Association between disruption of CD4 receptor dimerization and increased human immunodeficiency virus type 1 entry

Affiliation: Département de microbiologie et immunologie, Faculté de médecine, Université de Montréal & Institut de Recherches Cliniques de Montréal

Death for life : a study of targeted killing by States in international law

"Mémoire présenté à la faculté des études supérieures en vue de l'obtention du grade de Maîtrise en droit (LL.M.)". Ce mémoire a été accepté à l'unanimité et classé parmi les 10% des mémoires de la discipline.

Liquid Chromatography-Electrospray Linear Ion Trap Mass Spectrometry Analysis of Targeted Neuropeptides in Tac1-/- Mouse Spinal Cords Reveal Significant Lower Concentration of Opioid Peptides.

Tachykinin and opioid peptides play a central role in pain transmission, modulation and inhibition. The treatment of pain is very important in medicine and many studies using NK1 receptor antagonists failed to show significant analgesic effects in humans. Recent investigations suggest that both pronociceptive tachykinins and the analgesic opioid systems are important for normal pain sensation. The analysis of opioid peptides in Tac1-/- spinal cord tissues offers a great opportunity to verify the influence of the tachykinin system on specific opioid peptides. The objectives of this study were to develop a HPLC–MS/MRM assay to quantify targeted peptides in spinal cord tissues. Secondly, we wanted to verify if the Tac1-/- mouse endogenous opioid system is hampered and therefore affect significantly the pain modulatory pathways. Targeted neuropeptides were analyzed by high performance liquid chromatography linear ion trap mass spectrometry. Our results reveal that EM-2, Leu-Enk and Dyn A were down-regulated in Tac1-/- spinal cord tissues. Interestingly, Dyn A was almost 3 fold down-regulated (p < 0.0001). No significant concentration differences were observed in mouse Tac1-/- spinal cords for Met-Enk and CGRP. The analysis of Tac1-/- mouse spinal cords revealed noteworthy decreases of EM-2, Leu-Enk and Dyn A concentrations which strongly suggest a significant impact on the endogenous pain-relieving mechanisms. These observations may have insightful impact on future analgesic drug developments and therapeutic strategies.

Assessment of meat authenticity using bioinformatics, targeted peptide biomarkers and high-resolution mass spectrometry

In recent years, we observed a significant increase of food fraud ranging from false label claims to the use of additives and fillers to increase profitability. Recently in 2013, horse and pig DNA were detected in beef products sold from several retailers. Mass spectrometry has become the workhorse in protein research and the detection of marker proteins could serve for both animal species and tissue authentication. Meat species authenticity will be performed using a well defined proteogenomic annotation, carefully chosen surrogate tryptic peptides and analysis using a hybrid quadrupole-Orbitrap mass spectrometer. Selected mammalian meat samples were homogenized, proteins were extracted and digested with trypsin. The samples were analyzed using a high-resolution mass spectrometer. The chromatography was achieved using a 30 minutes linear gradient along with a BioBasic C8 100 × 1 mm column at a flow rate of 75 µL/min. The mass spectrometer was operated in full-scan high resolution and accurate mass. MS/MS spectra were collected for selected proteotypic peptides. Muscular proteins were methodically analyzed in silico in order to generate tryptic peptide mass lists and theoretical MS/MS spectra. Following a comprehensive bottom-up proteomic analysis, we were able to detect and identify a proteotypic myoglobin tryptic peptide [120-134] for each species with observed m/z below 1.3 ppm compared to theoretical values. Moreover, proteotypic peptides from myosin-1, myosin-2 and -hemoglobin were also identified. This targeted method allowed a comprehensive meat speciation down to 1% (w/w) of undesired product.