Linking post-translational modifications and protein turnover by site-resolved protein turnover profiling

Proteome-wide measurements of protein turnover have largely ignored the impact of post-translational modifications (PTMs). To address this gap, we employ stable isotope labeling and mass spectrometry to measure the turnover of >120,000 peptidoforms including >33,000 phosphorylated, acetylated, and ubiquitinated peptides for >9,000 native proteins. This site-resolved protein turnover (SPOT) profiling discloses global and site-specific differences in turnover associated with the presence or absence of PTMs. While causal relationships may not always be immediately apparent, we speculate that PTMs with diverging turnover may distinguish states of differential protein stability, structure, localization, enzymatic activity, or protein-protein interactions. We show examples of how the turnover data may give insights into unknown functions of PTMs and provide a freely accessible online tool that allows interrogation and visualisation of all turnover data. The SPOT methodology is applicable to many cell types and modifications, offering the potential to prioritize PTMs for future functional investigations.

An Optical Acoustic Detection System Based on Fabry Pérot Etalon Stability Structure

The optical acoustic detection system based on the Fabry Pérot Etalon (FPE) with high quality–factor (High Q) and stability structure is described and tested. The FPE contains two high–reflectivity Plano–Concave lenses, achieving high fineness and stability. The protective structure of the confocal stabilized FPE is composed of an invar tube, copper sheath, Bakelite sheath and aluminum housing to protect the sensor from the effects of ambient temperature and vibration. The audio signal is injected into the cavity through the sound hole located in the center of the cavity. Acoustic waves induce the vibration of the medium in the cavity, which leads to a simultaneous change in the FPE optical path and a shift of the interference spectrum. The acoustic detection system is built, and the frequency of the laser is locked on the resonant frequency points of the FPE by using phase modulation technology, so as to detect acoustic signals of different frequencies and amplitudes. In addition, the sensitivity of the proposed sensor exceeds 34.49 mV/Pa in the range of 20 Hz–20 kHz. A Signal-to-Noise Ratio (SNR) of 37 dB can be achieved at 20 Hz. Acoustic signal detection technology based on the FPE stability model is used to test the theoretical feasibility of the future high sensitivity Fabry Pérot Interferometric (FPI) acoustic sensors.

Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2

The human transmembrane protease serine 2 (TMPRSS2) protein plays an important role in prostate cancer progression. It also facilitates viral entry into target cells by proteolytically cleaving and activating the S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current study, we used different available tools like SIFT, PolyPhen2.0, PROVEAN, SNAP2, PMut, MutPred2, I-Mutant Suite, MUpro, iStable, ConSurf, ModPred, SwissModel, PROCHECK, Verify3D, and TM-align to identify the most deleterious variants and to explore possible effects on the TMPRSS2 stability, structure, and function. The six missense variants tested were evaluated to have deleterious effects on the protein by SIFT, PolyPhen2.0, PROVEAN, SNAP2, and PMut. Additionally, V160M, G181R, R240C, P335L, G432A, and D435Y variants showed a decrease in stability by at least 2 servers; G181R, G432A, and D435Y are highly conserved and identified posttranslational modifications sites (PTMs) for proteolytic cleavage and ADP-ribosylation using ConSurf and ModPred servers. The 3D structure of TMPRSS2 native and mutants was generated using 7 meq as a template from the SwissModeller group, refined by ModRefiner, and validated using the Ramachandran plot. Hence, this paper can be advantageous to understand the association between these missense variants rs12329760, rs781089181, rs762108701, rs1185182900, rs570454392, and rs867186402 and susceptibility to SARS-CoV-2.

Detection of nanostructures in solutions of Zincum metallicum and the vehicle lactose

Background: Nanoparticles (NP), because of their size (< 1μm) and high relative surface area, are highly reactive forms of their source material with biological, chemical, optical, electromagnetic, and thermal properties different from larger bulk forms of the same material. It has been speculated that NPs can occur in homeopathic products as a function of trituration and shaking into glass containers. Moreover, the presence of sugars additives like lactose and of silicates leaked from the glassware are reported to stabilize the nanoparticles.1 Up to now some authors observed nanoparticles in highly diluted samples2, 3, but further studies are needed to know the nature of the NPs. Actually, nanostructures in the solutions may derive from the source materials but also from stuff contaminations and also may be constituted by nano-bubbles.4, 5 Moreover, the mechanism by which the nanostructures can be formed and the effect of serial dilution/succussions of the NPs suspension should be studied.6 Many tools are available to analyze the nanostructures both in solutions or in dried samples and these give complementary information about the concentration, stability, structure and chemical nature of the NPs. In the present report we describe preliminary observations obtained by the nanoparticle tracking analysis (NTA) in Zincum metallicum (Zinc met.) solutions at low-grade dilution/dynamization and their lactose controls. This study is part of a formal Brazilian-Italian inter-university collaboration.

Reporting the magnetic profile of cobalt ferrite nanoparticles at different temperatures

Cobalt ferrite nanoparticles (CFNs) were synthesized using cobalt nitrate hexahydrate and ferric nitrate nonahydrate through a wet chemical method. Various characterization techniques were used to confirm the synthesis of CFNs. The thermal stability, structure, morphology and crystallinity of the synthesized CFNs were determined by thermogravimetric analysis, field emission scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction. The results show that the synthesized nanoparticles are stable and crystalline with fine homogenized structure. Vibrating sample magnetometry was used to determine the magnetic properties of the synthesized material. The coercivity was noted to be decreased and the hysteresis loop gradually flattens as the temperature increases toward the Curie temperature.

Thermochemical electronegativities of the elements

Electronegativity is a key property of the elements. Being useful in rationalizing stability, structure and properties of molecules and solids, it has shaped much of the thinking in the fields of structural chemistry and solid state chemistry and physics. There are many definitions of electronegativity, which can be roughly classified as either spectroscopic (these are defined for isolated atoms) or thermochemical (characterizing bond energies and heats of formation of compounds). The most widely used is the thermochemical Pauling’s scale, where electronegativities have units of eV−1/2. Here we identify drawbacks in the definition of Pauling’s electronegativity scale—and, correcting them, arrive at our thermochemical scale, where electronegativities are dimensionless numbers. Our scale displays intuitively correct trends for the 118 elements and leads to an improved description of chemical bonding (e.g., bond polarity) and thermochemistry.