Mechanisms and ecological consequences of plant defence induction and suppression in herbivore communities.

BACKGROUND: Plants are hotbeds for parasites such as arthropod herbivores, which acquire nutrients and energy from their hosts in order to grow and reproduce. Hence plants are selected to evolve resistance, which in turn selects for herbivores that can cope with this resistance. To preserve their fitness when attacked by herbivores, plants can employ complex strategies that include reallocation of resources and the production of defensive metabolites and structures. Plant defences can be either prefabricated or be produced only upon attack. Those that are ready-made are referred to as constitutive defences. Some constitutive defences are operational at any time while others require activation. Defences produced only when herbivores are present are referred to as induced defences. These can be established via de novo biosynthesis of defensive substances or via modifications of prefabricated substances and consequently these are active only when needed. Inducibility of defence may serve to save energy and to prevent self-intoxication but also implies that there is a delay in these defences becoming operational. Induced defences can be characterized by alterations in plant morphology and molecular chemistry and are associated with a decrease in herbivore performance. These alterations are set in motion by signals generated by herbivores. Finally, a subset of induced metabolites are released into the air as volatiles and function as a beacon for foraging natural enemies searching for prey, and this is referred to as induced indirect defence. SCOPE: The objective of this review is to evaluate (1) which strategies plants have evolved to cope with herbivores and (2) which traits herbivores have evolved that enable them to counter these defences. The primary focus is on the induction and suppression of plant defences and the review outlines how the palette of traits that determine induction/suppression of, and resistance/susceptibility of herbivores to, plant defences can give rise to exploitative competition and facilitation within ecological communities "inhabiting" a plant. CONCLUSIONS: Herbivores have evolved diverse strategies, which are not mutually exclusive, to decrease the negative effects of plant defences in order to maximize the conversion of plant material into offspring. Numerous adaptations have been found in herbivores, enabling them to dismantle or bypass defensive barriers, to avoid tissues with relatively high levels of defensive chemicals or to metabolize these chemicals once ingested. In addition, some herbivores interfere with the onset or completion of induced plant defences, resulting in the plant's resistance being partly or fully suppressed. The ability to suppress induced plant defences appears to occur across plant parasites from different kingdoms, including herbivorous arthropods, and there is remarkable diversity in suppression mechanisms. Suppression may strongly affect the structure of the food web, because the ability to suppress the activation of defences of a communal host may facilitate competitors, whereas the ability of a herbivore to cope with activated plant defences will not. Further characterization of the mechanisms and traits that give rise to suppression of plant defences will enable us to determine their role in shaping direct and indirect interactions in food webs and the extent to which these determine the coexistence and persistence of species.

Herbivory-associated degradation of tomato trichomes and its impact on biological control of Aculops lycopersici.

Tomato plants have their leaves, petioles and stems covered with glandular trichomes that protect the plant against two-spotted spider mites and many other herbivorous arthropods, but also hinder searching by phytoseiid mites and other natural enemies of these herbivores. This trichome cover creates competitor-free and enemy-free space for the tomato russet mite (TRM) Aculops lycopersici (Acari: Eriophyidae), being so minute that it can seek refuge and feed inbetween the glandular trichomes on tomato cultivars currently used in practice. Indeed, several species of predatory mites tested for biological control of TRM have been reported to feed and reproduce when offered TRM as prey in laboratory experiments, yet in practice these predator species appeared to be unable to prevent TRM outbreaks. Using the phytoseiid mite, Amblydromalus limonicus, we found exactly the same, but also obtained evidence for successful establishment of a population of this predatory mite on whole plants that had been previously infested with TRM. This successful establishment may be explained by our observation that the defensive barrier of glandular plant trichomes is literally dropped some time after TRM infestation of the tomato plants: the glandular trichome heads first rapidly develop a brownish discoloration after which they dry out and fall over onto the plant surface. Wherever TRM triggered this response, predatory mites were able to successfully establish a population. Nevertheless, biological control was still unsuccessful because trichome deterioration in TRM-infested areas takes a couple of days to take effect and because it is not a systemic response in the plant, thereby enabling TRM to seek temporary refuge from predation in pest-free trichome-dense areas which continue to be formed while the plant grows. We formulate a hypothesis unifying these observations into one framework with an explicit set of assumptions and predictions to be tested in future experiments.

Variants of the human NR1I2 (PXR) locus in chronic periodontitis.

BACKGROUND AND OBJECTIVE: Recent studies on genetic variants of the pregnane X receptor (PXR) revealed associations with the mucosal immune response. This study aimed to investigate the potential association of functional polymorphisms of the NR1I2 (PXR)-encoding gene (rs12721602, rs3814055, rs1523128, rs1523127, rs45610735, rs6785049, rs2276707 and rs3814057) with chronic periodontitis. MATERIAL AND METHODS: At total of 402 periodontitis patients and 793 healthy individuals were genotyped using PCR and melting-curve analysis. RESULTS: Frequency distribution of genotypes for the eight single nucleotide polymorphisms showed no significant difference between patients with periodontitis and controls. Among the eight tested polymorphisms, two blocks were defined showing complete or almost complete linkage disequilibrium (linkage disequilibrium block 1: rs3814055 and rs1523127; and linkage disequilibrium block 2: rs6785049, rs2276707 and rs3814057). For one haplotype (GTGAG) composed of rs12721602, rs3814055, rs1523128, rs12721607 and rs6785049, a significant association with periodontitis was found [p-value after permutation with 100,000 iterations (p(permut.)) = 0.011, odds ratio = 0.46, 95% confidence interval: 0.25-0.84) following adjustment for age, gender and smoking. CONCLUSION: A rare haplotype of the NR1I2 (PXR) locus was associated with the individual susceptibility for chronic periodontitis in a German cohort. As a result of the borderline significance and the small effect size the present results need further confirmation.

Impact of MICA-TM, MICB-C1_2_A and C1_4_1 microsatellite polymorphisms on the susceptibility to chronic periodontitis in Germany.

The major histocompatibility complex class I chain-related gene A (MICA)-TM exon 5 trinucleotide polymorphism, the MICB-C1_2_A intron 1 dinucleotide polymorphism and the tetranucleotide polymorphism C1_4_1 located in the major histocompatibility complex class I region on chromosome 6 were shown to influence various chronic inflammatory conditions. We investigated the association of these microsatellite polymorphisms with chronic periodontitis, a highly prevalent oral inflammatory disease in 389 periodontitis patients and 771 healthy controls with South German genetic background. Genotyping of the MICA-TM, MICB-C1_2_A and C1_4_1 microsatellite polymorphisms was performed by PCR amplification and fragment analysis. Global frequency distribution of MICB-C1_2_A (P = 0.006) and C1_4_1 (P = 0.028) alleles was significantly different between both study groups. Allele-specific analysis revealed that the MICA-TM allele A5 was more prevalent among male periodontitis patients [P = 0.0001; odds ratio (OR) 2.17, 95% confidence interval (CI) 1.55-3.03]. In C1_4_1 allele, three was significantly higher in healthy controls (P = 0.006; OR 0.74, 95% CI 0.60-0.91). Two haplotypes (MICA:A5-C1_4_1:5; P = 0.002; OR 2.63, 95% CI 1.46-4.74 and MICB:CA16-C1_4_1:3; P = 0.014; OR 0.68, 95% CI 0.50-0.92) showed significant differences between periodontitis patients and controls. The MICA-TM, MICB-C1_2_A and C1_4_1 microsatellite polymorphism seem to influence the individual susceptibility to chronic periodontitis in patients with German genetic background.

A 3' UTR transition within DEFB1 is associated with chronic and aggressive periodontitis.

Periodontal diseases are complex inflammatory diseases and affect up to 20% of the worldwide population. An unbalanced reaction of the immune system toward microbial pathogens is considered as the key factor in the development of periodontitis. Defensins have a strong antimicrobial function and are important contributors of the immune system toward maintaining health. Here, we present the first systematic association study of DEFB1. Using a haplotype-tagging single nucleotide polymorphism (SNP) approach, including described promoter SNPs of DEFB1, we investigated the associations of the selected variants in a large population (N=1337 cases and 2887 ethnically matched controls). The 3' untranslated region SNP, rs1047031, showed the most significant association signal for homozygous carriers of the rare A allele (P=0.002) with an increased genetic risk of 1.3 (95% confidence interval: 1.11-1.57). The association was consistent with the specific periodontitis forms: chronic periodontitis (odds ratio=2.2 (95% confidence interval: 1.16-4.35), P=0.02), and aggressive periodontitis (odds ratio=1.3 (95% confidence interval 1.04-1.68), P=0.02). Sequencing of regulatory and exonic regions of DEFB1 identified no other associated variant, pointing toward rs1047031 as likely being the causative variant. Prediction of microRNA targets identified a potential microRNA-binding site at the position of rs1047031.

Association of MICA-TM and MICB C1_2_A microsatellite polymorphisms with tumor progression in patients with colorectal cancer.

PURPOSE: The major histocompatibility complex class I related A (MICA) and MICB molecules are ligands of NKG2D receptors on natural killer cells, gamma/delta T cells, and CD8ass T cells that mediate host antitumor immune response. The role of MICA-TM and MICB C1_2_A alleles in patients with colorectal cancer has not yet been investigated. METHODS: We have analyzed the MICA-TM and MICB C1_2_A polymorphisms in colorectal cancer patients (n = 79) by polymerase chain reaction amplification, subsequent electrophoresis, and sequencing in comparison to a previously analyzed cohort of healthy controls (n = 306). Allele frequencies obtained for MICA-TM and MICB C1_2_A were compared to histopathological data regarding tumor invasion, disease progression, microsatellite instability, and the presence of KRAS mutations (codon 12) and analyzed for possible impact on tumor-related survival (n = 61). RESULTS: Allele frequencies of MICA-TM and MICB C1_2_A polymorphisms were not different in patients with colorectal cancer in comparison to normal controls. In colorectal cancer patients, MICA-TM A4 allele was directly and MICA-TM A5 allele was inversely associated with lymph node involvement and advanced UICC stages. Tumor-related survival in colorectal cancer patients was significantly reduced in the presence of the MICA-TM A4 allele (p = 0.015). In patients with microsatellite stable tumors, survival was reduced in association with the MICA-TM A4 allele (p = 0.006) and MICA-TM A9 allele (p = 0.034), but increased in patients showing the MICA-TM A5 allele (p = 0.042). CONCLUSIONS: Specific MICA-TM alleles seem to influence tumor progression and midterm survival of patients with colorectal cancer, indicating an important role of host innate immune predisposition involving NKG2D mediated antitumor response.

Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts.

BACKGROUND: DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. METHODS: DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. RESULTS: The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. CONCLUSION: DLG5 30Q is associated with a small reduction in risk of CD in women.

MICA*055: a new allele with eight GCT repeats in the exon 5 microsatellite.

The new allele MICA*055 contains eight GCT repeats within the exon 5 MICA-TM microsatellite polymorphism.

Prognostic relevance of p53 and bcl-2 immunoreactivity for early invasive pT1/pT2 gastric carcinomas: indicators for limited gastric resections?

BACKGROUND: Laparoscopic or endoscopic limited resection is intended to be an additional therapeutic option for the treatment of early gastric cancer. However, tumorbiologic markers to predict the outcome for patients after limited resections are missing. This study therefore investigated the prognostic relevance of p53 and bcl-2 immunoreactivity as well as the percentage of apoptotic tumor cells in early invasive pT1/pT2 tumors managed with standard operations for gastric adenocarcinoma. METHODS: Histologic slides of 65 pT1/pT2 gastric carcinomas were investigated for bcl-2 and p53 immunoreactivity. For 35 patients, DNA fragmentation of tumor cell nuclei was determined by the terminal uridine 5'-triphosphate (UTP) nick end-labeling (TUNEL) method. Follow-up evaluation of the patients was prospectively documented for 53.4 +/- 4.1 months. RESULTS: Findings showed that bcl-2 immunoreactivity was associated with tumors of the intestinal type according to Lauren s classification (p = 0.042), and that p53 immunoreactivity was increased in more invasive tumors (pT1 vs pT2 tumors; p = 0.047). Mean survival time was significantly longer for patients with bcl-2-negative tumors (74.3 +/- 6.8 months) than for patients with bcl-2-positive tumors (50.8 +/- 7.6 months; p = 0.024). The percentage of apoptotic tumor cell nuclei did not have prognostic relevance in the population studied and was not associated with several histopathologic parameters or bcl-2 and p53 immunoreactivity. Subgroup analysis indicated that the survival of patients with differentiated G2 and bcl-2-negative/p53-negative tumors was significantly longer (82 +/- 6 months) than the survival of patients with G2 bcl-2- and/or p53-positive tumors (41.8 +/- 12.5 months; p = 0.005), with independent prognostic relevance determined by multivariate analysis (p = 0.024). CONCLUSION: The data reported indicate that the analysis of bcl-2 and p53 immunoreactivity seems to have prognostic implications for early invasive (pT1/pT2) gastric adenocarcinomas and may subclassify patients for minimally invasive laparoscopic or endoscopic gastric resections.

The leukocyte count predicts the efficacy of treatment with azathioprine in inflammatory bowel disease.

INTRODUCTION: Azathioprine has variable efficacy in inflammatory bowel disease. Previous studies suggested that either neutropenia, an increase in the mean corpuscular volume, the assessment of thiopurine methyl-transferase activity or erythrocyte 6-thioguanine values might predict the treatment response. However, due to the conflicting results of the preceding studies there are yet no established laboratory values which allow an estimation of the clinical response. PATIENTS AND METHODS: 45 patients with Crohn's disease and 39 patients with ulcerative colitis were enrolled in this retrospective evaluation. After a minimum of six months therapy with azathioprine patients in remission were compared with those who did not achieve a stable remission with respect to the number of leucocytes, lymphocytes, neutrophil granulocytes and the mean corpuscular volume. RESULTS: Patients who went into remission during treatment with azathioprine displayed significantly lower leukocyte counts if compared to patients who were not in remission (p = 0.004 in Crohn's disease and 0.003 in ulcerative colitis). A similar tendency was also observed with respect to the granulocyte count (p = 0.007 in Crohn's disease and 0.004 in ulcerative colitis). The mean corpuscular volume did not correlate with the response to purine analogues. DISCUSSION: The absolute leukocyte count and the percentage of granulocytes seem to predict the response to purine analogues in inflammatory bowel disease and possibly offers a feasible and cost effective diagnostic tool for the assessment of therapeutic efficacy. Subsequent preferably prospective studies should aim to define the optimal cut-off value for the leukocyte count.

Detection of occult high graded microsatellite instabilities in MMR gene mutation negative HNPCC tumors by addition of complementary marker analysis.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant tumor syndrome predisposing to predominantly colorectal and endometrial cancer. In 90% of the cases, molecular analyses reveal microsatellite instabilities due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2, among these tumors. PATIENTS AND METHODS: Tumors from 40 HNPCC index patients (31 Amsterdam positive, 9 Bethesda positive; 21 females, 19 males; mean age 48.0 +/- 13.2 years) were examined. In contrast to the classical constellation, their tumors revealed only a microsatellite stable (MSS, n=31)--or low instable (MSI-L, n=9)--tumor phenotype following the international reference panel of 5 microsatellites. No MLH1 and MSH2 mutations were detectable. Complementary microsatellites (BAT40, D10S197, D13S153, D18S58, MYCL1) were investigated by PCR and fragment analysis to find other instabilities which might hint to the MIN-pathway of the tumors. RESULTS: Due to ten microsatellites in total tumors were now reclassified in 4 MSI-H (10%), 24 MSI-L (60%) and 12 in MSS (30%) phenotypes. The mean age of onset for CRCs was the lowest in the MSI-H group with 45.7 +/- 9.6 years (vs. 48.7 +/- 14.3 and 49.0 +/- 12.9 years in MSI-L and MSS group). MSI-H-and MSI-L tumors were often localized in the proximal colon (50 and 52%), whereas MSS tumors were preferentially localized in the distal colon (77%). - CONCLUSION: Complementary microsatellites help to subdive "non-classical" HNPCC in subgroups with different clinical appearance. It allows to detect occult MSI-H tumors with up to 10% and to confirm MSS tumors who seem to have a similar biological behaviour like sporadic CRC. Maybe that this genetic reclassification influence the decision of whether to offer patients chemotherapy or not, since it is known that patients with instable tumors do not benefit from chemotherapy as well as patients with microsatellite stable tumors.

Open wound drainage versus wound excision in treating the modern assault rifle wound.

Military dogma of the past 20 years preaches that excision of all injured tissue around the path of a penetrating projectile is essential in wound treatment. To find out whether excising injured muscle surrounding a bullet path benefits healing over and above the benefit provided by a simple release of tension by incision, two groups of 90 kg swine were shot in the hind leg with a replica of the AK-74 assault rifle projectile. One group was treated by excision of injured tissue around the projectile path; in the other group no tissue was excised. Both groups were given parenteral penicillin for 5 days, and simple gauze dressings were used to cover the wounds. No difference in healing time occurred; the wounds in both groups had closed, and no epithelial defect remained by 20 to 22 days. These results indicate that the simple extremity wound caused by the modern-generation assault rifle, provided with adequate open drainage and systemic penicillin, heals as rapidly when the body defense mechanisms handle the disrupted tissue as when an attempt is made to excise it surgically.

Argon laser treatment of port wine stain.

The authors achieved excellent results using argon laser treatment of PWS in 45% of 84 patients. Punch biopsies were taken preoperatively in all patients. Their classification according to fullness of erythrocytes of the vessels was found to be of relative value in predicting the treatment result. It is thus found to be advisable to administer a test treatment of a limited area in all patients.

Treatment of keloids with surgical excision and postoperative X-ray radiation.

124 patients with keloids were treated with surgical excision followed by postoperative X-ray radiation, begun within 24 hours after surgery. Only patients with a two-year keloid history were included in this study. The treatment results were evaluated 6 and 24 months after treatment. There was good correlation agreement between subjective and objective evaluations. Good or excellent results were observed in 92% of the patients. Side effects were moderate. Slight hyperpigmentation was found in 31% of the patients and telangiectasis in 15%. It was concluded that excision and early postoperative irradiation constitute effective keloid treatment.

Oviposition behaviors in relation to rotation resistance in the western corn rootworm.

Across a large area of the midwestern United States Corn Belt, the western corn rootworm beetle (Diabrotica virgifera virgifera LeConte, Coleoptera: Chrysomelidae) exhibits behavioral resistance to annual crop rotation. Resistant females exhibit increased locomotor activity and frequently lay eggs in soybean (Glycine max L.) fields, although they also lay eggs in fields of corn (Zea mays L.) and other locations. The goals of this study were (1) to determine whether there were any differences in ovipositional behavior and response to plant cues between individual rotation-resistant and wild-type females in the laboratory and (2) to examine the roles of, and interaction between, host volatiles, diet, and locomotor behavior as they related to oviposition. Because rootworm females lay eggs in the soil, we also examined the influence of host plant roots on behavior. In the first year of the study, rotation-resistant beetles were significantly more likely to lay eggs in the presence of soybean foliage and to feed on soybean leaf discs than wild-type females, but this difference was not observed in the second year. Oviposition by rotation-resistant females was increased in the presence of soybean roots, but soybean herbivory did not affect ovipositional choice. Conversely, ovipositional choice of wild-type females was not affected by the presence or identity of host plant roots encountered, and wild-type females consuming soybean foliage were more likely to lay eggs.

COX-2 is associated with periodontitis in Europeans.

COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were associated with periodontitis in populations of European ethnicity, we genotyped the single-nucleotide polymorphisms (SNPs) rs689466 and rs6681231, the latter a haplotype tagging SNP (htSNP) for rs20417 (r2>0.95), in our large-analysis population of individuals with aggressive (n = 532) and chronic periodontitis (n = 1052), and 2873 healthy control individuals. The rare G allele of htSNP rs6681231 was associated with aggressive periodontitis prior to and after adjustment for the covariates smoking, diabetes, and gender, with an odds ratio of 1.57 (95% confidence interval 1.18-2.08; p = 0.002). The validation of the association of rs20417 by the htSNP rs6681231 provides evidence for a general genetic risk of COX-2 variants in the pathogenesis of periodontitis.