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Uncontrolled macrophage activation is now considered to be a critical event in the pathogenesis of chronic inflammatory diseases such as atherosclerosis, multiple sclerosis, and chronic venous leg ulcers. However, it is still unclear which environmental cues induce persistent activation of macrophages in vivo and how macrophage-derived effector molecules maintain chronic inflammation and affect resident fibroblasts essential for tissue homeostasis and repair. We used a complementary approach studying human subjects with chronic venous leg ulcers, a model disease for macrophage-driven chronic inflammation, while establishing a mouse model closely reflecting its pathogenesis. Here, we have shown that iron overloading of macrophages--as was found to occur in human chronic venous leg ulcers and the mouse model--induced a macrophage population in situ with an unrestrained proinflammatory M1 activation state. Via enhanced TNF-α and hydroxyl radical release, this macrophage population perpetuated inflammation and induced a p16(INK4a)-dependent senescence program in resident fibroblasts, eventually leading to impaired wound healing. This study provides insight into the role of what we believe to be a previously undescribed iron-induced macrophage population in vivo. Targeting this population may hold promise for the development of novel therapies for chronic inflammatory diseases such as chronic venous leg ulcers.

Innovative approaches could enhance scientific insights into how climate change affects mountain ecosystems and livelihoods and enrich climate action. Using an inter- and transdisciplinary approach in a remote tropical dry forest region of the Andes in southern Ecuador, this article combines local knowledge about climate change and adaptation, based on perceptions and experiences, with quantitative climate measurements. Our theoretical framework is based on the concept of vulnerability and sustainable livelihoods perspectives. Methodologically, we draw on the Participatory Rural Appraisal approach. Participatory workshops and qualitative interviews were carried out in the canton of Macará between 2015 and 2017. Local and regional climate data series were analyzed for climate trends and extreme events. Our study improves understanding of the social and physical dimension of climate change. Especially in mountain areas, differing scales of climate data must be considered to capture local climate conditions and changes. Thus, local knowledge could make a major contribution to selecting representative climate datasets, estimating local impacts of climate change, and developing adaptation policies.

The incidence of cutaneous melanoma is rapidly escalating in many developed countries, particularly among the aging populations. Extensive evidence shows epigenetic changes have a strong correlation between cutaneous malignant melanoma and exposure to sunlight, particularly its ultraviolet (UV) components, in the aging skin. While significant research has been conducted on aging and its associated S enescence- A ssociated S ecretory P henotype (SASP) contributed by senescent fibroblasts in old individuals, less is known about the role of UVA radiation in such SASP melanoma microenvironment, its effects on gene function, and the underlying mechanisms following U VA-induced D NA D amage (UDD). It is established that UVA radiation induces D ouble- S trand B reaks (DSBs) in DNA and activates checkpoint kinase 2 (Chk2) at these breaks, leading to p53-mediated apoptosis. But p53, beyond its role in regulating cell fate, its mutated form is also involved in the transcriptional regulation of potent pro-survival pathways by actively transcribing genes that counteract apoptosis in genetically abnormal melanoma cells. However, the molecular mechanisms that govern the fine balance between cell death and survival mediated by the p53 transcription factor under UVA exposure remain largely elusive. In this study, we report for the first time that UVA induces global DNA methylation as a compensatory mechanism in response to U VA-induced D NA D amage (UDD) in melanoma and melanocyte cells. However, melanoma cells in the vicinity of senescent fibroblasts under genotoxic stress are epigenetically altered by the paracrine secretion of interleukin-6 (IL-6) from senescent fibroblasts, which upregulates the anti-apoptotic gene GDF-15 as well as the DNA damage repair system. This upregulation occurs via hypomethylation of GDF-15 orphan CpG island promoters, followed by its active gene transcription of GDF-15 via both WT p53 Ser392 and Mutated p53 N239Y transcription factors, thereby enhancing pro-survival mechanisms that contribute to melanoma progression.

In the search to develop tools that are able to modify surfaces on the nanometre scale, the use of heavy ions with energies of several tens of MeV is becoming more attractive. Low-energy ions are mostly stopped by nuclei, which causes the energy to be dissipated over a large volume. In the high-energy regime, however, the ions are stopped by electronic excitations 1 , 2 , 3 , and the extremely local (∼10 nm 3 ) nature of the energy deposition leads to the creation of nanosized ‘hillocks’ or nanodots under normal incidence 4 , 5 , 6 . Usually, each nanodot results from the impact of a single ion, and the dots are randomly distributed. Here we demonstrate that multiple, equally spaced dots, each separated by a few tens of nanometres, can be created if a single high-energy xenon ion strikes the surface at a grazing angle. By varying this angle, the number of dots, as well as their spacing, can be controlled.

Stem diameter increments of the broadleaved deciduous tree species Tabebuia chrysantha were measured with high-resolution dendrometers in a tropical lower montane forest and in a dry forest in southern Ecuador, the latter showing a distinct dry season. Those analyses were complemented by wood anatomical studies on regularly collected microcores to determine the season of active cambial growth and the time of formation of annual growth boundaries. The length of the cambial active period varied between 3 and 7 months at the tropical lower montane forest and 2 and 4 months in the dry forest, respectively. During dry days, amplitudes of daily stem diameter variations correlated with vapour pressure deficit. During October and November, inter-annual climate variations may lead to dry and sunny conditions in the tropical lower montane forest, causing water deficit and stem diameter shrinkage in T. chrysantha. The results of the climate-growth analysis show a positive relationship between tree growth and rainfall as well as vapour pressure deficit in certain periods of the year, indicating that rainfall plays a major role for tree growth.

Psoriasis is a chronic skin disorder of unsolved pathogenesis affecting skin in 2–3% of the general population. Research into the pathogenesis of psoriasis has profited from suitable animal models. Previously, we reported on the CD18 hypomorphic (CD18hypo) PL/J mouse model clinically resembling human psoriasis, which is characterized by reduced expression of the common chain of β2-integrins (CD11/CD18) to only 2–16% of wild-type levels. Aside from common clinical and pathophysiological features shared with human psoriasis, the psoriasiform skin disease in CD18hypo PL/J mice also depends on the presence of CD4+ T-cells. This review focuses on the role of activated macrophages in the pathogenesis of CD18hypo T-cell-mediated mouse model of psoriasis, and extends our understanding in unrestrained pathogenic T-cells whose activation may be crucial for the recruitment and activation of macrophages within skin. The findings in the CD18hypo PL/J model are discussed in the context of current literatures of human and other autoimmune disorders.

We studied the mechanisms underlying the severely impaired wound healing associated with human leukocyte‐adhesion deficiency syndrome‐1 (LAD1) using a murine disease model. In CD18 −/− mice, healing of full‐thickness wounds was severely delayed during granulation‐tissue contraction, a phase where myofibroblasts play a major role. Interestingly, expression levels of myofibroblast markers α‐smooth muscle actin and ED‐A fibronectin were substantially reduced in wounds of CD18 −/− mice, suggesting an impaired myofibroblast differentiation. TGF‐β signalling was clearly involved since TGF‐β 1 and TGF‐β receptor type‐II protein levels were decreased, while TGF‐β 1 injections into wound margins fully re‐established wound closure. Since, in CD18 −/− mice, defective migration leads to a severe reduction of neutrophils in wounds, infiltrating macrophages might not phagocytose apoptotic CD18 −/− neutrophils. Macrophages would thus be lacking their main stimulus to secrete TGF‐β 1 . Indeed, in neutrophil–macrophage cocultures, lack of CD18 on either cell type leads to dramatically reduced TGF‐β 1 release by macrophages due to defective adhesion to, and subsequent impaired phagocytic clearance of, neutrophils. Our data demonstrates that the paracrine secretion of growth factors is essential for cellular differentiation in wound healing.

The Andes of Ecuador are one of the world's hotspots of vascular plants. These hotspot characteristics apply particularly to the divergence zone of the study site situated in the Cordillera Real near the Estación Científica San Francisco (ECSF) in the northernmost part of Podocarpus National Park (3°58′S; 79°04′W). Here, family and species numbers vary considerably between primary mountain forest stands and anthropogenic sites at similar altitudes. The highest family as well as species numbers (95 and 491, respectively, at 2000–2100 m; 68 and 296 at 2400–2500 m, with sample areas of 400 m2 each) document the extraordinarily high plant diversity of primary mountain forest stands. Comparatively, on anthropogenic sites, the analogous numbers are much smaller, with only 64 families/186 species at the lower altitudinal level and 54 families/155 species at the higher altitudinal level.

Key message Striking hydro-climatic differences of 2 years (wet; dry) dramatically control the increment pattern of L. huasango in varying extent , even causing a “growth collapse” during the La Niña drought 2010/2011. We present the first multi-year long time series of local climate data in the seasonally dry tropical forest in Southern Ecuador and related growth dynamics of Loxopterygium huasango , a deciduous tree species. Local climate was investigated by installing an automatically weather station in 2007 and the daily tree growth variability was measured with high-resolution point dendrometers. The climatic impact on growth behaviour was evaluated. Hydro-climatic variables, like precipitation and relative humidity, were the most important factors for controlling tree growth. Changes in rainwater input affected radial increment rates and daily amplitudes of stem diameter variations within the study period from 2009 to 2013. El Niño Southern Oscillation (ENSO) related variations of tropical Pacific Ocean sea surface temperatures influenced the trees’ increment rates. Average radial increments showed high inter-annual (up to 7.89 mm) and inter-individual (up to 3.88 mm) variations. Daily amplitudes of stem diameter variations differed strongly between the two extreme years 2009 (wet) and 2011 (dry). Contrary to 2009, the La Niña drought in 2011 caused a rapid reduction of the daily amplitudes, indicating a total cessation (‘growth collapse’) of stem increment under ENSO-related drought conditions and demonstrating the high impact of climatic extreme events on carbon sequestration of the dry tropical forest ecosystem.

The CD18 hypomorphic (CD18hypo) PL/J mouse model clinically resembling human psoriasis is characterized by reduced expression of the common chain of beta2 integrins (CD11/CD18) to only 2-16% of WT levels. Previously we found that this chronic psoriasiform skin inflammation also depends on the presence of CD4+ T cells. Herein we investigated the role of macrophages in this CD18hypo mouse model. Activated macrophages were significantly increased in lesional skin as well as in inflamed skin draining lymph nodes (DLNs) of affected CD18hypo mice and were identified as being an important source of TNF-alpha in vivo. Both depletion of macrophages and neutralization of TNF-alpha resulted in a significant alleviation of psoriasiform skin inflammation. As monocyte chemotactic protein 1 was enhanced in lesional skin of affected CD18hypo mice, we intradermally injected recombinant murine monocyte chemotactic protein-1 (rJE/MCP-1) alone or in combination with rTNF-alpha into the skin of healthy CD18hypo mice. Only simultaneous injection of rJE/MCP-1 and rTNF-alpha, but neither substance alone, resulted in the induction of psoriasiform skin inflammation around the injection sites with recruitment and activation of macrophages. Collectively, our data suggest that maintenance of psoriasiform skin inflammation critically depends on efficient recruitment and activation of macrophages with sufficient release of TNF-alpha.