The dual nature of DNA damage response in obesity and bariatric surgery-induced weight loss.

This novel study applies targeted functional proteomics to examine tissues and cells obtained from a cohort of individuals with severe obesity who underwent bariatric surgery (BS), using a Reverse-Phase Protein Array (RPPA). In obese individuals, visceral adipose tissue (VAT), but not subcutaneous adipose tissue (SAT), shows activation of DNA damage response (DDR) markers including ATM, ATR, histone H2AX, KAP1, Chk1, and Chk2, alongside senescence markers p16 and p21. Additionally, stress-responsive metabolic markers, such as survivin, mTOR, and PFKFB3, are specifically elevated in VAT, suggesting both cellular stress and metabolic dysregulation.

Spectroscopic confirmation of two luminous galaxies at a redshift of 14.

The first observations of the James Webb Space Telescope (JWST) have revolutionized our understanding of the Universe by identifying galaxies at redshift z ≈ 13 (refs. ). In addition, the discovery of many luminous galaxies at Cosmic Dawn (z > 10) has suggested that galaxies developed rapidly, in apparent tension with many standard models.

Impact of water level management on organic carbon availability and nitrogen transformations in wetland sediments.

The impact of water level management via water retention on benthic carbon and nitrogen fluxes was studied in a wetland of the Seine estuary. Carbon and inorganic nitrogen fluxes at the sediment-water interface were determined during periods of intermittent and permanent immersion along a lateral gradient. In addition to fluxes, nitrate reduction rates, quantity and quality of both sedimentary and dissolved organic carbon, and organic matter lability via external enzymatic activities were analyzed.

Changes over time in organic matter dynamics and copper solubility in a vineyard soil after incorporation of cover crop residues: Insights from a batch experiment.

Cover crops (CCs) are increasingly used in viticulture because they benefit the soil and the environment in many ways. This study investigated the extent to which the incorporation of CC residues altered organic matter (OM) and Cu dynamics in a Cu-contaminated vineyard topsoil. A 92-day incubation period was used to monitor changes over time in carbon mineralization, carbon hydrolytic enzyme activity, concentration and optical properties of dissolved organic matter (DOM), and Cu solubility after the addition (or not) of two CC residues, oat or faba bean.

Sampling terrigenous diffuse sources in watercourse: Influence of land use and hydrological conditions on dissolved organic matter characteristics.

Diffuse and point sources of dissolved organic matter (DOM) in streams influence its composition, interactions and fate in the aquatic ecosystem. These inputs can be very numerous at the scale of a watershed, and their identification remains a challenge, especially for diffuse sources related to land use. The complexity of the transfer mechanisms and the reactivity of DOM throughout the soil-water column continuum raise questions about the sampling of diffuse sources in watercourses.

Do DOM optical parameters improve the prediction of copper availability in vineyard soils?

Accumulation of copper (Cu) in soils due to the application of fungicides may be toxic for organisms and hence affect winegrowing sustainability. Soil parameters such as pH and dissolved organic matter (DOM) are known to affect the availability of Cu. In this study, we investigated the contribution of chromophoric and fluorescent DOM properties to the prediction of Cu availability in 18 organic vineyard soils in the Bordeaux winegrowing area (France).

The interplay between mitochondrial functionality and genome integrity in the prevention of human neurologic diseases.

As mitochondria are vulnerable to oxidative damage and represent the main source of reactive oxygen species (ROS), they are considered key tuners of ROS metabolism and buffering, whose dysfunction can progressively impact neuronal networks and disease. Defects in DNA repair and DNA damage response (DDR) may also affect neuronal health and lead to neuropathology. A number of congenital DNA repair and DDR defective syndromes, indeed, show neurological phenotypes, and a growing body of evidence indicate that defects in the mechanisms that control genome stability in neurons acts as aging-related modifiers of common neurodegenerative diseases such as Alzheimer, Parkinson's, Huntington diseases and Amyotrophic Lateral Sclerosis.

Correction: Krokidis, M.G., et al. Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells. 2020, , 1671.

The originally published article [...

Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells.

Cockayne Syndrome (CS) is an autosomal recessive neurodegenerative premature aging disorder associated with defects in nucleotide excision repair (NER). Cells from CS patients, with mutations in or genes, present elevated levels of reactive oxygen species (ROS) and are defective in the repair of a variety of oxidatively generated DNA lesions. In this study, six purine lesions were ascertained in wild type (wt) CSA, defective CSA, wtCSB and defective CSB-transformed fibroblasts under different oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%).

Study of the dissolved organic matter (DOM) of the Auzon cut-off meander (Allier River, France) by spectral and photoreactivity approaches.

Wetlands are recognized for the importance of their hydrological function and biodiversity, and there is now a consensus to protect and restore them as well as to complete the knowledge on their functioning. Here, we studied the dissolved organic matter (DOM) of a wetland composed of the Auzon cut-off meander, the Allier River, the alluvial fluvial flow, and watershed aquifer. Water was sampled at different locations, in spring, summer, and autumn.

Purine DNA Lesions at Different Oxygen Concentration in DNA Repair-Impaired Human Cells (EUE-siXPA).

Xeroderma Pigmentosum (XP) is a DNA repair disease characterized by nucleotide excision repair (NER) malfunction, leading to photosensitivity and increased incidence of skin malignancies. The role of XP-A in NER pathways has been well studied while discrepancies associated with ROS levels and the role of radical species between normal and deficient XPA cell lines have been observed. Using liquid chromatography tandem mass spectrometry we have determined the four 5',8-cyclopurines (cPu) lesions (i.

CSA and CSB play a role in the response to DNA breaks.

CS proteins have been involved in the repair of a wide variety of DNA lesions. Here, we analyse the role of CS proteins in DNA break repair by studying histone H2AX phosphorylation in different cell cycle phases and DNA break repair by comet assay in CS-A and CS-B primary and transformed cells. Following methyl methane sulphate treatment a significant accumulation of unrepaired single strand breaks was detected in CS cells as compared to normal cells, leading to accumulation of double strand breaks in S and G2 phases.

The influence of natural dissolved organic matter on herbicide toxicity to marine microalgae is species-dependent.

Microalgae, which are the foundation of aquatic food webs, may be the indirect target of herbicides used for agricultural and urban applications. Microalgae also interact with other compounds from their environment, such as natural dissolved organic matter (DOM), which can itself interact with herbicides. This study aimed to evaluate the influence of natural DOM on the toxicity of three herbicides (diuron, irgarol and S-metolachlor), singly and in ternary mixtures, to two marine microalgae, Chaetoceros calcitrans and Tetraselmis suecica, in monospecific, non-axenic cultures.

Asymmetrical flow field-flow fractionation of white wine chromophoric colloidal matter.

Two analytical separation methods-size-exclusion chromatography and asymmetrical flow field-flow fractionation-were implemented to evaluate the integrity of the colloidal composition of Chardonnay white wine and the impact of pressing and fermentations on the final macromolecular composition. Wine chromophoric colloidal matter, representing UV-visible-absorbing wine macromolecules, was evaluated by optical and structural measurements combined with the description of elution profiles obtained by both separative techniques. The objective of this study was to apply these two types of fractionation on a typical Chardonnay white wine produced in Burgundy and to evaluate how each of them impacted the determination of the macromolecular chromophoric content of wine.

Single nucleotide polymorphisms in DNA glycosylases: From function to disease.

Oxidative stress is associated with a growing number of diseases that span from cancer to neurodegeneration. Most oxidatively induced DNA base lesions are repaired by the base excision repair (BER) pathway which involves the action of various DNA glycosylases. There are numerous genome wide studies attempting to associate single-nucleotide polymorphisms (SNPs) with predispositions to various types of disease; often, these common variants do not have significant alterations in their biochemical function and do not exhibit a convincing phenotype.

Crosstalk between mismatch repair and base excision repair in human gastric cancer.

DNA repair gene expression in a set of gastric cancers suggested an inverse association between the expression of the mismatch repair (MMR) gene MLH1 and that of the base excision repair (BER) gene DNA polymerase β (Polβ). To gain insight into possible crosstalk of these two repair pathways in cancer, we analysed human gastric adenocarcinoma AGS cells over-expressing Polβ or Polβ active site mutants, alone or in combination with MLH1 silencing. Next, we investigated the cellular response to the alkylating agent methyl methanesulfonate (MMS) and the purine analogue 6-thioguanine (6-TG), agents that induce lesions that are substrates for BER and/or MMR.

The Response to Oxidative DNA Damage in Neurons: Mechanisms and Disease.

There is a growing body of evidence indicating that the mechanisms that control genome stability are of key importance in the development and function of the nervous system. The major threat for neurons is oxidative DNA damage, which is repaired by the base excision repair (BER) pathway. Functional mutations of enzymes that are involved in the processing of single-strand breaks (SSB) that are generated during BER have been causally associated with syndromes that present important neurological alterations and cognitive decline.

An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients.

Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability.

Development of solid-phase microextraction to study dissolved organic matter--polycyclic aromatic hydrocarbon interactions in aquatic environment.

Solid-phase microextraction coupled with gas chromatography and mass spectrometry (SPME-GC-MS) was developed for the study of interactions between polycyclic aromatic hydrocarbons (PAHs) and dissolved organic matter (DOM). After the determination of the best conditions of extraction, the tool was applied to spiked water to calculate the dissolved organic carbon water distribution coefficient (K(DOC)) in presence of different mixtures of PAHs and Aldrich humic acid. The use of deuterated naphthalene as internal standard for freely dissolved PAH quantification was shown to provide more accuracy than regular external calibration.

The cross talk between pathways in the repair of 8-oxo-7,8-dihydroguanine in mouse and human cells.

Although oxidatively damaged DNA is repaired primarily via the base excision repair (BER) pathway, it is now evident that multiple subpathways are needed. Yet, their relative contributions and coordination are still unclear. Here, mouse embryo fibroblasts (MEFs) from selected nucleotide excision repair (NER) and/or BER mouse mutants with severe (Csb(m/m)/Xpa(-/-) and Csb(m/m)/Xpc(-/-)), mild (Csb(m/m)), or no progeria (Xpa(-/-), Xpc(-/-), Ogg1(-/-), Csb(m/m)/Ogg1(-/-)) or wild-type phenotype were exposed to an oxidizing agent, potassium bromate, and genomic 8-oxo-7,8-dihydroguanine (8-oxoGua) levels were measured by HPLC-ED.

Role of nucleotide excision repair proteins in oxidative DNA damage repair: an updating.

DNA repair is a crucial factor in maintaining a low steady-state level of oxidative DNA damage. Base excision repair (BER) has an important role in preventing the deleterious effects of oxidative DNA damage, but recent evidence points to the involvement of several repair pathways in this process. Oxidative damage may arise from endogenous and exogenous sources and may target nuclear and mitochondrial DNA as well as RNA and proteins.

Copper addition by organic matter degradation in the freshwater reaches of a turbid estuary.

This study reports on the relationship between copper (Cu) behavior and organic matter (OM) transformation along the turbidity gradient in the freshwater reaches of the Gironde Estuary. During a one-year survey, surface water and suspended particulate matter (SPM) were sampled at least monthly at three sites along the Garonne Branch, representing the main fluvial branch of the Gironde Estuary. Additionally, a longitudinal high resolution profile was sampled along the Garonne Branch, covering the turbidity gradient from the river water endmember to the maximum turbidity zone (MTZ).

Mechanism of oxidative DNA damage repair and relevance to human pathology.

Since DNA is prone to oxidative attack cells have evolved multiple protective strategies to prevent the deleterious effects of DNA oxidation. Base excision repair is the major mechanism for repair of DNA base damage by reactive oxygen species but recent evidence indicate that nucleotide excision repair proteins, that are mutated in human syndromes, are involved too. The mechanisms of repair dealing with the direct oxidation of DNA will be reviewed taking as prototype the oxidized base 7,8-dihydro-8-hydroxyguanine.

The role of CSA in the response to oxidative DNA damage in human cells.

Cockayne syndrome (CS) is a rare genetic disease characterized by severe growth, mental retardation and pronounced cachexia. CS is most frequently due to mutations in either of two genes, CSB and CSA. Evidence for a role of CSB protein in the repair of oxidative DNA damage has been provided recently.