[The effects of nucleotide-binding oligomerization domain-like receptor 3 inflammasome on obstructive sleep apnea and its complications].

Obstructive sleep apnea (OSA) is a sleep disorder with a high incidence and severe impact on the human body, which can induce systemic chronic inflammatory responses. Chronic inflammation is an important cause of exacerbation of OSA and its associated complications. Nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) is an inflammasome that is widely found in epithelial cells and immune cells and plays an important role in inflammatory diseases as an important component of innate immunity. Research evidence suggests that the activation of NLRP3 inflammasomes can exacerbate the damage to neurons, endothelial cells, lung and kidney caused by OSA, and these effects can be eliminated by genetic or pharmacological deletion of NLRP3. Targeting inhibition of NLRP3 inflammasome may serve as a co-therapeutic strategy for OSA-induced related complications. This article reviews NLRP3 inflammasome and its mechanism in OSA-related concurrent diseases, which can provide scientific basis for prevention and intervention of OSA and its related complications.

Missense SNP of the MC1R gene is associated with plumage variation in the Gyrfalcon (Falco rusticolus).

A single nucleotide polymorphism (MC1R: c.376A>G) in the MC1R gene was found to be highly correlated with pigment phenotype in the Gyrfalcon. Homozygous genotypes c.376GG and c.376AA were found to dominate the extreme white and dark plumage types respectively, and heterozygotes occurred mainly in intermediate phenotypes. However, some heterozygotes were associated with extreme phenotypes, indicating that melanism/albinism might also involve other loci.

[Assessment of the brain volume alterations in patients with hyposmia based on voxel-based morphometry].

Objective: To investigate the brain volume alterations in patients with hyposmia using voxel-based morphometry (VBM) and to correlate these alterations with the degree and duration of hyposmia. Methods: Forty patients with hyposmia from Department of Otorhinolaryngology Head and Neck Surgery, Beijing Anzhen Hospital since 2013 to 2016 and forty age and sex matched normal subjects were recruited in this study. Sniffin' Sticks olfactory test was performed to evaluate the olfactory function of all subjects. We acquired T1-weighted magnetic resonance images from all subject on a 3T scanner. VBM was performed using VBM8 toolbox and SPM8 in a Matlab environment. Independent sample t test analysis was used to compare the volume of gray and white matter between the controls and patients. In addition, the Pearson or Spearman correlation analysis was used for the correlation between the voxel value of cerebral volume alterations area and the degree and duration of hyposmia on patients (threshold discrimination identification, TDI). Results: Compared with the controls, patients showed significantly decreased volume in the gray matter of right orbitofrontal cortex (number of voxel in clusters was 226, t=-4.46, P<0.001, uncorrected). There was negative correlation between decreased gray matter volume of the right orbitofrontal cortex with significantly decreased area and the TDI results (r=-0.40, P=0.01), but positive correlation with duration of hyposmia (r=0.37, P=0.02). Conclusions: The patients with hyposmia show gray matter atrophy of the right orbitofrontal cortex. The duration may be an important risk factor for decreased gray matter in patients with hyposmia.

[The preliminary study of white matter integrity in patients with olfactory dysfunction].

Objective: To investigate the white matter integrity in patients with olfactory dysfunction using diffusion tensor imaging (DTI). Methods: Twenty-one patients with olfactory dysfunction and sixteen age, sex and level of education matched normal subjects were recruited in this study. Sniffin' Sticks olfactory test was performed to evaluate the olfactory function of all subjects. We acquired diffusion tensor images with a echo planar imaging (EPI) sequence from all subjects on a 3T scanner. The fractional anisotropy (FA) images were performed using DTI-studio, and bilateral piriform cortex, orbitofrontal cortex, hippocampus and insula cortex adjacent white matter as well as capsula interna were delineated from the FA images as the region of interest associated with olfactory (ROI(awo)) manually. Independent sample t test analysis was used to compare the FA value of all ROI(awo) between the controls and patients. Results: In olfactory dysfunction group, the FA value of adjacent white matter of right piriform cortex and orbitofrontal cortex were significantly lower than those of control group (0.42±0.05 (x±s) vs 0.45±0.05, 0.43±0.06 vs 0.49±0.07, t value was 2.32, 2.79, respectively, all P<0.05). The FA value of adjacent white matter of left piriform cortex and orbitofrontal cortex had no significant difference compared with those of control group (0.43±0.05 vs 0.45±0.04, 0.44±0.04 vs 0.47±0.06, t value was 1.65, 1.37, respectively, all P>0.05). The FA value of the adjacent white matter of bilateral hippocampus, insula cortex and capsula interna had no significant difference compared with those of control group, neither (0.45±0.08 vs 0.44±0.08, 0.45±0.09 vs 0.44±0.10, 0.41±0.08 vs 0.39±0.07, 0.41±0.07 vs 0.38±0.05, 0.64±0.08 vs 0.63±0.08, 0.64±0.07 vs 0.63±0.07, t value was 0.30, 0.15, 0.88, 1.34, 0.14, 0.35, respectively, all P>0.05). Conclusions: The patients with olfactory dysfunction showed abnormal white matter connection in the major primary and secondary olfactory cortex. The reduced white matter integrity in ROI(awo) might contribute to the pathogenesis of olfactory dysfunction.

Dendritic depolarization efficiently attenuates low-threshold calcium spikes in thalamic relay cells.

Thalamic relay cells respond in two distinct modes, burst and tonic, that depend on a voltage-dependent, low-threshold, transient Ca(2+) current (I(T)), and these modes relay different forms of information to cortex. I(T) activation evokes a low-threshold spike (LTS), producing a burst of action potentials. Modulatory inputs from cortex and brainstem are known to activate metabotropic receptors on relay cell dendrites at which the T channels underlying I(T) may be concentrated. We thus investigated the influence of activating these receptors on the LTS, using current-clamp intracellular recording in an in vitro slice preparation of the cat's lateral geniculate nucleus. We found a strong correlation between LTS amplitude and the number of action potentials evoked in the burst. We then found that activation of either metabotropic glutamate or muscarinic receptors produced a hyperpolarizing shift in the sigmoid relationship between LTS amplitude and the initial holding potential without affecting the maximum LTS amplitude or slope of the relationship. This hyperpolarizing shift in the voltage dependency of LTS amplitude is best explained by space-clamp limitations and significantly more depolarization of T channels near the dendritic location of activated receptors than at the soma. Thus, nonretinal modulatory inputs may have a stronger influence on I(T) and number of action potentials generated in a burst than previously imagined from somatic recording, because the EPSP amplitudes generated by these inputs at the dendritic location of most T channels are greater than after their electrotonic decay recorded at the soma.

An efficient method that reveals both the dendrites and the soma mosaics of retinal ganglion cells.

A method of using neurobiotin to stain both the dendrites and the soma mosaics of retinal ganglion cells in fresh retinae is described. This method is simple to use and efficient in revealing morphological details for a large number of retinal ganglion cells. It has five advantages over currently available staining methods. (1) It stains all ganglion cells in the whole retina or in a selected retinal area, permitting ganglion cell distributions across the retina to be obtained. (2) It reveals cell dendrites in great detail, especially in regions outside the area centralis. The dendritic field mosaics and, therefore the dendritic field coverage factors, of different ganglion cell types across the whole retina can be obtained easily. (3) It works reliably, efficiently, and does not require the expensive set-up or the pains-taking work needed when staining cells through intracellular injection. (4) It works under both in vivo and in vitro settings, permitting the use of retinae from animals sacrificed for other purposes and the use of postmortem human retinae. (5) The end product of the visualization process is optically dark and electron dense, permitting specimens to be examined under both light and electron microscopes.

Further assessment of the clinically effective dose range of etoricoxib: a randomized, double-blinded, placebo-controlled trial in rheumatoid arthritis.

OBJECTIVE: To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA). METHODS: RA patients were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind, 12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were allowed in stable doses. The primary endpoint was the proportion of patients completing the study and achieving an American College of Rheumatology 20% (ACR20) response. Secondary endpoints included individual components of the ACR index and Patient Global Assessment of Pain. Safety was assessed by physical exam and adverse experiences (AEs) occurrences. RESULTS: Etoricoxib 90 mg was the only dose to reach a statistically significant difference from placebo (p < 0.001) on the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057). Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p < 0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background biologics and corticosteroids, a dose response was still apparent. A higher proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema and hypertension) compared with placebo, although discontinuations for renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0). LIMITATIONS: The present study was not powered to detect differences in cardiovascular or gastrointestinal safety by dose. Additionally, further research is needed to clarify the role of doses less than the etoricoxib 90 mg dose for pain management in RA patients. CONCLUSION: Etoricoxib 90 mg demonstrated statistically superior efficacy (ACR20) compared with placebo and numerical superiority over the other doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant pain improvement versus placebo, suggesting utility for some patients.

Molecular analysis of dispersal in giant pandas.

Although dispersal in the giant panda (Ailuropoda melanoleuca) is a demographic mechanism which can potentially counteract the negative effect of habitat fragmentation, little is known about dispersal in this species because of difficulties in observing individuals. Using data from faecal microsatellite genotyping, we compared the spatial distribution of giant pandas in two populations and the proximity of relatives in one key population to infer their dispersal pattern. We conclude that giant pandas exhibit female-biased dispersal because: (i) vAIc (variance of assignment index) for females was significantly larger than for males, suggesting that females comprise both 'local' and 'foreign' genotypes; (ii) the average spatial distance of related female dyads was significantly larger than that of males; (iii) larger r (relatedness), F(ST) (genetic variance among populations) and mAIc (mean of assignment index) values were found in males using the software FSTAT, although the differences were not significant; (iv) males set up territories neighbouring to their birth place; (v) significant population structure using microsatellites with a concomitant lack of mitochondrial structure was found in a previous study, possibly indicating more extensive female dispersal; and (vi) female-biased dispersal was strongly supported by evidence from concomitant ecological studies. Considering previous ecological data and life-history characteristics of the giant panda, female-biased dispersal is most likely to be due to competition for birth dens among females, inbreeding avoidance and enhancing inclusive fitness among related males.

Modeling cat retinal beta-cell arrays.

There were three objectives to the work undertaken for this paper: (1) to provide a comprehensive characterization of the statistical properties of arrays of beta-cell somata; (2) to develop a model that simulates cellular arrays with the same properties; and (3) to use this model to examine whether the array of beta-cells should be viewed as one array or as two arrays, one each for its OFF- and ON-center cells. Beta-cells are morphological correlates of the electrophysiological X-cells and those beta-cells whose dendrites stratify within the outer and inner sublamina of the retina's inner plexiform layer correspond, respectively, to OFF- and ON-center X-cells. Arrays of peripheral beta-cell somata from two retinas were studied. A Delaunay triangulation and a Voronoi tessellation were generated for each array and measures derived from these constructs used to analyze the arrays' spatial organization. As others have shown previously with a less complete statistical characterization, we found that the arrays of OFF- and ON-center beta-cells have similar spatial properties and are more regular than the array of all beta-cells. We developed a model to simulate cellular arrays with spatial properties like those of arrays of beta-cells. A good fit between model and real arrays was found when the model assumed an explicit spatial dependence between the placement of OFF- and ON-center cells. We propose therefore that a single array of beta-cells formed of both OFF- and ON-center cells is consistent with the data currently available for beta-cell somatic arrays.

Current clamp and modeling studies of low-threshold calcium spikes in cells of the cat's lateral geniculate nucleus.

Current clamp and modeling studies of low-threshold calcium spikes in cells of the cat's lateral geniculate nucleus. All thalamic relay cells display a voltage-dependent low-threshold Ca2+ spike that plays an important role in relay of information to cortex. We investigated activation properties of this spike in relay cells of the cat's lateral geniculate nucleus using the combined approach of current-clamp intracellular recording from thalamic slices and simulations with a reduced model based on voltage-clamp data. Our experimental data from 42 relay cells showed that the actual Ca2+ spike activates in a nearly all-or-none manner and in this regard is similar to the conventional Na+/K+ action potential except that its voltage dependency is more hyperpolarized and its kinetics are slower. When the cell's membrane potential was hyperpolarized sufficiently to deinactivate much of the low-threshold Ca2+ current (IT) underlying the Ca2+ spike, depolarizing current injections typically produced a purely ohmic response when subthreshold and a full-blown Ca2+ spike of nearly invariant amplitude when suprathreshold. The transition between the ohmic response and activated Ca2+ spikes was abrupt and reflected a difference in depolarizing inputs of <1 mV. However, activation of a full-blown Ca2+ spike was preceded by a slower period of depolarization that was graded with the amplitude of current injection, and the full-blown Ca2+ spike activated when this slower depolarization reached a sufficient membrane potential, a quasithreshold. As a result, the latency of the evoked Ca2+ spike became less with stronger activating inputs because a stronger input produced a stronger depolarization that reached the critical membrane potential earlier. Although Ca2+ spikes were activated in a nearly all-or-none manner from a given holding potential, their actual amplitudes were related to these holding potentials, which, in turn, determined the level of IT deinactivation. Our simulations could reproduce all of the main experimental observations. They further suggest that the voltage-dependent K+ conductance underlying IA, which is known to delay firing in many cells, does not seem to contribute to the variable latency seen in activation of Ca2+ spikes. Instead the simulations indicate that the activation of IT starts initially with a slow and graded depolarization until enough of the underling transient (or T) Ca2+ channels are recruited to produce a fast, "autocatalytic" depolarization seen as the Ca2+ spike. This can produce variable latency dependent on the strength of the initial activation of T channels. The nearly all-or-none nature of Ca2+ spike activation suggests that when a burst of action potentials normally is evoked as a result of a Ca2+ spike and transmitted to cortex, this signal is largely invariant with the amplitude of the input activating the relay cell.

Cellular mechanisms underlying activity patterns in the monkey thalamus during visual behavior.

We show for the first time with in vitro recording that burst firing in thalamic relay cells of the monkey is evoked by activation of voltage-dependent, low threshold Ca(2+) spikes (LTSs), as has been described in other mammals. Due to variations in LTS amplitude, the number of action potentials evoked by an LTS could vary between 1 and 8. These data confirm the presence of two modes of firing in the monkey for thalamic relay cells, tonic and burst, the latter related to the activation of LTSs. With these details of the cellular processes underlying burst firing, we could account for many of the firing patterns we recorded from the lateral geniculate nucleus of the thalamus in behaving monkeys. In particular, we found clear evidence of burst firing during alert wakefulness, which had been thought to occur only during sleep or certain pathological states. This makes it likely that the burst firing seen in awake humans has the same cellular basis of LTSs, and this supports previous suggestions that burst firing represents an important relay mode for visual processing.