Surface Analysis of Materials in Aqueous Solution by Localized Alternating Current Impedance Measurements

Differences in electrical conductivity provide a basis for identification of different components present at a material surface. Here it is demonstrated that this effect can be exploited for surface analysis of compound materials in solution by making localized alternating current impedance measurements

Uniform loss of type 3 OFF and 5 ON cone bipolar cells across <i>rd1</i> retinas over age.

<p><b>A</b>–<b>B</b>, Calcium-binding protein 5 (Cabp5), is expressed by three subsets of bipolar cells (type 3 OFF and type 5 ON cone bipolar cells, and rod bipolar cells). Their axonal terminals stratified in the stratum 2 (type 3 OFF bipolars) (<b>A,</b> red, blue open arrowheads), the stratum 3 (type 5 ON bipolars) (<b>A,</b> red, red open arrowheads) and the stratum 5 (rod bipolars) (<b>A,</b> red, green open arrowheads) of the IPL, respectively. Cabp5 was not detected in type 7 cone bipolar cells (<b>A</b>, <b>B</b>, arrows), but was detected in rod bipolar cells (<b>A</b>, solid arrowheads). The density of cabp5 positive cells was decreased with age (<b>A</b>, <b>B</b>). <b>C</b>, The graph shows a gradual reduction in the densities of both type 3 OFF and type 5 ON bipolar cells over time. Cells were counted in the dorsal retinas of 8 retinal sections from 8 mice in each age group (mean ± s.d.). <b>D</b>, The graph shows a gradual decline in the densities of type 7 bipolar cells with age (mean ± s.d.). Cells were counted in the dorsal retinas of 8 flat mounted retinas along dorsoventral axe from 8 mice in each age group (mean ± s.d.). OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer. Scale bar, 10 µm.</p

Development of dendrites, axon terminals and a regular organization of type 7 bipolar cells in <i>rd1</i> mice.

<p><b>A</b>–<b>B</b>, The distributions of somata and the dendritic tilings of type 7 bipolar cells in the flat-mounted retinas of 357 (<b>A</b>) and 357/<i>rd1</i> (<b>B</b>) mice. The somata of type 7 bipolar cells showed regular distributions, and the dendrites of type 7 bipolar cells tiled the retinal surface with little overlap in both 357 (<b>A</b>) and 357/<i>rd1</i> (<b>B</b>) retinas. The boundaries of individual dendritic fields are shown by white polygons. Type 7 bipolar cells have similar dendritic and axonal arbors in WT (<b>A, </b><b>C</b>) and <i>rd1</i> retinas (<b>B, </b><b>D</b>). <b>E</b>, Analysis of the spatial distribution of type 7 bipolar cell somata in <i>rd1</i> retinas: density recovery profile. Three retinas from 3 mice were measured (mean ± s.d.). An exclusion zone is present (arrow), indicating that type 7 bipolar cells are prevented from occupying nearby positions on the retina – they form regular mosaics. Dotted line indicates the random distribution of the same number of cells. <b>F</b>, Histogram showing the average diameters of both dendritic and axonal arbors of type 7 bipolar cells. Twenty cells from 5 mice were measured in each age group (mean ± s.d.). ns, not significant. Scale bar, 5 µm.</p

Horizontal views of the dendritic arbors of type 7 bipolar cells in flat-mounted <i>rd1</i> retinas.

<p><b>A–B</b>, High-power images show the whole dendritic arbors of individual type 7 cone bipolar cells, illustrating a progressive dendritic retraction with growing age. <b>E</b>, Histogram showing the average diameter of dendritic arbors at different stages of degeneration. Twenty cells from 4 mice were measured in each age group (mean ± s.d.). <b>F</b>, Histogram showing the average diameter of axon arbors at different stages of degeneration. Twenty cells from 4 mice were measured in each age group (mean ± s.d.). <b>G</b>. Gradual loss of synaptic ribbons in the axonal arbors of individual type 7 cone bipolar cells in the IPL of <i>rd1</i> retinas. Six axonal terminals from 3 mice were measured in each age group (mean ± s.d.). ns, not significant, * = P<0.05, ** = P<0.01, *** = P<0.001, one-way ANOVA. Scale bar, 5 µm.</p

Different degeneration patterns of cone photoreceptors and type 7 bipolar cells in <i>rd1</i> mice.

<p>Counterstaining of retinal sections with an antibody against red/green opsins shows cone photoreceptors (red). <b>A–C</b>, Images were taken from three dorsal regions (<b>M</b>) of 357 mice at 1 month old, illustrating normal densities and morphologies of both type 7 cone bipolar cells (green) and cone photoreceptors (red). <b>D–L</b>, Representative images were taken from three dorsal regions of <i>rd1</i> retinas at three different ages. Insets illustrate highly magnified image from the boxed regions. Cone photoreceptors degeneration shows a central-to-peripheral progression (from <b>D</b> to <b>F; G</b> to <b>I; J</b> to <b>L</b>). Cone bipolar cell in the same regions, however, did not follow this spatiotemporal degeneration pattern (from <b>D</b> to <b>F; G</b> to <b>I; J</b> to <b>L</b>). ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer; ONH, optic nerve head. Scale bar, 20 µm.</p

The correlation of the time course of cone degeneration and type 7 cone bipolar development in <i>rd1</i> mice.

<p>Counterstaining of retinal sections with antibodies against red/green opsins and Ctbp2 shows cone photoreceptors (blue) and synaptic ribbons (red) in the both OPL and IPL. Type 7 cone bipolar cell dendrites invaded cone terminals to form ribbon synapse complex starting from P8. By P10, a high density of synaptic ribbons were present in the OPL of WT mice (<b>A,</b> red, arrowheads), while few were observed in the OPL of <i>rd1</i> mice (<b>B,</b> red). Insets illustrate highly magnified image from the boxed regions. Cone photoreceptors did not appear to have a normal morphology by this age (<b>B,</b> blue) compared with their counterparts in WT (<b>A,</b> blue). At P14 (<b>C</b>, <b>D</b>), some cone photoreceptors lost OS and IS, axons and axonal terminals became much smaller in <i>rd1</i> retinas (<b>D,</b> blue) compared to their counterparts in WT (<b>C,</b> blue). Synaptic ribbons were barely observed in the OPL (<b>D,</b> red, arrowheads). By P21 (<b>E</b>, <b>F</b>), most cones lost OS, IS and axonal terminals, and the absolute number of S cones was decreased (<b>F,</b> blue). Synaptic ribbons were absent from the OPL by this age (<b>F,</b> red, arrewheads). Type 7 cone bipolar cells appeared identical in morphology between WT mice and <i>rd1</i> mice at each of age-matched retinas (green). ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer; ONH, optic nerve head; OS, outer segment; IS, inner segment. Scale bar, 20 µm.</p

Data_Sheet_1_Association of cannabis use disorder with cardiovascular diseases: A two-sample Mendelian randomization study.PDF

BackgroundThe use of cannabis has increased globally due to more regions decriminalizing marijuana use for therapeutic and recreational aims. Several observational studies have revealed that cannabis use is associated with an increased risk of adverse cardiovascular pathologies and diseases. Nevertheless, the causal associations between cannabis use and cardiovascular diseases remain unclear. Hence, we performed single-variable and multivariable Mendelian randomization (MR) to evaluate the association between cannabis use disorder and various cardiovascular diseases.Materials and methodsSummary statistics were collected from the largest-to-date genome-wide association studies (GWAS) of cannabis use disorder. The 12 SNPs for cannabis use disorder were used as instrumental variables in this study. MR estimates were pooled using a random-effects inverse-variance weighted (IVW) method. Simple median and weighted median methods were conducted as sensitivity analyses.ResultsThe genetic liability to cannabis use disorder was associated with an augmented risk of coronary artery disease, myocardial infarction, atrial fibrillation, heart failure, deep venous thrombosis, pulmonary embolism, and stroke. Except for stroke, the results were inconsistent in the sensitivity analyses. The overall patterns for the associations of cannabis use disorder with atrial fibrillation, heart failure, pulmonary embolism and stroke remained in multivariable MR analyses adjusting for potential mediators, including smoking, alcohol, body mass index, blood lipid, type 2 diabetes, hypertension, and depression. However, the association with coronary artery disease, myocardial infarction, and deep venous thrombosis did not persist in multivariable MR analyses. Mediation analysis demonstrated that smoking, body mass index, low-density lipoprotein, hypertension, and depression have more significant mediation effects, which suggests that these factors partly mediate the link from cannabis use disorder to coronary artery disease, myocardial infarction, and deep venous thrombosis.ConclusionThe genetic liability to cannabis use disorder was associated with a higher risk of atrial fibrillation, heart failure, pulmonary embolism, and stroke. The evidence for the association between cannabis use disorder, coronary artery disease, myocardial infarction, and deep venous thrombosis was weak. Hence, future use of cannabis for therapeutic and recreational aims should consider its potential impact on cardiovascular diseases.</p

Image_1_Association of cannabis use disorder with cardiovascular diseases: A two-sample Mendelian randomization study.TIF

BackgroundThe use of cannabis has increased globally due to more regions decriminalizing marijuana use for therapeutic and recreational aims. Several observational studies have revealed that cannabis use is associated with an increased risk of adverse cardiovascular pathologies and diseases. Nevertheless, the causal associations between cannabis use and cardiovascular diseases remain unclear. Hence, we performed single-variable and multivariable Mendelian randomization (MR) to evaluate the association between cannabis use disorder and various cardiovascular diseases.Materials and methodsSummary statistics were collected from the largest-to-date genome-wide association studies (GWAS) of cannabis use disorder. The 12 SNPs for cannabis use disorder were used as instrumental variables in this study. MR estimates were pooled using a random-effects inverse-variance weighted (IVW) method. Simple median and weighted median methods were conducted as sensitivity analyses.ResultsThe genetic liability to cannabis use disorder was associated with an augmented risk of coronary artery disease, myocardial infarction, atrial fibrillation, heart failure, deep venous thrombosis, pulmonary embolism, and stroke. Except for stroke, the results were inconsistent in the sensitivity analyses. The overall patterns for the associations of cannabis use disorder with atrial fibrillation, heart failure, pulmonary embolism and stroke remained in multivariable MR analyses adjusting for potential mediators, including smoking, alcohol, body mass index, blood lipid, type 2 diabetes, hypertension, and depression. However, the association with coronary artery disease, myocardial infarction, and deep venous thrombosis did not persist in multivariable MR analyses. Mediation analysis demonstrated that smoking, body mass index, low-density lipoprotein, hypertension, and depression have more significant mediation effects, which suggests that these factors partly mediate the link from cannabis use disorder to coronary artery disease, myocardial infarction, and deep venous thrombosis.ConclusionThe genetic liability to cannabis use disorder was associated with a higher risk of atrial fibrillation, heart failure, pulmonary embolism, and stroke. The evidence for the association between cannabis use disorder, coronary artery disease, myocardial infarction, and deep venous thrombosis was weak. Hence, future use of cannabis for therapeutic and recreational aims should consider its potential impact on cardiovascular diseases.</p

Image_2_Association of cannabis use disorder with cardiovascular diseases: A two-sample Mendelian randomization study.TIF

BackgroundThe use of cannabis has increased globally due to more regions decriminalizing marijuana use for therapeutic and recreational aims. Several observational studies have revealed that cannabis use is associated with an increased risk of adverse cardiovascular pathologies and diseases. Nevertheless, the causal associations between cannabis use and cardiovascular diseases remain unclear. Hence, we performed single-variable and multivariable Mendelian randomization (MR) to evaluate the association between cannabis use disorder and various cardiovascular diseases.Materials and methodsSummary statistics were collected from the largest-to-date genome-wide association studies (GWAS) of cannabis use disorder. The 12 SNPs for cannabis use disorder were used as instrumental variables in this study. MR estimates were pooled using a random-effects inverse-variance weighted (IVW) method. Simple median and weighted median methods were conducted as sensitivity analyses.ResultsThe genetic liability to cannabis use disorder was associated with an augmented risk of coronary artery disease, myocardial infarction, atrial fibrillation, heart failure, deep venous thrombosis, pulmonary embolism, and stroke. Except for stroke, the results were inconsistent in the sensitivity analyses. The overall patterns for the associations of cannabis use disorder with atrial fibrillation, heart failure, pulmonary embolism and stroke remained in multivariable MR analyses adjusting for potential mediators, including smoking, alcohol, body mass index, blood lipid, type 2 diabetes, hypertension, and depression. However, the association with coronary artery disease, myocardial infarction, and deep venous thrombosis did not persist in multivariable MR analyses. Mediation analysis demonstrated that smoking, body mass index, low-density lipoprotein, hypertension, and depression have more significant mediation effects, which suggests that these factors partly mediate the link from cannabis use disorder to coronary artery disease, myocardial infarction, and deep venous thrombosis.ConclusionThe genetic liability to cannabis use disorder was associated with a higher risk of atrial fibrillation, heart failure, pulmonary embolism, and stroke. The evidence for the association between cannabis use disorder, coronary artery disease, myocardial infarction, and deep venous thrombosis was weak. Hence, future use of cannabis for therapeutic and recreational aims should consider its potential impact on cardiovascular diseases.</p

Identification of a Role for the PI3K/AKT/mTOR Signaling Pathway in Innate Immune Cells

<div><p>The innate immune system is the first line of host defense against infection and involves several different cell types. Here we investigated the role of the phosphatidylinositol 3 kinase (PI3K) signaling pathway in innate immune cells. By blocking this pathway with pharmacological inhibitors, we found that the production of proinflammatory cytokines was drastically suppressed in monocytes and macrophages. Further study revealed that the suppression was mainly related to the mammalian target of rapamycin (mTOR)/p70^S6K signaling. In addition, we found that the PI3K pathway was involved in macrophage motility and neovascularization. Our data provide a rationale that inhibition of the PI3K signaling pathway could be an attractive approach for the management of inflammatory disorders.</p></div