Table_1_Trends and disparities in disease burden of age-related macular degeneration from 1990 to 2019: Results from the global burden of disease study 2019.doc

ObjectivesThis study aims to estimate the trends and disparities in the worldwide burden for health of AMD, overall and by age, sex, socio-demographic index (SDI), region, and nation using prevalence and years lived with disability (YLDs) from Global Burden of Disease (GBD) study 2019.MethodsThis retrospective study presents the prevalent AMD cases and YLDs from 1990–2019, as well as the age-standardized prevalence rate (ASPR) and age-standardized YLD rate (ASYR) of AMD. To measure changes over time, estimated annual percentage changes (EAPCs) of the age-standardized rates (ASRs) were analyzed globally, then studied further by sex, SDI, region, and nation. We included data from the 2019 Global Burden of Disease (GBD) database to examine AMD prevalence and YLDs from 1990–2019 in 204 countries and territories, as well as demographic information such as age, sex, SDI, region, and nation.ResultsGlobally, the number of prevalent AMD cases increased from 3,581,329.17 (95% uncertainty interval [UI], 3,025,619.4–4,188,835.7) in 1990 to 7,792,530 (95% UI, 6,526,081.5–9,159,394.9) in 2019, and the number of YLDs increased from 296,771.93 (95% uncertainty interval [UI], 205,462.8–418,699.82) in 1990 to 564,055.1 (95% UI, 392,930.7–789,194.64) in 2019. The ASPR of AMD had a decreased trend with an EAPC of −0.15 (95% confidence interval [CI], −0.2 to −0.11) from 1990 to 2019, and the ASYR of AMD showed a decreased trend with an EAPC of −0.71 (95% confidence interval [CI], −0.78 to −0.65) during this period. The prevalence and YLDs of AMD in adults over 50 years of age showed a significant increase. The prevalence and YLDs of AMD were significantly higher in females than males, overall. The ASPRs and ASYRs in low SDI regions was greater than in high SDI regions from 1990 to 2019. In addition, increases in prevalence and YLDs differed by regions and nations, as well as level of socio-economic development.ConclusionThe number of prevalent cases and YLDs due to AMD increased over 30 years and were directly linked to age, sex, socio-economic status, and geographic location. These findings can not only guide public health work but also provide an epidemiological basis for global strategy formulation regarding this global health challenge.</p

Dissecting structures and functions of SecA-only protein-conducting channels: ATPase, pore structure, ion channel activity, protein translocation, and interaction with SecYEG/SecDF•YajC

<div><p>SecA is an essential protein in the major bacterial Sec-dependent translocation pathways. <i>E</i>. <i>coli</i> SecA has 901 aminoacyl residues which form multi-functional domains that interact with various ligands to impart function. In this study, we constructed and purified tethered C-terminal deletion fragments of SecA to determine the requirements for N-terminal domains interacting with lipids to provide ATPase activity, pore structure, ion channel activity, protein translocation and interactions with SecYEG-SecDF•YajC. We found that the N-terminal fragment SecAN493 (SecA_1-493) has low, intrinsic ATPase activity. Larger fragments have greater activity, becoming highest around N619-N632. Lipids greatly stimulated the ATPase activities of the fragments N608-N798, reaching maximal activities around N619. Three helices in amino-acyl residues SecA_619-831, which includes the “Helical Scaffold” Domain (SecA_619-668) are critical for pore formation, ion channel activity, and for function with SecYEG-SecDF•YajC. In the presence of liposomes, N-terminal domain fragments of SecA form pore-ring structures at fragment-size N640, ion channel activity around N798, and protein translocation capability around N831. SecA domain fragments ranging in size between N643-N669 are critical for functional interactions with SecYEG-SecDF•YajC. In the presence of liposomes, inactive C-terminal fragments complement smaller non-functional N-terminal fragments to form SecA-only pore structures with ion channel activity and protein translocation ability. Thus, SecA domain fragment interactions with liposomes defined critical structures and functional aspects of SecA-only channels. These data provide the mechanistic basis for SecA to form primitive, low-efficiency, SecA-only protein-conducting channels, as well as the minimal parameters for SecA to interact functionally with SecYEG-SecDF•YajC to form high-efficiency channels.</p></div

Synthesis and Characterization of Macroporous Photonic Structure that Consists of Azimuthally Shifted Double-Diamond Silica Frameworks

A macroporous silica with azimuthally shifted double-diamond frameworks has been synthesized by the self-assembly of an amphiphilic ABC triblock terpolymer poly­(<i>tert</i>-butyl acrylate)-<i>b</i>-polystyrene-<i>b</i>-poly­(ethylene oxide) and silica source in a mixture of tetrahydrofuran and water. The structure of the macroporous silica consists of a porous system separated by two sets of hollow double-diamond frameworks shifted 0.25<i>c</i> along ⟨001⟩ and adhered to each other crystallographically due to the loss of the mutual support in the unique synthesis, forming a tetragonal structure (space group <i>I</i>4₁/<i>amd</i>). The unit cell parameter was changed from <i>a</i> = 168 to ∼240 nm with <i>c</i> = √2<i>a</i> by tuning the synthesis condition and the wide edge of the macropore size was ∼100 to ∼140 nm. Electron crystallography was applied to solve the structure. Our studies demonstrate electron crystallography is the only way to solve the complex structure in such length scale. Besides, this structure exhibits structural color that ranged from violet to blue from different directions with the bandgap in the visible wavelength range, which is attributed to the structural feature of the adhered frameworks that have lower symmetry. Calculations demonstrate that this is a new type of photonic structure. A complete gap can be obtained with a minimum dielectric contrast of 4.6, which is inferior to the single diamond but superior to the single gyroid structure. A multilayer core–shell bicontinuous microphase templating route was speculated for the formation of the unique macroporous structure, in which common solvent tetrahydrofuran in hydrophobic shell and selective solvent water in hydrophilic core to enlarge each microphase sizes

(A) Transgenic strategy for expression of ChR2 (H134R) in GABAergic neurons. (B) A sagittal schematic representation of the brain region used in this study (left). Black area: LC region; Green contours: GABAergic interneurons. (C) The coronal section of a mouse brain slice containing LC region (left). High magnification image showing that a group of YFP fluorescence-positive GABAergic neurons is located immediately to LC. (D) Left schematics showing a brain slice with patch clamp electrode on LC neuron. The dmLC area labeled with green color for light excitation. (E) Representative photomicrographs of transverse pontine sections containing the LC neurons from a brain slice of transgenic mice. Transverse pontine section presented was obtained from transgenic mice (E). The framed areas showed the typical large LC neurons, distributed along the lateral floor of 4^th ventricle. The same section was incubated with Anti-DBH (conjugated with biotin) antibody, followed by Alexa Fluor

<p>LC, locus coeruleus; B, Barrington’s nucleus; dmLC, dorsomedial locus coeruleus; DTN, dorsal tegmental nucleus; LDT, dorsolateral tegmental nucleus, MeV, mesencephalic trigeminal tract nucleus. The location of each region was manually annotated using the Allen brain atlas representations of the mouse coronal section containing LC region (Bregma: -5.655mm) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146470#pone.0146470.ref017" target="_blank">17</a>].</p

Summary of critical SecA domains for structure and function with lipids.

<p>Summary of critical SecA domains for structure and function with lipids.</p

Optostimulation evoked lateral inhibition among GABAergic neurons.

<p>(A) Voltage clamp recording for light evoked inward currents. The holding potential were stepped from -20 to -70 mV. (B) Enlarged traces from holding potentials at -30 (upper) and -70 mV (lower).</p

The electrophysiology properties of the GABAergic neurons in dmLC area.

<p>(A) Whole-cell clamp recording of the GABAergic neurons in dmLC area. The membrane potential was held at 0 mV and stepped from -180 to 20 mV every 1s. (B) I-V curve of GABAergic neurons in dmLC area. (C) Spike frequency adaptation (SFA) properties of GABAergic neurons in dmLC area, accompanied with depolarization. (D) The firing frequency in peak state (Fp) and in the steady state (Fs) was compared and represented in bar graph. Data are presented as means ± SE (n = 18 cells, six animals). (E) The ratio of Fp/Fs were calculated following the current injection steps (from 10–90 pA). (F) The optical responses to 10 ms 470 nm optostimulation in both current-clamp recording. Black trace, a typical individual trace. (G) Voltage-clamp recording from GABAergic neuron in dmLC, where strong inward photocurrent are evoked by 5 (top) and 50 ms (bottom) light pulses. (H) <i>I-V</i> relationship of light-evoked current in GABAergic neuron.</p

Response of LC neurons to the inhibitory postsynaptic potentials (IPSPs) that were evoked by optostimulation of these dmLC GABAergic neurons.

<p>(A) LC neuronal spontaneous firing activity was reset by light-evoked IPSP (top). The effect of light-evoked IPSPs on LC neuron firing activity was measured in instantaneous firing frequency histogram (bottom) Light pulse: 10 ms. (B) Light-evoked IPSPs are better seen at extended scale of A. (C) The effect of light-evoked IPSPs on inter-spike interval (ISI) were represented by bar graph. (D) The light-evoked IPSP is strongly influenced by membrane potential of LC neuron. (E) The equilibrium potential for IPSP close to -60 mV. (F) A GABA_A receptor antagonist, 20 μM bicuculline completely abolished light-evoked IPSPs of LC neuron. Data are presented as means ± SE (n = 15 cells, three animals).</p

Function of SecA-liposomes with SecYEG/SecDF-YajC.

<p>(A) SecA-domain-SecYEG channel activity. (B) SecA-domain with SecYEG-SecDF-YajC Channel activity. (C) Translocation activity in membranes: 1 μg SecA/fragment and 4.5 μg urea treated OmpA-depleted 773 membranes or 120 μg liposomes were used. The translocation in 100 μL were conducted under 37C for 30 min and analyzed as in Experimental procedures.</p

Postsynaptic responses to GABAergic neurons in LC region.

<p>Same Cl^<i>‒</i> concentrations were applied to the internal peptide and bath solutions for whole cell voltage clamp. The GABA_A-mediated inward currents were recorded at a holding potential of –70 mV. All glutamate and the glycine receptors were pharmacologically blocked by application of 10 μM CNQX, 10 μM APV, and 1 μM STY to bath solution. (A) The IPSCs in LC neurons produced by applying 10 ms 470 nm light to the dmLC GABAergic neurons (upper). Lower panel displays enlarged IPSCs from upper trace. The averaged trace (black) was carried out within 50 individual traces (gray). Perfusion with 20 μM bicuculine (B) or 1 μM tetrodotoxin (TTX) (C) eliminated the IPSCs. The rise time (D), the decay time (E) and the amplitudes (F) of light evoked (eIPSCs) and spontaneous IPSCs (sIPSCs) were compared in bar graph. (G) Representative recording of light-evoked action potentials in a presynaptic GABAergic neuron aligned to light-evoked IPSCs in a LC neuron (black trace, average of 30 individual traces). Histograms of action potentials (H) and IPSCs (I) latencies. (J) Twenty consecutive traces of IPSCs elicited by pair light-stimulation of GABAergic neurons. (K) The multiple light-stimulation evoked IPSCs in a LC neuron.</p