Endothelin‐1 is a transcriptional target of p53 in epidermal keratinocytes and regulates ultraviolet‐induced melanocyte homeostasis

Keratinocytes contribute to melanocyte activity by influencing their microenvironment, in part, through secretion of paracrine factors. Here, we discovered that p53 directly regulates Edn1 expression in epidermal keratinocytes and controls UV‐induced melanocyte homeostasis. Selective ablation of endothelin‐1 (EDN1) in murine epidermis (EDN1^ep?/?) does not alter melanocyte homeostasis in newborn skin but decreases dermal melanocytes in adult skin. Results showed that keratinocytic EDN1 in a non‐cell autonomous manner controls melanocyte proliferation, migration, DNA damage, and apoptosis after ultraviolet B (UVB) irradiation. Expression of other keratinocyte‐derived paracrine factors did not compensate for the loss of EDN1. Topical treatment with EDN1 receptor (EDNRB) antagonist BQ788 abrogated UV‐induced melanocyte activation and recapitulated the phenotype seen in EDN1^ep?/? mice. Altogether, the present studies establish an essential role of EDN1 in epidermal keratinocytes to mediate UV‐induced melanocyte homeostasis in vivo.     

‘Same procedure as last year?‘ Repeatedly tracked swifts show individual consistency in migration pattern in successive years

Individual migration pattern during non‐breeding season is still a black box in many migratory birds. However, knowledge on both individual level and population level in migration and overwintering is fundamental to understand the life cycle of these birds and the constraints affecting them. We showed in a highly aerial migrant, the common swift Apus apus, that repeatedly tracked birds breeding at one site in Germany used the same individual‐specific migration routes and wintering areas in subsequent years. In contrast, different individuals from the same breeding colony showed diverse movement patterns during non‐breeding season suggesting that several suitable areas for overwintering coexist. We found lower variation in timing of autumn and spring migration within than between individuals. Our findings provide first indication of individual consistency but between‐individual variation in migration pattern in a small non‐passerine bird revealed by geolocators. This supports that swifts have diverse but individual‐specific ‘step‐by‐step’ migration patterns revealing high flexibility through individual strategies.     

FK506 positively regulates the migratory potential of melanocyte‐derived cells by enhancing syndecan‐2 expression

Although topical tacrolimus (FK506) is known to promote repigmentation by increasing the pigmentation and migration of melanocytes, the mechanism through which FK506 regulates cell migration remains unclear. Here, we report that FK506 treatment enhanced cell spreading on laminin‐332 and increased migration in both melanocytes and melanoma cells. Interestingly, FK506 also increased the expression of syndecan‐2, a transmembrane heparan sulfate proteoglycan through c‐jun terminal kinase activation. Moreover, siRNA‐mediated reduction of syndecan‐2 expression decreased FK506‐mediated cell spreading and migration in melanoma cells and decreased focal adhesion kinase phosphorylation in both melanocytes and melanoma cells. Consistent with these effects on syndecan‐2 expression, FK506 enhanced the membrane and melanosome localizations of PKCβII, a regulator of tyrosinase activity. This suggests that FK506 may play a dual regulatory role by affecting both melanogenesis and migration in melanocyte‐derived cells. Interestingly, however, FK506 failed to show any synergistic effect on the migration of UVB‐treated melanocyte‐derived cells. Taken together, these data indicate that FK506 regulates cell migration by enhancing syndecan‐2 expression, further suggesting that syndecan‐2 could be a potential target for the treatment of patients with vitiligo.     

Breeding latitude leads to different temporal but not spatial organization of the annual cycle in a long‐distance migrant

The temporal and spatial organization of the annual cycle according to local conditions is of crucial importance for individuals’ fitness. Moreover, which sites and when particular sites are used can have profound consequences especially for migratory animals, because the two factors shape interactions within and between populations, as well as between animal and the environment. Here, we compare spatial and temporal patterns of two latitudinally separated breeding populations of a trans‐Equatorial passerine migrant, the collared flycatcher Ficedula albicollis, throughout the annual cycle. We found that migration routes and non‐breeding residency areas of the two populations largely overlapped. Due to climatic constraints, however, the onset of breeding in the northern population was approximately two weeks later than that of the southern population. We demonstrate that this temporal offset between the populations carries‐over from breeding to the entire annual cycle. The northern population was consistently later in timing of all subsequent annual events – autumn migration, non‐breeding residence period, spring migration and the following breeding. Such year‐round spatiotemporal patterns suggest that annual schedules are endogenously controlled with breeding latitude as the decisive element pre‐determining the timing of annual events in our study populations.     

Quantifying full phenological event distributions reveals simultaneous advances,temporal stability and delays in spring and autumn migration timing in long‐distance migratory birds

Phenological changes in key seasonally expressed life‐history traits occurring across periods of climatic and environmental change can cause temporal mismatches between interacting species, and thereby impact population and community dynamics. However, studies quantifying long‐term phenological changes have commonly only measured variation occurring in spring, measured as the first or mean dates on which focal traits or events were observed. Few studies have considered seasonally paired events spanning spring and autumn or tested the key assumption that single convenient metrics accurately capture entire event distributions. We used 60 years (1955–2014) of daily bird migration census data from Fair Isle, Scotland, to comprehensively quantify the degree to which the full distributions of spring and autumn migration timing of 13 species of long‐distance migratory bird changed across a period of substantial climatic and environmental change. In most species, mean spring and autumn migration dates changed little. However, the early migration phase (≤10th percentile date) commonly got earlier, while the late migration phase (≥90th percentile date) commonly got later. Consequently, species' total migration durations typically lengthened across years. Spring and autumn migration phenologies were not consistently correlated within or between years within species and hence were not tightly coupled. Furthermore, different metrics quantifying different aspects of migration phenology within seasons were not strongly cross‐correlated, meaning that no single metric adequately described the full pattern of phenological change. These analyses therefore reveal complex patterns of simultaneous advancement, temporal stability and delay in spring and autumn migration phenologies, altering species' life‐history structures. Additionally, they demonstrate that this complexity is only revealed if multiple metrics encompassing entire seasonal event distributions, rather than single metrics, are used to quantify phenological change. Existing evidence of long‐term phenological changes detected using only one or two metrics should consequently be interpreted cautiously because divergent changes occurring simultaneously could potentially have remained undetected.     

EDNRB/EDN3 and Hirschsprung Disease Type II

The study of vertebrate pigmentary anomalies has greatly improved our understanding of melanocyte biology. One such disorder, Waardenburg syndrome (WS), is a mendelian trait characterized by hypopigmentation and sensorineural deafness. It is commonly subdivided into four types (WS1–4), defined by the presence or absence of additional symptoms. WS type 4 (WS4), or Shah‐Waardenburg syndrome, is also known as Hirschsprung disease Type II (HSCR II) and is characterized by an absence of epidermal melanocytes and enteric ganglia. Mutations in the genes encoding the endothelin type‐B receptor (EDNRB) and its physiological ligand endothelin 3 (EDN3) are now known to account for the majority of HSCR II patients. Null mutations in the mouse genes Ednrb and Edn3 have identified a key role for this pathway in the normal development of melanocytes and other neural crest‐derived lineages. The pleiotropic effects of genes in this pathway, on melanocyte and enteric neuron development, have been clarified by the embryologic identification of their common neural crest (NC) ancestry. EDNRB and EDN3 are transiently expressed in crest‐derived melanoblast and neuroblast precursors, and in the surrounding mesenchymal cells, respectively. The influence of EDNRB‐mediated signaling on the emigration, migration, proliferation, and differentiation of melanocyte and enteric neuron precursors, in vivo and in vitro has recently been the subject of great scrutiny. A major emergent theme is that EDN3‐induced signaling prevents the premature differentiation of melanocyte and enteric nervous system precursors and is essential between 10 and 12.5 days post‐coitum. We review the present understanding of pigment cell development in the context of EDNRB/EDN3 – a receptor‐mediated pathway with pleiotropic effects.     

First histopathological and immunophenotypic analysis of early dynamic events in a patient with segmental vitiligo associated with halo nevi

Segmental vitiligo is often ascribed to the neurogenic theory of melanocyte destruction, although data about the initial etiopathological events are scarce. Clinical, histopathological and T-cell phenotypic analyses were performed during the early onset of a segmental vitiligo lesion in a patient with associated halo nevi. Histopathological analysis revealed a lymphocytic infiltrate, mainly composed of CD8⁺ T-cells and some CD4⁺ T-cells around the dermo–epidermal junction. Flow cytometry analysis of resident T-cells revealed a clear enrichment of pro-inflammatory IFN-γ producing CD8⁺ T-cells in lesional skin compared to the non-lesional skin. Using human leukocyte antigen-peptide tetramers (MART-1, tyrosinase, gp100), increased numbers of T cells, recognizing melanocyte antigens were found in segmental vitiligo lesional skin, as compared with the non-lesional skin and the blood. Our findings indicate that a CD8⁺ melanocyte specific T cell-mediated immune response, as observed in generalized vitiligo, also plays a role in segmental vitiligo with associated halo nevi.     

Across a migratory divide: divergent migration directions and non‐breeding grounds of Eurasian reed warblers revealed by geolocators and stable isotopes

Migratory divides represent narrow zones of overlap between parapatric populations with distinct migration directions and, consequently, expected divergent non‐breeding distributions. The composition of the mixed population at a migratory divide and the corresponding non‐breeding ranges remain, however, unknown for many Palaearctic‐African migrants. Here, we used light‐level geolocation to track migration direction and non‐breeding grounds of Eurasian reed warblers Acrocephalus scirpaceus from three breeding populations across the species’ migratory divide. Moreover, by using feathers grown at non‐breeding grounds, we quantified stable isotope composition for individuals with known southwestern (SW) and southeastern (SE) migration directions. On a larger sample per population, we then assessed the proportions of SW‐ and SE‐migrating phenotypes in each of the three populations. All tracked reed warblers from Germany and two thirds of the birds tagged from the Czech population headed initially SW. Nevertheless, about one third of the birds from the Czech site migrated towards SE. No tracking data have been obtained for the Bulgarian population. The initial migration direction determined by geolocators was a strong predictor of the non‐breeding region, with SW migrants staying in west Africa and SE migrants in central Africa. Feather δ³⁴S and δ¹⁵N values confirmed the predominance of SW migrants in the German population, the co‐occurrence of SW and SE migrants in the Czech population, and indicated a high (72%) proportion of SE migrants in the Bulgarian population. Thus, the combined approach of geolocator tracking and stable isotopic assignments provided clear evidence for the existence of a migratory divide in the southeast of central Europe and predicted non‐breeding range in central and central‐eastern Africa for the eastern population.     

CXCR7 mediates SDF1‐induced melanocyte migration

Melanoblasts are derived from the neural crest and migrate to the dermal/epidermal border of skin and hair bulges. Although melanoblast migration during embryogenesis has been well investigated, there are only a few reports regarding the migration of mature melanocytes. Here, we demonstrate that a chemokine, stromal‐derived factor‐1 (SDF1, also known as CXCL12), and one of its receptor CXCR7 regulate normal human epidermal melanocyte (NHEM) migration. We found that SDF1 induces the directional migration of NHEMs. Interestingly, although both CXCR4 and CXCR7 are expressed in NHEMs, blockade of CXCR4 using a CXCR4‐specific neutralizing antibody did not exert any influence on the SDF1‐induced migration of NHEMs, whereas blockade of CXCR7 using a CXCR7‐specific neutralizing antibody did influence migration. Furthermore, SDF1‐induced NHEMs migration exhibited the early hallmark events of CXCR7 signaling associated with MAP kinase activation. It is known that the phosphorylation of ERK through CXCR7 signaling is mediated by β‐arrestins. The treatment of NHEMs with SDF1 resulted in the phosphorylation of ERK in a β‐arrestin 2‐dependent manner. These results suggest that melanocytes may have a unique mechanism of migration via SDF1/CXCR7 signaling that is different from that of other cell types.     

Novel expression patterns of Pax3/Pax7 in early trunk neural crest and its melanocyte and non‐melanocyte lineages in amniote embryos

Neural crest cells are considered a key vertebrate feature that is studied intensively because of their relevance to development and evolution. Here we report the expression of Pax7 in the dorsal non‐neural ectoderm and in the trunk neural crest of the early chick embryo. Pax7 is expressed in the trunk neural crest migrating along the ventral and dorsolateral routes. Pax7 is first downregulated in the neural crest‐derived neuronal precursors, secondly in the glial, and finally in the melanocyte precursors. Conserved developmental expression in the melanocyte lineage of both Pax3 and Pax7 was evidenced in chick and quail, but only Pax3 in mouse and rat.     

The contribution made by cells from a single somite to tissues within a body segment and assessment of their integration with similar cells from adjacent segments

Somites represent the first visual evidence of segmentation in the developing vertebrate embryo and it is becoming clear that this segmental pattern of the somites is used in the initial stages of development of other segmented systems such as the peripheral nervous system. However, it is not known whether the somites continue to contribute to the maintenance of the segmental pattern after the dispersal of the somitic cells. In particular, the extent to which cells from a single somite contribute to all of the tissues of a single body segment and the extent to which they mix with cells from adjacent segments during their migration is not known. In this study, we have replaced single somites in the future cervical region of 2-day-old chick embryos with equivalent, similarly staged quail somites. The chimerae were then allowed to develop for a further 6 days when they were killed. The cervical region was dissected and serially sectioned. The sections were stained with the Feulgen reaction for DNA to differentiate between the chick and quail cells. The results showed that the cells from a single somite remained as a clearly delimited group throughout their migration. Furthermore, the sclerotome, dermatome and myotome portions from the single somites could always be recognised as being separate from similar cells from other somites. The somitic cells formed all of the tissues within a body segment excluding the epidermis, notochord and neural tissue. There was very little mixing of the somitic cells between adjacent segments. The segmental pattern of the somites is therefore maintained during the migration of the somitic cells and this might be fundamental to a mechanism whereby the segmentation of structures, such as the peripheral nervous system, is also maintained during development.     

Vegetation dynamics and avian seasonal migration: clues from remotely sensed vegetation indices and ecological niche modelling

Aim Regional movements of tropical birds are among the least understood patterns of migration, generally assumed to be related to seasonality of vegetation and food resources. We used readily available remotely sensed data to analyse this relationship in the three‐wattled bellbird (Procnias tricarunculatus), an IUCN Vulnerable canopy frugivorous bird that undergoes localized altitudinal and latitudinal movements between several non‐breeding and breeding ranges. Location Central America. Methods We generated ecological niche models (GARP and Maxent) based on remotely sensed vegetation indices (enhanced vegetation index, EVI; red index, RI; and normalized difference water index, NDWI) that were used as proxies for canopy characteristics and phenological changes between seasons. The variation in EVI was also analysed in relation to known bellbird seasonal migration patterns. Results Remotely sensed summaries of intra‐annual vegetation variation could not explain known movement patterns of bellbirds breeding in Monteverde Cloud Forest Reserve, Costa Rica. The ecological niche modelling (ENM) framework used for exploring potential movement patterns of another population of bellbirds, observed in March 2004 in Corcovado National Park, Costa Rica, showed that the Atlantic and Pacific lowlands are suitable for the bellbirds year‐round, while middle elevations, where breeding may occur, have limited suitability. Main conclusions Our findings suggest that: (1) the Corcovado population tracks similar environmental conditions during the non‐breeding season; (2) migration to middle elevation breeding sites might be related to factors other than vegetation seasonality or breeding might not be restricted to these elevation ranges; and (3) the lowlands comprising most of the suitable areas for bellbirds are where anthropogenic pressure is highest, so conservation status should consider this threat, and conservation planning should emphasize these areas.     

Cross‐continental migratory connectivity and spatiotemporal migratory patterns in the great reed warbler

Migratory connectivity describes to which degree different breeding populations have distinct (non‐overlapping) non‐breeding sites. Uncovering the level of migratory connectivity is crucial for effective conservation actions and for understanding of the evolution of local adaptations and migratory routes. Here we investigate migration patterns in a passerine bird, the great reed warbler Acrocephalus arundinaceus, over its wide Western Palearctic breeding range using geolocators from Spain, Sweden, Czech Republic, Bulgaria and Turkey. We found moderate migratory connectivity: a highly significant spatial structure in the connections between breeding and sub‐Saharan non‐breeding grounds, but at the same time a partial overlap between individual populations, particularly along the Gulf of Guinea where the majority of birds from the Spanish, Swedish and Czech populations spent their non‐breeding period. The post‐breeding migration routes were similar in direction and rather parallel for the five populations. Birds from Turkey showed the most distinctive migratory routes and sub‐Saharan non‐breeding range, with a post‐breeding migration to east Africa and, together with birds from Bulgaria, a previously unknown pre‐breeding migration over the Arabian Peninsula indicating counter‐clockwise loop migration. The distances between breeding and sub‐Saharan non‐breeding sites, as well as between first and final sub‐Saharan non‐breeding sites, differed among populations. However, the total speed of migration did not differ significantly between populations; neither during post‐breeding migration in autumn, nor pre‐breeding migration in spring. There was also no significant relationship between the total speed of migration and distance between breeding and non‐breeding sites (neither post‐ nor pre‐breeding) and, surprisingly, the total speed of migration generally did not differ significantly between post‐breeding and pre‐breeding migration. Future challenges include understanding whether non‐breeding environmental conditions may have influenced the differences in migratory patterns that we observed between populations, and to which extent non‐breeding habitat fluctuations and loss may affect population sizes of migrants.     

A comprehensive framework for the evaluation of metacommunity structure

The metacommunity framework is a powerful platform for evaluating patterns of species distribution in geographic or environmental space. Idealized patterns (checkerboard, Clementsian, evenly spaced, Gleasonian and nested distributions) give the framework shape. Each pattern represents an area in a multidimensional continuum of metacommunity structures; however, the current approach to analysis of spatial structure of metacommunities is incomplete. To address this, we describe additional non‐random structures and illustrate how they may be discerned via objective criteria. First, we distinguish three distinct forms of species loss in nested structures, which should improve identification of structuring mechanisms for nested patterns. Second, we define six quasi‐structures that are consistent with the conceptual underpinnings of Clementsian, Gleasonian, evenly spaced and nested distributions. Finally, we demonstrate how combinations of structures at smaller spatial extents may aggregate to form Clementsian structure at larger extents. These refinements should facilitate the identification of best‐fit patterns, associated structuring mechanisms, and informative scales of analysis and interpretation. This conceptual and analytical framework may be applied to network properties within communities (i.e. structure of interspecific interactions) and has broad application in ecology and biogeography.     

Global macroecology of bird assemblages in urbanized and semi‐natural ecosystems

Aim Despite the increasing pace of urbanization, little is known about how this process affects biodiversity globally. We investigate macroecological patterns of bird assemblages in urbanized areas relative to semi‐natural ecosystems. Location World‐wide. Methods We use a database of quantitative bird surveys to compare key assemblage structure parameters for plots in urbanized and semi‐natural ecosystems controlling for spatial autocorrelation and survey methodology. We use the term ‘urbanized’ instead of ‘urban’ ecosystems as many of the plots were not located in the centre of towns but in remnant habitat patches within conurbations. Results Some macroecological relationships were conserved in urbanized landscapes. Species–area, species–abundance and species–biomass relationships did not differ significantly between urbanized and non‐urbanized environments. However, there were differences in the relationships between productivity and assemblage structure. In forests, species richness increased with productivity; in both forests and open habitats, the evenness of species abundances declined as productivity increased. Among urbanized plots, instead, both species richness and the evenness of species abundances were independent of variation in productivity. Main conclusions Remnant habitats within urbanized areas are subject to many ecological alterations, yet key macroecological patterns differ remarkably little in urbanized versus non‐urbanized plots. Our results support the need for increased conservation activities in urbanized landscapes, particularly given the additional benefits of local experiences of biodiversity for the human population. With increasing urbanization world‐wide, broad‐scale efforts are needed to understand and manage the effects of this driver of change on biodiversity.     

Climatic responses in spring migration of boreal and arctic birds in relation to wintering area and taxonomy

Large‐scale climate fluctuations, such as the North Atlantic Oscillation (NAO), have a marked effect on the timing of spring migration of birds. It has however been suggested that long‐distance migrants wintering in Africa could respond less to NAO than short‐distance migrants wintering in Europe, making them more vulnerable to climatic changes. We studied whether migratory boreal and arctic bird species returning from different wintering areas show differences in responses to the NAO in the timing of their spring migration. We used data on 75 species from two bird observatories in northern Europe (60°N). By extending the examination to the whole distribution of spring migration and to a taxonomically diverse set of birds, we aimed at finding general patterns of the effects of climate fluctuation on the timing of avian migration. Most species arrived earlier after winters with high NAO index. The degree of NAO‐response diminished with the phase of migration: the early part of a species’ migratory population responded more strongly than the later part. Early phase waterfowl responded strongest to NAO, but in later phases their response faded to non‐significant. This pattern may be related to winter severity and/or ice conditions in the Baltic. In the two other groups, gulls and waders and passerines, all phases of migration responded to NAO and fading with phase was non‐significant. The difference between waterfowl and other groups may be related to differences between the phenological development of their respective macrohabitats. Wintering area affected the strength of NAO response in a complicated way. On average medium distance migrants responded most strongly, followed by short‐distance migrants and partial migrants. Our results concerning the response of long‐distance migrants were difficult to interpret: there is an overall weak yet statistically significant effect, but patterns with phase of migration need further study. Our results highlight the importance of examining the whole distribution of migration and warrant the use of data sets from several sampling sites when studying climatic effects on the timing of avian life‐history events.     

IL‐17A is not a treatment target in progressive vitiligo

Multiple reports confirm elevated circulating IL‐17 levels and increased numbers of Th17 lymphocytes in patients with non‐segmental vitiligo. Additionally, melanocyte damaging characteristics have been ascribed to IL‐17. A single‐arm pilot study using secukinumab in active non‐segmental vitiligo was conducted. The large majority of patients developed additional skin depigmentations limiting further enrollment. Overall, laboratory analysis revealed no change in secreted chemokines or Th subsets. Th17 lymphocytes correlated with Th2, Th9, and Th22 cells while an inverse link with Th1 cells and serum sCD25 levels was observed. In contrast, Th17.1 cells correlated positively with Th1 lymphocytes. Confirmatory results were found in an independent group of patients with vitiligo showing a significant increase in Th17.1 and Th1 lymphocytes in progressive vitiligo patients compared to healthy controls, which was not found for Th17 cells. These results do not support a direct pathogenic role of IL‐17 or Th17 cells in vitiligo. Nonetheless, a delicate Th17/Th17.1/Th1 balance seems evident which changes markedly according to disease activity. This may offer new treatment options by interfering with cytokines that drive differentiation of Th17 cells toward Th1.     

Variation in migration pattern,broodstock origin,and family productivity of coho salmon hatchery populations in British Columbia,Canada, derived from parentage‐based tagging

In salmonid parentage‐based tagging (PBT) applications, entire hatchery broodstocks are genotyped, and subsequently, progeny can be nonlethally sampled and assigned back to their parents using parentage analysis, thus identifying their hatchery of origin and brood year (i.e., age). Inter‐ and intrapopulation variability in migration patterns, life history traits, and fishery contributions can be determined from PBT analysis of samples derived from both fisheries and escapements (portion of a salmon population that does not get caught in fisheries and returns to its natal river to spawn). In the current study of southern British Columbia coho salmon (Oncorhynchus kisutch) populations, PBT analysis provided novel information on intrapopulation heterogeneity among males in the total number of progeny identified in fisheries and escapements, the proportion of progeny sampled from fisheries versus escapement, the proportion of two‐year‐old progeny (jacks) produced, and the within‐season return time of progeny. Fishery recoveries of coho salmon revealed heterogeneity in migration patterns among and within populations, with recoveries from north and central coast fisheries distinguishing “northern migrating” from “resident” populations. In northern migrating populations, the mean distance between fishery captures of sibs (brothers and sisters) was significantly less than the mean distance between nonsibs, indicating the possible presence of intrapopulation genetic heterogeneity for migration pattern. Variation among populations in productivity and within populations in fish catchability indicated that population selection and broodstock management can be implemented to optimize harvest benefits from hatcheries. Application of PBT provided valuable information for assessment and management of hatchery‐origin coho salmon in British Columbia.