Genetic diversification may help H. pylori to adapt to a new host after transmission, and to different micro-niches within a single host and to changing conditions in the host over time. Genetic diversity arises from within-genome diversification and from integration of DNA from other H. pylori strains. Central to this is the ability of H. pylori to take up exogenous DNA and incorporate it into its genome. The H. pylori machinery for exogenous dsDNA uptake is composed

of the type-IV secretion system ComB, which transports dsDNA across the outer membrane at the cell poles, and by ComEC, which mediates the subsequent transport into the cytoplasm through the inner membrane with higher specificity for DNA structure [1]. Adaptation to varying gastric conditions is enabled by several H. pylori genes that display phase variation; these include MEK inhibitor genes encoding outer membrane proteins (OMPs), like BabA which is a Lewis b ligand, and genes involved in lipopolysaccharide (LPS) biosynthesis. In animal model systems of H. pylori infection, Styer et al. [2] provided evidence that BabA expression is lost during persistent infection by phase variation and nonreciprocal gene conversion of babA with a duplicate copy of babB, a paralog of babA with unknown function. H. pylori Gefitinib not only binds to human Lewis antigens but also expresses Lewis antigens (H. pylori is a fucose expressing pathogen). The variable O-antigen

chain part of the H. pylori LPS is uniquely composed of host-related Lewis antigens and this host-cell surface mimicry is thought to facilitate immune escape. Two studies [3,4] explored phenotype variation of H. pylori Lewis antigen expression. Both studies employed a mouse infection model to medchemexpress demonstrate that bacterial subpopulations expressing both Lewis x and Lewis y coexist and are stable during persistent infection. New subpopulations expressing Lewis b inevitably appear when Lewis b transgenic mice

are infected. This finding supports the hypothesis of an increased fitness of H. pylori variants that match the Lewis phenotype of their host [4]. Changes in Lewis phenotypes could be linked to phase variation of the metastable poly-C tracts of the galactosyltransferase gene encoding β-(1,3)galT and the fucosyltransferase-encoding genes futA, futB and futC that are all involved in Lewis antigen biosynthesis. Skoglund et al. [3] demonstrated that a neutral pH favors Lewis y expression, while a more acidic pH favors a switch from solely Lewis y to both Lewis x and Lewis y glycosylation. In agreement with the above findings, Lehours et al. [5] demonstrated an increased prevalence of Lewis x negative/Lewis y positive strains among the cagPAI negative isolates form patients with MALT lymphoma versus patients with gastritis, possibly representing the result of H. pylori adaptation through futA and futB phase variation. Next to Lewis antigens, H.

5 ± 13.7 kg), and higher IHL values (10.7 ± 9.4 versus 7.1 ± 6.2%; P = 0.05) compared with subjects with normal glucose tolerance. Bodyweight loss was similar in both groups regardless of the

dietary intervention. IHL loss was not related to diet or glucose tolerance state (impaired glucose tolerance: reduced carbohydrates: Δ −4.8 ± 6.2%; reduced fat: Δ −4.0 ± 5.9%, both P < 0.01; normal glucose tolerance: reduced carbohydrates: Δ −2.4 ± 2.6%; reduced fat: Δ −3.2 ± 4.1%, both P < 0.01). Glucose tolerance improved only in subjects with impaired glucose tolerance regardless of diet. The main finding of our study is that IHL content decreased similarly in overweight and obese subjects assigned to B-Raf assay moderately reduced carbohydrate or moderately reduced fat hypocaloric diets. The observation holds true for both subjects with low and subjects with elevated IHL content at baseline. Our findings provide insight in mechanisms regulating IHL in human subjects and may have a bearing on therapeutic decision-making. Previous studies compared low-carbohydrate to low-fat hypocaloric diets. A meta-analysis including earlier trials revealed Depsipeptide that low-carbohydrate diets appear to be at least as effective as low-fat diets in terms of weight loss.20 More recent trials

showed advantages29 or no differences15 for reduced carbohydrate diets. However, most of these trials assessed changes in overall adiposity rather than fat distribution between adipose tissue depots and ectopic fat storage in the liver. The issue is relevant given the central role of intrahepatic fat in the pathogenesis of obesity-associated disease, such as insulin resistance and type 2 diabetes. Indeed, animal and human studies show that increasing dietary fat content predisposes to IHL accumulation and insulin resistance.13, 30 We observed virtually identical medchemexpress weight loss with reduced carbohydrate and reduced fat

diets. Both groups adhered to their assigned interventions in terms of macronutrient content. Physical fitness is negatively correlated with IHL content.1 Dieticians reminded participants to keep physical activity constant throughout the study. Moreover, cardiorespiratory fitness did not change during either intervention. Thus, differences in fat distribution, lipoprotein metabolism, or glucose metabolism between interventions are mainly explained by macronutrient composition rather than differences in weight loss or physical fitness between groups. Abdominal visceral, abdominal subcutaneous, and IHL loss was similar with low-fat and low-carbohydrate diets. These observations suggest that over a 6-month period, success in losing visceral fat and IHL is primarily related to caloric restriction rather than macronutrient composition. IHL is associated with metabolic disease including insulin resistance2, 4 independently of visceral fat.

Such attenuated Venetoclax price infiltration and dysfunction of NK cells in the intratumoral region was positively associated with the increased level of activated monocyte/Mψ in peritumoral stroma of HCC tissues, and accordingly, activated monocytes isolated from HCC tissues caused transient activation, but subsequent exhaustion, and ultimate apoptosis of NK cells. This process was mediated by cell-cell interactions by way of 2B4-CD48, but not NKG2D and NKp30. Ab, antibody; APCs, antigen-presenting

cells; HCC, hepatocellular carcinoma; IL, interleukin; Mψ, macrophage(s); NK, natural killer; TAM, tumor-associated Mψ. Detailed information about the patients and specimens is described in the Supporting Materials and Methods and Supporting Table 1. Peripheral leukocytes were isolated by Ficoll density gradient centrifugation.15, 18 Tumor- and nontumor-infiltrating leukocytes were obtained from paired fresh tissue samples as described.19 The mononuclear AT9283 chemical structure cells were washed and resuspended in medium supplemented with 1% heat-inactivated fetal calf serum (FCS) for fluorescent-activated cell sorter (FACS) analysis. Leukocytes were stained with surface markers, fixed, permeabilized with IntraPre Reagent (Beckman Coulter, Fullerton, CA), and further stained with antibodies against intracellular markers.

Data were acquired on Gallios (Beckman Coulter, Brea, CA). For the measurement of intracellular cytokine production, cells were stimulated at 37°C for 5 hours with Leukocyte Activation Cocktail (BD Bioscience) before staining as described.20 The fluorochrome-conjugated monoclonal antibodies (mAbs) are listed in Supporting Table 2. Paraffin-embedded and formalin-fixed samples

were cut into 5-μm sections, which were then processed for immunohistochemistry as described.21 After incubation with an antibody against human NK-1 (Thermo Fisher Scientific, Fremont CA) or CD68 (Dako, Denmark), the adjacent sections were stained with diaminobenzidine or 3-amino-9-ethylcarbazole in an Envision System (Dako). For immunofluorescence analysis, tissues were stained with monoclonal mouse antihuman NK-1 and rabbit 上海皓元 antihuman CD68 or with mouse antihuman NK-1 and goat antihuman CD69. Secondary antibodies included Alexa Fluor 488-conjugated goat antimouse IgG with Alexa Fluor 568-conjugated goat antirabbit IgG and Alexa Fluor 488-conjugated donkey antigoat IgG with Alexa Fluor 568-conjugated donkey antimouse IgG (Molecular Probes, Eugene, OR). Positive cells were quantified using ImagePro Plus software (Media Cybernetics) and expressed as the mean of the percentage of positive cells ± standard error of the mean (SEM) in 10 high-powered fields detected by confocal microscopy. The evaluation of immunohistochemical variables is detailed in the Supporting Materials and Methods.

The histological benefits observed in the long-term histology cohort were therefore more likely driven by the durable antiviral suppression and avoidance of antiviral drug resistance

observed with entecavir therapy in these nucleoside-naive patients. click here This assessment is supported by a separate long-term histology cohort of 19 Japanese patients who received continuous therapy with entecavir (0.5 mg once daily) for 3 years; histological improvement and improvement in fibrosis were observed in 100% and 63% of the patients, respectively.31 Clinical data on the degree of fibrosis or cirrhosis were not collected as part of the entecavir phase 3 studies or the rollover study. Thus, it is not clear from this data set whether the macroscopic architectural abnormalities typically observed in patients with advanced fibrosis or cirrhosis remain among patients who have experienced histological regression. However, the reductions in portal pressure observed among patients with cirrhosis receiving treatment with entecavir or lamivudine suggest that architectural remodeling does occur to some degree.39, 40 The possibility that successful treatment of CHB could result in reversal of cirrhosis was first suggested in a case series of three patients who were treated with SB203580 chemical structure either interferon or lamivudine.41 Three subsequent publications have reported the effects of nucleos(t)ide analogues on

histological outcomes beyond 48 weeks. A cohort of previously nucleoside-naive, HBeAg-positive CHB patients were treated with lamivudine and were followed for 3 years.25 In this report, 35 of 65 patients (56%) experienced histological improvement. Forty-one 上海皓元医药股份有限公司 of these patients (63%) developed YMDD resistance, and the histological improvement was lost

in many of those patients. Two smaller cohorts of nucleoside-naive, HBeAg-negative CHB patients treated with adefovir were followed for 4 (n = 22) or 5 years (n = 24).26 In this report, 12 of 22 patients (55%) treated for 4 years and 17 of 24 patients (71%) treated for 5 years demonstrated improvements in the Ishak fibrosis score. In a recently published cohort of 65 nucleoside-naive, HBeAg-positive CHB patients treated with adefovir for 5 years, 39% achieved a serum HBV DNA level <1000 copies/mL, and resistance emerged to adefovir in 20% of patients. A subset of 15 patients had paired baseline and long-term biopsy samples, and improvement in necroinflammation and fibrosis was shown in 9 of 15 patients (60%) with the Knodell scoring system.27 These data support the conclusion that in most nucleoside-naive patients, including those with advanced fibrosis or cirrhosis at the baseline, long-term entecavir therapy leads to potent suppression of HBV DNA, normalization of ALT, and improvement in liver histology with accompanying regression of fibrosis.

Nonscientists will appreciate the writing style, the history of local sealing, the definitions of common biological terms such as parturition and philopatry, and an introduction to the anatomical and behavioral adaptations required for an amphibious life. But, the book includes many detailed discussions of subtle island to island and temporal differences in foraging patterns, reproductive biology, and the like that will not interest lay readers. It also discusses complex technologies like DNA haplotypes (Figure 7.4) that these readers will not have the background to understand. On the other hand, the book does not seem specifically tailored RG7204 datasheet for the research

audience either. It does not include typical scientific citations that would help a specialist verify specific statements in the text. It does link the names of SAHA HDAC in vivo Australian researchers with some of the facts, and the reader can sometimes match this information

to papers listed in the book’s bibliography. However, the bibliography is more a list of suggested further reading than a scholarly guide for specialists. It does not include all relevant or important otariid research. Although the book does mention by name all Australian researchers past and present who have worked on fur seals and sea lions, it does not mention nonAustralians who have provided data, concepts, or technological advances (such as dive instruments, DNA haplotype analysis, stable isotope analysis, Crittercam, etc.) that the Australian researchers have used or relied upon. It is not written as a strictly scientific review. No factual errors are evident in the book, but there is one minor interpretation that specialists may see differently. Most otariids wean their young by 1 yr of age (occasionally longer). But, Antarctic (Arctophoca gazella) and Northern fur seals (Callorhinus ursinus) wean their young at 4 mo of age. The book attributes this shorter suckling period to seasonally cold weather that jeopardizes pup survival on shore. 上海皓元 The more

compelling explanation is that the onset of cold weather forces these mothers to wean, leave shore, and migrate to lower latitudes. These two migrations, which are noteworthy features of otariid behavioral ecology, are not mentioned in this book. Similarly, the book does not discuss the research findings for any other species of fur seal or sea lion. The voluminous research on Northern and Antarctic fur seals, and on Steller and California sea lions is not mentioned. South American eared seals are mentioned once, and the problem of domoic acid and California sea lions is discussed briefly. The book does not compare or contrast the results of Australian research with what is known of the other species, thereby missing the opportunity to improve our understanding of eared seal behavior and ecology globally. This book is exclusively about Australian species, research, and researchers.

10 This subtype, which has intermediate features between HCC and CC, showed distinct pathobiological characteristics enriched with stem-cell–like gene traits check details and therefore poorer clinical outcomes. However, the histopathological characteristics of these intermediate tumors have not yet been fully evaluated. Therefore, we hypothesized that the HCC phenotype with a fibrous stromal component (S-HCC) may share common genomic features with CC-like HCC, such as CC-like and/or stem-cell–like expression traits. To evaluate our hypothesis, we performed a gene-expression

profiling analysis of S-HCC and compared the profiles of S-HCC with those of HCC (i.e., classical HCC without fibrous tissue) and CC. In addition, it has been reported that scirrhous-type cancers, including gastric cancer, become invasive and metastatic by stimulating epithelial-mesenchymal transition (EMT).11 EMT is the differentiation

switch from polarized epithelial cells to contractile and motile mesenchymal cells.12 EMT is thought to be a fundamental process that governs morphogenesis during embryogenesis and is reactivated in fibrogenic disease, provoking tumor progression.13 Snail and Twist, the key molecules of EMT, are associated with invasion Everolimus molecular weight and tumor metastasis and are also independent markers for worse prognosis in HCC.14, 15 A recent study also demonstrated that EMT induction by ectopic expression of either Snail or Twist transcription factors is able to generate cancer stem-cell properties in human breast cancer cells.16 These results suggest that EMT may play a critical role in the aggressive behavior and acquisition of stem-cell–like traits in S-HCC. With respect to these notions, we further evaluated whether EMT is involved in the HCC phenotype with fibrous stroma (S-HCC). AFP, alpha-fetoprotein; CC, cholangiocarcinoma; CD, cluster of differentiation; CHC, combined hepatocellular-cholangiocarcinoma; cRNA, complementary 上海皓元 RNA; DFS, disease-free survival; EMT, epithelial-mesenchymal

transition; EpCAM, epithelial cell adhesion molecule; GSEA, gene set enrichment analysis; HCC, hepatocellular carcinoma; IHC, immunohistochemistry; K, keratin; mRNA, messenger RNA; qRT-PCR, quantitative reverse-transcription polymerase chain reaction; RT, reverse transcription; S-HCC, scirrhous hepatocellular carcinoma; SPC, stem/progenitor cell; TGF-β, transforming growth factor beta; TGFβRI, transforming growth factor beta receptor I; TGFβRII, transforming growth factor beta receptor II. A total of 57 cases of primary liver carcinomas showing the following features were studied: (1) 14 patients with S-HCC, which had fibrous stroma in ≥50% of the tumor area by histological morphometry in the greatest dimension of cut surface9, 10, 17; (2) 24 patients with HCC, which had very little or no fibrous stroma; and (3) 19 patients with typical CCs.

FITC anti-PD-1, FITC/PE-Cy7/APC-H7 anti-CD8, APC anti-CD107a, anti-CD38, anti-CD69, and anti-HLA-DR, peridinin chlorophyll protein complex (PerCP) anti-CD14, anti-CD19, anti-CD3, Via-Probe, and Monensin were purchased from BD Biosciences (San Jose, CA). APC anti–T-cell immunoglobulin domain and mucin domain 3 (TIM-3) was purchased from R&D Systems (Minneapolis, MN). Low endotoxin anti-CD244 (2B4, clone 2B4) was purchased

from AbD Serotec (Oxford, UK).9 Micro-Beads for T-cell enrichment were purchased from Miltenyi Biotec (Bergisch-Gladbach, Germany). If the CD244 expression in chronic HBV exceeded 80%, CD244 expression was defined as CD244high. The following PE-labeled/APC-labeled HLA-A*0201-restricted www.selleckchem.com/products/ink128.html MHC class I pentamers were used: HBV core (c)18-27 (FLPSD FFPSV), HBV envelope (e)183-191 (FLLTRILTI), HBV polymerase (p)573-581 (FLLSLGIHL), EBV BMLF1, and Flu Matrix 1. PBMCs (2 × 106) were incubated for 10 minutes at room temperature in culture medium (RPMI 1640, 2 mM glutamine, 1 mM sodium pyruvate, 5% human AB serum, 100 IU/mL penicillin,

100 μg/mL streptomycin). After wash step surface markers were added for 20 minutes at 4°C. Cells were then washed and incubated with anti-PE/anti-APC check details Micro-Beads for 15 minutes. After the wash step, 90% of cells were applied to MS columns (Miltenyi Biotec) according to the manufacturer’s instructions. The other 10% were reserved for fluorescence-activated cell sorting (FACS) analysis. PE-positive/APC-positive cells were eluted from the column and analyzed by FACS. Cells were gated on the CD8+, CD14−, CD19−, and Via-Probe− population. Frequencies of Pent+ T-cells medchemexpress were calculated as described previously.10 The 96-well culture plates were coated with IFN-γ antibody (Mabtech, Stockholm, Sweden). Before use, unbound antibodies

were removed and blocked with RPMI containing 10% human AB serum. PBMCs (2.5 × 105) were incubated with HBV core peptide (10 μg/mL) for 48 hours at 37°C in the presence or absence of 10 μg/mL anti-CD244 or 5 μg/mL anti-CD48. Biotin-conjugated anti-IFN-γ was added after a wash step, followed by 2 hours of incubation. The unbound antibodies were washed and cells were incubated in detection solution. The number of spots was scored by an Elispot reader (AID, Straßberg, Germany). If the mean value plus two standard deviations (2SD) in healthy individuals was exceeded, the increase of virus-specific IFN-γ release after CD244 blockade was defined as positive.

10), supporting the hypothesis that the NF-κB pathway is involved in the suppressive effects of miR-370 on HCC. IL-6 is a downstream target gene of NF-κB that plays a crucial role in hepatocarcinogenesis.[4, 5] Previous studies reported that IL-6 inhibited miR-370 through modulation of DNA methylation in human cholangiocarcinoma (CCA).[12, 13] In this study, we confirmed that treatment of HCC cells with IL-6 significantly decreased miR-370 levels, followed by an increase in LIN28A protein (Fig. 6E and Supporting Fig. 11A,B). Furthermore, the methylation inhibitor, 5-aza-2′-deoxycytidine

markedly increased expression of primary miR-370 (Supporting Fig. 11C), suggesting that miR-370 is down-regulated in HCC in an epigenetic manner. These results indicate that a positive feedback loop, consisting of miR-370, LIN28A, RelA/p65, and IL-6, is involved in the progression of HCC GDC-0449 manufacturer (Fig. 6F). We further validated the

roles of miR-370 and LIN28A in the development of HCC by using real-time PCR to examine miR-370 and LIN28A mRNA levels in liver tissues from diethylinitrosamine (DEN)-treated rats, 86 paired primary HCC and adjacent nontumorous liver tissues from primary HCC patients with complete clinical data (excluding the 20 pairs of samples referred to above), and 24 healthy human liver tissue samples. miR-370 expression was significantly down-regulated in cirrhotic liver tissues from rats at week 11 after DEN administration, compared to normal rat livers, and was further reduced in HCC tissues, relative to adjacent fibrotic tissues (Fig. 7A). In contrast, LIN28A mRNA was gradually up-regulated during the development GPCR Compound Library of DEN-induced HCC (Fig. 7B). Consistently, miR-370 expression was substantially repressed in the surrounding nontumorous livers from HCC patients, compared to healthy human

livers (median, 0.859 and 0.003, MCE respectively; P < 0.001; Mann-Whitney’s U test), and was further reduced in HCC tissues (Fig. 7C). In contrast, LIN28A mRNA levels were increased 19-fold in nontumorous livers, compared to healthy livers. LIN28A mRNA was only slightly augmented in HCC tissues, relative to surrounding nontumorous tissues (median, 3.59 × 10−4 and 6.08 × 10−4, respectively; Fig. 7D). Correlation studies displayed that miR-370 levels were inversely correlated with LIN28A and IL6 mRNA levels in human HCC specimens (Fig. 7E), and LIN28A expression was positively correlated with IL-6 expression (Fig. 7E). Specifically, low expression of miR-370 was more likely in human HCC specimens with high levels of LIN28A and IL-6 mRNAs, whereas high expression of LIN28A was more likely in human tissues with high IL-6 levels. More interesting, clinicopathologic analysis demonstrated that down-regulation of miR-370 in human HCCs was significantly correlated with aggressive pathologic characteristics, including larger tumor size (P = 0.028), advanced tumor stage (P = 0.

35 Other NF-κB–dependent protective factors may have been up-regulated by this perfusion-induced NF-κB activation that compensated for the loss of C/EBPβ. Alternatively, the null mice may have up-regulated other compensatory protective factors that negated the loss of C/EBPβ. Nonetheless, the findings identify C/EBPβ as a new antiapoptotic protein regulated by NF-κB at the level of protein degradation. Confirmatory of the in vitro hepatocyte data were findings that C/EBPβ was up-regulated and functioned in hepatotoxic liver injury in vivo. Identical to results in RALA hepatocytes, hepatic C/EBPβ protein levels were markedly increased by the TNFα inducer LPS. Consistent with the ability

of GalN to block the up-regulation of NF-κB–induced Ensartinib mouse protective signaling, mice cotreated with GalN and LPS failed to up-regulate C/EBPβ. buy NVP-BGJ398 C/EBPβ was protective against TNFα cytotoxicity, because null mice but not wild-type mice developed liver injury from low-dose LPS or TNFα alone. Injury in C/EBPβ

null mice was far less than that elicited by the combination of GalN and LPS in wild-type mice. These results suggest that C/EBPβ functions as one of a redundant set of NF-κB–regulated antiapoptotic factors in the hepatocyte. Alternatively, as with the studies in cultured hepatocytes from these mice, the null mice may have responded to the knockout of C/EBPβ by up-regulating other antiapoptotic factors in compensation for the loss of C/EBPβ that in part masked the true importance of C/EBPβ as an antiapoptotic factor in vivo. The mechanism of the antiapoptotic effect of C/EBPβ was at least in part at the level of initiator caspase 8 activation, because C/EBPβ blocked the activation of this caspase and therefore the downstream mitochondrial

death pathway and effector caspase cleavage. However, further studies must be performed to delineate the mechanism by which MCE C/EBPβ blocks caspase 8 activation to confirm this possibility. Our finding is consistent with that of Buck et al.,22 who similarly found that C/EBPβ inhibited caspase 8 activation in hepatic stellate cells. This effect in hepatocytes appears to be specific for the TNFα death pathway. In contrast to the present finding of an antiapoptotic function for C/EBPβ in TNFα-mediated hepatocyte injury, studies in C/EBPβ null mice demonstrated that C/EBPβ promotes hepatocyte apoptosis from the Fas death receptor.25 Fas-mediated cell death is also caspase 8 mediated, yet C/EBPβ promoted this form of apoptosis. The mechanism of the differential effect of C/EBPβ on the TNFα and Fas death receptor pathways remains to be determined, but the current study suggests the interesting possibility that TNFα, through induction of C/EBPβ, may potentiate Fas toxicity. A protective mechanism of NF-κB signaling is its inhibition of proapoptotic JNK overactivation.

The fact that no ecological factor explained the distribution of S. atra could be due to the fact that the species was widespread in Nidwalden and comparatively rare in Zug. With such a pattern of distribution, differences between Zug and Nidwalden rather than differences (i.e. ecological

factors) within the areas Zug and Nidwalden are likely to explain Gemcitabine concentration the distribution. The possibility of interspecific interactions was suggested for contact zones where alpine and fire salamanders co-occur (Werner et al., in press). Competing species of salamanders often show little spatial overlap in their distributions (Hairston, 1951; Jaeger, 1970; Arif et al., 2007). Yet, our analysis of site occupancy within contact zones provided no evidence that one salamander species affected the occupancy probability of the other, although species interactions were observed in the field (P. Werner, unpubl. data). This may imply that the species distributions are independent or influenced by different habitat characteristics or that

competition does not lead to spatial segregation (Rissler, Barber & Wilbur, click here 2000; MacKenzie et al., 2004; Indermaur et al., 2010). However, absence of evidence is not evidence for the absence of competition, as competition may affect species’ traits such as growth, body size, morphology or abundance (Price & Secki Shields, 2002; MacKenzie et al., 2004; Adams, West & Collyer, 2007; Arif et al., 2007).

If interspecific competition occurs, the parameter estimates in Table 3 suggest that competitive interaction may possibly be asymmetric (the effect of S. salamandra on S. atra was close to zero, whereas the effect of S. atra on S. salamandra was negative), as it was found in other pairs of parapatric salamanders (e.g. Arif et al., 2007). In conclusion, our results underline the complexity of the mechanisms that determine the range margins of parapatric species. The analysis of local syntopic and allotopic occurrences within the species’ contact zones provided evidence for dissimilar species–habitat relationships, PLEK2 but the expected effect of competition on the occupancy probabilities of the species was not detected even though competition can affect occupancy (MacKenzie et al., 2004; Yackulic et al., in press). We suggest that these findings provide an important basis for studies that aim to investigate the role of interspecific competition within contact zones at smaller scales. Furthermore, although parapatry describes a distributional pattern, the study of patterns of species’ distributions may not be sufficient to entirely unravel the role of interspecific interactions for the parapatric range margins. It may be informative to study functional traits (i.e.