Real-Time Insights into Biological Events: In-Cell Processes and Protein-Ligand Interactions

FlowNMR has the aim of continuously monitoring processes that occur in conditions that are not compatible with being carried out within a closed tube. However, it is sample intensive and not suitable for samples, such as proteins or living cells, that are often available in limited volumes and possibly low concentrations. We here propose a dialysis-based modification of a commercial flowNMR setup that allows for recycling the medium while confining the sample (proteins and cells) within the active volume of the tube. This approach is demonstrated in the specific cases of in-cell NMR and protein-based ligand studies

Peri-lead edema and local field potential correlation in post-surgery subthalamic nucleus deep brain stimulation patients

Implanting deep brain stimulation (DBS) electrodes in patients with Parkinson's disease often results in the appearance of a non-infectious, delayed-onset edema that disappears over time. However, the time window between the DBS electrode and DBS stimulating device implant is often used to record local field potentials (LFPs) which are used both to better understand basal ganglia pathophysiology and to improve DBS therapy. In this work, we investigated whether the presence of post-surgery edema correlates with the quality of LFP recordings in eight patients with advanced Parkinson's disease implanted with subthalamic DBS electrodes. The magnetic resonance scans of the brain after 8.5 +/- 1.5 days from the implantation surgery were segmented and the peri-electrode edema volume was calculated for both brain hemispheres. We found a correlation (rho = -0.81, p < 0.0218, Spearman's correlation coefficient) between left side local field potentials of the low beta band (11-20 Hz) and the edema volume of the same side. No other significant differences between the hemispheres were found. Despite the limited sample size, our results suggest that the effect on LFPs may be related to the edema localization, thus indicating a mechanism involving brain networks instead of a simple change in the electrode-tissue interface

Untargeted metabolomics to go beyond the canonical effect of acetylsalicylic acid

15openInternationalItalian coauthor/editorGiven to its ability to irreversibly acetylate the platelet cyclooxygenase-1 enzyme, acetylsalicylic acid (ASA) is successfully employed for the prevention of cardiovascular disease. Recently, an antitumoral effect of ASA in colorectal cancer has been increasingly documented. However, the molecular and metabolic mechanisms by which ASA exerts such effect is largely unknown. Using a new, untargeted liquid chromatography–mass spectrometry approach, we have analyzed urine samples from seven healthy participants that each ingested 100 mg of ASA once daily for 1 week. Of the 2007 features detected, 25 metabolites differing after ASA ingestion (nominal p 1) were identified, and pathway analysis revealed low levels of glutamine and of metabolites involved in histidine and purine metabolisms. Likewise, consistent with an altered fatty acid β-oxidation process, a decrease in several short- and medium-chain acyl-carnitines was observed. An abnormal β-oxidation and a lower than normal glutamine availability suggests reduced synthesis of acetyl-Co-A, as they are events linked to one another and experimentally related to ASA antiproliferative effects. While giving an example of how untargeted metabolomics allows us to explore new clinical applications of drugs, the present data provide a direction to be pursued to test the therapeutic effects of ASA—e.g., the antitumoral effect—beyond cardiovascular protectionopenDi Minno, Alessandro; Porro, Benedetta; Turnu, Linda; Manega, Chiara Maria; Eligini, Sonia; Barbieri, Simone; Chiesa, Mattia; Poggio, Paolo; Squellerio, Isabella; Anesi, Andrea; Fiorelli, Susanna; Caruso, Donatella; Veglia, Fabrizio; Cavalca, Viviana; Tremoli, ElenaDi Minno, A.; Porro, B.; Turnu, L.; Manega, C.M.; Eligini, S.; Barbieri, S.; Chiesa, M.; Poggio, P.; Squellerio, I.; Anesi, A.; Fiorelli, S.; Caruso, D.; Veglia, F.; Cavalca, V.; Tremoli, E

Optimal quantum cloning of orbital angular momentum photon qubits via Hong-Ou-Mandel coalescence

The orbital angular momentum (OAM) of light, associated with a helical structure of the wavefunction, has a great potential for quantum photonics, as it allows attaching a higher dimensional quantum space to each photon. Hitherto, however, the use of OAM has been hindered by its difficult manipulation. Here, exploiting the recently demonstrated spin-OAM information transfer tools, we report the first observation of the Hong-Ou-Mandel coalescence of two incoming photons having nonzero OAM into the same outgoing mode of a beam-splitter. The coalescence can be switched on and off by varying the input OAM state of the photons. Such effect has been then exploited to carry out the 1 \rightarrow 2 universal optimal quantum cloning of OAM-encoded qubits, using the symmetrization technique already developed for polarization. These results are finally shown to be scalable to quantum spaces of arbitrary dimension, even combining different degrees of freedom of the photons.Comment: 5 pages, 3 figure

A propensity score-weighted comparison between adalimumab originator and its biosimilars, ABP501 and SB5, in inflammatory bowel disease: a multicenter Italian study

Background: Adalimumab is an effective and safe biological drug for the treatment of inflammatory bowel disease (IBD). Nowadays, several biosimilar agents are available, but data regarding their efficacy and safety in patients with IBD are still lacking. We aimed to compare the effectiveness and tolerability between adalimumab originator, ABP501 and SB5 biosimilars in patients with IBD in the short term (after induction and after 6 months of treatment) through a propensity score-weighted multicenter cohort study. Methods: We included 156 patients with IBD, 69 patients with ulcerative colitis and 87 patients with Crohn's disease (CD) receiving ABP501 or SB5 biosimilars from January 2019 to April 2020 for moderate-to-severe disease. For comparison, a group of age- and sex-matched patients treated with adalimumab originator was used. We collected clinical and biochemical data after induction and at 6 months of treatment. Endoscopic data were recorded only at baseline. Results: Overall, clinical benefit was achieved by 86.4% and 85.3% after induction and at 6 months, respectively, without a statistically significant difference between the three treatment groups (p = 0.68 and p = 0.46). However, after induction, we found significant differences between the two types of the disease (ulcerative colitis or CD, p = 0.004), with a greater clinical benefit achieved by patients with CD. Also, the therapeutic optimization rate between the three drugs was not statistically significant different (p = 0.30). All treatments showed a good safety profile, with only 10 patients who needed to stop therapy because of adverse events. Conclusion: Adalimumab biosimilars seem to be as effective and safe as the originator in patients with IBD. Surely, they represent a great opportunity to reduce the costs of biological therapies, however larger and longer real-life studies are necessary

Biomolecular NMR at 1.2 GHz

The development of new superconducting ceramic materials, which maintain the superconductivity at very intense magnetic fields, has prompted the development of a new generation of highly homogeneous high field magnets that has trespassed the magnetic field attainable with the previous generation of instruments. But how can biomolecular NMR benefit from this? In this work, we review a few of the notable applications that, we expect, will be blooming thanks to this newly available technology.Comment: 17 pages, 13 figure