[New paths or advances in bioethics].

This paper examines the impact of the exceptional events of the 2020 pandemic and the government containment responses it triggered on two ethical issues that arose before the virus took its toll. These two questions - chosen among others - were those of the unity of the medical ethics and of the specific nature of the pharmacist's ethics. The answers to these questions were deeply changed in meaning and value after the events we experienced.

The IL-1β Antibody Gevokizumab Limits Cardiac Remodeling and Coronary Dysfunction in Rats With Heart Failure.

This study reports preclinical data showing that the interleukin (IL)-1β modulation is a new promising target in the pathophysiological context of heart failure. Indeed, in nondiabetic Wistar and diabetic Goto-Kakizaki rats with chronic heart failure induced by myocardial infarction, administration of the IL-1β antibody gevokizumab improves 'surrogate' markers of survival (i.e.

Vascular Smooth Muscle Mineralocorticoid Receptor Contributes to Coronary and Left Ventricular Dysfunction After Myocardial Infarction.

Mineralocorticoid receptor (MR) antagonists slow down the progression of heart failure after myocardial infarction (MI), but the cell-specific role of MR in these benefits is unclear. In this study, the role of MR expressed in vascular smooth muscle cells (VSMCs) was investigated. Two months after coronary artery ligation causing MI, mice with VSMC-specific MR deletion (MI-MR(SMKO)) and mice treated with the MR antagonist finerenone (MI-fine) had improved left ventricular compliance and elastance when compared with infarcted control mice (MI-CTL), as well as reduced interstitial fibrosis.

Selective Heart Rate Reduction Improves Metabolic Syndrome-related Left Ventricular Diastolic Dysfunction.

Background: Enhanced heart rate observed in metabolic syndrome (MS) contributes to the deterioration of left ventricular (LV) function via impaired LV filling and relaxation, increased myocardial O2 consumption, and reduced coronary perfusion. However, whether heart rate reduction (HRR) opposes LV dysfunction observed in MS is unknown.

Methods: We assessed in Zucker fa/fa rats, a rat model of MS, the cardiovascular effects of HRR induced by the If current inhibitor S38844 (3 mg · kg(-1) · d(-1)).

Performance of the BODE index in patients with α1-antitrypsin deficiency-related COPD.

The BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) index is used to decide on referral and transplantation of patients with chronic obstructive pulmonary disease (COPD). The BODE index has not been validated in patients with α1-antitrypsin deficiency, who account for 15% of COPD patients undergoing lung transplantation. We sought to validate the BODE index in α1-antitrypsin deficiency-related COPD.

50nm-scale localization of single unmodified, isotopically enriched, proteins in cells.

Imaging single proteins within cells is challenging if the possibility of artefacts due to tagging or to recognition by antibodies is to be avoided. It is generally believed that the biological properties of proteins remain unaltered when (14)N isotopes are replaced with (15)N. (15)N-enriched proteins can be localised by dynamic Secondary Ion Mass Spectrometry (D-SIMS).

Sensor potency of the moonlighting enzyme-decorated cytoskeleton: the cytoskeleton as a metabolic sensor.

Background: There is extensive evidence for the interaction of metabolic enzymes with the eukaryotic cytoskeleton. The significance of these interactions is far from clear.

Presentation Of The Hypothesis: In the cytoskeletal integrative sensor hypothesis presented here, the cytoskeleton senses and integrates the general metabolic activity of the cell.

[Interpretation of writings in the psychopathologic approach to spiritualism (1850 - 1950)].

We propose a chronological review of the psychopathological interpretations of writings produced by spiritualists during their practices of trance or by spiritualists turned delirious. The interest is to highlight the exemplary role that psychiatrists or psychopathologists made attributed to mediumnism in the elaboration of psychiatric knowledge.

Combed single DNA molecules imaged by secondary ion mass spectrometry.

Studies of replication, recombination, and rearrangements at the level of individual molecules of DNA are often limited by problems of resolution or of perturbations caused by the modifications that are needed for imaging. The Combing-Imaging by Secondary Ion Mass Spectrometry (SIMS) (CIS) method helps solve these problems by combining DNA combing, cesium flooding, and quantitative imaging via the NanoSIMS 50. We show here that CIS can reveal, on the 50 nm scale, individual DNA fibers labeled with different, nonradioactive isotopes and, moreover, that it can quantify these isotopes so as to detect and measure the length of one or more short nucleic acid fragments associated with a longer fiber.

Hybolites: novel therapeutic tools for targeting hyperstructures in bacteria.

The scarcity of new molecules that can act on bacteria is a major problem. New strategies for developing such molecules might be based on recent concepts in microbiology. Hyperstructures are large assemblies of molecules and macromolecules that perform functions such as DNA replication, RNA degradation and chemotaxis and the interactions between hyperstructures have been proposed to constitute an intermediate level of organisation in cells.

Chemical microscopy of biological samples by dynamic mode secondary ion mass spectrometry.

3D chemical microscopy is one of the emerging applications of secondary ion mass spectrometry (SIMS) in biology. Tissues, cells, extracellular matrices, and polymer films can be imaged at present with a lateral resolution of 50 nm and depth resolution of 1 nm using the latest generation of CAMECA magnetic sector NanoSIMS 50 or with a lower lateral resolution (above 100 nm) using IMS 4f Cameca SIMS equipped with cold stage. Dynamic mode SIMS analysis is performed in ultrahigh vacuum and thus requires specific and careful preparation of biological samples aimed at preserving and minimizing destruction of the original structural and chemical properties of the samples.

Atomic force microscopy measurements of intermolecular binding forces.

Atomic force microscopy (AFM) measurements of intermolecular binding strength between a single pair of complementary cell adhesion molecules in physiological solutions provided the first quantitative evidence for their cohesive function. This novel AFM-based nanobiotechnology opens a molecular mechanic approach for studying structure- to function-related properties of any type of individual biological macromolecules. The presented example of Porifera cell adhesion glyconectin proteoglycans showed that homotypic carbohydrate to carbohydrate interactions between two primordial proteoglycans can hold the weight of 1,600 cells.

Method for macromolecular colocalization using atomic recombination in dynamic SIMS.

Localizing two or more components of assemblies in biological systems requires both continued development of fluorescence techniques and invention of entirely new techniques. Candidates for the latter include dynamic secondary ion mass spectrometry (D-SIMS). The latest generation of D-SIMS, the Cameca NanoSIMS 50, permits the localization of specific, isotopically labeled molecules and macromolecules in sections of biological material with a resolution in the tens of nanometers and with a sensitivity approaching in principle that of a single protein.

Pharmacological evidence for calcium involvement in the long-term processing of abiotic stimuli in plants.

Information about abiotic conditions is stored for long periods in plants and, in flax seedlings, can lead to the production of meristems. To investigate the underlying mechanism, flax seedlings were given abiotic stimuli that included a mechanical stimulus (by manipulation), one or two cold shocks, a slow cold treatment and a drought stress and, if these seedlings were then subjected to a temporary (1 to 3 days) depletion of calcium, epidermal meristems were produced in the seedling hypocotyls. This production was inhibited by the addition to the nutrient media of EGTA, ruthenium red, lanthanum or gadolinium that affect calcium availability or calcium transport.

Steady-state kinetic behaviour of two- or n-enzyme systems made of free sequential enzymes involved in a metabolic pathway.

The overall rate of functioning of a set of free sequential enzymes of the Michaelis-Menten type involved in a metabolic pathway has been computed as a function of the concentration of the initial substrate under steady-state conditions. Curves monotonically increasing up to a saturation plateau have been obtained in all cases. The shape of these curves is sometimes, but not usually, close to that of a hyperbola.

Steady-state kinetic behaviour of functioning-dependent structures.

A fundamental problem in biochemistry is that of the nature of the coordination between and within metabolic and signalling pathways. It is conceivable that this coordination might be assured by what we term functioning-dependent structures (FDSs), namely those assemblies of proteins that associate with one another when performing tasks and that disassociate when no longer performing them. To investigate a role in coordination for FDSs, we have studied numerically the steady-state kinetics of a model system of two sequential monomeric enzymes, E(1) and E(2).

Neutron capture radiography: a technique for isotopic labelling and analytical imaging with a few stable isotopes.

NCR (neutron capture radiography) may be used successfully for the imaging of one of the stable isotopes of a few chemical elements (especially 6Li and 10B, possibly also 14N, 17O, and others) and for labelling experiments using these stable isotopes. Other physical techniques compete with NCR. However, NCR can remain extremely useful in a certain number of cases, because it is usually more easily done and is less expensive than the other techniques.

Relative sensitivity factors of inorganic cations in frozen-hydrated standards in secondary ion MS analysis.

We describe the measurement, at 100 K, of the SIMS relative sensitivity factors (RSFs) of the main physiological cations Na+, K+, Mg2+, and Ca2+ in frozen-hydrated (F-H) ionic solutions. Freezing was performed by either plunge freezing or high-pressure freezing. We also report the measurement of the RSFs in flax fibers, which are a model for ions in the plant cell wall, and in F-H ionic samples, which are a model for ions in the vacuole.

Dynamic-SIMS imaging and quantification of inorganic ions in frozen-hydrated plant samples.

We present here SIMS images of the distribution of inorganic cations (Na, K, Mg and Ca) in frozen-hydrated samples of three plant species, ivy, camomile, and flax. The samples were cryofixed using fast plunge-freezing. Stigmatic images were obtained, at 100 K, under dynamic SIMS conditions by fast atom bombarding (FAB).

Memory processes in the response of plants to environmental signals.

Plants are sensitive to stimuli from the environment (e.g., wind, rain, contact, pricking, wounding).

Synthesis and cytotoxic activity of acronycine analogues in the benzo[c]pyrano[3,2-h]acridin-7-one and naphtho[1,2-b][1,7] and [1,10]-phenanthrolin-7(14H)-one series.

Condensation of 1-bromo-2-naphthalenecarboxylic acid (9) with 7-methoxy-2,2-dimethyl-2H-1-benzopyran-5-ylamine (13) followed by acid-mediated cyclization afforded 6-methoxy-3,3-dimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (15), which was further methylated into 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (benzo[c]acronycine) (3) and 6,7-dimethoxy-3,3-dimethyl-3H-benzo[c]pyrano[3,2-h]acridine (4). Osmium tetroxide oxidation of 15 gave the (+/-)-cis-diol 16, which afforded the benzopyranoacridine and benzopyranoacridone esters 17-22 upon acylation. Condensation of 9 with suitable aminoquinolines 23-25 afforded the carboxylic naphthylquinolylamines 26-28.

[Structure activity relationships and mechanism of action of antitumor benzo[b]acronycine antitumor agents].

The acridone alkaloid acronycine, isolated from several Sarcomelicope species (Rutaceae) was shown to exhibit a promising activity against a broad spectrum of solid tumors. Nevertheless, subsequent clinical trials only gave poor results, probably due to the moderate potency of this drug. The isolation of the unstable acronycine epoxide from several New-Caledonian Sarcomelicope led to a hypothesis of bioactivation of acronycine by transformation of the 1.