Ten simple rules for making training materials FAIR.

Everything we do today is becoming more and more reliant on the use of computers. The field of biology is no exception; but most biologists receive little or no formal preparation for the increasingly computational aspects of their discipline. In consequence, informal training courses are often needed to plug the gaps; and the demand for such training is growing worldwide. To meet this demand, some training programs are being expanded, and new ones are being developed. Key to both scenarios is the creation of new course materials. Rather than starting from scratch, however, it's sometimes possible to repurpose materials that already exist. Yet finding suitable materials online can be difficult: They're often widely scattered across the internet or hidden in their home institutions, with no systematic way to find them. This is a common problem for all digital objects. The scientific community has attempted to address this issue by developing a set of rules (which have been called the Findable, Accessible, Interoperable and Reusable [FAIR] principles) to make such objects more findable and reusable. Here, we show how to apply these rules to help make training materials easier to find, (re)use, and adapt, for the benefit of all.

Expression Atlas: gene and protein expression across multiple studies and organisms.

Expression Atlas (http://www.ebi.ac.uk/gxa) is an added value database that provides information about gene and protein expression in different species and contexts, such as tissue, developmental stage, disease or cell type. The available public and controlled access data sets from different sources are curated and re-analysed using standardized, open source pipelines and made available for queries, download and visualization. As of August 2017, Expression Atlas holds data from 3,126 studies across 33 different species, including 731 from plants. Data from large-scale RNA sequencing studies including Blueprint, PCAWG, ENCODE, GTEx and HipSci can be visualized next to each other. In Expression Atlas, users can query genes or gene-sets of interest and explore their expression across or within species, tissues, developmental stages in a constitutive or differential context, representing the effects of diseases, conditions or experimental interventions. All processed data matrices are available for direct download in tab-delimited format or as R-data. In addition to the web interface, data sets can now be searched and downloaded through the Expression Atlas R package. Novel features and visualizations include the on-the-fly analysis of gene set overlaps and the option to view gene co-expression in experiments investigating constitutive gene expression across tissues or other conditions.

Defining a pro-inflammatory neutrophil phenotype in response to schistosome eggs.

Neutrophils contribute to the pathological processes of a number of inflammatory disorders, including rheumatoid arthritis, sepsis and cystic fibrosis. Neutrophils also play prominent roles in schistosomiasis japonica liver fibrosis, being central mediators of inflammation following granuloma formation. In this study, we investigated the interaction between Schistosoma japonicum eggs and neutrophils, and the effect of eggs on the inflammatory phenotype of neutrophils. Our results showed significant upregulated expression of pro-inflammatory cytokines (IL-1α, IL-1ß and IL-8) and chemokines (CCL3, CCL4 and CXCL2) in neutrophils after 4 h in vitro stimulation with S. japonicum eggs. Furthermore, mitochondrial DNA was released by stimulated neutrophils, and induced the production of matrix metalloproteinase 9 (MMP-9), a protease involved in inflammation and associated tissue destruction. We also found that intact live eggs and isolated soluble egg antigen (SEA) triggered the release of neutrophil extracellular traps (NETs), but, unlike those reported in bacterial or fungal infection, NETs did not kill schistosome eggs in vitro. Together these show that S. japonicum eggs can induce the inflammatory phenotype of neutrophils, and further our understanding of the host-parasite interplay that takes place within the in vivo microenvironment of schistosome-induced granuloma. These findings represent novel findings in a metazoan parasite, and confirm characteristics of NETs that have until now, only been observed in response to protozoan pathogens.

Transcriptional profiling of chronic clinical hepatic schistosomiasis japonica indicates reduced metabolism and immune responses.

Schistosomiasis is a significant cause of human morbidity and mortality. We performed a genome-wide transcriptional survey of liver biopsies obtained from Chinese patients with chronic schistosomiasis only, or chronic schistosomiasis with a current or past history of viral hepatitis B. Both disease groups were compared with patients with no prior history or indicators of any liver disease. Analysis showed in the main, downregulation in gene expression, particularly those involved in signal transduction via EIF2 signalling and mTOR signalling, as were genes associated with cellular remodelling. Focusing on immune associated pathways, genes were generally downregulated. However, a set of three genes associated with granulocytes, MMP7, CLDN7, CXCL6 were upregulated. Differential gene profiles unique to schistosomiasis included the gene Granulin which was decreased despite being generally considered a marker for liver disease, and IGBP2 which is associated with increased liver size, and was the most upregulated gene in schistosomiasis only patients, all of which presented with hepatomegaly. The unique features of gene expression, in conjunction with previous reports in the murine model of the cellular composition of granulomas, granuloma formation and recovery, provide an increased understanding of the molecular immunopathology and general physiological processes underlying hepatic schistosomiasis.

An international consensus on effective, inclusive, and career-spanning short-format training in the life sciences and beyond.

Science, technology, engineering, mathematics, and medicine (STEMM) fields change rapidly and are increasingly interdisciplinary. Commonly, STEMM practitioners use short-format training (SFT) such as workshops and short courses for upskilling and reskilling, but unaddressed challenges limit SFT's effectiveness and inclusiveness. Education researchers, students in SFT courses, and organizations have called for research and strategies that can strengthen SFT in terms of effectiveness, inclusiveness, and accessibility across multiple dimensions. This paper describes the project that resulted in a consensus set of 14 actionable recommendations to systematically strengthen SFT. A diverse international group of 30 experts in education, accessibility, and life sciences came together from 10 countries to develop recommendations that can help strengthen SFT globally. Participants, including representation from some of the largest life science training programs globally, assembled findings in the educational sciences and encompassed the experiences of several of the largest life science SFT programs. The 14 recommendations were derived through a Delphi method, where consensus was achieved in real time as the group completed a series of meetings and tasks designed to elicit specific recommendations. Recommendations cover the breadth of SFT contexts and stakeholder groups and include actions for instructors (e.g., make equity and inclusion an ethical obligation), programs (e.g., centralize infrastructure for assessment and evaluation), as well as organizations and funders (e.g., professionalize training SFT instructors; deploy SFT to counter inequity). Recommendations are aligned with a purpose-built framework-"The Bicycle Principles"-that prioritizes evidenced-based teaching, inclusiveness, and equity, as well as the ability to scale, share, and sustain SFT. We also describe how the Bicycle Principles and recommendations are consistent with educational change theories and can overcome systemic barriers to delivering consistently effective, inclusive, and career-spanning SFT.

Cardiac remodelling, blood chemistry, haematology and oxygen consumption of Atlantic cod, Gadus morhua L., induced by experimental haemolytic anaemia with phenylhydrazine.

Anaemia is a common pathology associated with many infectious and non-infectious diseases. The effects of haemolytic anaemia induced by i.p. injection of phenylhydrazine (PHZ) were studied in Atlantic cod. Phenylhydrazine injection (0.3 mg kg(-1)) in a DMSO and saline vehicle induced a reproducible and stable anaemia reducing haematocrit, (Hct) by 62% over 3 weeks. Controls consisted of fish injected with saline and DMSO/saline vehicle with minimal effects on Hct or whole blood haemoglobin (Hb). Although anaemia resulted in reduced blood lactate and glucose in PHZ injected fish, there were no effects of anaemia on blood, sodium, chloride or potassium. Similarly, there were no changes in the relative proportions of leucocytes in the blood although an increase in the number of immature erythrocytes was observed in the anaemic fish. Anaemic fish showed a 29 and 22% increase in cardiac somatic index (CSI) relative to saline and vehicle controls, respectively, although there were no significant differences in the linear dimensions of the ventricle. Changes in cardiac somatic and ventricular somatic index correlated positively and significantly with Hct but not with whole blood Hb concentration. Anaemic fish had significantly reduced resting routine oxygen consumption compared with vehicle controls but were not able to increase oxygen consumption following a bout of exhaustive exercise. Plasma lactate concentrations increased significantly after exercise to a greater extent in anaemic fish compared with vehicle control fish. Phenylhydrazine is a useful model for studying haemolytic anaemia in Atlantic cod with minimal effects on blood biochemistry and haematology and clearly reduces the aerobic capacity in Atlantic cod.

Examination of the functional mobility assessment tool for children and adolescents with lower extremity amputations.

PURPOSE: To assess the validity of the Functional Mobility Assessment (FMA) for children and adolescents with lower extremity amputations. METHODS: Twenty-five subjects (mean age = 12.36 ± 1.42 years) with lower extremity amputations and 12 subjects (mean age = 10.25 ± 1.42 years) with typical development were examined using the FMA, which includes the Timed Up and Go, Timed Up and Down Stairs, 9-minute walk/run, heart rate, and Borg Rating of Perceived Exertion. A subjective interview was also performed including questions related to pain, walking satisfaction, and participation in and challenges with various physical activities. RESULTS: Significant differences were identified between the control and amputation groups in FMA score and 3 individual items (P < .05). However, no differences were identified between groups for other items on the FMA. CONCLUSION: Discriminant validity of the FMA as a whole is supported. However, reevaluation of the items within the FMA is warranted.

Transcriptomic Characterization of Tuberculous Sputum Reveals a Host Warburg Effect and Microbial Cholesterol Catabolism.

The crucial transmission phase of tuberculosis (TB) relies on infectious sputum and yet cannot easily be modeled. We applied one-step RNA sequencing (RNA-Seq) to sputum from infectious TB patients to investigate the host and microbial environments underlying transmission of Mycobacterium tuberculosis. In such TB sputa, compared to non-TB controls, transcriptional upregulation of inflammatory responses, including an interferon-driven proinflammatory response and a metabolic shift toward glycolysis, was observed in the host. Among all bacterial sequences in the sputum, approximately 1.5% originated from M. tuberculosis, and its transcript abundance was lower in HIV-1-coinfected patients. Commensal bacterial abundance was reduced in the presence of M. tuberculosis infection. Direct alignment to the genomes of the predominant microbiota species also reveals differential adaptation, whereby firmicutes (e.g., streptococci) displayed a nonreplicating phenotype with reduced transcription of ribosomal proteins and reduced activities of ATP synthases, while Neisseria and Prevotella spp. were less affected. The transcriptome of sputum M. tuberculosis more closely resembled aerobic replication and shared similarity in carbon metabolism to in vitro and in vivo models with significant upregulation of genes associated with cholesterol metabolism and downstream propionate detoxification pathways. In addition, and counter to previous reports on intracellular M. tuberculosis infection in vitro, M. tuberculosis in sputum was zinc, but not iron, deprived, and the phoP loci were also significantly downregulated, suggesting that the pathogen is likely extracellular in location. IMPORTANCE Although a few studies have described the microbiome composition of TB sputa based on 16S ribosomal DNA, these studies did not compare to non-TB samples and the nature of the method does not allow any functional inference. This is the first study to apply such technology using clinical specimens and obtained functional transcriptional data on all three aspects simultaneously. We anticipate that an improved understanding on the biological interactions in the respiratory tract may also allow novel interventions, such as those involving microbiome manipulation or inhibitor targeting disease-specific metabolic pathways.

Biocuration - mapping resources and needs.

Background: Biocuration involves a variety of teams and individuals across the globe. However, they may not self-identify as biocurators, as they may be unaware of biocuration as a career path or because biocuration is only part of their role. The lack of a clear, up-to-date profile of biocuration creates challenges for organisations like ELIXIR, the ISB and GOBLET to systematically support biocurators and for biocurators themselves to develop their own careers. Therefore, the ELIXIR Training Platform launched an Implementation Study in order to i) identify communities of biocurators, ii) map the type of curation work being done, iii) assess biocuration training, and iv) draw a picture of biocuration career development. Methods: To achieve the goals of the study, we carried out a global survey on the nature of biocuration work, the tools and resources that are used, training that has been received and additional training needs. To examine these topics in more detail we ran workshop-based discussions at ISB Biocuration Conference 2019 and the ELIXIR All Hands Meeting 2019. We also had guided conversations with selected people from the EMBL-European Bioinformatics Institute. Results: The study illustrates that biocurators have diverse job titles, are highly skilled, perform a variety of activities and use a wide range of tools and resources. The study emphasises the need for training in programming and coding skills, but also highlights the difficulties curators face in terms of career development and community building. Conclusion: Biocurators themselves, as well as organisations like ELIXIR, GOBLET and ISB must work together towards structural change to overcome these difficulties. In this article we discuss recommendations to ensure that biocuration as a role is visible and valued, thereby helping biocurators to proceed with their career.

Characterising granuloma regression and liver recovery in a murine model of schistosomiasis japonica.

For hepatic schistosomiasis the egg-induced granulomatous response and the development of extensive fibrosis are the main pathologies. We used a Schistosoma japonicum-infected mouse model to characterise the multi-cellular pathways associated with the recovery from hepatic fibrosis following clearance of the infection with the anti-schistosomal drug, praziquantel. In the recovering liver splenomegaly, granuloma density and liver fibrosis were all reduced. Inflammatory cell infiltration into the liver was evident, and the numbers of neutrophils, eosinophils and macrophages were significantly decreased. Transcriptomic analysis revealed the up-regulation of fatty acid metabolism genes and the identification of Peroxisome proliferator activated receptor alpha as the upstream regulator of liver recovery. The aryl hydrocarbon receptor signalling pathway which regulates xenobiotic metabolism was also differentially up-regulated. These findings provide a better understanding of the mechanisms associated with the regression of hepatic schistosomiasis.

Quantitative computed tomography perfusion of prostate cancer: correlation with whole-mount pathology.

PURPOSE: Microvessel density within the prostate is associated with presence of cancer, disease stage, and disease-specific survival. We evaluated multidetector computed tomography (CT) to estimate prostate perfusion and localize prostate cancer. PATIENTS AND METHODS: Ten subjects were evaluated with contrast enhanced CT before radical prostatectomy with the Mx8000IDT 16-slice scanner. Following baseline pelvic scan, 100 cc of Optiray 300 was administered intravenously (4 cc per second). Repeated dynamic scans through the prostate were obtained at 20, 30, 40, 50, and 60 seconds following initiation of contrast injection. Computed tomography perfusion was compared with pathologic findings of Gleason score and tumor volume on whole-mount prostatectomy specimens. RESULTS: Conventional adenocarcinoma (Gleason score, 6-10) was present in all subjects, including one who also demonstrated a mucinous variant of prostate cancer. Visible focal CT enhancement was noted in 1 patient with a high-volume tumor and a Gleason score of 10. A positive correlation between local estimates of CT perfusion and percent of prostate volume occupied by tumor in each sextant was found for half of the subjects (Pearson correlation coefficient, 0.3-0.95; mean, 0.48) but statistically significant correlation (P < 0.05; Pearson coefficient, 0.9-0.95) was present in only the 2 subjects with the highest Gleason scores (8 and 10) and the highest tumor volume (> or = 50% in > or = 1 sextant region). CONCLUSION: Visible enhancement of prostate cancer during dynamic CT is present in a minority of subjects. Correlation between quantitative CT perfusion and tumor location is statistically significant only in subjects with localized high-volume, poorly differentiated prostate cancer.

Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism.

Liver steatosis is associated with the development of insulin resistance and the pathogenesis of type 2 diabetes. We tested the hypothesis that protein signals originating from steatotic hepatocytes communicate with other cells to modulate metabolic phenotypes. We show that the secreted factors from steatotic hepatocytes induce pro-inflammatory signaling and insulin resistance in cultured cells. Next, we identified 168 hepatokines, of which 32 were differentially secreted in steatotic versus non-steatotic hepatocytes. Targeted analysis showed that fetuin B was increased in humans with liver steatosis and patients with type 2 diabetes. Fetuin B impaired insulin action in myotubes and hepatocytes and caused glucose intolerance in mice. Silencing of fetuin B in obese mice improved glucose tolerance. We conclude that the protein secretory profile of hepatocytes is altered with steatosis and is linked to inflammation and insulin resistance. Therefore, preventing steatosis may limit the development of dysregulated glucose metabolism in settings of overnutrition.

Assessment of Glut-1 expression in cholangiocarcinoma, benign biliary lesions and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), cholangiocarcinoma (Chca) and benign bile ductule proliferations represent uncommon but important differential diagnoses in liver masses, especially if the patient has no known primary malignancy. The glucose transporter protein Glut-1 is commonly expressed in adenocarcinomas but its expression in HCC, Chca, and benign bile ductules has not been systematically investigated. Forty-two cases of Chca, 27 cases of benign bile ductule proliferations and 19 cases of HCC were stained with Glut-1. Cases were evaluated for a membranous staining pattern in tumor cells and the results compared. Twenty-one of 42 (50%) Chca stained with Glut-1 while no HCC or benign bile ductule proliferations did, neither did benign hepatocytes or portal triad structures. Glut-1 is a highly specific but insensitive stain for Chca. It may prove to be a helpful part of a diagnostic panel used to evaluate liver lesions.

The Das-1 immunostain is useful for discriminating metastatic colon adenocarcinoma from cholangiocarcinoma and hepatocellular carcinoma.

The distinction between cholangiocarcinoma, hepatocellular carcinoma and liver metastasis is important but at times difficult solely on microscopic appearances. The Das-1 immunostain exhibits specificity for colonic epithelium. However, its staining of cholangiocarcinomas and hepatocellular carcinomas has not been extensively studied. We evaluated the staining properties of the Das-1 immunostain in cholangiocarcinoma and hepatocellular carcinoma. Forty-four cholangiocarcinomas, 16 hepatocellular carcinomas, 17 colon adenocarcinomas metastatic to the liver and 3 benign biliary tumors were studied. The cases were stained with the Das-1 antibody following deparaffinization and rehydration. The slides were evaluated for membranous and/or cytoplasmic staining in a blinded fashion. The percentage of tumor cells exhibiting strong staining was estimated. Of the intra-hepatic cholangiocarcinomas, 4 of 36 (11%) and 2 of 16 (13%) hepatocellular carcinomas were positive for Das-1, though typically only in rare cells. In comparison, 7 of 8 (88%) extra-hepatic cholangiocarcinomas, 13 of 17 (77%) of metastatic colon carcinomas and 3 of 3 (100%) benign tumors of the biliary tract were strongly positive in a diffuse pattern. The Das-1 immunostain may play a useful role in evaluating liver malignancies.

Innate immune pathways in afferent lymph following vaccination with poly(I:C)-containing liposomes.

Many modern vaccines use defined adjuvants to stimulate the innate immune system and shape the adaptive immune response. The exact nature of these innate signals and whether immune differentiation can originate within the periphery is not known. Here we used an ovine lymphatic cannulation model to characterise the cellular and transcriptomic profile of the afferent lymph following injection of a liposomal vaccine formulation incorporating diphtheria toxoid and the innate stimulator poly(I:C) over a 78-h period. The response to this vaccine featured an early activation of broad pro-inflammatory pathways (e.g. TLR signalling and inflammasome pathways) and the transient recruitment of granulocytes into the lymph. At 24 h a more monocytic cellular profile arose coinciding with a transition to a specific antiviral response characterised by the up-regulation of genes associated with the receptors typical for the viral mimic, poly(I:C) (e.g. TLR3, RIG-I and MDA5). At the latest time points the up-regulation of IL-17A and IL-17F suggested that Th17 cells may participate in the earliest adaptive response to this vaccine. These data provide the most comprehensive picture of the cellular and molecular mechanisms that link the periphery to the draining lymph node following vaccination, and indicate that the immune response is capable of specialising within the periphery.

Cellular and chemokine-mediated regulation in schistosome-induced hepatic pathology.

In hepatic schistosomiasis, pathology arises when schistosome eggs become lodged in the host liver, evoking an interleukin 4 (IL-4)- and IL-13-mediated dominant CD4(+) Th2 immune response. This response leads to the development of granulomas and fibrosis, with eosinophils, neutrophils, macrophages, hepatic stellate cells, and lymphocytes all identified as major cellular contributors to these events. This review outlines the cellular and molecular mechanisms of hepatic schistosomiasis, with an emphasis on the major cellular components and their release of chemokines. The differences between Schistosoma mansoni- and Schistosoma japonicum-induced hepatic granuloma are also discussed. This comprehensive overview of the processes associated with hepatic schistosomiasis may provide new insights into improved treatment for both schistosomiasis and other granulofibrotic diseases.

Cell recruitment and antigen trafficking in afferent lymph after injection of antigen and poly(I:C) containing liposomes, in aqueous or oil-based formulations.

After vaccination, innate cell populations transport antigen from the tissue, via the afferent lymphatic vessels, into the local lymph node where they provide critical signals for the generation of an adaptive immune response. The present study uses a unique lymphatic cannulation model to examine, in real time, changes in afferent lymph after injection of a liposome-based delivery system, incorporating diptheria toxoid (DT) and the innate stimulator, poly(I:C). There was a dramatic but temporal recruitment of innate cell populations over time, with neutrophils and monocytes peaking at 6h and 28h post vaccination respectively. The number of dendritic cells (DC) did not increase over the 198h time period, while lymphocytes were slightly elevated at the latest times, indicating the start of an adaptive response. Monocytes and neutrophils were the predominant cell types transporting antigen at the early time points while DC were the most dominant antigen-carrying cells after 78h, predominantly the Sirp-α(high) DC subtype. Resuspending liposomes in oil instead of aqueous solutions has recently been shown to dramatically increase the level and persistence of an immune response and forms the basis of the novel adjuvant formulations, Vaccimax© and Depovax©. In the present study, formulation of the DT and poly(I:C) containing liposomes in an oil carrier dramatically reduced antigen transport to the draining lymph nodes. Examination of the injection site revealed the creation of an ectopic lymphoid tissue with prominent antigen foci and organized lymphoid cells, providing a possible mechanism for the persistence of an immune response in liposome-in-oil adjuvant formulation. Together, the present studies demonstrate the real-time innate in vivo response to vaccination of two novel liposome-based adjuvant systems and the dramatic effect of different carrier formulations.

Spatial and temporal transcriptomics of Schistosoma japonicum-induced hepatic granuloma formation reveals novel roles for neutrophils.

The severity of schistosome egg-induced hepatic granulomatous pathology depends markedly on the nature of the host immune responses. In this study, we used LMM and microarray analysis to compare gene expression profiles of histologically distinct zones within, and directly proximal to, hepatic granulomas that developed in C57BL/6 mice infected with Schistosoma japonicum. There was significant up-regulation of type-1, type-2, and type-17 immune-associated genes within the granuloma core (adjacent to eggs), followed by increased expression of type-2 and fibrotic genes at the outer zones of granulomas. Neutrophil-associated genes were also found to be expressed differentially in the core and at the peripheral zone of granulomas, present at 7 weeks p.i., demonstrating a significant role of neutrophils in S. japonicum granulomatous pathology. The release of NETs was observed microscopically in granulomas obtained from the livers of infected mice and when human neutrophils were incubated in vitro in the presence of S. japonicum eggs. These finding are the first to suggest a novel, dual role for neutrophils in the mediation of tissue damage and repair in S. japonicum egg-induced hepatic granulomatous lesions. Together, these results provide an overview of the local events occurring within the granuloma microenvironment.

Severe hepatosplenic schistosomiasis: clinicopathologic study of 102 cases undergoing splenectomy.

We present the preoperative findings of 102 patients who underwent successful splenectomy for advanced schistosomiasis japonica. All patients were symptomatic for schistosomiasis and had splenomegaly greater than or equal to II according to the Hackett criteria. Before surgery, all patients underwent clinical examination including full blood count; fibrinogen and serum protein levels; liver function tests; and serology for hepatitis B, C, and D. Ultrasound examination of the liver and spleen and liver histology for evidence of pathology were also undertaken. Ninety patients had a treatment history for schistosomiasis. Fifty-six patients were seropositive for hepatitis B virus antibody, and 6 patients were seropositive for hepatitis C virus antibody. Immunohistochemical testing of the liver samples confirmed that 45 patients were positive for hepatitis B virus surface antigen, thereby indicating active infection. A total of 66.7% of patients had fibrosis stages II to III by ultrasound; and 76.5% of patients had portal vein inner diameter greater than 12 mm, indicating portal vein hypertension. A total of 83.2% of patients showed various stages of esophageal varicosis via x-ray, and 81.4% had fibrotic stages III to IV by liver biopsy. Coinfection with hepatitis B virus accelerated the development of liver fibrosis. There was moderate concordance between the fibrosis assessed by ultrasonography and histopathology, indicating that ultrasound underestimates the true pathology. Combined assessment is needed to improve the diagnosis of clinical hepatic fibrosis.

Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models.

The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.