DNA integrity and ecophysiological responses of Spanish populations of Ulmus glabra to increasing ozone levels.

Ulmus glabra is a deciduous tree with a wide distribution in the Eurosiberian region. The southernmost populations, in the Mediterranean area, are fragmented in mountain areas which act as a refugium. These small relict populations can act as sentinel of global change, including climate change and impacts of human activities such as air pollution. Besides, tropospheric ozone (O3) is an additional stress factor in the Mediterranean region affecting plant physiology and health. Moreover, oxidative stress caused by O3 could increase DNA damage in plants cells. U. glabra 4-year-old seedlings originated from a natural population growing in the Guadarrama mountain range (central Spain), were exposed in Open Top Chambers to four O3 treatments: charcoal filtered air, non-filtered air reproducing ambient levels, non-filtered air supplemented with 15 nl l-1 O3 and non- filtered air supplemented with 30 nl l-1 O3. Ozone effects on the DNA integrity through Comet assay were evaluated and eco-physiological responses were explored as well as. Comet assay showed a significant increase of DNA damage with increasing levels of O3 after only one-month exposure, when no eco-physiological symptoms of damage could be detected. Comet assay could thus be suggested as a predictive test to detect DNA damage induced in plants by other abiotic stresses as well as to identify tolerant and sensitive species or in preservation strategies of small relict populations. The discovery of a test for an early identification of stressed plants could be important to speed the selection of tolerant individuals for breeding programmes.

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. Conversely, peripheral blood mononuclear cells (PBMCs), while exhibiting elevated mTOR and JNK levels, did not present significant changes in DDR or senescence markers. Following BS, unexpected increases in phosphorylated ATM, ATR, and KAP1 levels, but not in Chk1 and Chk2 nor in senescence markers, were observed. This was accompanied by heightened levels of survivin and mTOR, along with improvement in markers of mitochondrial quality and health. This suggests that, following BS, pro-survival pathways involved in cellular adaptation to various stressors and metabolic alterations are activated in circulating PBMCs. Moreover, our findings demonstrate that the DDR has a dual nature. In the case of VAT from individuals with obesity, chronic DDR proves to be harmful, as it is associated with senescence and chronic inflammation. Conversely, after BS, the activation of DDR proteins in PBMCs is associated with a beneficial survival response. This response is characterized by metabolic redesign and improved mitochondrial biogenesis and functionality. This study reveals physiological changes associated with obesity and BS that may aid theragnostic approaches.

A multi-marker integrative analysis reveals benefits and risks of bariatric surgery.

Bariatric surgery (BS) is an effective intervention for severe obesity and associated comorbidities. Although several studies have addressed the clinical and metabolic effects of BS, an integrative analysis of the complex body response to surgery is still lacking. We conducted a longitudinal data study with 36 patients with severe obesity who were tested before, 6 and 12 months after restrictive BS for more than one hundred blood biomarkers, including clinical, oxidative stress and metabolic markers, peptide mediators and red blood cell membrane lipids. By using a synthetic data-driven modeling based on principal component and correlation analyses, we provided evidence that, besides the early, well-known glucose metabolism- and weight loss-associated beneficial effects of BS, a tardive, weight-independent increase of the hepatic cholesterol metabolism occurs that is associated with potentially detrimental inflammatory and metabolic effects. Canonical correlation analysis indicated that oxidative stress is the most predictive feature of the BS-induced changes of both glucose and lipids metabolism. Our results show the power of multi-level correlation analysis to uncover the network of biological pathways affected by BS. This approach highlighted potential health risks of restrictive BS that are disregarded with the current practice to use weight loss as surrogate of BS success.