Predominance of distal skin temperature changes at sleep onset across menstrual and circadian phases

Menstrual cycle-associated changes in reproductive hormones affect body temperature in women. We aimed to characterize the interaction between the menstrual, circadian, and scheduled sleep-wake cycles on body temperature regulation. Eight females entered the laboratory during the midfollicular (MF) and midluteal (ML) phases of their menstrual cycle for an ultradian sleep-wake cycle procedure, consisting of 36 cycles of 60-minute wake episodes alternating with 60-minute nap opportunities, in constant bed-rest conditions. Core body temperature (CBT) and distal skin temperature (DT) were recorded and used to calculate a distal-core gradient (DCG). Melatonin, sleep, and subjective sleepiness were also recorded. The circadian variation of DT and DCG was not affected by menstrual phase. DT and DCG showed rapid, large nap episode-dependent increases, whereas CBT showed slower, smaller nap episode-dependent decreases. DCG values were significantly reduced for most of the wake episode in an overall 60-minute wake/60-minute nap cycle during ML compared to MF, but these differences were eliminated at the wake-to-nap lights-out transition. Nap episode-dependent decreases in CBT were further modulated as a function of both circadian and menstrual factors, with nap episode-dependent deceases occurring more prominently during the late afternoon/evening in ML, whereas nap episode-dependent DT and DCG increases were not significantly affected by menstrual phase but only circadian phase. Circadian rhythms of melatonin secretion, DT, and DCG were significantly phase-advanced relative to CBT and sleep propensity rhythms. This study explored how the thermoregulatory system is influenced by an interaction between circadian phase and vigilance state and how this is further modulated by the menstrual cycle. Current results agree with the thermophysiological cascade model of sleep and indicate that despite increased CBT during ML, heat loss mechanisms are maintained at a similar level during nap episodes, which may allow for comparable circadian sleep propensity rhythms between menstrual phases.     

Mesenchymal stem cells - The challenge of a good therapeutic product

Mesenchymal stem cells (or stromal cells) have been initially characterized in bone marrow, but since, they have been identified in almost every tissue. Their multiple properties, namely differentiative capacity, production of cytokines and trophic molecules, and their immunosuppressive potential undoubtedly offer many therapeutic advantages, both for regenerative medecine or to relieve immune or inflammatory diseases. This is illustrated by the high number (>?100) of ongoing clinical trials with these cells. However, a prerequsite for their safe use in clinics is to guarantee that their production meet the good manufacturing practices, and that the final product is validated by adequate controls. It is thus quite a challenge to move from procedures defined for a research use to large scale production that fits with the national and international rules in terms of standardisation and controls. This underlines the importance of developping interacting networks between research teams, physicians and the industrial R&D departments. This fruitful collaboration will ensure the definition of appropriate and safe procedures for a successful therapeutic application.     

Light-sheet based fluorescence microscopy: the dark side of the sample finally revealed

Light-sheet based fluorescence microscopy (LSM) is an optical technique that becomes more and more popular for multi-view imaging of in vivo sample in its physiological environment. LSM combines the advantages of the direct optical sectioning to the ones of optical tomography by angular scanning. In fact, a thin light-sheet illuminates laterally a section of the sample, thus limiting the effects of photobleaching and phototoxicity only to the plane of interest. The spatial resolution can be improved by combining multiple views obtained along different angle into a single data, leading to a 3D isotropic rendering of the sample. Such an approach provides several advantages in comparison to conventional 3D microscopic techniques: confocal and multiphoton microscopies. It makes LSM an optical tool suited for imaging specimens with a subcellular resolution even inside an embryo and with temporal resolution adapted for real-time monitoring of biological processes.     

Comparative anatomy: all vertebrates do have vertebrae

In contrast to lampreys and jawed vertebrates, hagfishes were thought to lack vertebrae. Now, long overlooked vertebral rudiments have been analysed in hagfish, suggesting that vertebrae existed in the last common ancestor of all vertebrates.     

Mucosal junctions: open doors to HPV and HIV infections?

Throughout adult life, new developmental commitment of adult stem cells causes reversible epithelial replacements in various mucosal surfaces, including the uterine cervix and the anal canal. Located at the squamocolumnar junctions, these metaplastic conversions are associated with chronic inflammation and deregulated expression of soluble and cell-membrane factors important for antiviral immune response. In this paper, we propose that these histological and immunological features increase the susceptibility of these metaplastic microenvironments to human papillomavirus and human immunodeficiency virus infections. Identification of the anatomical sites and cell populations within the anogenital tract, which is the site primary infected by these viruses, is crucial for the understanding of the pathogenesis of viral disease and development of antiviral strategies.     

Synthesis and evaluation of bidentate ligands designed to interact with PDZ domains

We designed bidentate ligands to target PDZ domains through two binding sites: site S0, delimited by the GLGF loop, and site S1, a zone situated around loop β(B)/β(C). A molecular docking study allowed us to design a generic S0 binder, to which was attached a variable size linker, itself linked to an amino acid aimed to interact with the S1 site of PDZ domains. A series of 15 novel bidentate ligands was prepared in 6-11 steps in good overall yield (24-43%). Some of these ligands showed an inhibitory activity against serotonin 5-HT2A receptor/PSD-95 interaction. This was assessed by pull-down assay using a synthetic decapeptide corresponding to the C-terminal residues of the receptor as a bait.     

The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

The study of the proteins that bind to telomeric DNA in mammals has provided a deep understanding of the mechanisms involved in chromosome-end protection. However, very little is known on the binding of these proteins to nontelomeric DNA sequences. The TTAGGG DNA repeat proteins 1 and 2 (TRF1 and TRF2) bind to mammalian telomeres as part of the shelterin complex and are essential for maintaining chromosome end stability. In this study, we combined chromatin immunoprecipitation with high-throughput sequencing to map at high sensitivity and resolution the human chromosomal sites to which TRF1 and TRF2 bind. While most of the identified sequences correspond to telomeric regions, we showed that these two proteins also bind to extratelomeric sites. The vast majority of these extratelomeric sites contains interstitial telomeric sequences (or ITSs). However, we also identified non-ITS sites, which correspond to centromeric and pericentromeric satellite DNA. Interestingly, the TRF-binding sites are often located in the proximity of genes or within introns. We propose that TRF1 and TRF2 couple the functional state of telomeres to the long-range organization of chromosomes and gene regulation networks by binding to extratelomeric sequences.