Low-temperature wollastonite formed by carbonate reduction: a marker of serpentinite redox conditions

International audienceIn the Alpine blueschist- to eclogite-facies meta-ophiolitic units of northern Corsica, the contact between a serpentinite body and an immediately overlying siliceous marble is remarkable for the occurrence of wollastonite and, on the marble side, a dark halo around the serpentinite. The refolded, continuous contact is a rodingite-type reaction zone with a centimetre-thick nephritic selvage of diopside + andradite/grossular ± perovskite on the serpentinite side, followed towards the marble by a 1-5 cm thick zone of massive wollastonite (± grossular), followed by a 5-20 cm thick dark zone (the halo) consisting of wollastonite + quartz + graphitic material (± grossular ± diopside), with no carbonate. The transition to the overlying wollastonite-free, calcite + quartz-bearing layers is sharp. Considering the stability of calcite + quartz everywhere else in the regional metamorphic series, this low-temperature occurrence of wollastonite (c. 400-450°C) requires unusual conditions. A clue to its origin is the abundance of graphitic matter with the wollastonite within a few decimetres of the serpentinite body. We interpret this observation as evidence for local reduction of Ca-carbonate to form elemental carbon and wollastonite according to the reaction: SiO2 + CaCO3 + 2H2 = CaSiO3 + C + 2H2O. Thermochemical modelling of mineral stability in the successive reaction zones suggests a positive oxygen-fugacity gradient from the serpentinite to the marble (-6 < FMQ < -1), mediated through a CH4- and H2-bearing aqueous intergranular fluid

Antioxidant and Photoprotection Networking in the Coastal Diatom <i>Skeletonema marinoi</i>

Little is known on the antioxidant activity modulation in microalgae, even less in diatoms. Antioxidant molecule concentrations and their modulation in microalgae has received little attention and the interconnection between light, photosynthesis, photoprotection, and antioxidant network in microalgae is still unclear. To fill this gap, we selected light as external forcing to drive physiological regulation and acclimation in the costal diatom Skeletonema marinoi. We investigated the role of light regime on the concentration of ascorbic acid, phenolic compounds and among them flavonoids and their connection with photoprotective mechanisms. We compared three high light conditions, differing in either light intensity or wave distribution, with two low light conditions, differing in photoperiod, and a prolonged darkness. The change in light distribution, from sinusoidal to square wave distribution was also investigated. Results revealed a strong link between photoprotection, mainly relied on xanthophyll cycle operation, and the antioxidant molecules and activity modulation. This study paves the way for further investigation on the antioxidant capacity of diatoms, which resulted to be strongly forced by light conditions, also in the view of their potential utilization in nutraceuticals or new functional cosmetic products

In Vitro Evaluation of Antioxidant Potential of the Invasive Seagrass Halophila stipulacea

none10Marine organisms with fast growth rates and great biological adaptive capacity might have biotechnological interests, since ecological competitiveness might rely on enhanced physiological or biochemical processes’ capability promoting protection, defense, or repair intracellular damages. The invasive seagrass Halophila stipulacea, a non-indigenous species widespread in the Mediterranean Sea, belongs to this category. This is the premise to investigate the biotechnological interest of this species. In this study, we investigated the antioxidant activity in vitro, both in scavenging reactive oxygen species and in repairing damages from oxidative stress on the fibroblast human cell line WI-38. Together with the biochemical analysis, the antioxidant activity was characterized by the study of the expression of oxidative stress gene in WI-38 cells in presence or absence of the H. stipulacea extract. Concomitantly, the pigment pool of the extracts, as well as their macromolecular composition was characterized. This study was done separately on mature and young leaves. Results indicated that mature leaves exerted a great activity in scavenging reactive oxygen species and repairing damages from oxidative stress in the WI-38 cell line. This activity was paralleled to an enhanced carotenoids content in the mature leaf extracts and a higher carbohydrate contribution to organic matter. Our results suggest a potential of the old leaves of H. stipulacea as oxidative stress damage protecting or repair agents in fibroblast cell lines. This study paves the way to transmute the invasive H. stipulacea environmental threat in goods for human health.openClementina Sansone; Christian Galasso; Marco Lo Martire; Tomás Vega Fernández; Luigi Musco; Antonio Dell’Anno; Antonino Bruno; Douglas M. Noonan; Adriana Albini; Christophe BrunetSansone, Clementina; Galasso, Christian; Lo Martire, Marco; Vega Fernández, Tomás; Musco, Luigi; Dell’Anno, Antonio; Bruno, Antonino; Noonan, Douglas M.; Albini, Adriana; Brunet, Christoph

A small protein coded within the mitochondrial canonical gene nd4 regulates mitochondrial bioenergetics

BACKGROUND: Mitochondria have a central role in cellular functions, aging, and in certain diseases. They possess their own genome, a vestige of their bacterial ancestor. Over the course of evolution, most of the genes of the ancestor have been lost or transferred to the nucleus. In humans, the mtDNA is a very small circular molecule with a functional repertoire limited to only 37 genes. Its extremely compact nature with genes arranged one after the other and separated by short non-coding regions suggests that there is little room for evolutionary novelties. This is radically different from bacterial genomes, which are also circular but much larger, and in which we can find genes inside other genes. These sequences, different from the reference coding sequences, are called alternatives open reading frames or altORFs, and they are involved in key biological functions. However, whether altORFs exist in mitochondrial protein-coding genes or elsewhere in the human mitogenome has not been fully addressed. RESULTS: We found a downstream alternative ATG initiation codon in the + 3 reading frame of the human mitochondrial nd4 gene. This newly characterized altORF encodes a 99-amino-acid-long polypeptide, MTALTND4, which is conserved in primates. Our custom antibody, but not the pre-immune serum, was able to immunoprecipitate MTALTND4 from HeLa cell lysates, confirming the existence of an endogenous MTALTND4 peptide. The protein is localized in mitochondria and cytoplasm and is also found in the plasma, and it impacts cell and mitochondrial physiology. CONCLUSIONS: Many human mitochondrial translated ORFs might have so far gone unnoticed. By ignoring mtaltORFs, we have underestimated the coding potential of the mitogenome. Alternative mitochondrial peptides such as MTALTND4 may offer a new framework for the investigation of mitochondrial functions and diseases

Therapeutic Anticoagulant Does not Modify Thromboses Rate Vein after Venous Reconstruction Following Pancreaticoduodenectomy

Recommendations for anticoagulation following major venous reconstruction for pancreatic adenocarcinoma (PA) are not clearly established. The aim of our study was to find out the relation between postoperative anticoagulant treatment and thrombosis rate after portal venous resection. Materials and methods. Between 1986 and 2006, twenty seven portal vein resections were performed associated with pancreaticoduodenectomies (n = 27) (PD).We defined four types of venous resection: type I was performed 1 cm above the confluent of the superior mesenteric vein (SMV) (n = 12); type II lateral resection and venorrhaphy at the level of the confluent SMV (n = 12); type III (n = 1) resulted from a primary end-to-end anastomosis above confluent and PTFE graph was used for reconstruction for type IV (n = 2). Curative anticoagulant treatment was always indicated after type IV (n = 2) resection, and after resection of type II when the length of venous resection was longer than ≥2 cm. Results. Venous thrombosis rate reached: 0%, 41%, and 100% for type I, II, IV resections, respectively. Among them four patients received curative anticoagulant treatment. Conclusion. After a portal vein resection was achieved in the course of a PD, curative postoperative anticoagulation does not prevent efficiently the onset of thrombosis

Increased H3K27 trimethylation contributes to cone survival in a mouse model of cone dystrophy

Inherited retinal diseases (IRDs) are a heterogeneous group of blinding disorders, which result in dysfunction or death of the light-sensing cone and rod photoreceptors. Despite individual IRDs (Inherited retinal disease) being rare, collectively, they affect up to 1:2000 people worldwide, causing a significant socioeconomic burden, especially when cone-mediated central vision is affected. This study uses the Pde6c$^{cpfl1}$ mouse model of achromatopsia, a cone-specific vision loss IRD (Inherited retinal disease), to investigate the potential gene-independent therapeutic benefits of a histone demethylase inhibitor GSK-J4 on cone cell survival. We investigated the effects of GSK-J4 treatment on cone cell survival in vivo and ex vivo and changes in cone-specific gene expression via single-cell RNA sequencing. A single intravitreal GSK-J4 injection led to transcriptional changes in pathways involved in mitochondrial dysfunction, endoplasmic reticulum stress, among other key epigenetic pathways, highlighting the complex interplay between methylation and acetylation in healthy and diseased cones. Furthermore, continuous administration of GSK-J4 in retinal explants increased cone survival. Our results suggest that IRD (Inherited retinal disease)-affected cones respond positively to epigenetic modulation of histones, indicating the potential of this approach in developing a broad class of novel therapies to slow cone degeneration

Evaluation of the tuberculin skin test and the interferon-γ release assay for TB screening in French healthcare workers

<p>Abstract</p> <p>Introduction</p> <p>Using French cut-offs for the Tuberculin Skin Test (TST), results of the TST were compared with the results of an Interferon-γ Release Assay (IGRA) in Healthcare Workers (HCW) after contact to AFB-positive TB patients.</p> <p>Methods</p> <p>Between May 2006 and May 2007, a total of 148 HCWs of the University Hospital in Nantes, France were tested simultaneously with IGRA und TST. A TST was considered to indicate recent latent TB infection (LTBI) if an increase of >10 mm or if TST ≥ 15 mm for those with no previous TST result was observed. For those with a positive TST, chest X-ray was performed and preventive chemotherapy was offered.</p> <p>Results</p> <p>All HCWs were BCG-vaccinated. The IGRA was positive in 18.9% and TST ≥ 10 mm was observed in 65.5%. A recent LTBI was believed to be highly probable in 30.4% following TST. Agreement between IGRA and TST was low (kappa 0.041). In 10 (16.7%) out of 60 HCWs who needed chest X-ray following TST the IGRA was positive. In 9 (20%) out of 45 HCWs to whom preventive chemotherapy was offered following TST the IGRA was positive. Of those considered TST-negative following the French guidelines, 20.5% were IGRA-positive. In a two-step strategy - positive TST verified by IGRA - 18 out of 28 (64.3%) IGRA-positive HCWs would not have been detected using French guidelines for TST interpretation.</p> <p>Conclusion</p> <p>The introduction of IGRA in contact tracings of BCG-vaccinated HCWs reduces X-rays and preventive chemotherapies. Increasing the cut-off for a positive TST does not seem to be helpful to overcome the effect of BCG vaccination on TST.</p

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers

Introduction: Lynch syndrome (LS) and constitutional mismatch repair deficiency (CMMRD) are hereditary cancer syndromes associated with mismatch repair (MMR) deficiency. Tumours show microsatellite instability (MSI), also reported at low levels in non-neoplastic tissues. Our aim was to evaluate the performance of high-sensitivity MSI (hs-MSI) assessment for the identification of LS and CMMRD in non-neoplastic tissues. Materials and methods: Blood DNA samples from 131 individuals were grouped into three cohorts: baseline (22 controls), training (11 CMMRD, 48 LS and 15 controls) and validation (18 CMMRD and 18 controls). Custom next generation sequencing panel and bioinformatics pipeline were used to detect insertions and deletions in microsatellite markers. An hs-MSI score was calculated representing the percentage of unstable markers. Results: The hs-MSI score was significantly higher in CMMRD blood samples when compared with controls in the training cohort (p<0.001). This finding was confirmed in the validation set, reaching 100% specificity and sensitivity. Higher hs-MSI scores were detected in biallelic MSH2 carriers (n=5) compared with MSH6 carriers (n=15). The hs-MSI analysis did not detect a difference between LS and control blood samples (p=0.564). Conclusions: The hs-MSI approach is a valuable tool for CMMRD diagnosis, especially in suspected patients harbouring MMR variants of unknown significance or non-detected biallelic germline mutations. Keywords: constitutional mismatch repair deficiency; highly sensitive methodologies; lynch syndrome; microsatellite instability; next generation sequencing