N1,N5-Bis-Boc-spermidine

Neutrophils have been classically viewed as a homogenous population. Recently, neutrophils were phenotypically classified into pro-inflammatory N1 and anti-inflammatory N2 sub-populations, but the functional differences between the two subtypes are not completely understood. We aimed to investigate the phenotypic and functional differences between N1 and N2 neutrophils, and to identify the potential contribution of the S100A9 alarmin in neutrophil polarization. We describe distinct transcriptomic profiles and functional differences between N1 and N2 neutrophils. Compared to N2, the N1 neutrophils exhibited: i) higher levels of ROS and oxidative burst, ii) increased activity of MPO and MMP-9, and iii) enhanced chemotactic response. N1 neutrophils were also characterized by elevated expression of NADPH oxidase subunits, as well as activation of the signaling molecules ERK and the p65 subunit of NF-kB. Moreover, we found that the S100A9 alarmin promotes the chemotactic and enzymatic activity of N1 neutrophils. S100A9 inhibition with a specific small-molecule blocker, reduced CCL2, CCL3 and CCL5 chemokine expression and decreased MPO and MMP-9 activity, by interfering with the NF-kB signaling pathway. Together, these findings reveal that N1 neutrophils are pro-inflammatory effectors of the innate immune response. Pharmacological blockade of S100A9 dampens the function of the pro-inflammatory N1 phenotype, promoting the alarmin as a novel target for therapeutic intervention in inflammatory diseases.

Every night, we pass through a transitory zone at the borderland between wakefulness and sleep, named the first stage of nonrapid eye movement sleep (N1). N1 sleep is associated with increased hippocampal activity and dream-like experiences that incorporate recent wake materials, suggesting that it may be associated with memory processing. Here, we investigated the specific contribution of N1 sleep in the processing of memory traces. Participants were asked to learn the precise locations of 48 objects on a grid and were then tested on their memory for these items before and after a 30-min rest during which participants either stayed fully awake or transitioned toward N1 or deeper (N2) sleep. We showed that memory recall was lower (10% forgetting) after a resting period, including only N1 sleep compared to N2 sleep. Furthermore, the ratio of alpha/theta power (an electroencephalography marker of the transition toward sleep) correlated negatively with the forgetting rate when taking into account all sleepers (N1 and N2 groups combined), suggesting a physiological index for memory loss that transcends sleep stages. Our findings suggest that interrupting sleep onset at N1 may alter sleep-dependent memory consolidation and promote forgetting.

Some properties and applications of the N1-P2 complex (100-200 ms latency) are reviewed. N1-P2 is currently the auditory-evoked potential (AEP) of choice for estimating the pure-tone audiogram in certain subjects for whom a frequency-specific, non-behavioural measure is required. It is accurate in passively cooperative and alert older children and adults. Although generally underutilized, it is an excellent tool for assessment of functional hearing loss, and in medicolegal and industrial injury compensation claimants. Successful use of N1-P2 requires substantial tester training and skill, as well as carefully designed and efficient measurement protocols. N1-P2 reflects conscious detection of any discrete change in any subjective dimension of the auditory environment. In principle, it could be used to measure almost any threshold of discriminable change, such as in pitch, loudness, quality and source location. It is established as a physiologic correlate of phenomena such as the masking level difference. Thus, N1-P2 may have many applications as an 'objective' proxy for psychoacoustic measures that may be impractical in clinical subjects. Advances in dipole source localization and in auditory-evoked magnetic fields (AEMFs) have clarified the multiple, cortical origins of N1 and P2. These potentials are promising tools for the neurophysiologic characterization of many disorders of central auditory processing and of speech and language development. They also may be useful in direct 'functional imaging' of specific brain regions. A wide variety of potential research and clinical applications of N1 and P2, and considerable value as part of an integrated, goal-directed AEP/AEMF measurement scheme, have yet to be fully realized.