Summary In the past few years it has become increasingly clear that insomnia is a chronic disease that interacts with many other medical conditions. As our ability to examine complex physiological ...activity during sleep has increased, additional evidence continues to suggest that insomnia is associated with inappropriate physiological arousal. It is now known that patients with primary insomnia have increased high-frequency EEG activation, abnormal hormone secretion, increased whole body and brain metabolic activation, and elevated heart rate and sympathetic nervous system activation during sleep. This activation can be measured throughout the day and night and is chronic. Other research suggests that insomnia, probably based upon the associated chronic physiologic arousal, is associated with increased risk for medical disorders such as depression, hypertension, or cardiac disease. An animal model that has used odor stress to produce poor sleep in rats has identified specific activated brain sites similar to those found in human brain metabolic studies to suggest that insomnia is a state in which sleep and arousal systems are both simultaneously active. The animal studies have also shown that the inappropriate arousal can be blocked by lesions in the limbic and arousal systems. It is hoped that these findings can be extended to identify new compounds that improve insomnia by acting at these sites of abnormal brain activation.
Surface plasmon resonance (SPR) was used to investigate the interaction between N-methyl mesoporphyrin IX (NMM) and different G-quadruplex (G4) topologies. The study was associated with circular ...dichroism analysis (CD) to assess the topology of the G4s when they interacted with NMM. We demonstrate the high selectivity of NMM for the parallel G4 structure with a dissociation constant at least ten times lower than those of other G4 topologies. We also confirm the ability of NMM to shift the G4 conformation from both the hybrid and antiparallel topologies toward the parallel structure.
Insomnia is a highly prevalent, often debilitating, and economically burdensome form of sleep disturbance caused by various situational, medical, emotional, environmental and behavioral factors. ...Although several consensually-derived nosologies have described numerous insomnia phenotypes, research concerning these phenotypes has been greatly hampered by a lack of widely accepted operational research diagnostic criteria (RDC) for their definition. The lack of RDC has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment. Given this problem, the American Academy of Sleep Medicine (AASM) commissioned a Work Group (WG) to review the literature and identify those insomnia phenotypes that appear most valid and tenable. In addition, this WG was asked to derive standardized RDC for these phenotypes and recommend assessment procedures for their ascertainment. This report outlines the WG's findings, the insomnia RDC derived, and research assessment procedures the WG recommends for identifying study participants who meet these RDC.
Surface plasmon resonance (SPR) is a powerful technique for studying biomolecular interactions mainly due to its sensitivity and real-time and label free advantages. While SPR signals are usually ...positive, only a few studies have reported sensorgrams with negative signals. The aim of the present work is to investigate and to explain the observation of negative SPR signals with the hypothesis that it reflects major changes in ligand conformation resulting from target binding. We demonstrated that these negative unconventional signals were due to the negative complex (ligand/analyte) refractive index increment (RII) deviation from the sum of the RII of the individual entities which counterbalanced the theoretical increase of the signal triggered by the target recognition and the ligand folding. We also found that the conformation change of biomolecules can induce a negative or a positive complex RII deviation depending on its sequence and immobilization mode.
Aim
To compare the in vitro biocompatibility of Biodentine™ and White ProRoot® mineral trioxide aggregate (MTA®) with MG63 osteoblast‐like cells and to characterize the cement surface.
Methodology
A ...direct contact model for MG63 osteoblast‐like cells with cements was used for 1, 3 and 5 days. Four end‐points were investigated: (i) cement surface characterization by atomic force microscopy (AFM), (ii) cell viability by MTT assay, (iii) protein amount quantification by Bradford assay and (iv) cell morphology by SEM. Statistical analyses were performed by analysis of variance (anova) with a repetition test method.
Results
The roughness of the cements was comparable as revealed by AFM analysis. The MTT test for Biodentine™ was similar to that of MTA®. Biodentine™ and MTA® induced a similar but slight decrease in metabolic activity. The amount of total protein was significantly enhanced at day three (P < 0.05) but slightly decreased at day five for both tested samples. Biodentine™ was tolerated as well as MTA® in all cytotoxicity assays. SEM observations showed improvement of cell attachment and proliferation on both material surfaces following the three incubation periods.
Conclusion
The biocompatibility of Biodentine™ to bone cells was comparable to MTA®.
Common symptoms associated with sleep fragmentation and sleep deprivation include increased objective sleepiness (as measured by the Multiple Sleep Latency Test); decreased psychomotor performance on ...a number of tasks including tasks involving short term memory, reaction time, or vigilance; and degraded mood. Differences in degree of sleepiness are more related to the degree of sleep loss or fragmentation rather than to the type of sleep disturbance. Both sleep fragmentation and sleep deprivation can exacerbate sleep pathology by increasing the length and pathophysiology of sleep apnea. The incidence of both fragmenting sleep disorders and chronic partial sleep deprivation is very high in our society, and clinicians must be able to recognize and treat Insufficient Sleep Syndrome even when present with other sleep disorders.
We report on 75 mas resolution, near-IR imaging spectroscopy within the central 30 lt-days of the Galactic center, taken with the new adaptive optics-assisted integral-field spectrometer SINFONI on ...the ESO VLT. To a limiting magnitude of K 6 16, 9 of 10 stars in the central 0."4, and 13 of 17 stars out to 0."7 from the central black hole have spectral properties of B0-B9 main-sequence stars. Based on the 2.1127 km He I line width, all brighter early-type stars have normal rotation velocities, similar to solar neighborhood stars. We combine the new radial velocities with SHARP/NACO astrometry to derive improved three-dimensional stellar orbits for six of these "S stars" in the central 0."5. Their orientations in space appear random. Their orbital planes are not co-aligned with those of the two disks of massive young stars 1"-10" from Sgr A*. We can thus exclude the hypothesis that the S stars as a group inhabit the inner regions of these disks. They also cannot have been located/formed in these disks and then migrated inward within their planes. From the combination of their normal rotation and random orbital orientations, we conclude that the S stars were most likely brought into the central light-month by strong individual scattering events. The updated estimate of distance to the Galactic center from the S2 orbit fit is R sub(0) = 7.62 c 0.32 kpc, resulting in a central mass value of (3.61 c 0.32) x 10 super(6) M sub( ). We happened to catch two smaller flaring events from Sgr A* during our spectral observations. The 1.7-2.45 km spectral energy distributions of these flares are fit by a featureless, "red" power law of spectral index a' = -4 c 1 (S sub(u) 6 u super(a')). The observed spectral slope is in good agreement with synchrotron models in which the infrared emission comes from accelerated, nonthermal, high-energy electrons in a radiatively inefficient accretion flow in the central R 6 10R sub(S) region.
G‐quadruplex DNA structures (G4) are proven to interfere with most genetic and epigenetic processes. Small molecules binding these structures (G4 ligands) are invaluable tools to probe G4‐biology and ...address G4‐druggability in various diseases (cancer, viral infections). However, the large number of reported G4 ligands (>1000) could lead to confusion while selecting one for a given application. Herein we conducted a systematic affinity ranking of 11 popular G4 ligands vs 5 classical G4 sequences using FRET‐melting, G4‐FID assays and SPR. Interestingly SPR data globally align with the rankings obtained from the two semi‐quantitative assays despite discrepancies due to limits and characteristics of each assay. In the whole, PhenDC3 emerges as the most potent binder irrespective of the G4 sequence. Immediately below PDS, PDC‐360A, BRACO19, TMPyP4 and RHPS4 feature strong to medium binding again with poor G4 topology discrimination. More strikingly, the G4 drugs Quarfloxin, CX5461 and c‐PDS exhibit weak affinity with all G4s studied. Finally, NMM and Cu‐ttpy showed heterogeneous behaviors due, in part, to their physicochemical particularities poorly compatible with screening conditions. The remarkable properties of PhenDC3 led us to propose its use for benchmarking FRET‐melting and G4‐FID assays for rapid G4‐affinity evaluation of newly developed ligands.
We conducted a systematic affinity ranking of 11 popular G4 ligands vs 5 classical G4 sequences using FRET‐melting, G4‐FID assays and SPR. This comparative study enables the establishment of a precise affinity ranking of ligands while also highlighting discrepancies attributable to the limitations and characteristics of each assay.
Surface plasmon resonance (SPR) is a powerful technique to study the interactions of ligands with analytes and therefore a number of biosensor surfaces and injection methods have been developed so ...far. However, many experimental parameters can affect the interactions and consequently the affinity measurements. In particular, the interactions of positively charged analytes (often used for anionic nucleic acids targets) can be influenced by the sensing surfaces (e.g., negatively charged), leading to significant nonspecific interactions as well as regeneration problems. The aim of the present work is to investigate the effect of different parameters, including ionic strength, SPR biosensor (i.e., nature of the surfaces), and the injection method on the recognition of porphyrin G-quadruplex ligands. We demonstrate that the injection method does not influence the affinity whereas the ionic strength and the nature of the surface impact the recognition properties of the porphyrin for the G-quadruplex DNA. We also found that self-assembled monolayer coating surface presents many advantages in comparison with carboxymethylated dextran surface for SPR studies of G-quadruplex DNA/ligand interactions: (i) the electrostatic interaction with charged analytes is less important, (ii) its structure/composition is less sensitive to the ionic concentration and less prone to unspecific adsorption, (iii) it is easily homemade, and (iv) the cost is approximately 10 times cheaper.
It was hypothesized that psychophysiological insomniacs, who have been shown to have elevated heart rate, body temperature, and whole body metabolic rate, would also have increased low frequency and ...decreased high frequency power in the spectral analysis of their heart period data.
Groups of 12 objectively defined insomniacs and age-, sex-, and weight-matched controls with normal sleep were evaluated on sleep and EKG measures over a 36-hour sleep laboratory stay.
Heart period was decreased (ie, heart rate was increased) and its SD was decreased in all stages of sleep in the insomniacs compared with the controls. Spectral analysis revealed significantly increased low frequency power and decreased high frequency power in insomniacs compared with controls across all stages of sleep.
Because increased low frequency spectral power is an indicator of increased sympathetic nervous system activity, these data imply that chronic insomniacs could be at increased risk for the development of disorders, such as coronary artery disease, that are related to increased sympathetic nervous system activity.
PDF
