaFil: Baratoux, Lenka. Université Paul Sabatier; FranciaFil: Ferreira Trindade, Ricardo Ivan. Universidade de Sao Paulo; BrasilFil: Rousse, Sonia. Université Paul Sabatier; FranciaFil: Ayite, Anani. University Of Ghana; GhanaFil: Lana, Cristiano. Universidade Federal de Ouro Preto; BrasilFil: Macouin, Melina. Université Paul Sabatier; FranciaFil: Kobby Adu, Emmanuel Williams. University Of Ghana; GhanaFil: Sanchez, Caroline. Université Paul Sabatier; FranciaFil: Silva, Marco. Universidade Federal de Ouro Preto; BrasilFil: Firmin, Anne Sophie. Université Paul Sabatier; FranciaFil: Martínez Dopico, Carmen Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: Proietti, Arnaud. Centre de Microcaractérisation Raimond Castaing; FranciaFil: Amponsah, Prince Ofori. University Of Ghana; GhanaFil: Asamoah Sakyi, Patrick. University Of Ghana; GhanaEGU General Assembly 2021ViennaAustriaEuropean Geosciences Unio

Gliomatosis cerebri presenting as rapidly progressive dementia and parkinsonism in an elderly woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>Dementia is one of the most important neurological disorders in the elderly. Dementia of tumoral origin is rare and parkinsonism of neoplastic origin is unusual. We herein report a case of gliomatosis cerebri, a very rare brain tumor seldom affecting the elderly, which presented as rapidly progressive dementia and parkinsonism.</p> <p>Case presentation</p> <p>An 82-year-old woman very rapidly developed progressive dementia and akineto-rigid parkinsonism. Brain CT scan was normal. Cerebral magnetic resonance imaging (MRI) with gadolinium injection highlighted a diffuse tumor-related infiltration involving both lobes, the putamen, the pallidum, the substantia nigra, and the brainstem, corresponding to the specific description and definition of gliomatosis cerebri.</p> <p>Conclusion</p> <p>This atypical presentation of a gliomatosis cerebri, and the infiltration of the substantia nigra by the tumor, merits attention.</p