Singlet oxygen (1O2) is a biologically relevant reactive oxygen species capable of efficiently reacting with cellular constituents. The resulting oxidatively generated damage to nucleic acids, ...membrane unsaturated lipids, and protein components has been shown to be implicated in several diseases, including arthritis, cataracts, and skin cancer. Singlet oxygen may be endogenously produced, among various possibilities, by myeloperoxidase, an enzyme implicated in inflammation processes, and also efficiently in skin by the UVA component of solar radiation through photosensitization reactions. Emphasis is placed in this Review on the description of the main oxidation reactions initiated by 1O2 and the resulting modifications within key cellular targets, including guanine for nucleic acids, unsaturated lipids, and targeted amino acids. Most of these reactions give rise to peroxides and dioxetanes, whose formation has been rationalized in terms of 4+2 cycloaddition and 1,2-cycloaddition with dienes + olefins, respectively. The use of 18O-labeled thermolabile endoperoxides as a source of 18O-labeled 1O2 has been applied to study mechanistic aspects and preferential targets of 1O2 in biological systems. A relevant major topic deals with the search for the molecular signature of the 1O2 formation in targeted biomolecules within cells. It may be anticipated that 18O-labeled 1O2 and labeled peroxides in association with sensitive mass spectrometric methods should constitute powerful tools for this purpose.
In this review article, emphasis is placed on the critical survey of available data concerning modified nucleobase and 2-deoxyribose products that have been identified in cellular DNA following ...exposure to a wide variety of oxidizing species and agents including, hydroxyl radical, one-electron oxidants, singlet oxygen, hypochlorous acid and ten-eleven translocation enzymes. In addition, information is provided about the generation of secondary oxidation products of 8-oxo-7,8-dihydroguanine and nucleobase addition products with reactive aldehydes arising from the decomposition of lipid peroxides. It is worth noting that the different classes of oxidatively generated DNA damage that consist of single lesions, intra- and interstrand cross-links were unambiguously assigned and quantitatively detected on the basis of accurate measurements involving in most cases high performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. The reported data clearly show that the frequency of DNA lesions generated upon severe oxidizing conditions, including exposure to ionizing radiation is low, at best a few modifications per 106 normal bases. Application of accurate analytical measurement methods has also allowed the determination of repair kinetics of several well-defined lesions in cellular DNA that however concerns so far only a restricted number of cases.
Display omitted
•HPLC based methods are appropriate for monitoring oxidatively damage to DNA.•Single base lesions, intra- and interstrand cross-links were identified in cellular DNA.•Other modifications included halogenated bases and adducts with reactive aldehydes.•Paucity of reliable data on the base excision repair of oxidized bases in cells.
Summary
Background
The accuracy of available non‐invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited.
Aim
To assess the diagnostic ...performance of paired or serial combination of non‐invasive tools in NAFLD patients.
Methods
We analysed data from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI, AST/ALT, BARD, FIB‐4, and NAFLD Fibrosis Score (NFS) scores were calculated according to published algorithms. Liver stiffness measurement (LSM) was performed by FibroScan.
Results
LSM, NFS and FIB‐4 were the best non‐invasive tools for staging F3‐F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively), with LSM having the highest sensitivity (90%), and the highest NPV (94%), and NFS and FIB‐4 the highest specificity (97% and 93%, respectively), and the highest PPV (73% and 79%, respectively). The paired combination of LSM or NFS with FIB‐4 strongly reduced the likelihood of wrongly classified patients (ranging from 2.7% to 2.6%), at the price of a high uncertainty area (ranging from 54.1% to 58.2%), and of a low overall accuracy (ranging from 43% to 39.1%). The serial combination with the second test used in patients in the grey area of the first test and in those with high LSM values (>9.6 KPa) or low NFS or FIB‐4 values (<−1.455 and <1.30, respectively) overall increased the diagnostic performance generating an accuracy ranging from 69.8% to 70.1%, an uncertainty area ranging from 18.9% to 20.4% and a rate of wrong classification ranging from 9.2% to 11.3%.
Conclusion
The serial combination of LSM with FIB‐4/NFS has a good diagnostic accuracy for the non‐invasive diagnosis of severe fibrosis in NAFLD.
Linked ContentThis article is linked to Khan paper. To view this article visit https://doi.org/10.1111/apt.14267.
We present Atacama Large Millimeter Array 850 m continuum observations of the Orion Nebula Cluster that provide the highest angular resolution (∼0 1 40 au) and deepest sensitivity (∼0.1 mJy) of the ...region to date. We mosaicked a field containing ∼225 optical or near-IR-identified young stars, ∼60 of which are also optically identified "proplyds." We detect continuum emission at 850 m toward ∼80% of the proplyd sample, and ∼50% of the larger sample of previously identified cluster members. Detected objects have fluxes of ∼0.5-80 mJy. We remove submillimeter flux due to free-free emission in some objects, leaving a sample of sources detected in dust emission. Under standard assumptions of isothermal, optically thin disks, submillimeter fluxes correspond to dust masses of ∼0.5-80 Earth masses. We measure the distribution of disk sizes, and find that disks in this region are particularly compact. Such compact disks are likely to be significantly optically thick. The distributions of submillimeter flux and inferred disk size indicate smaller, lower-flux disks than in lower-density star-forming regions of similar age. Measured disk flux is correlated weakly with stellar mass, contrary to studies in other star-forming regions that found steeper correlations. We find a correlation between disk flux and distance from the massive star θ1 Ori C, suggesting that disk properties in this region are influenced strongly by the rich cluster environment.
TOPoS Bonifacio, P.; Monaco, L.; Salvadori, S. ...
Astronomy and astrophysics (Berlin),
07/2021, Volume:
651
Journal Article
Peer reviewed
Open access
Context.
The goal of the Turn-Off Primordial Stars survey (TOPoS) project is to find and analyse turn-off (TO) stars of extremely low metallicity. To select the targets for spectroscopic follow-up at ...high spectral resolution, we relied on low-resolution spectra from the Sloan Digital Sky Survey (SDSS).
Aims.
In this paper, we use the metallicity estimates we obtained from our analysis of the SDSS spectra to construct the metallicity distribution function (MDF) of the Milky Way, with special emphasis on its metal-weak tail. The goal is to provide the underlying distribution out of which the TOPoS sample was extracted.
Methods.
We made use of SDSS photometry,
Gaia
photometry, and distance estimates derived from the
Gaia
parallaxes to derive a metallicity estimate for a large sample of over 24 million TO stars. This sample was used to derive the metallicity bias of the sample for which SDSS spectra are available.
Results.
We determined that the spectroscopic sample is strongly biased in favour of metal-poor stars, as intended. A comparison with the unbiased photometric sample allows us to correct for the selection bias. We selected a sub-sample of stars with reliable parallaxes for which we combined the SDSS radial velocities with
Gaia
proper motions and parallaxes to compute actions and orbital parameters in the Galactic potential. This allowed us to characterise the stars dynamically, and in particular to select a sub-sample that belongs to the
Gaia
-Sausage-Enceladus (GSE) accretion event. We are thus also able to provide the MDF of GSE.
Conclusions.
The metal-weak tail derived in our study is very similar to that derived in the H3 survey and in the Hamburg/ESO Survey. This allows us to average the three MDFs and provide an error bar for each metallicity bin. Inasmuch as the GSE structure is representative of the progenitor galaxy that collided with the Milky Way, that galaxy appears to be strongly deficient in metal-poor stars compared to the Milky Way, suggesting that the metal-weak tail of the latter has been largely formed by accretion of low-mass galaxies rather than massive galaxies, such as the GSE progenitor.
We report new dynamical masses for five pre-main sequence (PMS) stars in the L1495 region of the Taurus star-forming region (SFR) and six in the L1688 region of the Ophiuchus SFR. Since these regions ...have VLBA parallaxes, these are absolute measurements of the stars' masses and are independent of their effective temperatures and luminosities. Seven of the stars have masses , thus providing data in a mass range with little data, and of these, six are measured to precision . We find eight stars with masses in the range 0.09-1.1 that agree well with the current generation of PMS evolutionary models. The ages of the stars we measured in the Taurus SFR are in the range 1-3 Myr, and Myr for those in L1688. We also measured the dynamical masses of 14 stars in the ALMA archival data for Akeson & Jensen's Cycle 0 project on binaries in the Taurus SFR. We find that the masses of seven of the targets are so large that they cannot be reconciled with reported values of their luminosity and effective temperature. We suggest that these targets are themselves binaries or triples.
IMPORTANCE Barrett esophagus containing low-grade dysplasia is associated with an increased risk of developing esophageal adenocarcinoma, a cancer with a rapidly increasing incidence in the western ...world. OBJECTIVE To investigate whether endoscopic radiofrequency ablation could decrease the rate of neoplastic progression. DESIGN, SETTING, AND PARTICIPANTS Multicenter randomized clinical trial that enrolled 136 patients with a confirmed diagnosis of Barrett esophagus containing low-grade dysplasia at 9 European sites between June 2007 and June 2011. Patient follow-up ended May 2013. INTERVENTIONS Eligible patients were randomly assigned in a 1:1 ratio to either endoscopic treatment with radiofrequency ablation (ablation) or endoscopic surveillance (control). Ablation was performed with the balloon device for circumferential ablation of the esophagus or the focal device for targeted ablation, with a maximum of 5 sessions allowed. MAIN OUTCOMES AND MEASURES The primary outcome was neoplastic progression to high-grade dysplasia or adenocarcinoma during a 3-year follow-up since randomization. Secondary outcomes were complete eradication of dysplasia and intestinal metaplasia and adverse events. RESULTS Sixty-eight patients were randomized to receive ablation and 68 to receive control. Ablation reduced the risk of progression to high-grade dysplasia or adenocarcinoma by 25.0% (1.5% for ablation vs 26.5% for control; 95% CI, 14.1%-35.9%; P < .001) and the risk of progression to adenocarcinoma by 7.4% (1.5% for ablation vs 8.8% for control; 95% CI, 0%-14.7%; P = .03). Among patients in the ablation group, complete eradication occurred in 92.6% for dysplasia and 88.2% for intestinal metaplasia compared with 27.9% for dysplasia and 0.0% for intestinal metaplasia among patients in the control group (P < .001). Treatment-related adverse events occurred in 19.1% of patients receiving ablation (P < .001). The most common adverse event was stricture, occurring in 8 patients receiving ablation (11.8%), all resolved by endoscopic dilation (median, 1 session). The data and safety monitoring board recommended early termination of the trial due to superiority of ablation for the primary outcome and the potential for patient safety issues if the trial continued. CONCLUSIONS AND RELEVANCE In this randomized trial of patients with Barrett esophagus and a confirmed diagnosis of low-grade dysplasia, radiofrequency ablation resulted in a reduced risk of neoplastic progression over 3 years of follow-up. TRIAL REGISTRATION trialregister.nl Identifier: NTR1198
Neoadjuvant chemo-radiotherapy (CRT) followed by total mesorectal excision (TME) represents the standard treatment for patients with locally advanced (≥ T3 or N+) rectal cancer (LARC). Approximately ...15% of patients with LARC shows a complete response after CRT. The use of pre-treatment MRI as predictive biomarker could help to increase the chance of organ preservation by tailoring the neoadjuvant treatment. We present a novel machine learning model combining pre-treatment MRI-based clinical and radiomic features for the early prediction of treatment response in LARC patients. MRI scans (3.0 T, T2-weighted) of 72 patients with LARC were included. Two readers independently segmented each tumor. Radiomic features were extracted from both the "tumor core" (TC) and the "tumor border" (TB). Partial least square (PLS) regression was used as the multivariate, machine learning, algorithm of choice and leave-one-out nested cross-validation was used to optimize hyperparameters of the PLS. The MRI-Based "clinical-radiomic" machine learning model properly predicted the treatment response (AUC = 0.793, p = 5.6 × 10
). Importantly, the prediction improved when combining MRI-based clinical features and radiomic features, the latter extracted from both TC and TB. Prospective validation studies in randomized clinical trials are warranted to better define the role of radiomics in the development of rectal cancer precision medicine.
We have illustrated the fabrication of nano-structures as a surface enhanced Raman scattering (SERS) substrate using electro-plating and electron-beam lithography techniques to obtain an array of ...gold nanograin-aggregate structures of diameter ranging between 80 and 100
nm with interstitial gap of 10–30
nm. The nanostructure based SERS substrate permits us to have better control and reproducibility on generation of plasmon polaritons. The calculation shows the possible detection of myoglobin concentration down to attomole. This SERS substrate is used to investigate the structural changes of different proteins; lysozyme, ribonuclease-B, bovin serum albumin and myoglobin in the temperature range between −65 and 90
°C. The in-depth analysis even for small conformational changes is performed using 2D Raman correlation analysis and difference Raman analysis in order to gain straightforward understanding of proteins undergoing thermodynamical perturbation.
Protecting human skin from sun exposure is a complex issue that involves unclear aspects of the interaction between light and tissue. A persistent misconception is that visible light is safe for the ...skin, although several lines of evidence suggest otherwise. Here, we show that visible light can damage melanocytes through melanin photosensitization and singlet oxygen (1O2) generation, thus decreasing cell viability, increasing membrane permeability, and causing both DNA photo-oxidation and necro-apoptotic cell death. UVA (355 nm) and visible (532 nm) light photosensitize 1O2 with similar yields, and pheomelanin is more efficient than eumelanin at generating 1O2 and resisting photobleaching. Although melanin can protect against the cellular damage induced by UVB, exposure to visible light leads to pre-mutagenic DNA lesions (i.e., Fpg- and Endo III-sensitive modifications); these DNA lesions may be mutagenic and may cause photoaging, as well as other health problems, such as skin cancer.
PDF
