•Our study found several SNPs related to pharmacogenetics among Lahu population.•The rs20417, rs776746, rs2115819, and rs3093105 variants are different in the Lahu.•The genotype frequency of the SNPs ...are associated with metabolism of drugs.•It will help optimize drug dose and recommend appropriate drugs for Lahu patients.
Pharmacogenomics has been widely used to study the very important pharmacogenetic (VIP) variants among populations, but information on pharmacogenomics in the Lahu population is limited. The purpose of this study was to determine the differences in the distribution of VIP variants between the Lahu and the other 26 populations.
We genotyped 55 VIP variants of 27 genes in the Lahu population from the PharmGKB database. χ2 test was used to compare the genotype and allele frequencies between the Lahu and the other 26 populations from the 1000 Genomes Project.
The genotype and allele frequencies of single nucleotide polymorphisms (SNPs) on rs20417 (PTGS2), rs776746 (CYP3A5), rs2115819 (ALOX5), and rs3093105 (CYP4F2) were considerably different in the Lahu population compared with those in the other 26 populations. Besides, based on the PharmGKB database, we identified several VIP variants that may alter the drug metabolism of aspirin (PTGS2), tacrolimus (CYP3A5), montelukast (ALOX5), and vitamin E (CYP4F2).
The results show that there are significant differences in the genotype frequency distribution between the Lahu and the other 26 populations. Our study supplements the pharmacogenomics information of the Lahu population and provides a theoretical basis for individualized medicine in Lahu.
•Melamine-formaldehyde (MF) microfibers were synthesized.•High thermal stability up to 260°C.•Base thermal conductivity of 2.3mWm−1K−1 measured at porosity 0.81.•Extremely low outgassing rate was ...recorded.•The outgassing rate was determined by the spinning rotor gauge.
Melamine-formaldehyde fibers were synthesized from a meltable pre-polymer of etherified melamine-formaldehyde in a form of a low density fleece, subsequently thermally cured in a conveyor belt oven at temperatures of up to 200°C and post-heated at 260°C. High thermal stability and small fiber diameter below 5μm made it a serious candidate as a novel core material for vacuum thermal insulation panels. Two most crucial core properties, thermal conductivity and outgassing rate, were investigated in thin-walled stainless steel envelopes, enabling thermal processing combined with a pump-out procedure. A base thermal conductivity of ∼2.3mWm−1K−1 was achieved with randomly oriented fibers at a density of ∼250kgm−3. The long-term pressure-rise measurements revealed extremely low outgassing rates, q∼10−15mbarLs−1cm−2. Additional measurements of thermal conductivity in a wide pressure range from 10−3mbar to the atmosphere indicate that these melamine-formaldehyde fibers could be the first organic candidates applied as the core material in vacuum insulating panels with an adequate service lifetime. Their performance is comparable to selected inorganic core materials like glass fibers.
Inhibitory interneurons in the neocortex often connect in a promiscuous and extensive fashion, extending a "blanket of inhibition" on the circuit. This raises the problem of how can excitatory ...activity propagate in the midst of this widespread inhibition. One solution to this problem could be the vasoactive intestinal peptide (VIP) interneurons, which disinhibit other interneurons. To explore how VIP interneurons affect the local circuits, we use two-photon optogenetics to activate them individually in mouse visual cortex in vivo while measuring their output with two-photon calcium imaging. We find that VIP interneurons have narrow axons and inhibit nearby somatostatin interneurons, which themselves inhibit pyramidal cells. Moreover, via this lateral disinhibition, VIP cells in vivo make local and transient "holes" in the inhibitory blanket extended by SOM cells. VIP interneurons, themselves regulated by neuromodulators, may therefore enable selective patterns of activity to propagate through the cortex, by generating a "spotlight of attention".
Most inhibitory interneurons have axons restricted to a nearby area and target excitatory neighbors indiscriminately, raising the issue of how neuronal activity can propagate through cortical circuits. Vasoactive intestinal peptide-expressing interneurons (VIPs) disinhibit cortical pyramidal cells through inhibition of other inhibitory interneurons, and they have very focused, "narrow" axons. By optogenetically activating single VIPs in live mice while recording the activity of nearby neurons, we find that VIPs break open a hole in blanket inhibition with an effective range of ∼120 μm in lateral cortical space where excitatory activity can propagate.
As a way to understand vegetation changes, trend analysis on NDVI (normalized difference vegetation index) time series data have been widely performed at regional to global scales. However, most ...long-term NDVI datasets are based upon multiple sensor systems and unsuccessful corrections related to sensor shifts potentially introduce substantial uncertainties and artifacts in the analysis of trends. The temporal consistency of NDVI datasets should therefore be evaluated before performing trend analysis to obtain reliable results. In this study we analyze the temporal consistency of multi-sensor NDVI time series by analyzing the co-occurrence between breaks in the NDVI time series and sensor shifts from GIMMS3g (Global Inventory Modeling and Mapping Studies 3rd generation), VIP3 (Vegetation Index and Phenology version 3), LTDR4 (Long Term Data Record version 4) and SPOT-VGT (Système Pour l'Observation de la Terre VEGETATION). Single sensor time series from MODIS (MODerate Resolution Imaging Spectroradiometer) Terra and Aqua are used as reference datasets. The global land surface is divided into six regions according to the world humidity zones and averaged NDVI time series in each region are analyzed separately using a multiple structural change detection approach. We find that artifacts exist in the VIP3 and LTDR4 NDVI datasets with an abrupt shift detected in all humidity zones coinciding with the shift from NOAA-9 to NOAA-11 in 1988 and that orbital drift effects are evident in arid regions, potentially introducing uncertainties in NDVI trend analysis. Platform/sensor change from VGT-1 to VGT-2 is found to cause a significant positive break in the SPOT-VGT NDVI time series. Potential artifacts exist in humid, dry-subhumid, semi-arid and hyper-arid regions of GIMMS3g NDVI, whereas no signs of artifacts are found in the arid region. Although temporal consistency throughout all examined datasets increases after 2000 due to the usage of advanced platforms and sensors, variations in NDVI values from 2010 to 2011 still result in different trends at global and regional scales.
•Averaged NDVI for global humidity zones were used to detect sensor shift effects.•A multiple structural change detection approach was implemented.•Orbital drift effects were found for all humidity zones of VIP3 and LTDR4 NDVI.•Orbital drift effects were found in humid areas of GIMMS3g NDVI.•Data discontinuity was found in SPOT-VGT NDVI in 2003.
Multiple cell types form the VIP amacrine cell population Pérez de Sevilla Müller, Luis; Solomon, Alexander; Sheets, Kristopher ...
Journal of comparative neurology (1911),
January 1, 2019, 2019-01-01, 2019-01-00, 20190101, Volume:
527, Issue:
1
Journal Article
Peer reviewed
Open access
Amacrine cells are a heterogeneous group of interneurons that form microcircuits with bipolar, amacrine and ganglion cells to process visual information in the inner retina. This study has ...characterized the morphology, neurochemistry and major cell types of a VIP‐ires‐Cre amacrine cell population. VIP‐tdTomato and ‐Confetti (Brainbow2.1) mouse lines were generated by crossing a VIP‐ires‐Cre line with either a Cre‐dependent tdTomato or Brainbow2.1 reporter line. Retinal sections and whole‐mounts were evaluated by quantitative, immunohistochemical, and intracellular labeling approaches. The majority of tdTomato and Confetti fluorescent cell bodies were in the inner nuclear layer (INL) and a few cell bodies were in the ganglion cell layer (GCL). Fluorescent processes ramified in strata 1, 3, 4, and 5 of the inner plexiform layer (IPL). All tdTomato fluorescent cells expressed syntaxin 1A and GABA‐immunoreactivity indicating they were amacrine cells. The average VIP‐tdTomato fluorescent cell density in the INL and GCL was 535 and 24 cells/mm2, respectively. TdTomato fluorescent cells in the INL and GCL contained VIP‐immunoreactivity. The VIP‐ires‐Cre amacrine cell types were identified in VIP‐Brainbow2.1 retinas or by intracellular labeling in VIP‐tdTomato retinas. VIP‐1 amacrine cells are bistratified, wide‐field cells that ramify in strata 1, 4, and 5, VIP‐2A and 2B amacrine cells are medium‐field cells that mainly ramify in strata 3 and 4, and VIP‐3 displaced amacrine cells are medium‐field cells that ramify in strata 4 and 5 of the IPL. VIP‐ires‐Cre amacrine cells form a neuropeptide‐expressing cell population with multiple cell types, which are likely to have distinct roles in visual processing.
VIP‐Confetti fluorescent amacrine cell types in the VIP‐Confetti (Brainbow2.1) retina and their stratification. (a, c, d) VIP‐1 cells. (b, e, f) VIP‐2 cells. VIP cells are in magenta and calretinin‐immunoreactive cells are in green. Scale bar: 25 μm.
Light-sensitive neurons are located in the ventral and central core of the suprachiasmatic nucleus (SCN), whereas stably oscillating clock neurons are found mainly in the dorsal shell. Signals ...between the SCN core and shell are believed to play an important role in light entrainment. Core neurons express vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), and Neuroglobin (Ngb), whereas the shell neurons express vasopressin (AVP), prokineticin 2, and the VIP type 2 (VPAC2) receptor. In rodents, light has a phase-shifting capacity at night, which induces rapid and transient expression of the EGR1 and FOS in the SCN.
The present study used immunohistochemical staining of FOS, EGR1, and phenotypical markers of SCN neurons (VIP, AVP, Ngb) to identify subtypes/populations of light-responsive neurons at early night.
Double immunohistochemistry and cell counting were used to evaluate the number of SCN neurons expressing FOS and EGR1 in the SCN. The number of neurons expressing either EGR1 or FOS was higher than the total number of neurons co-storing EGR1 and FOS. Of the total number of light-responsive cells, 42% expressed only EGR1, 43% expressed only FOS, and 15% expressed both EGR1 and FOS. Light-responsive VIP neurons represented only 31% of all VIP neurons, and EGR1 represents the largest group of light-responsive VIP neurons (18%). VIP neurons expressing only FOS represented 1% of the total light-responsive VIP neurons. 81% of the Ngb neurons in the mouse SCN were light-responsive, and of these neurons expressing only EGR1 after light stimulation represented 44%, whereas 24% expressed FOS. Although most light-responsive neurons are found in the core of the SCN, 29% of the AVP neurons in the shell were light-responsive, of which 8% expressed EGR1, 10% expressed FOS, and 11% co-expressed both EGR1 and FOS after light stimulation.
Our analysis revealed cell-specific differences in light responsiveness between different peptidergic and Ngb-expressing neurons in different compartments of the mouse SCN, indicating that light activates diverse neuronal networks in the SCN, some of which participate in photoentrainment.
Objective
To investigate the role of calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide in cluster headache, we ...measured these vasoactive peptides interictally and during experimentally induced cluster headache attacks.
Methods
We included patients with episodic cluster headache in an active phase (n = 9), episodic cluster headache patients in remission (n = 9) and patients with chronic cluster headache (n = 13). Cluster headache attacks were induced by infusion of calcitonin gene-related peptide (1.5 µg/min) in a randomized, double-blind, placebo controlled, two-way cross-over study. At baseline, we collected interictal blood samples from all patients and during 11 calcitonin gene-related peptide-induced cluster headache attacks.
Results
At baseline, episodic cluster headache patients in remission had higher plasma levels of calcitonin gene-related peptide, 100.6 ± 36.3 pmol/l, compared to chronic cluster headache patients, 65.9 ± 30.5 pmol/l, (p = 0.011). Episodic cluster headache patients in active phase had higher PACAP38 levels, 4.0 ± 0.8 pmol/l, compared to chronic cluster headache patients, 3.3 ± 0.7 pmol/l, (p = 0.033). Baseline levels of vasoactive intestinal polypeptide did not differ between cluster headache groups. We found no attack-related increase in calcitonin gene-related peptide, PACAP38 or vasoactive intestinal polypeptide levels during calcitonin gene-related peptide-induced cluster headache attacks.
Conclusions
This study suggests that cluster headache disease activity is associated with alterations of calcitonin gene-related peptide expression. Future studies should investigate the potential of using calcitonin gene-related peptide measurements in monitoring of disease state and predicting response to preventive treatments, including response to anti-calcitonin gene-related peptide monoclonal antibodies.
Sensory experience and perceptual learning changes receptive field properties of cortical pyramidal neurons (PNs), largely mediated by synaptic long-term potentiation (LTP). The circuit mechanisms ...underlying cortical LTP remain unclear. In the mouse somatosensory cortex, LTP can be elicited in layer 2/3 PNs by rhythmic whisker stimulation. We dissected the synaptic circuitry underlying this type of plasticity in thalamocortical slices. We found that projections from higher-order, posterior medial thalamic complex (POm) are key to eliciting N-methyl-D-aspartate receptor (NMDAR)-dependent LTP of intracortical synapses. Paired activation of cortical and higher-order thalamocortical inputs increased vasoactive intestinal peptide (VIP) and parvalbumin (PV) interneuron (IN) activity and decreased somatostatin (SST) IN activity, which together disinhibited the PNs. VIP IN-mediated disinhibition was critical for inducing LTP. This study reveals a circuit motif in which higher-order thalamic inputs gate synaptic plasticity via disinhibition. This motif may allow contextual feedback to shape synaptic circuits that process first-order sensory information.
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•Activation of higher-order (HO) thalamic inputs facilitates intracortical LTP•HO inputs increase VIP and PV interneuron (IN) activity and decrease SST IN activity•The activation of VIP INs disinhibits L2/3 pyramidal neurons (PNs)•The HO-to-VIP circuit gates the intracortically driven LTP on PNs
Using ex vivo patch-clamp recordings, optogenetics, and chemogenetics, Williams and Holtmaat dissect the circuits underlying sensory-driven LTP in the cortex. This reveals a circuit motif in which higher-order thalamocortical input gates plasticity of intracortical synapses via VIP-mediated disinhibition.
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