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In recent years, quantum Fourier transform infrared (QFTIR) spectroscopy has emerged as an alternative to conventional absorption spectroscopy in the mid-infrared region of the spectrum. By harnessing induced coherence and spectral correlations of photon pairs in a nonlinear Michelson interferometer, this technique offers promising potential for the practical detection of organic gases. However, little research was conducted to bring QFTIR spectrometers closer to domestic or in-field usage. In this work, we present the first use of a QFTIR spectrometer for open-path detection of multiple interfering organic gases in ambient air. We built a nonlinear Michelson interferometer with 1.7 m-long arms to increase the absorption length, coupled with analysis techniques from classical differential absorption spectroscopy used for gas-traces detection. We thus characterize our spectrometer’s sensitivity to acetone, methanol, and ethanol vapors and demonstrate the accurate identification of mixtures of these gases released in ambient air. We show this characteristic is preserved over time by performing a measurement overnight and tracking the evolution of different gases’ average concentrations. These results constitute the first use-case of a QFTIR spectrometer as a detector of organic gases and, thus, represent an important milestone toward the development of such detectors in practical situations.

Abstract The significant heterogeneity in smoking behavior among smokers, coupled with the inconsistent efficacy of approved smoking cessation therapies, supports the presence of individual variations in the mechanisms underlying smoking. This emphasizes the need to shift from standardized to personalized smoking cessation therapies. However, informed precision medicine demands precision fundamental research. Tobacco smoking is influenced and sustained by diverse psychopharmacological interactions between nicotine and environmental stimuli. In the classical experimental rodent model for studying tobacco dependence, namely intravenous self-administration of nicotine, seeking behavior is reinforced by the combined delivery of nicotine and a discrete cue (nicotine+cue). Whether self-administration behavior is driven by the same psychopharmacological mechanisms across individual rats remains unknown and unexplored. To address this, we employed behavioral pharmacology and unbiased cluster analysis to investigate individual differences in the mechanisms supporting classical intravenous nicotine self-administration (0.04 mg/kg/infusion) in male outbred Sprague–Dawley rats. Our analysis identified two clusters: one subset of rats sought nicotine primarily for its reinforcing effects, while the second subset sought nicotine to enhance the reinforcing effects of the discrete cue. Varenicline (1 mg/kg i.p.) reduced seeking behavior in the former group, whereas it tended to increase in the latter group. Crucially, despite this fundamental qualitative difference revealed by behavioral manipulation, the two clusters exhibited quantitatively identical nicotine+cue self-administration behavior. The traditional application of rodent models to study the reinforcing and addictive effects of nicotine may mask individual variability in the underlying motivational mechanisms. Accounting for this variability could significantly enhance the predictive validity of translational research.

Molecular autopsy is a very important tool in forensic toxicology. However, many determinants, such as co-medication and physiological parameters, should be considered for optimal results. These determinants could cause phenoconversion (PC), a discrepancy between the real metabolic profile after phenoconversion and the phenotype determined by the genotype. This study’s objective was to assess the PC of drug-metabolizing enzymes, namely CYP2D6, 2C19, and 3A4, in 45 post-mortem cases where medications that are substrates, inducers, or inhibitors of these enzymes were detected. It also intended to evaluate how PC affected the drug’s metabolic ratio (MR) in four cases. Blood samples from 45 cases of drug-related deaths were analyzed to detect and determine drug and metabolite concentrations. Moreover, all the samples underwent genotyping utilizing the HaloPlex Target Enrichment System for CYP2D6, 2C19, and 3A4. The results of the present study revealed a statistically significant rate of PC for the three investigated enzymes, with a higher frequency of poor metabolizers after PC. A compatibility was seen between the results of the genomic evaluation after PC and the observed MRs of venlafaxine, citalopram, and fentanyl. This leads us to focus on the determinants causing PC that may be mainly induced by drug interactions. This complex phenomenon can have a significant impact on the analysis, interpretation of genotypes, and accurate conclusions in forensic toxicology. Nevertheless, more research with more cases in the future is needed to confirm these results.

N-terminal ends of polypeptides are critical for the selective co-translational recruitment of N-terminal modification enzymes. However, it is unknown whether specific N-terminal signatures differentially regulate protein fate according to their cellular functions. In this work, we developed an in-silico approach to detect functional preferences in cellular N-terminomes, and identified in S. cerevisiae more than 200 Gene Ontology terms with specific N-terminal signatures. In particular, we discovered that Mitochondrial Targeting Sequences (MTS) show a strong and specific over-representation at position 2 of hydrophobic residues known to define potential substrates of the N-terminal acetyltransferase NatC. We validated mitochondrial precursors as co-translational targets of NatC by selective purification of translating ribosomes, and found that their N-terminal signature is conserved in Saccharomycotina yeasts. Finally, systematic mutagenesis of the position 2 in a prototypal yeast mitochondrial protein confirmed its critical role in mitochondrial protein import. Our work highlights the hydrophobicity of MTS N-terminal residues and their targeting by NatC as important features for the definition of the mitochondrial proteome, providing a molecular explanation for mitochondrial defects observed in yeast or human NatC-depleted cells. Functional mapping of N-terminal residues thus has the potential to support the discovery of novel mechanisms of protein regulation or targeting.

Lead (Pb), mercury (Hg), and cadmium (Cd) are identified as potent developmental neurotoxicants. Neonates are the main group receiving multiple blood transfusions. The exposure of neonates to these heavy metals (HMs) can occur through blood transfusions. This study aimed to determine the concentrations of lead (Pb), mercury (Hg), and cadmium (Cd) in various blood products (plasma, platelets, packed red blood cells (pRBCs), and whole blood (WB)) to explore the probability of concurrent exposure of these HMs and to identify the metal load per transfusion with risk assessment. Residual bloods from blood bank bags were collected after neonatal transfusion. Pb, Hg, and Cd concentrations were determined in 120 samples of blood products by inductively coupled plasma mass spectrometry (ICP-MS). Pb and Cd levels were over the normal levels in 19.2 and 5.9% of all blood units, respectively. In 35 and 0.8% of blood units, the Pb and Cd concentrations, respectively, were higher than that recommended for transfusions in premature neonates. The anticipated safe value was surpassed by 2.5% for Cd of all transfusions, primarily because of WB. However, Hg was detected only in 5.8% of all samples and their concentrations were within the normal range. The concurrent neonatal exposure to Pb, Hg, and Cd was statistically significant. Hazard quotients of Hg and Cr were >1 and Pb cancer risk was 2.41 × 10−4. To the best of our knowledge, this study is the first report examining Pb, Hg, and Cd in blood products other than WB and pRBCs using ICP-MS. This study demonstrated the exposure of neonates to Pb, Hg, and Cd during transfusion with a considerable amount of Pb. It confirms the significant concurrent exposure to the three HMs, which maximize their potential developmental neurotoxicity with a high probability of developing non-carcinogenic and carcinogenic health effects.