Stability-based approaches in chemoproteomics

\ua9 The Author(s), 2024. Published by Cambridge University Press. Target deconvolution can help understand how compounds exert therapeutic effects and can accelerate drug discovery by helping optimise safety and efficacy, revealing mechanisms of action, anticipate off-target effects and identifying opportunities for therapeutic expansion. Chemoproteomics, a combination of chemical biology with mass spectrometry has transformed target deconvolution. This review discusses modification-free chemoproteomic approaches that leverage the change in protein thermodynamics induced by small molecule ligand binding. Unlike modification-based methods relying on enriching specific protein targets, these approaches offer proteome-wide evaluations, driven by advancements in mass spectrometry sensitivity, increasing proteome coverage and quantitation methods. Advances in methods based on denaturation/precipitation by thermal or chemical denaturation, or by protease degradation are evaluated, emphasising the evolving landscape of chemoproteomics and its potential impact on future drug-development strategies

Sex chromosome and autosome divergence in Podisma (Orthoptera) in western Europe

International audienc

Effect of maturity and harvest season on antioxidant activity, phenolic compounds and ascorbic acid of Morinda citrifolia L. (noni) grown in Mexico (with track change)

Antioxidant activity diphenylpicrylhydrazyl (DPPH), the ferric-reducing antioxidant power assay (FRAP), nitric oxide (NO)], total polyphenols, phenolic compounds and ascorbic acid of Morinda citrifolia L. fruits were investigated as a function of maturity and three seasons patterns in Mexico. Maturity was evaluated in early, middle, sub-mature and mature stages (1 to 4) according to color and firmness. Significant differences were observed in the antioxidant activities and chemical composition of the fruits at different maturity and seasons. During February-March and May- June, fruits from middle and mature stages exhibited the highest antioxidant activities and total polyphenol content compared to other stages, while in November, ripe fruits reached the greatest antioxidant efficacy, total phenolic and ascorbic acid contents. Total polyphenols and ascorbic acid reached the highest amounts during May-June, although antioxidant activities were moderate compared to greater values in February-March or November depending upon maturity. The ability of M. citrifolia fruits to inhibit NO production by LPSactivated RAW 264.7 cells was quite comparable to or higher than N-nitro-L-arginine methyl ester (LNAME). This work shows that season and maturity stages have a profound effect on the antioxidant capacity, phenols and ascorbic acid of M. Citrifolia fruits.Keywords: Morinda citrifolia, diphenylpicrylhydrazyl (DPPH) radical scavenging, maturity, seasons, total polyphenol and phenolics compounds, reducing power, ascorbic acid, scavenging nitric oxide.African Journal of Biotechnology Vol. 12(29), pp. 4630-463

Proteomic Analysis Reveals Trilaciclib-Induced Senescence

\ua9 2024 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.Trilaciclib, a cyclin-dependent kinase 4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer. This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in hematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in hematological cancers. Utilizing mass spectrometry-based proteomics, we examined the alterations induced by trilaciclib in the chronic myeloid leukemia cell line, K562. Interestingly, trilaciclib promoted senescence in these cells rather than cell death, as observed in acute myeloid leukemia, acute lymphoblastic leukemia, and myeloma cells. In K562 cells, trilaciclib hindered cell cycle progression and proliferation by stabilizing cyclin-dependent kinase 4/6 and downregulating cell cycle–related proteins, along with the concomitant activation of autophagy pathways. Additionally, trilaciclib-induced senescence was also observed in the nonsmall cell lung carcinoma cell line, A549. These findings highlight trilaciclib\u27s potential as a therapeutic option for hematological cancers and underscore the need to carefully balance senescence induction and autophagy modulation in chronic myeloid leukemia treatment, as well as in nonsmall cell lung carcinoma cell line

Advances for Treating in-Hospital Cardiac Arrest: Safety and Effectiveness of a New Automatic External Cardioverter-Defibrillator

OBJECTIVES: The purpose of this study was to prospectively analyze the performance and safety of a new programmable, fully automatic external cardioverter-defibrillator (AECD) in a European multicenter trial. BACKGROUND Although, the response time to cardiac arrest (CA) is a major determinant of mortality and morbidity, in-hospital strategies have not significantly changed during the last 30 years. METHODS: Patients (n = 117) at risk of CA in monitored wards (n = 51) and patients undergoing electrophysiologic testing or implantable cardioverter-defibrillator (ICD) implantation (n = 66) were enrolled. The accuracy of the automatic response of the device to any change of rhythm (lasting >1 s and >4 beats) was confirmed by reviewing the simultaneously recorded Holter data and the programmed parameters. RESULTS: During 1,240 h, 1,988 episodes of rhythm changes were documented. A total of 115 episodes lasted > or =10 s or needed treatment (pacing, n = 32; ICD, n = 51; AECD, n = 35) for termination. The device detected ventricular tachyarrhythmias with a sensitivity of 100% and specificity of 97.6% (true negatives, n = 1,454; true positives, n = 499; false positives, n = 35; false negatives, n = 0). The false positives were all caused by T-wave oversensing during ventricular pacing. There were no complications or adverse events. The mean response time was 14.4 s for those episodes needing a full charge of the capacitor. CONCLUSIONS: This new AECD is safe and effective in detecting, monitoring, and treating spontaneous arrhythmias. This fully automatic device shortens the response time to treatment, and it is likely that it will significantly improve the outcome of patients with in-hospital CA

Carbon-fiber tips for scanning probe microscopes and molecular electronics experiments

We fabricate and characterize carbon-fiber tips for their use in combined scanning tunneling and force microscopy based on piezoelectric quartz tuning fork force sensors. An electrochemical fabrication procedure to etch the tips is used to yield reproducible sub-100-nm apex. We also study electron transport through single-molecule junctions formed by a single octanethiol molecule bonded by the thiol anchoring group to a gold electrode and linked to a carbon tip by the methyl group. We observe the presence of conductance plateaus during the stretching of the molecular bridge, which is the signature of the formation of a molecular junction.Comment: Conference Proceeding (Trends in NanoTechnology 2011, Tenerife SPAIN); Nanoscale Research Letters, (2012) 7:25

The ℓs\ell^s-boundedness of a family of integral operators on UMD Banach function spaces

We prove the $\ell^s$-boundedness of a family of integral operators with an operator-valued kernel on UMD Banach function spaces. This generalizes and simplifies earlier work by Gallarati, Veraar and the author, where the $\ell^s$-boundedness of this family of integral operators was shown on Lebesgue spaces. The proof is based on a characterization of $\ell^s$-boundedness as weighted boundedness by Rubio de Francia.Comment: 13 pages. Generalization of arXiv:1410.665

Modelization of anaerobic processes during co-digestion of slowly biodegradable substrates

The influence of the soluble substrates over the anaerobic processes has been extensively investigated, but little is known about the effects of particulate substrate. The biodegradation of these substrates starts with the hydrolytic step, this process is slower than the other ones involved in the biodegradation of particulate substrates and usually becomes the rate-limiting step. This study investigate the effect of the initial total solids (TS) concentration on the anaerobic co-digestion of two slowly biodegradable organic substrates. The wastes mixtures were prepared at different dilutions in the range from 10% to 28% TS. From these experiments it was observed that as TS concentration increased, the methane production decreased. These results were modelled and it was observed that neither hydrolysis nor fermentation stages controlled the methane production rate. Being a substrate inhibition event experienced at the methanogenic stage the responsible of the lower methane production when operating at high TS concentrations.La influencia de los sustratos solubles sobre los procesos anaeróbicos se ha investigado extensamente, pero se sabe poco acerca de los efectos del sustrato particulado. La biodegradación de estos sustratos comienza con el paso hidrolítico, este proceso es más lento que los otros involucrados en la biodegradación de sustratos particulados y generalmente se convierte en el paso limitante de la velocidad. Este estudio investiga el efecto de la concentración inicial de sólidos totales (TS) sobre la codigestión anaeróbica de dos sustratos orgánicos lentamente biodegradables. Las mezclas de desechos se prepararon a diferentes diluciones en el rango de 10% a 28% de TS. A partir de estos experimentos, se observó que a medida que aumentaba la concentración de TS, la producción de metano disminuía. Estos resultados se modelaron y se observó que ni las etapas de hidrólisis ni de fermentación controlaban la tasa de producción de metano. Siendo un evento de inhibición del sustrato experimentado en la etapa metanogénica el responsable de la menor producción de metano cuando se opera a altas concentraciones de TS

3Dpaleo.net, una plataforma web de fósiles en 3D hiperrealista para fomentar la difusión y el conocimiento del patrimonio paleontológico

3Dpaleo.net es una plataforma web en fase de desarrollo que muestra modelos tridimensionales hiperrealistas y en alta definición de algunos de fósiles más emblemáticos del Museo de Ciencias Naturales de la Universidad de Zaragoza y del Museo del Jurásico de Asturias (MUJA), colaboradores de la primera fase del proyecto. Se trata de una iniciativa promovida por la empresa Paleoymás con el fin de explorar y explotar las posibilidades de las nuevas tecnologías, aplicándolas a la divulgación de la paleontología y a la mejora de técnicas expositivas y de difusión del conocimiento. 3Dpaleo.net facilita, a través de internet, la visualización de los fósiles y de algunos de sus detalles más interesantes. 3Dpaleo.net is a website, under development, that shows high definition hyperrealistic 3D models of some emblematic fossils of the museums that have collaborated in this first stage of the project: The Natural Sciences Museum of the University of Zaragoza and the Jurassic Museum of Asturias (MUJA). It is promoted by Paleoymás with the aim of exploring and developing the possibilities of new technologies, applying them to the popularization of paleontology and the improvement of both; expositive technics and knowledge sharing. 3Dpaleo.net helps through the internet to display fossils and some of their most interesting details