A Bio-Guided Screening for Antioxidant, Anti-Inflammatory and Hypolipidemic Potential Supported by Non-Targeted Metabolomic Analysis of Crepis spp.

This study was designed to evaluate the chemical fingerprints and the antioxidant, anti-inflammatory and hypolipidemic activity of selected Crepis species collected in Greece, namely, C. commutata, C. dioscoridis, C. foetida, C. heldreichiana, C. incana, C. rubra, and Phitosia crocifolia (formerly known as Crepis crocifolia). For the phytochemical analyses, sample measurements were carried out by using nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled with mass spectrometry (LC-MS). Τhe extracts were evaluated both in vitro (radical scavenging activity: DPPH assay and total phenolic content: Folin-Ciocalteu) and in vivo (paw edema reduction and hypolipidemic activity: experimental mouse protocols). Among the tested extracts, C. incana presented the highest gallic acid equivalents (GAE) (0.0834 mg/mL) and the highest antioxidant activity (IC50 = 0.07 mg/mL) in vitro, as well as the highest anti-inflammatory activity with 32% edema reduction in vivo. Moreover, in the hypolipidemic protocol, the same extract increased plasma total antioxidant capacity (TAC) by 48.7%, and decreased cholesterol (41.3%) as well as triglycerides (37.2%). According to fractionation of the extract and the phytochemical results, this biological effect may be associated with the rich phenolic composition; caffeoyl tartaric acid derivatives (cichoric and caftaric acid) are regarded as the most prominent bioactive specialized metabolites. The present study contributes to the knowledge regarding the phytochemical and pharmacological profile of Crepis spp.

Molecular and Cytogenetic Analysis of rDNA Evolution in Crepis Sensu Lato.

Although Crepis was the first model plant group in which chromosomal changes were considered to play an important role in speciation, their chromosome structure and evolution have been barely investigated using molecular cytogenetic methods. The aim of the study was to provide a better understanding of the patterns and directions of Crepis chromosome evolution, using comparative analyses of rDNA loci number and localisation. The chromosome base number and chromosomal organisation of 5S and 35S rDNA loci were analysed in the phylogenetic background for 39 species of Crepis, which represent the evolutionary lineages of Crepis sensu stricto and Lagoseris, including Lapsana communis. The phylogenetic relationships among all the species were inferred from nrITS and newly obtained 5S rDNA NTS sequences. Despite high variations in rDNA loci chromosomal organisation, most species had a chromosome with both rDNA loci within the same (usually short) chromosomal arm. The comparative analyses revealed several independent rDNA loci number gains and loci repositioning that accompanied diversification and speciation in Crepis. Some of the changes in rDNA loci patterns were reconstructed for the same evolutionary lineages as descending dysploidy.

Descending Dysploidy and Bidirectional Changes in Genome Size Accompanied Crepis (Asteraceae) Evolution.

The evolution of the karyotype and genome size was examined in species of Crepis sensu lato. The phylogenetic relationships, inferred from the plastid and nrITS DNA sequences, were used as a framework to infer the patterns of karyotype evolution. Five different base chromosome numbers (x = 3, 4, 5, 6, and 11) were observed. A phylogenetic analysis of the evolution of the chromosome numbers allowed the inference of x = 6 as the ancestral state and the descending dysploidy as the major direction of the chromosome base number evolution. The derived base chromosome numbers (x = 5, 4, and 3) were found to have originated independently and recurrently in the different lineages of the genus. A few independent events of increases in karyotype asymmetry were inferred to have accompanied the karyotype evolution in Crepis. The genome sizes of 33 Crepis species differed seven-fold and the ancestral genome size was reconstructed to be 1C = 3.44 pg. Both decreases and increases in the genome size were inferred to have occurred within and between the lineages. The data suggest that, in addition to dysploidy, the amplification/elimination of various repetitive DNAs was likely involved in the genome and taxa differentiation in the genus.

Structural analysis and antidiabetic activity study of three acidic-type polysaccharides from Crepis crocea (Lam.) Babc.

In this article, we analyzed the structures of three acidic hetero-chain polysaccharides (CTP3-B, CTP3-C, and CTP3-D) fractionated from the herb Crepis crocea (Lam.) Babc. by a combination of ethanol precipitation, dialysis and gel permeation chromatography. Three polysaccharides were all highly branched polysaccharide. KK-Ay mice were chosen to determine the hypoglycemic effect of CTP3. The anti-diabetic activity of CTP3 was explored in detail from the aspects of body weight, daily dietary intake, blood glucose level and oral glucose tolerance test (OGTT). It was found that the body weight and daily food intake of the high dose group were significantly decreased compared with the diabetic control group. In addition, there was significant decrease in the levels of blood glucose in the middle and high dose group. These results suggest that CTP3 had a regulative role in blood glucose level. CTP3 may be useful in the treatment of type 2 diabetes mellitus.

Crepis vesicaria L. subsp. taraxacifolia Leaves: Nutritional Profile, Phenolic Composition and Biological Properties.

Crepis vesicaria subsp. taraxacifolia (Cv) of Asteraceae family is used as food and in traditional medicine. However there are no studies on its nutritional value, phenolic composition and biological activities. In the present work, a nutritional analysis of Cv leaves was performed and its phenolic content and biological properties evaluated. The nutritional profile was achieved by gas chromatography (GC). A 70% ethanolic extract was prepared and characterized by HLPC-PDA-ESI/MSn. The quantification of chicoric acid was determined by HPLC-PDA. Subsequently, it was evaluated its antioxidant activity by DPPH, ABTS and FRAP methods. The anti-inflammatory activity and cellular viability was assessed in Raw 264.7 macrophages. On wet weight basis, carbohydrates were the most abundant macronutrients (9.99%), followed by minerals (2.74%) (mainly K, Ca and Na), protein (1.04%) and lipids (0.69%), with a low energetic contribution (175.19 KJ/100 g). The Cv extract is constituted essentially by phenolic acids as caffeic, ferulic and quinic acid derivatives being the major phenolic constituent chicoric acid (130.5 mg/g extract). The extract exhibited antioxidant activity in DPPH, ABTS and FRAP assays and inhibited the nitric oxide (NO) production induced by LPS (IC50 = 0.428 ± 0.007 mg/mL) without cytotoxicity at all concentrations tested. Conclusions: Given the nutritional and phenolic profile and antioxidant and anti-inflammatory properties, Cv could be a promising useful source of functional food ingredients.

[Anti-inflammatory mechanism of Crepis crocea based on NF-κB signaling pathway and ~1H-NMR metabonomics].

Based on ~1H-NMR metabonomics technique and Western blot assay, the anti-inflammatory mechanism of Crepis crocea was discussed. In this study, male SD rats were treated with water extract(2.5 g·kg~(-1)) and dexamethasone acetate(6.25×10~(-4) g·kg~(-1)) for one week, and the inflammation model was induced by lipopolysaccharide(LPS). Then the counts of inflammatory cells white blood ceel(WBC), eosinophil(EO), lymphocyte(LY), basophils(BA) and neutrophils(NE) in whole blood of rats were observed. The levels of serum inflammatory factors tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), IL-6 and the expression of nuclear factor-κB(NF-κB) signaling pathway p65 and p-IκBα proteins in lung tissues were detected, and the change rules of serum endogenous metabolites were analyzed by ~1H-NMR metabonomics technique. The levels of TNF-α, IL-1ß, IL-6 and NF-κB signaling pathway p65 and p-IκBα proteins were combined with ~1H-NMR metabonomics to study the anti-inflammatory mechanism of C. crocea. The results showed that the water extract of C. crocea significantly decreased the number of WBC, NE, EO, increased the number of BA and LY, decreased the levels of TNF-α, IL-1ß, IL-6 and the expression of p65 and p-IκBα protein in NF-κB signaling pathway, and effectively alleviated the inflammatory symptoms. In the correlation analysis of differential metabolites regulated of C. crocea, four significant metabolites were obtained, including glycine, creatine, methionine and succinic acid. The anti-inflammatory mechanism of C. crocea may be related to the decrease of TNF-α, IL-1ß, IL-6 levels and the protein expression of NF-κB signaling pathway, as well as the regulation of glycine, creatine, methionine and succinic acid metabolism.

In vivo antiulcer activity, phytochemical exploration, and molecular modelling of the polyphenolic-rich fraction of Crepis sancta extract.

Bioactivity-guided investigation of the methanol extract of Crepis sancta aerial parts, collected off Al-Tafilah, South Jordan, was applied, and in this study, the extract was explored for its phytochemical components and in vivo antiulcer activity. In addition, a docking study involving the purified compounds with the newly crystalized gastric proton pump (PDB # 5YLU) was performed. In-depth phytochemical investigation using the state-of-the-art chromatographic and analytical techniques was implemented resulting in the identification of two eudesmane-type sesquiterpenoids, 3-oxo-γ-costic acid (1) and its methyl ester (2) together with seven different methoxylated flavonols (3-9) as the extract's major components. The in vivo antiulcer study at three different doses (50, 100, and 200 mg/kg) against ethanol-induced gastric ulcer in male albino rats, compared to omeprazole (20 mg/kg) as a standard proton pump inhibitor antiulcer drug, revealed that the tested extract, at the middle and the highest doses, featured comparable or even superior activities relative to omeprazole as deduced from histopathological examination, in particular with regard to reducing inflammatory cell infiltration and ceasing mucosal haemorrhage. The tested extract revealed also a dose-dependent reduction in the volume and titrable acidity of the gastric juice together with a dose-dependent increase in the protective gastric mucin content which may explain the noticeable gastroprotective effect. Molecular modelling study of the isolated compounds showed a binding mode similar to the co-crystallized substrate vonoprazan in 5YLU which strengthens the importance of the tested extract as a potential natural remedy for treating gastric ulcer.

Toxicity of Crepis lacera in grazing ruminants.

BACKGROUND: Crepis lacera is a plant from the Asteraceae family that is common in the Mediterranean region. Farmers believe that this plant may be deadly to small ruminants in areas of southern Italy. However, scientific evidence is lacking, and no proof exists that C. lacera is toxic to ruminants. Necropsies conducted on four sheep revealed lesions in their livers and kidneys. RESULTS: In the current study, we described sheep poisoning and isolated secondary metabolites from Crepis lacera to assess the metabolites' biological activity both in vitro and in vivo. Phytochemical study of the aerial portions of Crepis lacera led to the isolation of five sesquiterpene lactones and two phenolic compounds. Cellular viability was evaluated in cell cultures of the bovine kidney cell line Madin Darby Bovine Kidney (MDBK) after incubation with phytochemicals. Our results showed that three sesquiterpene lactones, 8-epidesacylcynaropicrin-3-O-ß-glucopyranoside (2), 8-epigrosheimin (3), and 8-ß-hydroxydehydrozaluzanin C (4), were cytotoxic after 48 h of incubation. In addition, in the in vivo study, animals that received 1 mg/kg body weight (bw) of Crepis lacera extract and were then sacrificed after 48 h showed significant lesions in their liver, lungs and kidneys. These lesions were also found in rats that received 2 mg/kg bw of the same extract and sacrificed after 24 and 48 h. CONCLUSIONS: These results validate the hypothesis that C. lacera is potentially dangerous when ingested in large quantities by grazing small domestic ruminants. Further studies are necessary to clarify the molecular mechanisms of Crepis spp. toxicity in animals.

Responses of Crepis japonica induced by supplemental blue light and UV-A radiation.

Crepis japonica (L.) D.C. (Asteraceae), a weed with antioxidant, antiallergenic, antiviral and antitumor properties displays both medicinal properties and nutritional value. This study aims to assess the effects of a supplementation of blue light and UV-A radiation on the growth, leaf anatomical structure and phenolic profile of the aerial parts of Crepis japonica. Plants were grown under two light treatments: W (control - white light), W + B (white light supplemented with blue light) and W + UV-A (white light supplemented with UV-A radiation). We recorded the length, width, and weight of fresh and dry leaves, the thickness of the epidermis and mesophyll, and stomata density. The phenolic profiles of the aqueous extracts of the aerial parts were analyzed by HPLC-DAD. There was an increase in the leaf size, stomatal density, and phenolic production, and a thickening of the mesophyll and epidermis. UV-A radiation increased the phenolic production more than blue light. Blue light and UV-A radiation both improved the production of caffeic acid by about 6 and 3 times, respectively, in comparison to control. This compound was first reported as a constituent of the extract from the aerial parts together with caftaric acid. UV-A also promoted the production of chlorogenic acid (about 1.5 times in comparison to the control). We observed that the morphological and chemical parameters of C. japonica are modified in response to blue light and UV-A radiation, which can be used as tools in the cultivation of this species in order to improve its medicinal properties and nutritional value.

Effects of fragmentation on plant adaptation to urban environments.

Urban ecosystems are relatively recent and heavily human-altered terrestrial ecosystems with a surprisingly high diversity of animals, plants and other organisms. Urban habitats are also strongly fragmented and subject to higher temperatures, providing a compelling model for studying adaptation to global change. Crepis sancta (Asteraceae), an annual Mediterranean wasteland weed, occupies fragmented urban environments as well as certain unfragmented landscapes in southern France. We tested for shifts in dispersal, reproductive traits and size across a rural-urban gradient to learn whether and how selection may be driving changes in life history in urban and fragmented habitats. We specifically compared the structure of quantitative genetic variation and of neutral markers (microsatellites) between urban and rural and between fragmented and unfragmented habitats. We showed that fragmentation provides a better descriptor of trait variation than urbanization per se for dispersal traits. Fragmentation also affected reproductive traits and plant size though one rural population did conform to this scheme. Our study shows the role of fragmentation for dispersal traits shift in urban environments and a more complex pattern for other traits. We discuss the role of pollinator scarcity and an inhospitable matrix as drivers of adaptation.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'.

A reexamination of the North American Crepis agamic complex and comparison with the findings of Babcock and Stebbins' classic biosystematic monograph.

PREMISE OF THE STUDY: Babcock and Stebbins coined the term agamic complex in their 1938 monograph of the North American Crepis agamic complex. Despite the historical role that this complex holds in the evolutionary literature, it has not been reexamined in over 75 years. We present a thorough reevaluation of the complex to test hypotheses proposed by Babcock and Stebbins about its origins and spread, the relationships of diploids, and the nature and origins of polyploids. METHODS: We used flow cytometry to infer ploidy of roughly 600 samples spanning the morphological and taxonomic diversity of the complex and a phylogenetic analysis of plastid DNA variation to infer maternal relationships among diploids and to infer maternal origins of polyploids. KEY RESULTS: We identified populations of all seven recognized diploids plus one new lineage. Phylogenetic analysis of plastid DNA variation in diploids revealed a well-resolved, but moderately supported phylogeny, with evidence for monophyly of the North America Crepis agamic complex and no evidence of widespread homoploid hybridization. Polyploids showed evidence of multiple origins and a pattern of frequent local co-occurrence consistent with repeated colonization of suitable sites. CONCLUSIONS: Our findings agree broadly with the distribution and variation of ploidy within and among species described by Babcock and Stebbins. One key difference is finding support for monophyly of North American species, and refuting their hypothesis of polyphyly. Our results provide an explicit phylogenetic framework for further study of this classic agamic complex.

Is it worth hyperaccumulating Ni on non-serpentine soils? Decomposition dynamics of mixed-species litters containing hyperaccumulated Ni across serpentine and non-serpentine environments.

BACKGROUND AND AIMS: Nickel (Ni)-hyperaccumulating species produce high-Ni litters and may potentially influence important ecosystem processes such as decomposition. Although litters resembling the natural community conditions are essential in order to predict decomposition dynamics, decomposition of mixed-species litters containing hyperaccumulated Ni has never been studied. This study aims to test the effect of different litter mixtures containing hyperaccumulated Ni on decomposition and Ni release across serpentine and non-serpentine soils. METHODS: Three different litter mixtures were prepared based on the relative abundance of the dominant species in three serpentine soils in the island of Lesbos, Greece where the Ni-hyperaccumulator Alyssum lesbiacum is present. Each litter mixture decomposed on its original serpentine habitat and on an adjacent non-serpentine habitat, in order to investigate whether the decomposition rates differ across the contrasted soils. In order to make comparisons across litter mixtures and to investigate whether additive or non-additive patterns of mass loss occur, a control non-serpentine site was used. Mass loss and Ni release were measured after 90, 180 and 270 d of field exposure. KEY RESULTS: The decomposition rates and Ni release had higher values on serpentine soils after all periods of field exposure. The recorded rapid release of hyperaccumulated Ni is positively related to the initial litter Ni concentration. No differences were found in the decomposition of the three different litter mixtures at the control non-serpentine site, while their patterns of mass loss were additive. CONCLUSIONS: Our results: (1) demonstrate the rapid decomposition of litters containing hyperaccumulated Ni on serpentine soils, indicating the presence of metal-tolerant decomposers; and (2) imply the selective decomposition of low-Ni parts of litters by the decomposers on non-serpentine soils. This study provides support for the elemental allelopathy hypothesis of hyperaccumulation, presenting the potential selective advantages acquired by metal-hyperaccumulating plants through litter decomposition on serpentine soils.

Genome size shifts: karyotype evolution in Crepis section Neglectoides (Asteraceae).

Plant genome size evolution is a very dynamic process: the ancestral genome of angiosperms was initially most likely small, which led to a tendency towards genome increase during evolution. However, findings in several angiosperm lineages demonstrate mechanisms that also led to genome size contraction. Recent molecular investigations on the Asteraceae genus Crepis suggest that several genomic reduction events have occurred during the evolution of the genus. This study focuses on the Mediterranean Crepis sect. Neglectoides, which includes three species with some of the smallest genomes within the whole genus. Crepis neglecta has the largest genome in sect. Neglectoides, approximately twice the size of the two species Crepis cretica and Crepis hellenica. Whereas C. cretica and C. hellencia are more closely related to each other than to C. neglecta the karyotypes of the latter species and C. cretica are similar, while that of C. hellenica differs considerably. Here, the karyotypic organisation of the three species is investigated with fluorescence in-situ hybridisation and studied in a molecular phylogenetic framework based on the nuclear markers Actin, CHR12, CPN60B, GPCR1 and XTH23. Our findings further corroborate the occurrence of genome size contraction in Crepis, and suggest that the difference in genome size between C. neglecta and C. cretica is mostly due to elimination of dispersed repetitive elements, whereas chromosomal reorganisation was involved in the karyotype formation of C. hellenica.

[Chemical constituents from Crepis crocea].

Thirteen compounds were isolated from the ethyl acetate fraction of Crepis crocea by column chromatographies on silica gel, Sephadex LH-20 and semi-preparative HPLC. The structures were elucidated on the basis of spectral analysis as tectorone I (1), 8ß- (2-methyl- 2-hydroxy-3-oxobutanoyloxy) -glucozaluzanin C (2), tectoroside (3), luteolin-7-O-glucoside (4), cosmosiin (5), esculetin (6), 3,4-dihydroxybenzaldehyde (7), trans-4-hydroxycinnamic acid (8), Caffeic acid (9), methyl p-hydroxyphenyllactate (10), ethylp- hydroxyphenyllactate (11), cis-3,4-dihydroxy-ß-ionion (12). All the compounds, except for compounds 4 and 9, were isolated from this plant for the first time, and tectorone I (1) is a new natural product.

Chemical constituents from Crepis crocea / 中国中药杂志

Thirteen compounds were isolated from the ethyl acetate fraction of Crepis crocea by column chromatographies on silica gel, Sephadex LH-20 and semi-preparative HPLC. The structures were elucidated on the basis of spectral analysis as tectorone I (1), 8β- (2-methyl- 2-hydroxy-3-oxobutanoyloxy) -glucozaluzanin C (2), tectoroside (3), luteolin-7-O-glucoside (4), cosmosiin (5), esculetin (6), 3,4-dihydroxybenzaldehyde (7), trans-4-hydroxycinnamic acid (8), Caffeic acid (9), methyl p-hydroxyphenyllactate (10), ethylp- hydroxyphenyllactate (11), cis-3,4-dihydroxy-β-ionion (12). All the compounds, except for compounds 4 and 9, were isolated from this plant for the first time, and tectorone I (1) is a new natural product.

Influence of the presence of B chromosomes on DNA damage in Crepis capillaris.

The sensitivity of different plant species to mutagenic agents is related to the DNA content and organization of the chromatin, which have been described in ABCW and bodyguard hypotheses, respectively. Plant species that have B chromosomes are good models for the study of these hypotheses. This study presents an analysis of the correlation between the occurrence of B chromosomes and the DNA damage that is induced by the chemical mutagen, maleic hydrazide (MH), in Crepis capillaris plants using comet assay. The presence of B chromosomes has a detectable impact on the level of DNA damage. The level of DNA damage after MH treatment was correlated with the number of B chromosomes and it was observed that it increased significantly in plants with 3B chromosomes. We did not find evidence of the protective role from chemical mutagens of the constitutive heterochromatin for euchromatin in relation to DNA damage. The DNA damage involving the 25S rDNA sequences was analyzed using the comet-FISH technique. Fragmentation within or near the 25S rDNA involved the loci on the A and B chromosomes. The presence of B chromosomes in C. capillaris cells had an influence on the level of DNA damage that involves the 25S rDNA region.

Effects of mating system on adaptive potential for leaf morphology in Crepis tectorum (Asteraceae).

BACKGROUND AND AIMS: A shift from outcrossing to selfing is thought to reduce the long-term survival of populations by decreasing the genetic variation necessary for adaptation to novel ecological conditions. However, theory also predicts an increase in adaptive potential as more of the existing variation becomes expressed as homozygous genotypes. So far, relatively few studies have examined how a transition to selfing simultaneously affects means, variances and covariances for characters that might be under stabilizing selection for a spatially varying optimum, e.g. characters describing leaf morphology. METHODS: Experimental crosses within an initially self-sterile population of Crepis tectorum were performed to produce an outbred and inbred progeny population to assess how a shift to selfing affects the adaptive potential for measures of leaf morphology, with special emphasis on the degree of leaf dissection, a major target of diversifying selection within the study species. KEY RESULTS: Three consecutive generations of selfing had a minor impact on survival, the total number of heads produced and the mean leaf phenotype, but caused a proportional increase in the genetic (co)variance matrix for foliar characters. For the degree of leaf dissection, the lowest 50th percentile of the inbred progeny population showed a disproportionate increase in the genetic variance, consistent with the recessive nature of the weakly lobed phenotype observed in interpopulation crosses. Comparison of inbreeding response with large-scale patterns of variation indicates a potential for selection in a (recently) inbred population to drive a large evolutionary reduction in degree of leaf dissection by increasing the frequency of particular sibling lines. CONCLUSIONS: The results point to a positive role for inbreeding in phenotypic evolution, at least during or immediately after a rapid shift in mating system.

Clastogenic and anticlastogenic activity of glucocorticoid hormones hydrocortisone and its synthetic analogs prednisolone and dexamethasone.

Clastogenic and anticlastogenic activity of glucocorticoid hormones hydrocortisone, prednisolone, and dexamethasone was studied by counting chromosome aberrations in Crepis capillaris test system. Hydrocortisone in a concentration of 12.5 mg/ml produced a clastogenic effect and increased the number of chromosome aberrations in comparison with spontaneous level. Hydrocortisone (6.25 and 3.13 mg/ml), prednisolone (15, 7.5, and 3.75 mg/ml), and dexamethasone (1, 0.5, 0.25, and 0.125 mg/ml) exhibited an anticlastogenic effect and reduced ethyl methanesulfonate-induced mutagenesis.

Inferring contemporary dispersal processes in plant metapopulations: comparison of direct and indirect estimates of dispersal for the annual species Crepis sancta.

Analyzing population dynamics in changing habitats is a prerequisite for population dynamics forecasting. The recent development of metapopulation modeling allows the estimation of dispersal kernels based on the colonization pattern but the accuracy of these estimates compared with direct estimates of the seed dispersal kernel has rarely been assessed. In this study, we used recent genetic methods based on parentage analysis (spatially explicit mating models) to estimate seed and pollen dispersal kernels as well as seed and pollen immigration in fragmented urban populations of the plant species Crepis sancta with contrasting patch dynamics. Using two independent networks, we documented substantial seed immigration and a highly restricted dispersal kernel. Moreover, immigration heterogeneity among networks was consistent with previously reported metapopulation dynamics, showing that colonization was mainly due to external colonization in the first network (propagule rain) and local colonization in the second network. We concluded that the differences in urban patch dynamics are mainly due to seed immigration heterogeneity, highlighting the importance of external population source in the spatio-temporal dynamics of plants in a fragmented landscape. The results show that indirect and direct methods were qualitatively consistent, providing a proper interpretation of indirect estimates. This study provides attempts to link genetic and demographic methods and show that patch occupancy models may provide simple methods for analyzing population dynamics in heterogeneous landscapes in the context of global change.