IsotopicLabelling: an R package for the analysis of MS isotopic patterns of labelled analytes.

Abstract Motivation Labelling experiments in biology usually make use of isotopically enriched substrates, with the two most commonly employed isotopes for metabolism being 2H and 13C. At the end of the experiment some metabolites will have incorporated the labelling isotope, to a degree that depends on the metabolic turnover. In order to propose a meaningful biological interpretation, it is necessary to estimate the amount of labelling, and one possible route is to exploit the fact that MS isotopic patterns reflect the isotopic distributions. Results We developed the IsotopicLabelling R package, a tool able to extract and analyze isotopic patterns from liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-MS (GC-MS) data relative to labelling experiments. This package estimates the isotopic abundance of the employed stable isotope (either 2H or 13C) within a specified list of analytes. Availability and Implementation The IsotopicLabelling R package is freely available at https://github.com/RuggeroFerrazza/IsotopicLabelling. Supplementary information Supplementary data are available at Bioinformatics online

Humoral and T-Cell Mediated Response after the Third Dose of mRNA Vaccines in Patients with Systemic Lupus Erythematosus on Belimumab

Objective: To evaluate humoral and T-cell cellular-mediated immune response after three doses of SARS-CoV-2 mRNA vaccines in patients with systemic lupus erythematosus (SLE) under Belimumab. Patients and methods: 12 patients on Belimumab and 13 age-matched healthy volunteers were recruited. Patients were in remission or in low disease activity, and they were taking no corticosteroids or only low doses. None of the patients and controls had detectable anti-SARS-CoV-2 antibodies due to previous exposure to the virus. All the patients received three doses of mRNA anti-SARS-CoV-2 vaccines and the humoral and cellular-mediated response were tested 4 weeks after the second dose (T0), 6 months after the second dose (T1) and 4 weeks after the third dose (T2). Comparison with the control group was performed at time T0 (i.e., 4 weeks after the second dose). Total anti-SARS-CoV-2 RBD antibodies were analyzed using a diagnostic assay, while cellular-mediated response was evaluated using the interferon-gamma release assay (IGRA). Results: A humoral response was documented in all the patients at T0 (median 459; IQR 225.25–758.5), but the antibody titer significantly declined from T0 to T1 (median 44.7; IQR: 30.3–202; p = 0.0066). At T2, the antibody titer significantly increased from T1 (median 2500; IQR: 2500–2500), and it was not different from T0 (respectively p < 0.0001, p = 0.66). Cellular-mediated response significantly declined from T0 to T1 (p = 0.003) but not from T0 to T2 (p = 0.3). No differences were found between patients and controls at T0 as regards both humoral and cellular responses (p = 1.0 and p = 0.09 for humoral and cellular responses, respectively). Conclusion: The third dose of mRNA COVID-19 vaccine can restore both humoral and cellular immune response in SLE patients on Belimumab

Complexing the Marine Sesquiterpene Euplotin C by Means of Cyclodextrin-Based Nanosponges: A Preliminary Investigation

Euplotin C is a sesquiterpene of marine origin endowed with significant anti-microbial and anti-tumor properties. Despite the promising functional profile, its progress as a novel drug candidate has failed so far, due to its scarce solubility and poor stability in aqueous media, such as biological fluids. Therefore, overcoming these limits is an intriguing challenge for the scientific community. In this work, we synthesized β-cyclodextrin-based nanosponges and investigated their use as colloidal carriers for stably complex euplotin C. Results obtained proved the ability of the carrier to include the natural compound, showing remarkable values of both loading efficiency and capacity. Moreover, it also allowed us to preserve the chemical structure of the loaded compound, which was recovered unaltered once extracted from the complex. Therefore, the use of β-cyclodextrin-based nanosponges represents a viable option to vehiculate euplotin C, thus opening up its possible use as pharmacologically active compound

FUNCTIONAL STUDY OF LIPOXYGENASE-MEDIATED RESISTANCE AGAINST ASPERGILLUS FLAVUS AND FUSARIUM VERTICILLIOIDES INFECTION IN MAIZE

Mycotoxin contamination of maize kernels by fungal pathogens Aspergillus flavus (Af) and Fusarium verticillioides (Fv) is a chronic global challenge impacting food security, health and trade. Current disease management practices are proven inadequate and strategies gearing towards hostmediated resistance can be an effective and sustainable approach to strengthen efforts to control the pathogens. Lipid modification into a diverse array of compounds, oxylipins, are recognized in response of plants to fungal pathogens. Lipoxygenase genes (LOXs) play a crucial role in the enzymatic oxidation of polyunsaturated fatty acids (PUFAs) into 9(S)- and 13(S)-hydroperoxides that are further metabolized into different oxylipins including jasmonates, oxo- and keto-fatty acids and volatiles. The involvement of maize LOXs (ZmLOXs) in this respect has been a subject of studies and their genetic manipulation resulted in the alteration of resistance or susceptibility to fungal pathogens in maize. However, the maize genome encodes six 9-LOX and seven 13-LOX isoforms and the specific role of each isoform remains elusive. The current study investigated the role of ZmLOXs in host resistance against the fungi Af and Fv using in silico and in planta approaches. The phylogenetic relationship, sequence similarity, protein domain structures, and transcript level structural variations were explored by comparing publicly available maize pan-genomes. Furthermore, the role of ZmLOXs against Af and Fv infection was investigated through their expression analysis along with further key genes involved in oxylipin biosynthesis, mycotoxin accumulation and lipid profiles in a ZmLOX4 mutant line (UFMulox4) together with W22, Mo17 and Tzi18 inbred lines at 3- and 7-days post-inoculation (dpi). ZmLOX proteins showed considerable variations in their sequences, functional domain structure and transcript structural variations among the pan-genome members. Among the studied lines, Tzi18 showed the highest resistance to the pathogens coupled with the lowest mycotoxin accumulation, while the mutant, UFMulox4, was highly susceptible to both pathogens with the most elevated content of mycotoxins. Fv inoculation determined a stronger induction of ZmLOXs and maize allene oxide synthase genes as compared to Af . Higher constitutive levels of 9-LOXs genes, ZmLOX1 and ZmLOX2 and an induction of ZmLOX4 were recorded in Tzi18, while the upregulation of ZmLOX1 and ZmLOX4 observed in Mo17 might have larger active role in resistance against Fv. Liquid chromatography-mass spectrometry further revealed an increased accumulation of the linoleic (18:2) derived 9-cyclopentenone, 10- oxo-11-phytoenoic acid (10-OPEA), in Fv inoculated kernels of Tzi18 and Mo17, which was previously identified to inhibit fungal growth in vitro. Hence, the results confirm the pivotal role of ZmLOXs in controlling the resistance mechanisms against these two pathogens

Functional Study of Lipoxygenase-Mediated Resistance against Fusarium verticillioides and Aspergillus flavus Infection in Maize

Mycotoxin contamination of maize kernels by fungal pathogens like Fusarium verticillioides and Aspergillus flavus is a chronic global challenge impacting food and feed security, health, and trade. Maize lipoxygenase genes (ZmLOXs) synthetize oxylipins that play defense roles and govern host-fungal interactions. The current study investigated the involvement of ZmLOXs in maize resistance against these two fungi. A considerable intraspecific genetic and transcript variability of the ZmLOX family was highlighted by in silico analysis comparing publicly available maize pan-genomes and pan-transcriptomes, respectively. Then, phenotyping and expression analysis of ZmLOX genes along with key genes involved in oxylipin biosynthesis were carried out in a maize mutant carrying a Mu transposon insertion in the ZmLOX4 gene (named UFMulox4) together with Tzi18, Mo17, and W22 inbred lines at 3- and 7-days post-inoculation with F. verticillioides and A. flavus. Tzi18 showed the highest resistance to the pathogens coupled with the lowest mycotoxin accumulation, while UFMulox4 was highly susceptible to both pathogens with the most elevated mycotoxin content. F. verticillioides inoculation determined a stronger induction of ZmLOXs and maize allene oxide synthase genes as compared to A. flavus. Additionally, oxylipin analysis revealed prevalent linoleic (18:2) peroxidation by 9-LOXs, the accumulation of 10-oxo-11-phytoenoic acid (10-OPEA), and triglyceride peroxidation only in F. verticillioides inoculated kernels of resistant genotypes

Theory and applications of atomic and ionic polarizabilities

Atomic polarization phenomena impinge upon a number of areas and processes in physics. The dielectric constant and refractive index of any gas are examples of macroscopic properties that are largely determined by the dipole polarizability. When it comes to microscopic phenomena, the existence of alkaline-earth anions and the recently discovered ability of positrons to bind to many atoms are predominantly due to the polarization interaction. An imperfect knowledge of atomic polarizabilities is presently looming as the largest source of uncertainty in the new generation of optical frequency standards. Accurate polarizabilities for the group I and II atoms and ions of the periodic table have recently become available by a variety of techniques. These include refined many-body perturbation theory and coupled-cluster calculations sometimes combined with precise experimental data for selected transitions, microwave spectroscopy of Rydberg atoms and ions, refractive index measurements in microwave cavities, ab initio calculations of atomic structures using explicitly correlated wave functions, interferometry with atom beams, and velocity changes of laser cooled atoms induced by an electric field. This review examines existing theoretical methods of determining atomic and ionic polarizabilities, and discusses their relevance to various applications with particular emphasis on cold-atom physics and the metrology of atomic frequency standards.Comment: Review paper, 44 page

Genome-Wide Association Studies in Atherosclerosis

Cardiovascular disease remains the major cause of worldwide morbidity and mortality. Its pathophysiology is complex and multifactorial. Because the phenotype of cardiovascular disease often shows a marked heritable pattern, it is likely that genetic factors play an important role. In recent years, large genome-wide association studies have been conducted to decipher the molecular mechanisms underlying this heritable and prevalent phenotype. The emphasis of this review is on the recently identified 17 susceptibility loci for coronary artery disease. Implications of their discovery for biology and clinical medicine are discussed. A description of the landscape of human genetics in the near future in the context of next-generation sequence technologies is provided at the conclusion of this review