Sulfur-isotope anomalies recorded in Antarctic ice cores as a potential proxy for tracing past ozone layer depletion events.

Changes in the cosmic-ray background of the Earth can impact the ozone layer. High-energy cosmic events [e.g. supernova (SN)] or rapid changes in the Earth's magnetic field [e.g. geomagnetic Excursion (GE)] can lead to a cascade of cosmic rays. Ensuing chemical reactions can then cause thinning/destruction of the ozone layer-leading to enhanced penetration of harmful ultraviolet (UV) radiation toward the Earth's surface. However, observational evidence for such UV "windows" is still lacking. Here, we conduct a pilot study and investigate this notion during two well-known events: the multiple SN event (≈10 kBP) and the Laschamp GE event (≈41 kBP). We hypothesize that ice-core-Δ33S records-originally used as volcanic fingerprints-can reveal UV-induced background-tropospheric-photochemical imprints during such events. Indeed, we find nonvolcanic S-isotopic anomalies (Δ33S ≠ 0‰) in background Antarctic ice-core sulfate during GE/SN periods, thereby confirming our hypothesis. This suggests that ice-core-Δ33S records can serve as a proxy for past ozone-layer-depletion events.

Study of thrombin generation with St Genesia to evaluate xaban pharmacodynamics: Analytical performances over 18 months.

INTRODUCTION: ST Genesia is a new automated system enabling quantitative standardized evaluation of thrombin generation (TG), for example, in patients receiving anti-Xa direct inhibitors (xabans). Data on its analytical performances are scarce. METHODS: Over an 18-month period, repeatability, reproducibility, and accuracy were assessed using STG-ThromboScreen (without or with thrombomodulin) or STG-DrugScreen reagents (corresponding to intermediate/high tissue-factor concentration, respectively), and controls. Furthermore, reproducibility was assessed using commercialized lyophilized and frozen normal pooled plasmas. Rivaroxaban and apixaban impacts on TG parameters were assessed using spiking experiments. Finally, a comparison with the Calibrated Automated Thrombogram method (CAT) (PPP reagent) was performed using plasma from healthy volunteers enrolled in the DRIVING-studyNCT01627665) before and after rivaroxaban intake. RESULTS: For all dedicated quality control (QC) levels, inter-series coefficients of variations (CV) were <7% for temporal TG parameters, peak height (PH), and endogenous thrombin potential (ETP), whether results were normalized with a dedicated reference plasma STG-RefPlasma or not. Noteworthy, STG-RefPlasma used for normalization displayed substantially high PH and ETP. Mean biases between the observed and manufacturer's assigned QC values were mostly <7%. Both rivaroxaban/apixaban plasma concentrations were significantly associated with TG parameters. Finally, Bland-Altman plots showed a good agreement between ST Genesia-STG-ThromboScreen and CAT method within the explored range of values, although biases could be observed (PH: 16.4 ± 13.2%, ETP: 17.8 ± 11.9%). CONCLUSION: ST Genesia® enables the reliable measurement of TG parameters in both in vitro and ex vivo xaban plasma samples using either STG-ThromboScreen or STG-DrugScreen according to xaban concentrations. The use of reference plasma, despite not completely reflecting a normal pooled plasma behavior, likely improves standardization and inter-laboratory comparisons.

Are boron isotopes a reliable tracer of anthropogenic inputs to rivers over time?

This study aims at determining how the boron signal of the Seine River evolved in terms of concentration and isotopic signatures over eighteen years (1994-95 and 2006-12) and if boron isotopes can reliably trace anthropogenic inputs over time. In the anthropised Seine River watershed, boron is widely released by human activities, and even if boron concentrations ([B]) are below the potability limit, our study confirms the potential of boron isotopes (δ11B) to trace urban anthropogenic contaminations. Between 1994 and 2012, [B] have decreased across the anthropised part of the Seine River basin (and by a factor of two in Paris) while δ11B has increased. This means either that urban inputs have been reduced or that the boron signature of urban inputs has changed over time. Both hypotheses are in agreement with the decrease of perborate consumption in Europe over 15years and are not mutually exclusive. Results of a thorough analysis of urban effluents from the sewage network of Paris conurbation that are in fine released to the Seine River suggest a shift of the urban δ11B from -10‰ in 1994 to 1.5±2.0‰ in 2012, in agreement with our second hypothesis. We attribute this change to the removal of perborates from detergents rather than to the modernisation of wastewater treatment network, because it does not significantly impact the wastewater boron signatures. Eighteen years after the first assessment and despite the decreased use of perborates, geochemical and isotopic mass budgets confirm, that boron in the Seine River basin is mainly released from urban activities (60-100%), especially in Paris and the downstream part of the basin. Contrastingly, in headwaters and/or tributaries with low urbanisation, the relative boron input to river from agricultural practices and rains increased, up to 10% and by 10 to 30%, respectively.

Kinematic patterns in normal and degenerative shoulders. Part II: Review of 3-D scapular kinematic patterns in patients with shoulder pain, and clinical implications.

BACKGROUND: The global range of motion of the arm is the result of a coordinated motion of the shoulder complex including glenohumeral (GH), scapulothoracic, sternoclavicular and acromioclavicular joints. METHODS: This study is a non-systematic review of kinematic patterns in degenerated shoulders. It is a based on our own research on the kinematics of the shoulder complex and clinical experience. RESULTS: For patients with subacromial impingement syndrome without rotator-cuff tears, most kinematic studies showed a small superior humeral translation relative to the glenoid and decreased scapular lateral rotation and posterior tilt. These scapular kinematic modifications could decrease the subacromial space and favor rotator-cuff tendon injury. For patients with shoulder pain and restricted mobility, the studies showed a significant increase in scapular lateral rotation generally seen as a compensation mechanism of GH decreased range of motion. For patients with multidirectional GH instability, the studies found an antero-inferior decentering of the humeral head, decreased scapular lateral rotation and increased scapular internal rotation. CONCLUSION: The clinical or instrumented assessment of the shoulder complex with a degenerative pathology must include the analysis of scapula-clavicle and trunk movements complementing the GH assessment. Depending on the individual clinical case, scapular dyskinesis could be the cause or the consequence of the shoulder degenerative pathology. For most degenerative shoulder pathologies, the rehabilitation program should take into account the whole shoulder complex and include first a scapular and trunk postural-correcting strategy, then scapulothoracic muscle rehabilitation (especially serratus anterior and trapezius inferior and medium parts) and finally neuromotor techniques to recover appropriate upper-limb kinematic schemas for daily and/or sports activities.

Synchronous volcanic eruptions and abrupt climate change ∼17.7 ka plausibly linked by stratospheric ozone depletion.

Glacial-state greenhouse gas concentrations and Southern Hemisphere climate conditions persisted until ∼17.7 ka, when a nearly synchronous acceleration in deglaciation was recorded in paleoclimate proxies in large parts of the Southern Hemisphere, with many changes ascribed to a sudden poleward shift in the Southern Hemisphere westerlies and subsequent climate impacts. We used high-resolution chemical measurements in the West Antarctic Ice Sheet Divide, Byrd, and other ice cores to document a unique, ∼192-y series of halogen-rich volcanic eruptions exactly at the start of accelerated deglaciation, with tephra identifying the nearby Mount Takahe volcano as the source. Extensive fallout from these massive eruptions has been found >2,800 km from Mount Takahe. Sulfur isotope anomalies and marked decreases in ice core bromine consistent with increased surface UV radiation indicate that the eruptions led to stratospheric ozone depletion. Rather than a highly improbable coincidence, circulation and climate changes extending from the Antarctic Peninsula to the subtropics-similar to those associated with modern stratospheric ozone depletion over Antarctica-plausibly link the Mount Takahe eruptions to the onset of accelerated Southern Hemisphere deglaciation ∼17.7 ka.

Intradiscal Glucocorticoid Injection for Patients With Chronic Low Back Pain Associated With Active Discopathy: A Randomized Trial.

BACKGROUND: Active discopathy is associated with a specific phenotype of chronic low back pain (LBP). Local inflammation has a role in active discopathy-associated symptoms. OBJECTIVE: To assess the efficacy of a single glucocorticoid intradiscal injection (GC IDI) in patients with chronic LBP with active discopathy. DESIGN: Prospective, parallel-group, double-blind, randomized, controlled study. (ClinicalTrials.gov: NCT00804531). SETTING: 3 tertiary care centers in France. PATIENTS: 135 patients with chronic LBP with active discopathy on magnetic resonance imaging (MRI). INTERVENTION: A single GC IDI (25 mg prednisolone acetate) during discography (n = 67) or discography alone (n = 68). MEASUREMENTS: The primary outcome was the percentage of patients with LBP intensity less than 40 on an 11-point numerical rating scale (0 [no pain] to 100 [maximum pain] in 10-point increments) in the previous 48 hours at 1 month after the intervention. The main secondary outcomes were LBP intensity and persistent active discopathy on MRI at 12 months and spine-specific limitations in activities, health-related quality of life, anxiety and depression, employment status, and use of analgesics and nonsteroidal anti-inflammatory drugs at 1 and 12 months. RESULTS: All randomly assigned patients were included in the primary efficacy analysis. At 1 month after the intervention, the percentage of responders (LBP intensity <40) was higher in the GC IDI group (36 of 65 [55.4%]) than the control group (21 of 63 [33.3%]) (absolute risk difference, 22.1 percentage points [95% CI, 5.5 to 38.7 percentage points]; P = 0.009). The groups did not differ in LBP intensity at 12 months and in most secondary outcomes at 1 and 12 months. LIMITATION: Tertiary care setting. CONCLUSION: In chronic LBP associated with active discopathy, a single GC IDI reduces LBP at 1 month but not at 12 months. PRIMARY FUNDING SOURCE: French Ministry of Health.

Biomimetic solution against dewetting in a highly hydrophobic nanopore.

A water molecule is the foundation of life and is the primary compound in every living system. While many of its properties are understood in a bulk solvent, its behavior in a small hydrophobic nanopore still raises fundamental questions. For instance, a wetting/dewetting transition in a hydrophobic solid-state or a polymer nanopore occurs stochastically and can only be prevented by external physical stimuli. Controlling these transitions would be a primary requirement to improve many applications. Some biological channels, such as gramicidin A (gA) proteins, show a high rate of water and ion diffusion in their central subnanochannel while their external surface is highly hydrophobic. The diameter of this channel is significantly smaller than the inner size of the lowest artificial nanopore in which water drying occurs (i.e. 1.4 nm). In this paper, we propose an innovative idea to generate nanopore wetting as a result of which the application of an external field is no longer required. In a nanopore, the drying or wetting of the inner walls occurs randomly (in experiments and in simulations). However, we have shown how the confinement of gA, in a dried hydrophobic nanopore, rapidly generates a stable wetting of the latter. We believe that this simple idea, based on biomimetism, could represent a real breakthrough that could help to improve and develop new nanoscale applications.

Is physical activity, practiced as recommended for health benefit, a risk factor for osteoarthritis?

In this critical narrative review, we examine the role of physical activity (PA), recreational and elite sports in the development of knee/hip osteoarthritis (OA), taking into account the role of injury in this relationship. The process of article selection was unsystematic. Articles were selected on the basis of the authors' expertise, self-knowledge, and reflective practice. In the general adult population, self-reported diagnosis of knee/hip OA was not associated with low, moderate or high levels of PA. For studies using radiographic knee/hip OA as a primary outcome, the incidence of asymptomatic radiographic OA was higher for subjects with the highest quartile of usual PA than the least active subjects. The risk of incident radiographic knee/hip OA features was increased for subjects with a history of regular sports participation (for osteophyte formation but not joint space narrowing). This risk depended on the type of sport (team and power sports but not endurance and running), and certain conditions (high level of practice) were closely related to the risk of injury. The prevalence of radiographic OA was significantly higher, especially the presence of osteophytes, in former elite athletes than controls. The risk of OA was higher with participation in mixed sports, especially soccer or power sports, than endurance sport. However, the prevalence of clinical OA between former elite athletes and controls was similar, with less hip/knee disability in former athletes. Moderate daily recreational or sport activities, whatever the type of sport, are not a consistent risk factor for clinical or radiographic knee/hip OA. Risk of injury in different sports may be the key factor to understanding the risk of OA related to sport.

A theoretical study of the unfolding pathway of reduced human serum albumin.

The unfolding of the reduced human serum albumin (HSA) was simulated by generating four molecular dynamics (MD) trajectories of 160 ns each at 350, 375, 400, and 425 K, respectively. A principal components analysis (PCA) was performed on the four trajectories. Based on this analysis, 17 representative protein conformers were identified and subsequently used to construct a sequence of partially unfolded structures. They were ordered according to their decreasing α-helix fractions. The structural evolution in this unfolding sequence was found to be continuous at global but also at local level supporting the hypothesis that the protein unfolding pathway is not significantly dependent on the simulation temperature. As a result, the α-helix fraction of the protein appears to be a good reaction coordinate for the unfolding process, as it was previously suggested by experiments. Based on this observation, two conformers in the unfolding sequence were predicted to be close to the equilibrium structure of reduced HSA thus providing a first theoretical model for this protein form.

Sulfate was a trace constituent of Archean seawater.

In the low-oxygen Archean world (>2400 million years ago), seawater sulfate concentrations were much lower than today, yet open questions frustrate the translation of modern measurements of sulfur isotope fractionations into estimates of Archean seawater sulfate concentrations. In the water column of Lake Matano, Indonesia, a low-sulfate analog for the Archean ocean, we find large (>20 per mil) sulfur isotope fractionations between sulfate and sulfide, but the underlying sediment sulfides preserve a muted range of δ(34)S values. Using models informed by sulfur cycling in Lake Matano, we infer Archean seawater sulfate concentrations of less than 2.5 micromolar. At these low concentrations, marine sulfate residence times were likely 10(3) to 10(4) years, and sulfate scarcity would have shaped early global biogeochemical cycles, possibly restricting biological productivity in Archean oceans.

A principal component analysis of the dynamics of subdomains and binding sites in human serum albumin.

The conformational dynamics of human serum albumin (HSA) was investigated by principal component analysis (PCA) applied to three molecular dynamics trajectories of 200 ns each. The overlap of the essential subspaces spanned by the first 10 principal components (PC) of different trajectories was about 0.3 showing that the PCA based on a trajectory length of 200 ns is not completely convergent for this protein. The contributions of the relative motion of subdomains and of the subdomains (internal) distortion to the first 10 PCs were found to be comparable. Based on the distribution of the first 3 PC, 10 protein conformers are identified showing relative root mean square deviations (RMSD) between 2.3 and 4.6 Å. The main PCs are found to be delocalized over the whole protein structure indicating that the motions of different protein subdomains are coupled. This coupling is considered as being related to the allosteric effects observed upon ligand binding to HSA. On the other hand, the first PC of one of the three trajectories describes a conformational transition of the protein domain I that is close to that experimentally observed upon myristate binding. This is a theoretical support for the older hypothesis stating that changes of the protein onformation favorable to binding can precede the ligand complexation. A detailed all atoms PCA performed on the primary Sites 1 and 2 confirms the multiconformational character of the HSA binding sites as well as the significant coupling of their motions.

About the structural role of disulfide bridges in serum albumins: evidence from protein simulated unfolding.

The role of the 17 disulfide (S-S) bridges in preserving the native conformation of human serum albumin (HSA) is investigated by performing classical molecular dynamics (MD) simulations on protein structures with intact and, respectively, reduced S-S bridges. The thermal unfolding simulations predict a clear destabilization of the protein secondary structure upon reduction of the S-S bridges as well as a significant distortion of the tertiary structure that is revealed by the changes in the protein native contacts fraction. The effect of the S-S bridges reduction on the protein compactness was tested by calculating Gibbs free energy profiles with respect to the protein gyration radius. The theoretical results obtained using the OPLS-AA and the AMBER ff03 force fields are in agreement with the available experimental data. Beyond the validation of the simulation method, the results here reported provide new insights into the mechanism of the protein reductive/oxidative unfolding/folding processes. It is predicted that in the native conformation of the protein, the thiol (-SH) groups belonging to the same reduced S-S bridge are located in potential wells that maintain them in contact. The -SH pairs can be dispatched by specific conformational transitions of the peptide chain located in the neighborhood of the cysteine residues.