University Medical Center Brackenridge

Sequencing of the genome of the butterfly Heliconius melpomene shows that closely related Heliconius species exchange protective colour-pattern genes promiscuously. Heliconius butterflies are an excellent system in which to study ecology, behaviour, mimicry and speciation. The genome of the postman butterfly Heliconius melpomene has now been sequenced. Using genomic resequencing of individuals from distinct lineages, the authors document heterogenous patterns of genomic diversity associated with adaptively divergent wing-colour patterns. As the second lepidopteran genome to be sequenced, Heliconius offers novel opportunities for comparative genomics within this economically significant insect order, which includes many pest species, as well as the only domesticated insect, the silkmoth Bombyx mori. The evolutionary importance of hybridization and introgression has long been debated1. Hybrids are usually rare and unfit, but even infrequent hybridization can aid adaptation by transferring beneficial traits between species. Here we use genomic tools to investigate introgression in Heliconius, a rapidly radiating genus of neotropical butterflies widely used in studies of ecology, behaviour, mimicry and speciation2,3,4,5. We sequenced the genome of Heliconius melpomene and compared it with other taxa to investigate chromosomal evolution in Lepidoptera and gene flow among multiple Heliconius species and races. Among 12,669 predicted genes, biologically important expansions of families of chemosensory and Hox genes are particularly noteworthy. Chromosomal organization has remained broadly conserved since the Cretaceous period, when butterflies split from the Bombyx (silkmoth) lineage. Using genomic resequencing, we show hybrid exchange of genes between three co-mimics, Heliconius melpomene, Heliconius timareta and Heliconius elevatus, especially at two genomic regions that control mimicry pattern. We infer that closely related Heliconius species exchange protective colour-pattern genes promiscuously, implying that hybridization has an important role in adaptive radiation.

The fire ant Solenopsis invicta Buren invaded southeastern United States from South America >50 yr ago. Urban and agricultural consequences of this invasion are well documented; however, ecological effects are still poorly understood. Increasing frequencies of p olygyne or multiple—queen fire ants in Texas and other areas of the Southeast are disturbing because nest densities of this new form are often ten times as great as those of the more familiar monogyne form. We studied the ecological impacts of a polygyne fire ant invasion on ants and other surface—active arthropods at a field station in central Texas. Arthropod abundance and species richness were assessed using a combination of baits, pitfall traps, and litter samples. This invasion decimated the indigenous ant fauna. Competitive replacement appears to be the primary mechanism behind this effect. Species richness of ants in infested areas dropped by 70%, while the total number of native individuals dropped by 90%. Of 35 species of ants collected in this study, 23 were either significantly less common or absent from infested sites; only S. invicta was more common at infested sites. The most dramatic effect of the invasion was a 10—30 fold increase in the total number of ants at infested sites–of which >99% were the imported fire ant S. invicta. The impact of this invasion on other surface—active arthropods was less severe, but still substantial. The abundance of isopods, erythraeid mites, and tumblebug scarabs declined significantly, while the abundance of ground crickets, a brachypterous roach, and a symbiotic scarab increased significantly. Overall, the species richness of non—ant arthropods was 30% lower in infested sites, and individual numbers were 75% lower. Total arthropod species richness (including ants) was 40% less at infested sites. These data indicate that polygyne fire ants pose a substantial threat to the biodiversity of native arthropod communities.

Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders.

Improving environmental adaptation in crops is essential for food security under global change, but phenotyping adaptive traits remains a major bottleneck. If associations between single-nucleotide polymorphism (SNP) alleles and environment of origin in crop landraces reflect adaptation, then these could be used to predict phenotypic variation for adaptive traits. We tested this proposition in the global food crop Sorghum bicolor, characterizing 1943 georeferenced landraces at 404,627 SNPs and quantifying allelic associations with bioclimatic and soil gradients. Environment explained a substantial portion of SNP variation, independent of geographical distance, and genic SNPs were enriched for environmental associations. Further, environment-associated SNPs predicted genotype-by-environment interactions under experimental drought stress and aluminum toxicity. Our results suggest that genomic signatures of environmental adaptation may be useful for crop improvement, enhancing germplasm identification and marker-assisted selection. Together, genome-environment associations and phenotypic analyses may reveal the basis of environmental adaptation.

Abstract In the latter years of the twentieth century, the social relevance of the leisure field diminished as consumption and individualism came to dominate leisure and recreation research and praxis across modern democratic nations. A consequence of this focus in leisure studies has been a neglect of community and the common good. Now, at the commencement of the twenty-first century, three interrelated crises become increasingly apparent - the crisis of identity or self, a social crisis, and a political crisis. If leisure studies is to contribute to an attempt to address these crises and rebuild community, how might this happen without returning to the norms, duties and traditional structures that have oppressed and marginalized citizens? In this paper the notion of social capital is used to examine community structures and their potential contribution to social cohesion, trust, mutuality, co-operation and openness. The challenge is to develop a concept of community that can provide spaces for the social self and civic engagement to emerge. The paper explores the role of leisure practices in this pursuit. Central to the discussion is Borgmann's notion of focal practices - those pursuits which bring an engagement of mind and body and a centring power - and the way in which such practices create shared meaning and communities of celebration. Participation in communities of celebration entails people coming together in sports, festivals, hobbies, volunteering, and the arts, and finding in these leisure activities common and public goods. This communitarian conceptualization of leisure stands in stark contrast to the privatization of leisure that has become commonplace in recent decades.

Prognostic value of histological grading of oligodendroglial tumors is controversial and interobserver reproducibility in grading of these tumors is unknown. Seven neuropathologists and 6 surgical pathologists experienced in brain tumor-diagnosis assessed 124 oligodendroglial tumors operated at the Mayo Clinic (1960-1990). Among histologic parameters upon which current oligodendroglioma grading systems are based, only high cellularity, presence of mitoses, microcalcifications, endothelial hypertrophy, endothelial proliferation, and necrosis appeared to be reproducible. Reproducible histologic features, based on consensus ratings among neuropathologists (defined as > 60%), were evaluated for the association with cause-specific survival by fitting Cox regression models. By univariate analysis, a significant association with survival was found for age, high cellularity, presence of mitoses, endothelial hypertrophy and proliferation and necrosis. On multivariable analysis with a stepwise variable selection method, only age and presence of endothelial proliferation were found to be independently associated with survival with a discriminatory index of the model of 0.68. Mitotic index was significantly associated with survival based on the grading from each separate neuropathologist, but it was not based on consensus, most likely because this was classified as indeterminate in 54% of cases. Alternatively, "models fit" considering the assessment of single neuropathologists, identified a model based on age and on mitotic index with similar discriminatory indices of 0.69-0.7. Our study found few factors independently associated with cause specific-survival among morphological parameters. These findings are consistent with the present WHO stratification of oligodendrogliomas into low- and high-grade variants.

BACKGROUND: A concern with the histologic grading of breast cancer is that tumor grading is a subjective evaluation that may have problems with reproducibility. METHODS: A single slide from 10 invasive breast cancers was submitted to 25 pathologists who practice in six separate groups. Pathologists graded the tumors using a modified Bloom-Richardson (B-R) scheme, and the results were compared. RESULTS: In 8 of the 10 cases, there was greater than 87% agreement by the pathologists as to the final combined B-R grade, with complete agreement in 2 cases. Only one case had any discrepant opinions that ranged from low to high grade, and this involved only 3 of the 25 pathologists. With respect to B-R score, the pathologists tended to score the tumors as either one of two adjacent scores. Due to this clustering, the B-R scheme appears reproducible into five groups: very low and very high grade tumors and B-R score "5,6," "6,7," and "7,8" tumors. This clustering was especially noticeable in two cases with split decisions, in which the discrepancy in final combined grade was largely due to the tumors being given B-R scores that straddled and were then condensed into two B-R grades. A consensus from each pathology group tended to merge with the majority opinion of all 25 pathologists and was correct for outliers. CONCLUSIONS: This study indicates that reproducibility of grading breast cancers can be achieved when a histologic grading scheme with specified guidelines is used. Pathologists must be aware of the limits of reproducibility, with appropriate guidelines being followed to help optimize agreement, and there should be an awareness of how pathologists group in their evaluations. Also, it may be advisable to better correlate or link reproducibility data with prognostic data in the design of grading schemes.

BACKGROUND: This multicenter, Phase II trial was performed to evaluate the antitumor activity and toxicity of irinotecan (CPT-11) in patients with metastatic colorectal carcinoma that had recurred or progressed after 5-fluorouracil (5-FU)-based chemotherapy. METHODS: CPT-11 was given as a 90-minute intravenous infusion in repeated 6-week (42-day) courses comprising weekly treatment for 4 consecutive weeks followed by a 2-week rest. Tumor measurements were obtained after every second course of therapy. Toxicity was assessed weekly using the National Cancer Institute Common Toxicity Criteria. RESULTS: A total of 166 patients were entered into the trial. The first 64 patients received a starting dose of 125 mg/m2. An additional 102 patients were enrolled at a starting dose of 100 mg/m2 to determine whether a reduction in the starting dose would result in lower toxicity without sacrificing efficacy. Objective responses to CPT-11 were observed in 18 patients (1 complete response and 17 partial responses) (response rate [RR] = 10.8%; 95% confidence interval [CI], 6.1-15.6%). An additional 67 patients (40.4%) had stable disease as their best response. At the 125 mg/m2 starting dose, the RR was 14.1% (9 of 64 patients; 95% CI, 5.5-22.6%). Among patients given a starting dose of 100 mg/m2, the RR was 8.8% (9 of 102 patients; 95% CI, 3.3-14.3%). The overall median survival was 9.9 months (range, 0.3-36.8 months). The most frequently observed Grade 3/4 toxicities were gastrointestinal events (i.e., diarrhea [27.1%], nausea [15.1%], emesis [9.6%], abdominal cramping [22.2%], and neutropenia [19.9%]). There were no significant differences in the frequencies of Grade 3/4 toxicities between the 125 mg/m2 and 100 mg/m2 starting dose levels except for Grade 3/4 emesis (21.9% vs. 2%; P < 0.001). Patients age > or = 65 years were twice as likely (38.6% vs. 18.8%; P < 0.008) to develop Grade 3/4 diarrhea compared with younger patients when all courses of therapy were evaluated. However, older age did not significantly predict for a higher incidence of first-course diarrhea (25.0% vs. 14.7%; P = 0.106). CONCLUSIONS: CPT-11 can induce tumor regression in patients with metastatic colorectal carcinoma that has progressed during or shortly after 5-FU-based chemotherapy. Gastrointestinal events and neutropenia were the most common serious toxicities. Given the trend toward a higher response rate without substantially greater toxicity, 125 mg/m2 has been selected as the preferred starting dose for further studies. Careful attention to appropriate CPT-11 dose modification and early intervention with loperamide may be especially important in elderly patients.

BACKGROUND: Few studies have investigated the effects of anemia in patients with traumatic brain injury (TBI). The objective of this study was to examine the role of anemia and blood transfusion on outcomes in TBI patients. STUDY DESIGN: We performed a retrospective review of all blunt trauma patients with TBI admitted to the ICU from July 1998 to December 2005. Admission and daily ICU blood hemoglobin (hemoglobin) levels and blood transfusions during the first week of hospitalization were measured. Anemia was defined as a hemoglobin<9 g/dL occurring on 3 consecutive blood draws. The role of anemia and blood transfusion was investigated using logistic regression adjusting for factors, with p<0.2 from the bivariate analysis. RESULTS: During the study period, 1,150 TBI patients were admitted to the ICU. When both anemia and blood transfusion were included in the full model, blood transfusion was significantly associated with higher mortality (adjusted odds ratio [AOR], 2.19 [95% CI, 1.27, 3.75]; p=0.0044) and more complications (AOR, 3.67 [95% CI, 2.18, 6.17]; p<0.0001), but anemia was not. But when transfusion was not included in the full model, anemia was a significant risk factor for mortality (AOR, 1.59 (95% CI, 1.13, 2.24); p=0.007) and for complications (AOR, 1.95 [95% CI, 1.42, 2.70]; p<0.0001). CONCLUSIONS: Blood transfusion is associated with significantly worse outcomes in traumatic brain injured patients. In addition, blood transfusion is a major contributing factor to worse outcomes in TBI patients who are anemic. We caution against the liberal use of blood in TBI patients.

Invasive ant species represent a serious threat to the integrity of many ecological communities, often causing decreases in the abundance and species richness of both native ants and other arthropods. One of the most in-depth and well-known studies of this type documented a severe impact of the imported red fire ant, Solenopsis invicta, on the native ant and arthropod fauna of a biological field reserve in central Texas (USA) during the initial invasion in the late 1980s. I sampled the community again in 1999, 12 years later, utilizing the same methodology, to compare the short- and long-term impacts of this invasion. Pitfall traps and baits were used to obtain quantitative measures of the ant and arthropod community, and hand collecting was additionally employed to determine the overall ant species composition. Although the abundance and species richness of native ants and several other arthropod groups decreased precipitously immediately after the S. invicta invasion, all measures of native ant and arthropod species diversity had returned to preinvasion levels after 12 years. Solenopsis invicta was still the most abundant ant species, but not nearly as abundant as it was during the initial phase of the invasion. The results of this study indicate that the impact of such invasive ants may be greatest during and shortly after the initial phase of an invasion.

BACKGROUND: The increased prevalence of ductal carcinoma in situ (DCIS) has produced a growing awareness of the importance of its diverse patterns. These differences in pattern have become clinically significant as predictive indicators of success for planned local excisions of small DCIS lesions. METHODS: The authors reviewed 100 sequentially collected DCIS cases from a consultation practice. Recognizing the bias of such a series toward exclusion of easily recognizable comedo DCIS, the authors investigated the spectrum of mixed pattern lesions to identify variations and common features in the architectural arrangement of the various histologic patterns. RESULTS: Patterns of atypical ductal hyperplasia (ADH) with specific criteria of recognition were intermixed in 17 cases (11 cribriform, 1 solid, 1 micropapillary, 4 mixed). Thirty-three cases of DCIS consisted of mixed patterns of comedo and noncomedo types. No case of comedo DCIS with associated areas of ADH was identified. In all cases of combined DCIS and ADH, the more advanced patterns of DCIS were present in the central portion of the lesion, with the ADH components arranged peripherally. This tendency for the more severely atypical areas to be located centrally was present throughout the study. CONCLUSIONS: Different patterns of DCIS are frequently present within individual lesions (46 of 100), and the more advanced features of architectural atypia are regularly present centrally. This strongly supports the hypothesis that these lesions develop from a central focus and expand peripherally. Also, those lesions with low-grade DCIS at the periphery may be as amenable to local excision for cure as purely low-grade lesions.

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought.

BACKGROUND: The optimal chest tube size for the drainage of traumatic hemothoraces and pneumothoraces is unknown. The purpose of this study was to compare the efficacy of small versus large chest tubes for use in thoracic trauma. Our hypothesis was that (1) there would be no difference in clinically relevant outcomes including retained hemothoraces, the need for additional tube insertion, and invasive procedures and (2) there would be an increase in pain with the insertion of large versus small tubes. METHODS: This is a prospective, institutional review board-approved observational study. All patients requiring open chest tube drainage within 12 hours of admission (January 2007-January 2010) were identified at a Level I trauma center. Clinical demographic data and outcomes including efficacy of drainage, complications, retained hemothoraces, residual pneumothoraces, need for additional tube insertion, video-assisted thoracoscopy, and thoracotomy were collected and analyzed by tube size. Small chest tubes (28-32 Fr) were compared with large (36-40 Fr). RESULTS: During the study period, a total of 353 chest tubes (small: 186; large: 167) were placed in 293 patients. Of the 275 chest tubes inserted for a hemothorax, 144 were small (52.3%) and 131 were large (47.7%). Both groups were similar in age, gender, and mechanism; however, large tubes were placed more frequently in patients with a Glasgow Coma Scale ≤8, severe head injury, a systolic blood pressure <90 mm Hg, and Injury Severity Score ≤25. The volume of blood drained initially and the total duration of tube placement were similar for both groups (small: 6.3 ± 3.9 days vs. large: 6.2 ± 3.6 days; adjusted (adj.) p = 0.427). After adjustment, no statistically significant difference in tube-related complications, including pneumonia (4.9% vs. 4.6%; adj. p = 0.282), empyema (4.2% vs. 4.6%; adj. p = 0.766), or retained hemothorax (11.8% vs. 10.7%; adj. p = 0.981), was found when comparing small versus large chest tubes. The need for tube reinsertion, image-guided drainage, video-assisted thoracoscopy, and thoracotomy was likewise the same (10.4% vs. 10.7%; adj. p = 0.719). For patients with a pneumothorax requiring chest tube drainage (n = 238), there was no difference in the number of patients with an unresolved pneumothorax (14.0% vs. 13.0%; adj. p = 0.620) or those needing reinsertion of a second chest tube. The mean visual analog pain score was similar for small and large tubes (6.0 ± 3.3 and 6.7 ± 3.0; p = 0.237). CONCLUSIONS: For injured patients with chest trauma, chest tube size did not impact the clinically relevant outcomes tested. There was no difference in the efficacy of drainage, rate of complications including retained hemothorax, need for additional tube drainage, or invasive procedures. Furthermore, tube size did not affect the pain felt by patients at the site of insertion. LEVEL OF EVIDENCE: : II.

OBJECTIVES: In pancreatic cancer (PaC), the prevalence of diabetes mellitus (DM), especially new-onset DM (≤36 months of PaC diagnosis), is high. To determine if this observation is unique to PaC, we compared the prevalence and characteristics of DM in lung, breast, prostate, and colorectal cancers with PaC and noncancer controls. METHODS: We retrospectively reviewed the medical records of 500 consecutive patients with cancer (100 each with lung, breast, prostate, and colorectal cancers and PaC) and 100 noncancer controls. RESULTS: Patients with PaC (mean age ± SD, 71.6 ± 9.4 years; 53% men) had a significantly (P < 0.0001) higher prevalence of DM (68%) compared to age-matched patients with lung (mean age ± SD, 71.6 ± 9.4 years; 59% men; and 19.6% DM), breast (mean age ± SD, 71.6 ± 9.6 years; 100% women; and 19.4% DM), prostate (mean age ± SD, 71.3 ± 9.4 years; 100% men; and 14.8% DM), and colorectal cancer (mean age ± SD, 71.6 ± 9.5 years; 56% men; and 20.7% DM), and noncancer controls (mean age ± SD, 70.7 ± 9.2 years; 57% men; and 23.5% DM). Among the patients with PaC, 40% developed DM in the 36 months preceding the diagnosis of PaC compared with 3.3% to 5.7% in the other groups (P < 0.0001). CONCLUSIONS: Whereas the prevalence of DM in PaC is very high, DM prevalence in other common cancers is no different from that in noncancer controls. In particular, new-onset DM is a phenomenon that is unique to PaC.

This article discusses the challenges of how to provide a transparent account of the use of the software program QSR*NVIVO (QSR, 2000) within a grounded theory framework (Glaser and Strauss, 1967; Strauss and Corbin, 1998). Psychology students are increasingly pursuing qualitative research projects to such an extent that the UK Economic and Social Research Council (ESRC) advise that students should have skill in the use of computer assisted qualitative data analysis software (CAQDAS) (Economic and Social Research Council, 2001). Unlike quantitative studies, rigid formulae do not exist for writing-up qualitative projects for doctoral theses. Most authors, however, agree that transparency is essential when communicating the findings of qualitative research. Sparkes (2001) recommends that evaluative criteria for qualitative research should be commensurable with the aims, objectives, and epistemological assumptions of the research project. Likewise, the use of CAQDAS should vary according to the research methodology followed, and thus researchers should include a discussion of how CAQDAS was used. This article describes how the evolving process of coding data, writing memos, categorizing, and theorizing were integrated into the written thesis. The structure of the written document is described including considerations about restructuring and the difficulties of writing about an iterative process within a linear document.

The inadvertent introduction of the fire ant Solenopsis invicta to the United States from South America provides the opportunity to study recent social evolution by comparing social organization in native and introduced populations. We report that several important elements of social organization in multiple-queen nests differ consistently and dramatically between ants in Argentina and the United States. Colonies in Argentina contain relatively few queens and they are close relatives, whereas colonies in the United States contain high numbers of unrelated queens. A corollary of these differences is that workers in the native populations are significantly related to the new queens that they rear in contrast to the zero relatedness between workers and new queens in the introduced populations. The observed differences in queen number and relatedness signal a shift in the breeding biology of the introduced ants that is predicted on the basis of the high population densities in the new range. An additional difference in social organization that we observed, greater proportions of permanently unmated queens in introduced than in native populations, is predicted from the loss of alleles at the sex-determining locus and consequent skewing of operational sex ratios in the colonizing ants. Thus, significant recent social evolution in fire ants is consistent with theoretical expectations based on the altered ecology and population genetics of the introduced populations.

The invasion of Brackenridge Field Laboratory, Austin, Texas, by the multiple-queen form of the red imported fire ant, Solenopsis invicta Buren, was monitored for 3 yr. This invasion provides a rare glimpse of competitive replacement in progress. It has been remarkable for two reasons. First, imported fire ant colonies replaced colonies of the native fire ant, Solenopsis geminata (F.), at a ratio of 6:1, indicating a radical restructuring of the arthropod community rather than a simple one-for-one substitution of an equivalent species. Secondly, the invasion proceeded at a very slow rate (about 35 m/yr) along a continuous front in a pattern best explained by colony budding and considerable biotic resistance from the native ant community. These data indicate that the invasion process may continue at the local level for years or even decades after the passage of the main invasion front.

Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23.

Mutualisms play key roles in the functioning of ecosystems. However, reciprocally beneficial interactions that involve introduced species also can enhance invasion success and in doing so compromise ecosystem integrity. For example, the growth and competitive ability of introduced plant species can increase when fungal or microbial associates provide limiting nutrients. Mutualisms also may aid animal invasions, but how such systems may promote invasion success has received relatively little attention. Here we examine how access to food-for-protection mutualisms involving the red imported fire ant (Solenopsis invicta) aids the success of this prominent invader. Intense interspecific competition in its native Argentina constrained the ability of S. invicta to benefit from honeydew-producing Hemiptera (and other accessible sources of carbohydrates), whereas S. invicta dominated these resources in its introduced range in the United States. Consistent with this strong pattern, nitrogen isotopic data revealed that fire ants from populations in the United States occupy a lower trophic position than fire ants from Argentina. Laboratory and field experiments demonstrated that honeydew elevated colony growth, a crucial determinant of competitive performance, even when insect prey were not limiting. Carbohydrates, obtained largely through mutualistic partnerships with other organisms, thus represent critical resources that may aid the success of this widespread invasive species. These results illustrate the potential for mutualistic interactions to play a fundamental role in the establishment and spread of animal invasions.

BACKGROUND: Acetaminophen (APAP) hepatotoxicity is currently the most frequent cause of acute liver failure in the US and many European countries. Although intracellular signalling mechanisms are critical for hepatocellular injury, a contribution of inflammatory cells, especially neutrophils, has been suggested. However, conflicting results were obtained when using immunological intervention strategies. AIMS: The role of neutrophils was investigated using a CD18-deficient mouse model. RESULTS: Treatment of C57Bl/6 wild type mice with 300 mg/kg APAP resulted in severe liver cell necrosis at 12 and 24 h. This injury was accompanied by formation of cytokines and chemokines and accumulation of neutrophils in the liver. However, there was no difference in the inflammatory response or liver injury in CD18-deficient mice compared with wild-type animals. In contrast to treatment with endotoxin, no upregulation of CD11b or priming for reactive oxygen was observed on neutrophils isolated from the peripheral blood or the liver after APAP administration. Furthermore, animals treated with endotoxin 3 h after APAP experienced an exaggerated inflammatory response as indicated by substantially higher cytokine and chemokine formation and twice the number of neutrophils in the liver. However, liver injury in the two-hit model was the same as with APAP alone. CONCLUSIONS: Our data do not support the hypothesis that neutrophils contribute to APAP hepatotoxicity or that a neutrophil-mediated injury phase could be provoked by a second, pro-inflammatory hit. Thus, APAP-induced liver injury in mice is dominated by intracellular mechanisms of cell death rather than by neutrophilic inflammation.