ATT for Indonesia and Seven National Parks.

<p>Note: This figure shows the ATT estimates based on the nearest neighbor covariate matching with replacement for all seven parks together as well as individually for each park. The percentage numbers indicate the ATT estimate in hectares divided by the total area of each parcel (i.e. 900 hectares). The error bars represent the standard errors for the ATT estimates.</p

Heterogeneous Impacts of Covariates on Forest Cover Change for Kerinci Seblat National Park.

<p>Note: This figure maps the coefficient estimates for the marginal effect of distance to city (Panel A), distance to road (Panel B) and slope (Panel C) for Kerinci Seblat National Park based on CPARLWR.</p

Average CPARLWR Treatment Effects for Indonesia and Seven National Parks.

<p>Note: This figure shows the average CPARLWR coefficient estimates for the treatment dummy for all seven parks together as well as individually for each park. The percentage numbers indicate the overall percentage gain or loss in forest cover based on these average coefficient estimates. The error bars represent the minimum and maximum coefficient estimates.</p

Heterogeneity in Marginal Effect of Protection across the Seven National Parks.

<p>Note: This figure maps the coefficient estimates in percentage for the effect of treatment on forest cover change based on the CPARLWR for each parcel with the seven national parks.</p

National Parks in Indonesia established after 1999.

<p>National Parks in Indonesia established after 1999.</p

Heterogeneity in Marginal Effect of Protection within Kerinci Seblat National Park.

<p>Note: This figures maps the coefficient estimates for the marginal effect of protection on the percentage change in forest cover across Kerinci Seblat National Park based on CPARLWR.</p

Islet vessel area increases in T2DM.

<p><b>(A)</b> Representative images of pancreatic sections from non-diabetic controls and patients with T2D, immune-labelled for CD31 (red) and insulin (green). <b>(B)</b> Graphs show ratio of vessel area to islet area (control: n = 6; T2D: n = 10). <b>(C)</b> Plot shows no correlation of vessel density with BMI. <b>(D-H)</b> qPCR analysis of Ang-2, Tie-1, Tie-2, CD-31 from isolated mouse islets from C57BL/6 WT mice kept on normal diet (ND) or high-fat high-sucrose diet (HFD) for <b>(D)</b> 8 weeks (n = 4/group), <b>(E)</b> 16 weeks (n = 9/group) and <b>(F)</b> 24 weeks (n = 7/group), <b>(G) of</b> eNOS and <b>(H) of</b> ICAM-1. <b>(I)</b> qPCR analysis of Ang-1, Ang-2, Tie-1 and Tie-2 of isolated islets from non-diabetic (control, n = 8) and from patients with T2D (n = 7). *p<0.05, HFD vs ND or T2D vs. control</p

Ang/Tie expression in isolated islets correlates with changes in vessel area.

<p>Isolated WT mouse and human islets were cultured for 3 days in control condition (11.1 mM glucose for mouse or 5.5 mM for human) or treated with diabetic conditions of 22.2 mM glucose + 0.5 mM palmitic acid or mixture of cytokines: 2 ng/mL IL-1β, 1000 U/ml IFN-ɣ and TNF-α (cyto). <b>(A,D)</b> GSIS is shown by the stimulatory index assessed by 16.7/2.8 mM glucose stimulation. <b>(B,C,E,F)</b> Graph shows ratio of vessel area to islet area for mouse <b>(B,C)</b> and human <b>(E,F)</b> islets, fixed and immune-labelled for vessel (CD-31,red) and islet (insulin, green). <b>(G-L)</b> qPCR analysis of treated mouse and human islets for mouse CD-31 <b>(G,J)</b>, Ang-1,-2 <b>(H,K)</b>, Tie-1,-2 <b>(I,L)</b>. All genes have been normalized to PPIA or 18s as housekeeping control. *p<0.05, treated vs. control 11.1 mM (mouse) or 5.5 mM (human). <b>(M)</b> Representative western blot from treated human islet lysates (left panel) and densitometric analyses of Ang-2 (right panel). Data are means +/-SE from 3–5 independent experiments from 3–5 different organ donors (human islets) or 3–5 independent mouse islet isolations.</p

Islet hypervascularization in T2D and effects of Ang-2 overexpression.

<p>A healthy islet is surrounded by intact capillaries, maintained by the Ang/Tie system and extracellular matrix supporting the function and survival of the islet. An increased insulin demand leads to more islet blood flow, β-cell mass and vascular expansion and consequent compensation. A transient Ang-2 upregulation promotes angiogenesis, leading islet endothelium to a non-quiescent state inhibiting Tie-2 signaling. Towards human T2D progression, β-cell failure and apoptosis occurs together with increased islet and endothelial inflammation and islet hypervascularization. Ang-2 overexpression on the other hand prevents β-cell mass and vascular expansion in response to HFD with persistent islet and endothelial inflammation.</p

Ang-2 over-expression impairs islet function but protects from cytokine treatment in isolated islets.

<p>Isolated islets from RIP-rtTA;tet-O-Ang-2 (Ang2-rtTA) and RIP-rtTA control (rtTA) mice were cultured for 3 days in presence of 10 μg/ml doxycycline to achieve Ang-2 overexpression. Mouse or human islets were cultured in 11.1 (mouse) or 5.5 mM glucose (human) or treated with diabetic conditions of 22.2 mM glucose + 0.5mM palmitic acid or mixture of cytokines: 2 ng/mL IL-1β, 1000 U/ml IFN-ɣ and TNF-α (cyto). <b>(A)</b> Western blot from treated mouse islets shows Ang-2 overexpression in islets by myc-Ang-2. <b>(B)</b> GSIS is shown by the stimulatory index assessed by 16.7/2.8 mM glucose stimulation and normalized to control. <b>(C,D)</b> Treated mouse islets fixed post-GSIS and apoptotic cells detected by double staining for TUNEL and insulin. Representative images from different treatments. <b>(E,F)</b> qPCR analysis for CD31 <b>(E)</b> and ICAM <b>(F)</b> from mouse islets overexpressing Ang-2. <b>(G,H)</b> Representative western blots (upper panel) and densitometric analyses of proteins (lower panels) showing myc-Ang-2, ICAM-1, cleaved caspase 3 and actin/tubulin as housekeeping control, in human islets overexpressing Ang-2 by Ad-Ang-2 or control Ad-GFP <b>(G;</b> MOI = 50) or treated with 100 nM Tie-2 inhibitor for 72h (<b>H)</b>. Data are means +/-SE from 3–5 independent experiments from 3–5 different organ donors (human islets) or 3–5 independent mouse islet isolations. *p<0.05, treated vs. 11.1 mM glucose control, #p<0.05, Ang2-rtTA vs. rtTA.</p