Highly diastereoselective entry into chiral spirooxindole-based 4-methyleneazetidines via formal [2+2] annulation reaction

We describe here a diastereoselective, DABCO-catalyzed reaction of allenoates with chiral N-tert-butanesulfinyl ketimines derived from isatin

On the Richardson-Lucy Algorithm with A Varying Point Spread Function along The Iterations

Abstract: This work analyses the soundness of two algorithms, Fishsint and Almexp to improve images using the Richardson-Lucy (RL) algorithm under a varying Point Spread Function (PSF) along the iterations. A plethora of methods based on Richardson-Lucy has been published, but no further proposal involving such an alternative has been published. Whereas the unnamed predecessor of Fishsint addressed only small size synthetic images under a blind fashion procedure, Fishsint and Almexp employs an algorithm Wdet to determine the initial PSF and all subsequent values after each iteration, respectively. Fishsint performs a loop, where the last determined PSF improves the previously obtained image and vice versa. Its original unnamed version has been modified in the present work by entering a previously determined initial PSF to accelerate the convergence. The algorithm Almexp, as well, uses the algorithm Wdet to determine the PSF of the last obtained image to deconvolve itself. Therefore, whereas the Fishsint unnamed predecessor used an initial guess PSF - chosen by the customer - Almexp determines the PSF always through the algorithm Wdet. Fishsint and Almexp furnish final images which outperform those obtained with the original Richardson-Lucy approach working under a constant PSF along the iterations. Hence, in order to carry out a comparison between their performances, all the algorithms have been embedded into an ad hoc written Fortran 90 program. The results corroborate the soundness of a varying PSF along the iterations with the Richardson Lucy algorithm. Keywords: Richardson-Lucy, varying PSF along iterations, image improvement, neutron radiograph

Reversible Cavitation-Induced Junctional Opening in an Artificial Endothelial Layer.

Targeting pharmaceuticals through the endothelial barrier is crucial for drug delivery. In this context, cavitation-assisted permeation shows promise for effective and reversible opening of intercellular junctions. A vessel-on-a-chip is exploited to investigate and quantify the effect of ultrasound-excited microbubbles-stable cavitation-on endothelial integrity. In the vessel-on-a-chip, the endothelial cells form a complete lumen under physiological shear stress, resulting in intercellular junctions that exhibit barrier functionality. Immunofluorescence microscopy is exploited to monitor vascular integrity following vascular endothelial cadherin staining. It is shown that microbubbles amplify the ultrasound effect, leading to the formation of interendothelial gaps that cause barrier permeabilization. The total gap area significantly increases with pressure amplitude compared to the control. Gap opening is fully reversible with gap area distribution returning to the control levels 45 min after insonication. The proposed integrated platform allows for precise and repeatable in vitro measurements of cavitation-enhanced endothelium permeability and shows potential for validating irradiation protocols for in vivo applications

Straight motion of half-integer topological defects in thin Fe-N magnetic films with stripe domains

International audienc

Early-life nicotine or cotinine exposure produces long-lasting sleep alterations and downregulation of hippocampal corticosteroid receptors in adult mice

Early-life exposure to environmental toxins like tobacco can permanently re-program body structure and function. Here, we investigated the long-term effects on mouse adult sleep phenotype exerted by early-life exposure to nicotine or to its principal metabolite, cotinine. Moreover, we investigated whether these effects occurred together with a reprogramming of the activity of the hippocampus, a key structure to coordinate the hormonal stress response. Adult male mice born from dams subjected to nicotine (NIC), cotinine (COT) or vehicle (CTRL) treatment in drinking water were implanted with electrodes for sleep recordings. NIC and COT mice spent significantly more time awake than CTRL mice at the transition between the rest (light) and the activity (dark) period. NIC and COT mice showed hippocampal glucocorticoid receptor (GR) downregulation compared to CTRL mice, and NIC mice also showed hippocampal mineralocorticoid receptor downregulation. Hippocampal GR expression significantly and inversely correlated with the amount of wakefulness at the light-to-dark transition, while no changes in DNA methylation were found. We demonstrated that early-life exposure to nicotine (and cotinine) concomitantly entails long-lasting reprogramming of hippocampal activity and sleep phenotype suggesting that the adult sleep phenotype may be modulated by events that occurred during that critical period of life

Obstructive sleep apneas naturally occur in mice during REM sleep and are highly prevalent in a mouse model of Down syndrome

Study objectives: The use of mouse models in sleep apnea study is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. We aimed to develop a protocol to investigate the presence of OSAs in wild-type mice and, then, to apply it to a validated model of Down syndrome (Ts65Dn), a human pathology characterized by a high incidence of OSAs. Methods: In a pilot study, nine C57BL/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), and diaphragmatic activity (DIA), and then placed in a whole-body-plethysmographic (WBP) chamber for 8 h during the rest (light) phase to simultaneously record sleep and breathing activity. CSA and OSA were discriminated on the basis of WBP and DIA signals recorded simultaneously. The same protocol was then applied to 12 Ts65Dn mice and 14 euploid controls. Results: OSAs represented about half of the apneic events recorded during rapid-eye-movement-sleep (REMS) in each experimental group, while the majority of CSAs were found during non-rapid eye movement sleep. Compared with euploid controls, Ts65Dn mice had a similar total occurrence rate of apneic events during sleep, but a significantly higher occurrence rate of OSAs during REMS, and a significantly lower occurrence rate of CSAs during NREMS. Conclusions: Mice physiologically exhibit both CSAs and OSAs. The latter appear almost exclusively during REMS, and are highly prevalent in Ts65Dn. Mice may, thus, represent a useful model to accelerate the understanding of the pathophysiology and genetics of sleep-disordered breathing and to help the development of new therapies

Polylactide/cellulose nanocrystals : The in situ polymerization approach to improved nanocomposites

The in situ polymerization of L-lactide in the presence of various amounts of cellulose nanocrystals (CNC) is described. CNC was prepared efficiently by acidic hydrolysis of cotton linters. Molecular weight, morphology, thermal, mechanical and crystallization properties of the PLA-CNC nanocomposites were evaluated. From size-exclusion chromatography (SEC) analysis, the actual occurrence of chemical bond between CNC and PLA can be assessed. The effect of CNC has been evaluated through differential scanning calorimetry (DSC) analysis, which highlights the probable formation of \uce\ub1\ue2\u80\ub2 crystals in the obtained materials. More importantly, from thermogravimetric analysis (TGA) a marked improvement in thermal stability of nanocomposites has been demonstrated, with respect to standard PLA and to previously described PLA-CNC blends. Nanocomposites show also an improvement in rheological properties with respect to standard PLA. In particular, storage modulus greatly increases, indicating a reinforcing effect of CNC. The described in situ synthetic methodology allows an optimal compatibilization between the two entities (PLA and CNC), facing one of the major problems inherent to the preparation of nanocomposites. It leads furthermore to remarkably improved thermal and rheological properties of the obtained materials

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Innovative molecular platforms for G-quadruplex stabilizatioN

Innovative molecular platforms for G-quadruplex stabilization S. Di Ciolo,a B. Airoldi,a L.C.M. Pariani,a C. F. Morelli,a C. Giannini,a A. Silvani,a D. Malpicci,a E. Cariati,a E. Lucenti,b C. Platella,c D. Musumeci,c R. Gaglione, c A. Arciello,c D. Montesarchioa aDipartimento di Chimica, Università degli studi di Milano, Milano bCNR-SCITEC, Istituto di Scienze e Tecnologie Chimiche “Giulio Natta”, Milano cDipartimento di Scienze Chimiche, Università di Napoli Federico II, Napoli e-mail: [email protected] G-quadruplexes (G4s) have received considerable attention in recent years, due to evidence of their occurrence in living cells. 1Formed by stacks of guanine quartets, G4s belong to the wide class of non-canonical nucleic acid structures. Putative G4 forming sequences are distributed in genomic regions relevant for a number of pathologies, spanning from cancer to viral infections, where they can act as regulators of genetic information transfer.2 In this context, G4-targeting is regarded as a novel potential therapeutic approach for the treatment of associated diseases.3 Taking inspiration from the recent literature on G4 ligands4 and relying on the scaffold hopping strategy,5 we selected three different heterocyclic frameworks, potentially able to bind G4s by stacking the external G-tetrads. We functionalized these scaffolds with proper polar or positively charged flexible groups for binding to G4 loops/grooves, and/or with alkylating warheads for more selective covalent targeting. To investigate the G4 binding properties of the new molecules, in vitro biophysical studies were performed employing both telomeric and oncogene promoter G4-forming sequences. Interestingly, the investigated compounds showed potent G4-stabilizing properties and a certain preference for G4 over duplex DNA. Under preliminary in vitro studies, some ligands proved to inhibit cancer cells proliferation, not affecting healthy cells used as control. References [1] S. Burge, G. N. Parkinson, P. Hazel, A. K. Todd, S. Neidle, Nucleic Acids Res. 2006, 34, 5402–5415. [2] R. Hänsel-Hertsch, M. Di Antonio, S. Balasubramanian, Nat. Rev. Mol. Cell Biol. 2017, 18, 279–284. [3] A. R. Duarte, E. Cadoni, A.S. Ressurreição, R. Moreira, A. Paulo ChemMedChem, 2018, 13, 869-893. [4] M. P. O'Hagan, J. C. Morales, M. C. Galan, Eur. J. Org. Chem. 2019, 4995–5017. [5] H. Sun,1, G. Tawa, A. Wallqvist Drug Discov Today. 2012 17(7-8), 310–324

Fire spread experiment across Mediterranean shrub: Influence of wind on flame front properties

International audienceA previous termfirenext term spread experiment was conducted in the field under wind-blown conditions. The fuel consists of tall and dense Mediterranean shrub vegetation. The plot area was about 30 m wide and 80 m long. This experiment was conducted not only in order to increase the knowledge and understanding of the previous termfirenext term behaviour in the field but to provide data for the validation of physics based models of previous termfirenext term spread. In particular, the effects of wind on the geometric and thermal properties of the flame front in the field were investigated. The flame temperature along the vertical direction and the radiation emitted ahead of the flame front, were measured. The methodology employed in this experiment and some quantitative measurements of wind velocity and direction, flame geometric properties, are also presented and discussed. The measurements and observations exhibit that the behaviour of the previous termfirenext term and the flame structure character are very different from the one encountered at laboratory scale. These preliminary results show that large scale turbulence influence previous termfirenext term spread and affects the flame shape, temperature and radiation emission